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Cochrane Database of Systematic Reviews Review - Intervention

Omega‐3 fatty acid addition during pregnancy

Authors' declarations of interest

Version published: 15 November 2018 Version history

https://doi.org/10.1002/14651858.CD003402.pub3
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Background

Higher intakes of foods containing omega‐3 long‐chain polyunsaturated fatty acids (LCPUFA), such as fish, during pregnancy have been associated with longer gestations and improved perinatal outcomes. This is an update of a review that was first published in 2006.

Objectives

To assess the effects of omega‐3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer‐term outcomes for mother and child.

Search methods

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 August 2018), and reference lists of retrieved studies.

Selection criteria

Randomised controlled trials (RCTs) comparing omega‐3 fatty acids (as supplements or as foods, stand‐alone interventions, or with a co‐intervention) during pregnancy with placebo or no omega‐3, and studies or study arms directly comparing omega‐3 LCPUFA doses or types. Trials published in abstract form were eligible for inclusion.

Data collection and analysis

Two review authors independently assessed study eligibility, extracted data, assessed risk of bias in trials and assessed quality of evidence for prespecified birth/infant, maternal, child/adult and health service outcomes using the GRADE approach.

Main results

In this update, we included 70 RCTs (involving 19,927 women at low, mixed or high risk of poor pregnancy outcomes) which compared omega‐3 LCPUFA interventions (supplements and food) compared with placebo or no omega‐3. Overall study‐level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials. Most trials were conducted in upper‐middle or high‐income countries; and nearly half the trials included women at increased/high risk for factors which might increase the risk of adverse maternal and birth outcomes.

Preterm birth < 37 weeks (13.4% versus 11.9%; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 RCTs, 10,304 participants; high‐quality evidence) and early preterm birth < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high‐quality evidence) were both lower in women who received omega‐3 LCPUFA compared with no omega‐3. Prolonged gestation > 42 weeks was probably increased from 1.6% to 2.6% in women who received omega‐3 LCPUFA compared with no omega‐3 (RR 1.61 95% CI 1.11 to 2.33; 5141 participants; 6 RCTs; moderate‐quality evidence).

For infants, there was a possibly reduced risk of perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, 7416 participants; moderate‐quality evidence: 62/3715 versus 83/3701 infants) and possibly fewer neonatal care admissions (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, 6920 participants; moderate‐quality evidence ‐ 483/3475 infants versus 519/3445 infants). There was a reduced risk of low birthweight (LBW) babies (15.6% versus 14%; RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high‐quality evidence); but a possible small increase in large‐for‐gestational age (LGA) babies (RR 1.15, 95% CI 0.97 to 1.36; 6 RCTs, 3722 participants; moderate‐quality evidence, for omega‐3 LCPUFA compared with no omega‐3. Little or no difference in small‐for‐gestational age or intrauterine growth restriction (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, 6907 participants; moderate‐quality evidence) was seen.

For the maternal outcomes, there is insufficient evidence to determine the effects of omega‐3 on induction post‐term (average RR 0.82, 95% CI 0.22 to 2.98; 3 trials, 2900 participants; low‐quality evidence), maternal serious adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low‐quality evidence), maternal admission to intensive care (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low‐quality evidence), or postnatal depression (average RR 0.99, 95% CI 0.56 to 1.77; 2 trials, 2431 participants; low‐quality evidence). Mean gestational length was greater in women who received omega‐3 LCPUFA (mean difference (MD) 1.67 days, 95% CI 0.95 to 2.39; 41 trials, 12,517 participants; moderate‐quality evidence), and pre‐eclampsia may possibly be reduced with omega‐3 LCPUFA (RR 0.84, 95% CI 0.69 to 1.01; 20 trials, 8306 participants; low‐quality evidence).

For the child/adult outcomes, very few differences between antenatal omega‐3 LCPUFA supplementation and no omega‐3 were observed in cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour (mostly low‐quality to very low‐quality evidence). The effect of omega‐3 LCPUFA on body mass index at 19 years (MD 0, 95% CI ‐0.83 to 0.83; 1 trial, 243 participants; very low‐quality evidence) was uncertain. No data were reported for development of diabetes in the children of study participants.

Authors' conclusions

In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega‐3 LCPUFA compared with no omega‐3. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega‐3 LCPUFA.

For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high‐quality (e.g. preterm birth) or moderate‐quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision.

Omega‐3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post‐term pregnancies. More studies comparing omega‐3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega‐3 LCPUFA against placebo or no intervention. However, further follow‐up of completed trials is needed to assess longer‐term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega‐3 LCPUFA, timing and doses; or by characteristics of women.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Omega‐3 fatty acid addition during pregnancy

What is the issue?

Do omega‐3 long chain polyunsaturated fatty acids (LCPUFA) taken during pregnancy ‐ either as supplements or as dietary additions in food (such as some types of fish) ‐ improve health outcomes for babies and their mothers? This is an update of a Cochrane Review that was first published in 2006.

Why is this important?

Preterm birth (babies born before 37 weeks pregnancy (gestation)) is a leading cause of disability or death in the first five years of life. Fish and fish oil contain omega‐3 LCPUFA (particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) and have been associated with longer pregnancies. So it is suggested that additional omega‐3 LCPUFAs in pregnancy may reduce the number of babies born preterm and may improve outcomes for children and mothers. However, many pregnant women do not eat fish very often. Encouraging pregnant women to eat fatty fish (which generally have low toxin levels) or to use omega‐3 LCPUFA supplements may improve children’s and women's health. This is an update of a Cochrane Review that was first published in 2006.

What evidence did we find?

We searched for evidence in August 2018 and found 70 randomised controlled trials (RCTs; this type of trial provides the most reliable results) (involving 19,927 women). Most trials evaluated a group of women who received omega‐3 LCPUFA and compared them with a group of women who received something that looked like omega‐3 LCPUFA but did not contain it (placebo) or received no omega‐3. The trials were mostly undertaken in upper‐middle or high‐income countries. Some studies included women at increased risk of preterm birth. The quality of the evidence from the included studies ranged from high to very low; this affected the certainty of the findings for different outcomes.

We found the incidence of preterm birth (before 37 weeks) and very preterm birth (before 34 weeks) was lower in women who received omega‐3 LCPUFA compared with no additional omega‐3. There were also fewer babies with low birthweight. However, omega‐3 LCPUFA probably increased the incidence of pregnancies continuing beyond 42 weeks, although there was no difference identified in induction of labour for post‐term pregnancies. The risk of the baby dying or being very sick and going to neonatal intensive care may be lower with omega‐3 LCPUFA compared with no omega‐3. We did not see any differences between groups for serious adverse events for mothers or in postnatal depression. Very few differences between the omega‐3 LCPUFA groups and no omega‐3 groups were observed in child development and growth.

Eleven trials reported that they had received industry funding. When we omitted these trials from the main outcomes (such as preterm birth and very preterm birth) it made very little, or no difference, to the results.

What does this mean?

Increasing omega‐3 LCPUFA intake during pregnancy, either through supplements or in foods, may reduce the incidence of preterm birth (before 37 weeks and before 34 weeks) and there may be less chance of having a baby with a low birthweight. Women who take omega‐3 LCPUFA supplements during pregnancy may also be more likely to have longer pregnancies. More studies are underway and their results will be included in a further update of this review. Future studies could consider if and how outcomes may vary in different populations of women, and could test different ways of increasing omega‐3 LCPUFA during pregnancy.

Authors' conclusions

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Implications for practice

Omega‐3 long‐chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), supplementation during pregnancy is a simple and effective way to reduce preterm, early preterm birth and low birthweight, with low cost and little indication of harm. The effect of omega‐3 LCPUFA on most child development and growth outcomes is minimal or remains uncertain. A universal strategy of supplementation may be reasonable, although ideally, with more knowledge, this would be targeted to women who would benefit the most. A further consideration is the present reliance on non‐sustainable sources of fish to manufacture omega‐3 LCPUFA supplements. Ideally, universal or targeted omega‐3 LCPUFA supplementation would be accompanied by other ways of improving women's overall nutrition during pregnancy.

Implications for research

More studies comparing omega‐3 LCPUFA and placebo are not needed at this stage. In addition to the 70 trials included in this review, there are 23 ongoing trials, including the large ORIP trial of over 5000 women which is due to report in 2019 (Makrides 2013 (ORIP)). It is important for trials to assess longer‐term outcomes for mother and child, in order to improve understanding of metabolic, growth, and neurodevelopment pathways, in particular.

Using data from completed trials and other studies, we also need to establish if, and how, outcomes vary by different types of omega‐3 fatty acids, timing and doses; and by characteristics of women (such as baseline DHA status, body‐mass index and previous pregnancy outcomes). Future priority research questions include establishing the minimum effective (and optimal) dose(s) of omega‐3 LCPUFA, the optimal balance of DHA and eicosapentaenoic acid and effects of different forms of omega‐3 LCPUFA. The ORIP trial will provide evidence on whether stopping supplementation at 34 weeks' gestation, instead of continuing supplementation until birth, helps prevent prolonged pregnancies. A planned individual participant meta‐analysis will also address some of these questions. Further mechanistic studies are needed for a broader understanding of the anti‐inflammatory actions of omega‐3 LCPUFA and the circumstances under which these may prevent preterm birth and other adverse birth outcomes.

Summary of findings

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Summary of findings for the main comparison. Birth/infant outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: birth/infant outcomes

Population: pregnant women and their babies

Settings: Angola (1 RCT), Australia (1 RCT), Belgium (1 RCT), Canada (1 RCT), Chile (1 RCT), Croatia (1 RCT), Chile (1 RCT), Denmark (3 RCTs), Egypt (1 RCT), Germany (2 RCTs), India (1 RCT), Iran (3 RCTs), Italy (1 RCT), Mexico (1 RCT), Netherlands (3 RCTs), Norway (1 RCT), Russia (1 RCT), Sweden (1 RCT), Turkey (1 RCT), UK (4 RCTs), USA (8 RCTs)

Intervention: omega 3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Preterm birth < 37 weeks

134/1000

119 per 1000

(109 to 130)

RR 0.89 (0.81 to 0.97)

10,304 (26 RCTs)

⊕⊕⊕⊕

HIGH1

Early preterm birth < 34 weeks

46/1000

27 per 1000

(20 to 35)

RR 0.58 (0.44 to 0.77)

5204 (9 RCTs)

⊕⊕⊕⊕

HIGH2

Perinatal death

20/1000

15 per 1000

(11 to 21)

RR 0.75 (0.54 to 1.03)

7416 (10 RCTs)

⊕⊕⊕⊝

MODERATE3

SGA/IUGR

129/1000

130 per 1000

(116 to 146)

RR 1.01 (0.90 to 1.13)

6907 (8 RCTs)

⊕⊕⊕⊝

MODERATE3

LBW

156/1000

140

(128 to 154)

RR 0.90 (0.82 to 0.99)

8449 (15 RCTs)

⊕⊕⊕⊕

HIGH

LGA

117/1000

134 per 1000

(113 to 159)

RR 1.15 (0.97 to 1.36)

3722 (6 RCTs)

⊕⊕⊕⊝

MODERATE4

Serious adverse events for neonate/infant

63/1000

45 per 1000 (37 to 62)

RR 0.72 (0.53 to 0.99)

2690 (2 RCTs)

⊕⊕⊝⊝

low:5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; LBW: low birth weight LGA: large‐for‐gestational age;RCT: randomised controlled trial; RR: risk ratio; SGA/IUGR: small‐for‐gestational age/intrauterine growth restriction

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

1 Design limitations: larger studies of high quality, but some smaller studies with unclear risk of selective reporting and some smaller studies with unclear or high attrition bias at the time of birth (not downgraded for study limitations)

2 Design limitations: larger studies of higher quality, but several studies with unclear or high attrition bias at the time of birth, or baseline imbalances (not downgraded for study limitations)

3 Imprecision (‐1): downgraded one level due to crossing line of no effect and/or wide confidence intervals

4 Imprecision (‐1): downgraded one level due to wide confidence intervals

5 Design limitations (‐2): downgraded two levels; one study with unclear allocation concealment and attrition bias; specific adverse events not detailed in this study

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Summary of findings 2. Maternal outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: maternal outcomes

Population: pregnant women

Settings: Angola (1 RCT), Australia (2 RCTs), Belgium (1 RCT), Brazil (1 RCT), Chile (1 RCT), Croatia (1 RCT), Denmark (3 RCTs), Egypt (1 RCT), Germany (3 RCTs), Hungary (1 RCT), Iran (5 RCTs), India (1 RCT), Italy (2 RCTs), Mexico (1 RCT), Netherlands (4 RCTs), Norway (2 RCTs), Russia (1 RCT), Scotland (2 RCTs), Spain (4 RCTs) Sweden (2 RCTs), Turkey (1 RCT), UK (3 RCTs) USA (12 RCTs), Venezuela (1 RCT)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Prolonged gestation > 42 weeks

16/1000

26/1000

(18 to 37)

RR 1.61 (1.11 to 2.33)

5141 (6)

⊕⊕⊕⊝

MODERATE6

Induction post‐term

83/1000

68/1000

(18 to 247)

Average RR 0.82 (0.22 to 2.98)

2900 (3)

⊕⊕⊝⊝

LOW7

Pre‐eclampsia

53/1000

44/1000

(37 to 53)

RR 0.84 (0.69 to 1.01)

8306 (20)

⊕⊕⊝⊝

LOW7

Defined as hypertension with proteinuria

Gestational length

The mean gestational age in the intervention group was 1.67 days greater (0.95 greater to 2.39 days greater)

Average MD 1.67 days (0.95 to 2.39)

12,517 (41)

⊕⊕⊕⊝

MODERATE8

Maternal serious adverse events

6/1000

6/1000

(2 to 16)

RR 1.04 (0.40 to 2.72)

2690 (2)

⊕⊕⊝⊝

LOW9

Maternal admission to intensive care

1/1000

1/1000

(0 to 3)

RR 0.56 (0.12 to 2.63)

2458 (2)

⊕⊕⊝⊝

LOW9

Postnatal depression

112/1000

100

(80 to 125)

Average RR 0.99 (0.56 to 1.77)

2431 (2)

⊕⊕⊝⊝

LOW10

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

6 Design limitations (‐1): downgraded one level due to some studies with attrition bias and some selective reporting bias; and some imprecision (not downgraded)

7 Design limitations (‐1): downgraded one level for combined study limitations (mostly attrition bias and selective reporting bias); Imprecision (‐1): downgraded one level due to confidence intervals including line of no effect

8 Design limitations (‐1): downgraded one level for study limitations (mainly attrition bias): heterogeneity I2 = 54%, but not downgraded due to use of a random‐effects model

9 Imprecision (‐2): downgraded two levels for wide confidence intervals and only 2 studies

10 Design limitations (‐1): downgraded one level for study limitations (unclear randomisation in 1 study); downgraded one level for imprecision (wide confidence intervals; 2 studies only)

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Summary of findings 3. Child/adult outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: child/adult outcomes

Population: children of women randomised to omega‐3 or no omega‐3 during pregnancy

Settings: Australia (2 RCTs), Bangladesh (1 RCT), Canada (1 RCT), Denmark (1 RCT), Hungary (1 RCT), Germany (1 RCT), Spain (2 RCTs), Mexico (1 RCT), Netherlands (1 RCT)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Cognition:

BSID II score at < 24 months

The mean BSID II score at 24 months in the intervention group was 0.37 points lower in the intervention group (1.47 lower to 0.76 higher)

MD ‐0.37 (‐1.49 to 0.76)

1154 (4)

⊕⊕⊝⊝

LOW11

Cognition:

BSID III score at < 24 months

The mean BSID III score at 24 months in the intervention group was 0.04 points higher (1.59 lower to 1.68 higher)

MD 0.04 (‐1.59 to 1.68)

809 (2)

⊕⊕⊝⊝

LOW12

IQ: WASI at 7 years

The mean WASI at 7 years in the intervention group was identical to the mean in the control group (0.79 points lower to 2.79 higher)

MD 1.00 (‐0.79 to 2.79)

543 (1)

⊕⊕⊝⊝

LOW12

IQ: WISC‐IV at 12 years

The WISC‐IV at 12 years in the intervention group was identical to in the control group (5.16 points lower to 7.16 higher)

MD 1.00 (‐5.16 to 7.16)

50 (1)

⊕⊝⊝⊝

VERY LOW13

Behaviour: BSID III adaptive behaviour score at 12‐18 months

The mean BSID III adaptive behaviour score in the intervention group at 12‐18 months was 1.20 points lower (3.12 lower to 0.72 higher)

MD ‐1.20 (‐3.12 to 0.72)

809 (2)

⊕⊕⊝⊝

LOW14

At 12 months (one study), 18 months (one study)

Behaviour: SDQ Total Difficulties at 7 years

The mean SDQ total difficulties score at 7 years in the intervention group was 1.08 higher (0.18 higher to 1.98 higher)

MD 1.08 (0.18 to 1.98)

543 (1)

⊕⊕⊝⊝

LOW12

BMI at 19 years

The mean BMI at 19 years in the intervention group was identical to that in the control group (0.83 lower to 0.83 higher)

MD 0 (‐0.83 to 0.83)

243 (1)

⊕⊝⊝⊝

VERY LOW15

Diabetes

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
BMI: body mass index; BSID: Bayley Scales of Infant Development; CI: confidence interval; IQ: Intelligence Quotient; MD: mean difference; SDQ: Strengths and Difficulties Questionnaire; WASI: Weschler Abbreviated Scale of Intelligence; WISC: Weschler Intelligence Scale for Children

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

11 Design limitations (‐1): downgraded one level due to unclear randomisation in 3 studies (that contributed 40% to meta‐analysis) and some studies at high risk of attrition bias; Imprecision (‐1): downgraded one level for wide confidence intervals including line of no effect

12 Imprecision (‐2): downgraded one level for confidence intervals including line of no effect; and one level for small number of studies/single study

13 Design limitations (‐1): downgraded one level for unclear selection bias (not clear if random sequence generated), possible attrition and/or reporting bias; Imprecision (‐2): downgraded two levels for wide confidence intervals including line of no effect and 1 study with small number of participants

14 Design limitations (‐1): downgraded one level for unclear randomisation (possible lack of allocation concealment), possible attrition and/or selective bias in 1 of the trials (contributing 15% to analysis); Imprecision (‐1): downgraded one level for confidence intervals including line of no effect and few studies

Design limitations (‐1): downgraded one level for unclear sequence generation and unclear blinding: Imprecision (‐2): downgraded two levels for confidence intervals including line of no effect and 1 study with small number of participants

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Summary of findings 4. Health service outcomes

Omega‐3 compared with no omega‐3 during pregnancy: health services outcomes

Population: pregnant women and their infants

Settings: Australia (1 RCT), Belgium (1 RCT), Denmark (2 RCTs), Egypt (1), Iran (2 RCTs), Italy (1 RCT), Netherlands (1 RCT), Norway (1 RCT), Russia (1 RCT), Scotland (1 RCT), UK (1 RCT), USA (5 RCTs)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

no omega‐3

omega‐3

Maternal hospital admission (antenatal)

273/1000

251/1000

(221 to 284)

RR 0.92 (0.81 to 1.04)

2876 (5)

⊕⊕⊝⊝

LOW 16

Infant admission to neonatal care

151/1000

139/1000

(125 to 156)

RR 0.92 (0.83 to 1.03)

6920 (9)

⊕⊕⊕⊝

MODERATE 17

Maternal length of hospital stay (days)

The mean length of stay in the intervention group was 0.18 days greater (0.20 less to 0.57 days greater)

MD 0.18 (‐0.20 to 0.57)

2290 (2)

⊕⊕⊝⊝

LOW 8

Infant length of hospital stay (days)

The mean length of stay in the intervention group was 0.11 days greater (1.40 less to 1.62 days greater)

MD 0.11 (‐1.40 to 1.62)

2041 (1)

⊕⊕⊝⊝

LOW 8

Costs

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; MD: mean difference; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

16 Design limitations (‐1): downgraded one level due to some studies with possible risk of attrition bias; Imprecision (‐1): downgraded one level for confidence intervals including line of no effect

17 Imprecision (‐1): downgraded one level for confidence intervals including line of no effect

18 Imprecision (‐2): downgraded one level for confidence intervals including line of no effect and once for small number of studies

Background

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Description of the condition

Complications of pregnancy such as preterm birth, fetal growth restriction, postnatal depression and pre‐eclampsia are relatively common and are associated with poorer outcomes for both the mother and child.

Of these, preterm birth has the highest burden of mortality and morbidity. Worldwide, approximately 15 million infants are born preterm (< 37 weeks completed gestation) every year (World Health Organization 2017). National rates range from 5% to 18%, and are rising in most countries (World Health Organization 2017). Preterm birth is the leading cause of death in newborns, accounting for more than 85% of all perinatal complications and death (Thornton 2008). Preterm birth is also the leading cause of deaths in children under five years of age, with 1 million of the 5.9 million child deaths each year due to preterm birth complications (Liu 2016).

Advances in perinatal and neonatal care mean more preterm babies are surviving, but many of these infants go on to suffer the short‐ and long‐term consequences of being born before their organs are mature (Saigal 2008). Infants born before 34 weeks often require intensive care and are at increased risk of respiratory distress syndrome, intraventricular haemorrhage, necrotising enterocolitis, blindness and cerebral palsy (Saigal 2008). In early childhood, developmental difficulties may emerge, with later societal and economic impacts due to low educational achievement, high unemployment, and deficits in social and emotional well‐being (Westrupp 2014).

For mothers, postnatal depression is the most prevalent mood disorder associated with childbirth; symptoms include mood disturbances, sleep disturbances (not related to the infant), appetite disturbances or weight loss, and suicidal ideation. Systematic reviews report that nearly 20% of women experience depression within 12 weeks of giving birth (Gaynes 2005), with symptoms persisting beyond the first year in 8% of affected women (Dennis 2012). Postnatal depression impairs maternal social and psychological functioning with possible subsequent adverse effects on child development outcomes (Conroy 2012; Zhu 2014).

Fetal growth restriction is associated with stillbirth, neonatal death and perinatal morbidity and an increased risk of adverse health outcomes into adulthood (Stillbirth CRE 2018). Pre‐eclampsia, characterised by high blood pressure and protein in the urine, can affect the kidneys, liver and blood‐clotting systems and have serious life‐threatening complications for the mother, such as eclampsia and can also result in preterm birth and fetal growth restriction (Mol 2016).

Description of the intervention

Maternal diet, including type and quantity of fat consumed, can have profound effects on pregnancy outcomes (Nordgren 2017). Omega‐3 long chain polyunsaturated fatty acid status (LCPUFA) in pregnancy was first linked to longer gestation, higher birthweight and less preterm birth by researchers observing longer pregnancies among Faroe Islanders (who consume a diet high in fish) than the Danish population (Olsen 1985; Olsen 1986; Olsen 1991).

A prospective observational study in 8729 Danish women showed that reporting low consumption of fish in pregnancy was a strong risk factor for preterm and early preterm birth (Olsen 2002; Olsen 2006) particularly if low intake occurred during a prolonged period of pregnancy (Olsen 2006). A study pooling results from 19 European birth cohorts with over 150,000 mother‐child pairs has subsequently shown an association between consumption of fish more than once a week by the mother and lower risk of preterm birth (Leventakou 2014), while a later study from Norway of over 67,000 women has also shown an association between increased fish consumption (particularly lean fish) and a lower prevalence of preterm birth (Brantsaeter 2017). Brantsaeter 2017 also examined the effect of omega‐3 LCPUFA in the form of supplements, and found an association with reduced early, but not later, preterm birth. Observational studies have also shown links between fish consumption in pregnancy and child neurodevelopment (Hibbeln 2007).

In this review we have taken a comprehensive approach and specified any form or dose of omega‐3 fatty acid as eligible, whether as fish or algal oil supplements, as food, or advice to consume particular foods rich in omega‐3 LCPUFA (such as fish). We have also specified any type of omega‐3 fatty acid (e.g. docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA)); and any combination of omega‐3 LCPUFAs as eligible. We have also included the omega‐3 PUFA alpha‐linolenic acid for completeness, although it is not a LCPUFA.

How the intervention might work

Consumption of omega‐3 fatty acids during pregnancy and lactation, particularly those forms derived from fish or marine sources, are thought to influence a wide range of maternal, fetal, neonatal, and later outcomes. These include child growth and development outcomes (Borge 2017; Jensen 2006), preventing childhood allergies (see separate Cochrane Review ‐ Gunaratne 2015), prevention of pre‐eclampsia, decreasing maternal depression and anxiety (Golding 2009; Vaz Jdos 2013), and increasing gestational length (as discussed above).

When consumed in the diet, the essential fatty acid alpha‐linolenic acid (ALA; 18:3 omega‐3) can be converted to biologically active derivatives including eicosapentaenoic acid (EPA; 20:5 omega‐3), docosapentaenoic acid (DPA; 22:5 omega‐3) and docosahexaenoic acid (DHA; 22:6 omega‐3). These fatty acids are precursors to a range of compounds that are known to minimise and help resolve inflammatory responses and oxidative stress (Leghi 2016). Pregnancy outcomes with an inflammatory component, such as preterm birth, are thought to be reduced by increasing omega‐3 LCPUFA concentrations through including fish in the maternal diet or taking fish oil supplements. Maintaining a balance between the metabolites of omega‐3 LCPUFA and the often pro‐inflammatory omega‐6 arachidonic acid is important in maintaining normal gestation length and is a critical element in cervical ripening and the initiation of labour (Zhou 2017). Adequate DHA, in particular, is thought to be crucial in fetal and early‐life brain development (Shulkin 2018).

Fish and seafood are the richest dietary sources of DHA (Greenberg 2008). However, fish consumption is low in many countries, and women of childbearing age may be reluctant to increase their fish intake due to perceptions that mercury and other pollutants in fish may affect their unborn child (Oken 2018). For example only 10% of women of childbearing age in Australia meet the recommended docosahexaenoic acid (DHA) intake (Koletzko 2007; Meyer 2016), which includes fish as well as fish oil supplementation. Many pregnant women are likely to have low concentrations of omega‐3 LCPUFA and may benefit from increasing DHA in their diet, either from food sources or as supplements.

Why it is important to do this review

Over the last 40 years, a slew of observational studies, randomised trials and reviews addressing omega‐3 fatty acids and pregnancy (e.g. Newberry 2016), involving hundreds of thousands of women, have been published. However many of these studies and reviews have concentrated on a particular focus such as allergy or child development, and reported only a selection of outcomes. Some outcomes such as preterm birth have not always been reported, despite the growing realisation that omega‐3 LCPUFA supplementation may have a role in preventing it. Furthermore, studies and reviews on omega‐3 LCPUFAs in pregnancy have differed in their findings and conclusions (e.g. Saccone 2016), sometimes due to selective reporting and other methodological issues.

Therefore, a comprehensive systematic review of omega‐3 fatty acids in pregnancy that covers all relevant maternal, perinatal and child outcomes (except allergy which is covered in Gunaratne 2015), all forms of omega‐3 fatty acids, and comparisons of doses, timing and types of omega‐3 fatty acids is required.

Objectives

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To assess the effects of omega‐3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer‐term outcomes for mother and child.

Methods

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Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs), including quasi‐randomised trials, and trials published in abstract form were eligible for inclusion.

We intended to include RCTs that use a cluster‐randomised design but identified none for inclusion in this update. Cross‐over trials are not eligible for inclusion in this review.

Types of participants

Pregnant women, regardless of their risk for pre‐eclampsia, preterm birth or intrauterine growth restriction (IUGR).

Types of interventions

  • Omega‐3 fatty acids (usually fish or algal oils) compared with placebo or no omega‐3 fatty acids

  • Trials that assessed omega‐3 fatty acid co‐interventions (e.g. omega‐3 with another agent)

  • Studies or study arms that compared omega‐3 doses or types of omega‐3 (e.g. DHA versus EPA) directly

Types of outcome measures

Primary outcomes

  • Preterm birth < 37 weeks

  • Early preterm birth < 34 weeks

  • Prolonged gestation (> 42 weeks)

Secondary outcomes
For the woman

  • Hypertension

  • Pre‐eclampsia

  • Eclampsia

  • Admission to hospital (antenatal or postnatal)

  • Caesarean section

  • Caesarean section (post‐term)

  • Induction (post‐term)

  • Haemorrhage; blood loss

  • Serious morbidity/mortality

  • Length of gestation

  • Adverse effects

  • Gestational diabetes

  • Depression

  • Anxiety

  • Stress (scale or response to challenge)

  • Gestational weight gain

  • Miscarriage

For babies

  • Stillbirths

  • Neonatal deaths

  • Perinatal deaths

  • Birthweight

  • Birth length

  • Head circumference

  • Low birthweight (< 2.5 kg)

  • Small‐for‐gestational age (SGA) (< 10th percentile)/IUGR

  • Large‐for‐gestational age

  • Intraventricular haemorrhage (and grade)

  • Respiratory distress syndrome

  • Necrotising enterocolitis

  • Jaundice requiring phototherapy

  • Sepsis

  • Retinopathy of prematurity

  • Neonatal convulsion

  • Admission to a neonatal intensive care unit

Longer term infant/child follow‐up

  • Physical growth

  • Mental and emotional health

  • Behaviour

  • Neurological/neurosensory and developmental outcomes (including cognitive domains: attention, executive function, language, memory, visuospatial and motor development)

  • Neurological disorders (e.g. cerebral palsy)

For health service resources

  • Admission and length of stay in hospital and intensive care facilities

  • Use of community health services

Search methods for identification of studies

The following methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.

Electronic searches

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register by contacting their Information Specialist (16 August 2018)

The Register is a database containing over 25,000 reports of controlled trials in the field of pregnancy and childbirth. It represents over 30 years of searching. For full current search methods used to populate Pregnancy and Childbirth’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link

Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is maintained by their Information Specialist and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

  2. weekly searches of MEDLINE (Ovid);

  3. weekly searches of Embase (Ovid);

  4. monthly searches of CINAHL (EBSCO);

  5. handsearches of 30 journals and the proceedings of major conferences;

  6. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Search results are screened by two people and the full text of all relevant trial reports identified through the searching activities described above is reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set that has been fully accounted for in the relevant review sections (Included studies; Excluded studies; Studies awaiting classification; Ongoing studies).

In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (29 August 2017) using the search terms given in Appendix 1.

Searching other resources

We searched the reference lists of retrieved studies.

We did not apply any language or date restrictions.

Data collection and analysis

Selection of studies

Two review authors independently assessed all the potential studies we identified as a result of the search strategy for inclusion. We resolved any disagreement through discussion or, if required, we consulted a third review author.

Data extraction and management

We designed a form to extract data. For eligible trials, two review authors extracted the data using the agreed form. We resolved discrepancies through discussion or, if required, we consulted a third review author. We entered data into Review Manager 5 software (Review Manager 2014), and checked for accuracy.

When information regarding any of the above was unclear, we attempted to contact authors of the original reports to request further details.

Assessment of risk of bias in included studies

Two review authors independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreement by discussion or by involving a third assessor.

(1) Random sequence generation (checking for possible selection bias)

For each included study we described the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We assessed the method as:

  • low risk of bias (any truly random process, e.g. random number table; computer random number generator);

  • high risk of bias (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number);

  • unclear risk of bias.

(2) Allocation concealment (checking for possible selection bias)

For each included study we described the method used to conceal allocation to interventions prior to assignment and assessed whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We assessed the methods as:

  • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);

  • high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth);

  • unclear risk of bias.

(3.1) Blinding of participants and personnel (checking for possible performance bias)

For each included study we described the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding unlikely to affect results. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed the methods as:

  • low, high or unclear risk of bias for participants;

  • low, high or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias)

For each included study we described the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed methods used to blind outcome assessment as:

  • low, high or unclear risk of bias.

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

For each included study we described, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported, or could be supplied by the trial authors, we planned to reinclude missing data in the analyses which we undertook.

We assessed methods as:

  • low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups);

  • high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomisation);

  • unclear risk of bias.

(5) Selective reporting (checking for reporting bias)

For each included study we described how we investigated the possibility of selective outcome reporting bias and what we found.

We assessed the methods as:

  • low risk of bias (where it is clear that all of the study’s prespecified outcomes and all expected outcomes of interest to the review were reported);

  • high risk of bias (where not all the study’s prespecified outcomes were reported; one or more reported primary outcomes was not prespecified; outcomes of interest are reported incompletely and so cannot be used; study failed to include results of a key outcome that would have been expected to have been reported);

  • unclear risk of bias.

(6) Other bias (checking for bias due to problems not covered by (1) to (5) above)

For each included study we described any important concerns we had about other possible sources of bias.

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Handbook (Higgins 2011).

Assessment of the quality of the evidence using the GRADE approach

For this update, we evaluated the quality of the evidence for the outcomes below using the GRADE approach as outlined in the GRADE handbook. The GRADE approach uses five considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of the body of evidence for each outcome. In randomised controlled trials, the evidence can be downgraded from 'high quality' by one level for serious (or by two levels for very serious) limitations, depending on assessments for risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates or potential publication bias.

Baby/infant

  • Preterm birth < 37 weeks

  • Preterm birth < 34 weeks

  • Perinatal death

  • SGA/IUGR

  • Low birthweight

  • Large‐for‐gestational age

Mother

  • Prolonged gestation (> 42 weeks)

  • Induction post‐term

  • Pre‐eclampsia

  • Length of gestation

  • Maternal adverse events

  • Maternal morbidity composite (serious morbidity)

  • Depression and/or anxiety (postnatal)

Child/adult

  • Cognition

  • Vision (neurosensory outcome)

  • Neurodevelopment

  • Behaviour

  • BMI (long‐term growth outcome)

  • Diabetes (long‐term development outcome)

Health services

  • Maternal hospital admission (antenatal; postnatal)

  • NICU admission

  • Maternal length of hospital stay

  • Infant length of hospital stay

  • Resource use

'Summary of findings' table

We used the GRADEpro Guideline Development Tool to import data from Review Manager 5 in order to create 'Summary of findings’ tables for maternal, baby/infant, child and health service outcomes (Review Manager 2014). We created 'Summary of findings' tables for the main comparison: omega‐3 LCPUFA versus no omega‐3 (e.g. placebo or no supplement). We have presented summaries of the intervention effect and measures of quality according to the GRADE approach in the 'Summary of findings' tables.

Measures of treatment effect

Dichotomous data

For dichotomous data, we have presented results as summary risk ratios with 95% confidence intervals.

Continuous data

For continuous data, we have used the mean differences if outcomes were measured in the same way between trials. In future updates, we plan to use the standardised mean difference to combine trials that measure the same outcome, but use different methods.

Unit of analysis issues

Cluster‐randomised trials

We did not identify any cluster‐randomised trials.

In future updates of this review, if cluster‐randomised trials are included, we will adjust their sample sizes and event rates using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), using an estimate of the intra‐cluster correlation co‐efficient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. If we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC. If we identify both cluster‐randomised trials and individually‐randomised trials, we plan to synthesise the relevant information. We will consider it reasonable to combine the results from both if there is little heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely.

We will also acknowledge heterogeneity in the randomisation unit and we will perform a subgroup analysis to investigate the effects of the randomisation unit.

Cross‐over trials

We considered cross‐over designs to be an inappropriate design for this research question.

Multi‐arm trials

For included multi‐arm trials, we used methods described in the Cochrane Handbook for Systematic Reviews of Interventions to overcome possible unit‐of analysis errors (Higgins 2011), by combining groups to make a single pair‐wise comparison (where appropriate), or by splitting the 'shared' group into two (or more) groups with smaller sample sizes, and including the two (or more) comparisons (see Included studies text for details of how this was done for each of the 10 multi‐arm trials we included).

Dealing with missing data

For included trials, we noted levels of attrition.

For all outcomes, we carried out analyses, as far as possible, on an intention‐to‐treat basis, that is, we have attempted to include all participants randomised to each group in the analyses, and all participants were analysed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial was the number randomised minus any participants whose outcomes were known to be missing.

Assessment of heterogeneity

We assessed statistical heterogeneity in each meta‐analysis using the Tau², I² and Chi² statistics. We regarded heterogeneity as substantial if I² was greater than 30% and either Tau² was greater than zero, or there was a low P value (less than 0.10) in the Chi² test for heterogeneity.

Assessment of reporting biases

Where there were 10 or more trials in a meta‐analysis we investigated reporting biases (such as publication bias) using funnel plots. We assessed funnel plot asymmetry visually.

Data synthesis

We carried out statistical analysis using Review Manager 5 software (Review Manager 2014). We used fixed‐effect meta‐analysis for combining data where it was reasonable to assume that trials were estimating the same underlying treatment effect, that is, where trials were examining the same intervention, and the trials’ populations and methods were judged to be sufficiently similar. Where there was clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials, or where substantial statistical heterogeneity was detected (I² > 30%), we used random‐effects meta‐analysis to produce an overall summary, if an average treatment effect across trials was considered clinically meaningful. The random‐effects summary was treated as the average of the range of possible treatment effects and we have discussed the implications of treatment effects differing between trials. If the average treatment effect was not clinically meaningful, we would not have combined trials.

Where we have used random‐effects analyses, the results have been presented as the average treatment effect with 95% confidence intervals, and the estimates of T² and I².

Subgroup analysis and investigation of heterogeneity

We investigated substantial heterogeneity using subgroup analyses and sensitivity analyses.

We carried out the following subgroup analyses.

1. Type of intervention

All the following interventions compared with each other:

  • omega‐3 LCPUFA supplements only;

  • omega‐3 supplements plus omega enriched food or dietary advice;

  • omega enriched food only;

  • omega‐3 LCPUFA supplements plus advice and/or other agents.

2. Dose of omega‐3 LCPUFA

The following doses compared to each other:

  • low (< 500 mg/day);

  • mid (500 mg to 1 g/day);

  • high (> 1 g/day).

3. Timing

Comparison of the following gestational ages when omega‐3 LCPUFA supplements commenced:

  • ≤ 20 weeks' gestation;

  • > 20 weeks' gestation.

4. Type of omega‐3

Comparison of the following types of omega‐3:

  • DHA/largely DHA;

  • mixed EPA/DHA;

  • mixed DHA/EPA/other

5. Risk of poorer maternal/perinatal outcomes

Comparison of the following risk levels with each other:

  • increased or high risk

  • low risk

  • any or mixed risk

For subgroup 1 type of intervention (Analysis 2) we did not restrict this analysis to the selected group of outcomes used in the other subgroup analyses. This was done to help readers to see results across all outcomes by type of omega‐3 intervention (except for longer term outcomes or other outcomes reporting multiple time points (analyses 1.63 to 1.92) which were sparsely reported).

The following outcomes were used in the other four subgroup analyses (analyses 2‐5):

  • preterm birth < 37 weeks;

  • early preterm birth < 34 weeks;

  • prolonged gestation (> 42 weeks);

  • pre‐eclampsia;

  • caesarean section;

  • length of gestation;

  • perinatal death;

  • stillbirth;

  • neonatal death;

  • low birthweight;

  • SGA/IUGR;

  • birthweight.

We assessed subgroup differences by interaction tests available within Review Manager 5 (Review Manager 2014). We reported the results of subgroup analyses quoting the Chi² statistic and P value, and the interaction test I² value.

Sensitivity analysis

We carried out sensitivity analyses (Analysis 9) to explore the effects of trial quality assessed by sequence generation and concealment of allocation, and inadequate blinding, by omitting trials rated as 'high risk of bias' or 'unclear risk of bias' for any one or more of these sources of bias, to assess whether this made any difference to the overall result. We restricted this analysis to 12 outcomes:

  • preterm birth < 37 weeks;

  • early preterm birth < 34 weeks;

  • prolonged gestation > 42 weeks;

  • pre‐eclampsia;

  • caesarean section;

  • birthweight;

  • perinatal death;

  • stillbirth;

  • neonatal death;

  • gestational age;

  • low birthweight;

  • SGA/IUGR

These outcomes are this review's three primary outcomes, plus nine secondary outcomes that were selected for use in subgroup analyses 3, 4 and 5).

Results

Description of studies

Results of the search

For this update, we assessed 447 trial reports in total. This included 406 new reports, plus we reassessed the six included studies (17 reports), 15 excluded studies (20 reports), three ongoing studies and one awaiting further classification in the previous version of the review (Makrides 2006Makrides 2006).

Where required, we reclassified some of the studies/records which were listed as excluded, ongoing or awaiting classification in the previous version of this review (Makrides 2006).

Overall, we have included 70 trials (374 reports). The six trials originally included are still included. The three trials originally listed as ongoing have reported results and are now included. Eight trials that were previously excluded are now included (either due to the enlarged scope of the review or changes in review methodology (e.g. fulfilling inclusion criteria, even if the trial does not report any of the review's prespecified outcomes)).

As of August 2018, we have:

See Figure 1 which outlines the study flow.

Figure 1
Study flow diagram.

Study flow diagram.

Included studies

Following application of eligibility criteria, we included 70 RCTs comparing an omega‐3 fatty acid intervention (stand‐alone or with a co‐intervention), with placebo or no omega‐3 fatty acids in this review (Ali 2017; Bergmann 2007; Bisgaard 2016; Boris 2004; Bosaeus 2015; Bulstra‐Ramakers 1994; Carlson 2013; Chase 2015; D'Almedia 1992; de Groot 2004; Dilli 2018; Dunstan 2008; England 1989; Freeman 2008; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Hauner 2012; Helland 2001; Horvaticek 2017; Hurtado 2015; Ismail 2016; Jamilian 2016; Jamilian 2017; Judge 2007; Judge 2014; Kaviani 2014; Keenan 2014; Khalili 2016;. Knudsen 2006; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Makrides 2010; Malcolm 2003; Mardones 2008; Martin‐Alvarez 2012; Miller 2016; Min 2014; Min 2016; Mozurkewich 2013; Mulder 2014; Noakes 2012; Ogundipe 2016; Oken 2013; Olsen 1992; Olsen 2000; Onwude 1995; Otto 2000; Pietrantoni 2014; Ramakrishnan 2010; Ranjkesh 2011;Razavi 2017; Rees 2008; Ribeiro 2012; Rivas‐Echeverria 2000; Samimi 2015; Sanjurjo 2004; Smuts 2003a; Smuts 2003b; Su 2008; Taghizadeh 2016; Tofail 2006; Valenzuela 2015; Van Goor 2009; Van Winden 2017; Vaz 2017).

All the included trials were individually randomised. Ten were multi‐arm trials (Bergmann 2007; Harris 2015; Jamilian 2017; Knudsen 2006; Krauss‐Etschmann 2007; Laivuori 1993; Mozurkewich 2013; Oken 2013; Razavi 2017; Van Goor 2009).

A total of 19,927 women were involved in the included trials. Knudsen 2006 was the largest trial, randomising 3098 women, followed by Makrides 2010 and Olsen 2000, in which 2399 and 1647 women, respectively, were randomised. Ribeiro 2012 was the smallest trial, randomising 11 women, followed by Van Winden 2017 and Laivuori 1993 (14 and 18 women, respectively). For the majority of the included trials, fewer women were included in analyses than were randomised.

The included trials have been published over nearly three decades ‐ from 1989 to 2018.

Review structure

The analyses in the review are structured as follows.

  • Overall: omega‐3 fatty acids versus placebo or no omega‐3 fatty acids (Analysis 1)

  • Type of intervention subgroups: omega‐3 supplementation alone; combined with food and/or advice; omega‐3 rich food; omega‐3 plus another agent ‐ all versus no omega‐3 (Analysis 2)

  • Dose subgroups (DHA/EPA): low (< 500 mg/day) versus mid (500 mg to 1 g/day) versus high (> 1 g/day) (Analysis 3)

  • Timing subgroups: gestational age when omega‐3 supplements commenced: ≤ 20 weeks' gestation versus > 20 weeks' gestation (Analysis 4)

  • Type of omega‐3: DHA/largely DHA; mixed EPA/DHA; mixed DHA/EPA/other (Analysis 5)

  • Risk subgroups: increased/high risk versus low risk versus any/mixed risk (Analysis 6)

  • Direct comparisons of omega‐3 doses (Analysis 7)

  • Direct comparisons of omega‐3 types (Analysis 8)

  • Sensitivity analysis (Analysis 9)

Further details are given below and in the Characteristics of included studies tables.

Settings

The 70 trials were conducted in a wide range of countries, and most (but not all) in upper‐middle or high‐income countries:

Two of the 70 trials were performed in more than one country: Krauss‐Etschmann 2007 (Germany, Spain and Hungary); and Olsen 2000 (Denmark, Scotland, Sweden, United Kingdom, Italy, the Netherlands, Norway, Belgium and Russia). Van Winden 2017 did not report where the study was conducted.

Participants

All participants were pregnant women (and their children). Most pregnancies were singletons, with some studies specifically excluding multiple births. Characteristics of the women are summarised below, including age, parity, eligibility criteria relating to omega‐3 consumption, socioeconomic status, ethnicity, smoking status and risk of adverse pregnancy outcomes. Further details are included in the Additional tables.

Age

Where reported, the mean age of the women ranged from 22 years in Smuts 2003a to 40 years in several studies. The mean age of the women in both groups was at least 30 years in 18 of the included trials (Bergmann 2007; Bisgaard 2016; Bosaeus 2015; Dilli 2018; Dunstan 2008; Furuhjelm 2009; Hauner 2012; Jamilian 2016; Jamilian 2017; Krauss‐Etschmann 2007; Laivuori 1993; Miller 2016; Min 2014 [diabetic women]; Min 2016; Mulder 2014; Rees 2008; Su 2008; Van Goor 2009). Maternal age of women across the included trials is summarised further in Table 1.

Open in table viewer
Table 1. Maternal age (years)

Study ID

Omega‐3 (mean (SD)unless otherwise reported)

No omega‐3 (mean (SD)unless otherwise reported)

Ali 2017

27 (4.3)

27 (4.8)

Bergmann 2007

30.9 (4.6) for DHA/FOS group

30.0 (4.62) in vitamin/mineral group; 31 (4.71) for FOS group

Bisgaard 2016;

32.3 (4.3)

32.2 (4.5)

Boris 2004

"The three study groups were similar in baseline characteristics with regard to maternal age at delivery (data not shown)".

Bosaeus 2015

31.4 (3.9)

31.2 (4.0)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

25.3 (4.9)

24.8 (4.7)

Chase 2015

Not reported

D'Almedia 1992

"Ages ranged from 14‐40 years"

de Groot 2004

30.0 (3.3)

29.2 (3.8)

Dilli 2018

30.9 (5.3)

32.7 (5.9)

Dunstan 2008

30.9 (3.7)

32.6 (3.6)

England 1989

Not reported

Freeman 2008

31.0 (5.8)

29.7 (6.2)

Furuhjelm 2009

31.1 (4.1)

31.7 (3.9)

Giorlandino 2013

32.6 (4.6)

32.2 (4.8)

Gustafson 2013

25.5 (4.3)

25.6 (4.8)

Haghiac 2015

27 (5)

27 (5)

Harper 2010

Median (interquartile range): 28 (23 ‐ 32)

Median (interquartile range): 27 (24‐32)

Harris 2015

In high‐dose group 24.5 (12.72);

In low‐dose group 24.3 (12.72)

27.0 (9.05)

Hauner 2012

31.9 (4.9)

31.6 (4.5)

Helland 2001

28.6 (3.4)

27.6 (3.2)

Horvaticek 2017

29.8 (5.5)

29.6 (4.8)

Hurtado 2015

30.5 (4.8)

29.9 (4.7)

Ismail 2016

27.17 (6.34)

26.71 (5.66)

Jamilian 2016

30.1 (5.3)

30.0 (5.5)

Jamilian 2017

30.7 (3.5) for omega‐3 group

31.2 (4.3) for omega‐3 + vitamin D group

30.7 (4.1) for placebo group

31.5 (7.0) for vitamin D group

Judge 2007

23.9 (4.3)

24.7 (4.8)

Judge 2014

Not reported

Kaviani 2014

26.33 (4.2)

25.15 (4.2)

Keenan 2014

Not reported

Khalili 2016

25.9 (4.8)

26.9 (4.5)

Knudsen 2006

28.4 for 0.1 g/day EPA + DHA group

28.7 for 0.3 g/day EPA + DHA group

28.4 for 0.7 g/day EPA + DHA group

28.9 for 1.4 g/day EPA + DHA group

28.8 for 2.8 g/day EPA + DHA group

28.8 for 2.2g/day ALA group

28.5 for no treatment group

Krauss‐Etschmann 2007

Median (range): 30.6 (20.1 ‐ 41.1) for DHA/EPA group

Median (range): 31.1 (21.5 ‐ 40.1) for DHA/EPA+folate group

Median (range): 31.1 (18.8 ‐ 40.8) for folate group

Median (range): 31.1 (18.4 ‐ 40.3) for no treatment (placebo) group

Krummel 2016

27.9 (4.6)

26.3 (5.0)

Laivuori 1993

Median (IQR): 30.3 (24‐40)

Median (IQR): 30.2 (26‐32) in placebo group; 32.0 (23‐40) in primrose oil group

Makrides 2010

28.9 (5.7)

28.9 (5.6)

Malcolm 2003

Not reported

Mardones 2008

25.06 (5.73)

25.11 (7.45)

Martin‐Alvarez 2012

Not reported

Miller 2016

31.7 (4.4)

31.2 (4.4)

Min 2014

Median (range): 29 (18 ‐ 42)

Median (range): 29 (18 ‐ 44)

Min 2014 [diabetic women]

Median (range): 34 (20 ‐ 45)

Median (range): 37 (27‐45)

Min 2016

Median (range): 31.0 (21.0 ‐ 41.0)

Median (range): 32.0 (21.0 ‐ 44.0)

Mozurkewich 2013

30.6 (4.5) in DHA rich fish oil group; 29.9 (5.0) in EPA rich fish oil group

30.4 (5.9)

Mulder 2014

32.6 (4.04)

33.4 (3.61)

Noakes 2012

29.5 (3.94)

28.4 (4.69)

Ogundipe 2016

Not reported

Oken 2013

Median (IQR): 32.6 (27.9 ‐ 35.9) advice group;

27.6 (24.5 ‐ 32.0) advice + gift card group

Median (IQR): 32.4 (27.7 to 34.3)

Olsen 1992

29.4 (4.4)

olive oil group 29.7 (4.3); placebo/no oil group 29.1 (4.1)

Olsen 2000

Prophylactic trials

PD trial 29.3 (4.87)

IUGR trial 30 (4.64)

PIH trial 30.3 (7.01)

Twins trial 30.2 (6.18)

Therapeutic trials

Threat‐PE trial 32.1 (11.7)

Susp‐IUGR trial 29.3 (7.88)

Prophylactic trials

PD trial 30.0 (6.22)

IUGR trial 29.0 (3.93)

PIH trial 28.9 (5.32)

Twins trial 30.2 (6.35)

Therapeutic trials

Threat‐PE trial 32.9 (14.6)

Susp‐IUGR trial 29.8 (10.3)

Olsen 2000 [twins]

see Olsen 2000

Onwude 1995

Mean (range): 26.6 (18‐39)

Mean (range): 26.1 (16‐40)

Otto 2000

30.3 (5.2)

28.3 (4.85)

Pietrantoni 2014

30.86 (4.18)

29.92 (4.80)

Ramakrishnan 2010

26.2 (4.6)

26.3 (4.8)

Ranjkesh 2011

30.06 (7.59)

28.96 (6.40)

Razavi 2017

29.7 (3.6) for omega‐3 group

29.9 (4.0) for omega‐3 + vitamin D group

29.2 (3.4) for placebo group

29.9 (5.0) for vitamin D group

Rees 2008

31.2 (4.4)

34.5 (3.8)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Median (range): 26.8 (18‐39)

Median (range): 26.1 (16‐40)

Sanjurjo 2004

34.5 (7.41)

31.25 (5.18)

Smuts 2003a

21.7 (4.3)

21.6 (4.2)

Smuts 2003b

High DHA egg group 19.9 (4.1)

Ordinary egg group 24.8 (7.8)

Su 2008

30.9 (3.9)

31.3 (5.7)

Taghizadeh 2016

28.6 (6.3)

29.4 (4.4)

Tofail 2006

22.1 (4.2)

23.4 (4.5)

Valenzuela 2015

29 (4.7)

28.3 (6.7)

Van Goor 2009

Median (range): 32.3 (22.3 ‐ 43.3) in DHA group;

31.5 (24.8 ‐ 41.4) in DHA + AA group

Median (range): 33.5 (26.0 ‐ 40.3)

Van Winden 2017

Not reported

Vaz 2017

Median (IQR): 25.5 (22.0‐34.5)

Median (IQR): 27.0 (21.0 ‐ 31.0)

Abbreviations: IQR (interquartile range)

Parity

Five trials specifically reported parity: Rivas‐Echeverria 2000 excluded nulliparous women; Smuts 2003b excluded women with more than four prior pregnancies; Valenzuela 2015 included women with one to four prior births; Van Goor 2009 included women with a first or second pregnancy. Olsen 2000, for the prophylactic trials, included women who in an early pregnancy had experienced preterm birth (before 259 days gestation). Twenty‐eight of the trials did not report baseline information related to parity clearly (Boris 2004; Bulstra‐Ramakers 1994; Chase 2015; D'Almedia 1992; Dilli 2018; England 1989; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Harper 2010; Harris 2015; Jamilian 2016; Jamilian 2017; Judge 2014; Kaviani 2014; Keenan 2014; Krummel 2016; Malcolm 2003; Martin‐Alvarez 2012; Miller 2016; Noakes 2012; Ogundipe 2016; Ramakrishnan 2010; Razavi 2017; Ribeiro 2012; Samimi 2015; Taghizadeh 2016; Van Winden 2017). Both nulliparous and multiparous women were included in the remaining 38 trials (Ali 2017; Bergmann 2007; Bisgaard 2016; Bosaeus 2015; Carlson 2013; de Groot 2004; Dunstan 2008; Freeman 2008; Haghiac 2015; Hauner 2012; Helland 2001 (nulliparous and primiparous only); Horvaticek 2017; Hurtado 2015; Ismail 2016; Judge 2007; Khalili 2016; Knudsen 2006; Krauss‐Etschmann 2007; Laivuori 1993; Makrides 2010; Mardones 2008; Min 2014; Min 2016; Mozurkewich 2013; Mulder 2014; Oken 2013; Olsen 1992; Olsen 2000 (therapeutic trials only); Onwude 1995; Otto 2000; Pietrantoni 2014; Ranjkesh 2011; Rees 2008; Sanjurjo 2004; Smuts 2003a; Su 2008; Tofail 2006; Vaz 2017). Detailed information relating to parity is reported in Table 2.

Open in table viewer
Table 2. Maternal parity

Study ID

Omega‐3

No omega‐3

Ali 2017

Mean (SD): 2.9 (4.8)

Mean (SD): 2.8 (1.6)

Bergmann 2007

> 1: 22 (45.8%) in DHA/FOS group

> 1: 28 (57.1%) in vitamin/mineral group

24 (51.1%) in FOS group

Bisgaard 2016;

1: 155 (44.8%)

1: 166 (47.6%)

Boris 2004

Not reported

Bosaeus 2015

Median (IQR): 0.5 (0,1)

Median (IQR): 0 (0,1)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

Prior pregnancies, N

Mean (SD): 1.2 (1.3)

Prior pregnancies, N

Mean (SD): 1.3 (1.4)

Chase 2015

Not reported

D'Almedia 1992

Not reported

de Groot 2004

0: 11 (38%)

1: 15 (52%)

2: 3 (10%)

3: 0 (0%)

0: 12 (41%)

1: 11 (38%)

2: 5 (17%)

3: 1 (3%)

Dunstan 2008

≥ 1: 15 (45.5%)

≥ 1: 21 (53.8%)

England 1989

Not reported

Freeman 2008

Primiparous: 24 (77.4%)

Primiparous: 22 (78.6%)

Furuhjelm 2009

Not reported

Giorlandino 2013

Not reported

Gustafson 2013

Not reported

Haghiac 2015

0: 7 (28%)

1:18 (72%)

0: 5 (21%)

1: 19 (79%)

Harper 2010

Not reported

Harris 2015

Not reported

Hauner 2012

Primiparous: 55.8%

Primiparous: 61.2%

Helland 2001

Mean (SD): 0.3 (0.5)

Mean (SD): 0.3 (0.5)

Horvaticek 2017

Nulliparous: 25 (53%)

Primiparous: 22 (47%)

Nulliparous: 26 (60%)

Primiparous: 17 (40%)

Hurtado 2015

Multiparous: 35.6%

Multiparous: 31.8%

Ismail 2016

Mean (SD): 1.38 (1.67)

Mean (SD): 1.53 (1.55)

Jamilian 2016

Not reported

Jamilian 2017

Not reported

Judge 2007

Mean (SD): 1.5 (0.8)

Mean (SD): 1.8 (0.8)

Judge 2014

Not reported

Kaviani 2014

Not reported

Keenan 2014

Not reported

Khalili 2016

1: 38 (50.7%)

2: 28 (37.3%)

≥ 3: 9 (12.0%)

1: 37 (49.3%)

2: 27 (36%)

≥ 3: 11 (14.7%)

Knudsen 2006

Primiparous women

0.1 g/day EPA + DHA group: 257 (66.2%)

0.3 g/day EPA + DHA group: 267 (69.5%)

0.7 g/day EPA + DHA group: 244 (63.5%)

1.4 g/day EPA + DHA group: 247 (64.7%)

2.8 g/day EPA + DHA group: 246 (62.9%)

2.2 g/day ALA group: 258 (66.3%)

Primiparous women

No treatment group: 513 (66.4%)

Krauss‐Etschmann 2007

< 2: 56 (86%) for DHA/EPA group; 56 (88%) for DHA/EPA+folate group

2: 7 (11%) for DHA/EPA group; 6 (9%) for DHA/EPA+folate group

> 2: 2 (3%) for DHA/EPA group; 2 (3%) for DHA/EPA+folate group

< 2: 65 (90%) for folate group; 61 (88%) for placebo group

2: 7 (10%).for folate group; 7 (10%) for placebo group

> 2: 0 (0) for folate group; 1 (1%) for placebo group

Krummel 2016

Not reported

Laivuori 1993

Nulliparous: 2 (66%) in fish oil group

Primiparous: 1 in (33%) fish oil group

Nulliparous: 1 (25%) in primrose oil group; 3 (75%) in placebo group

Primiparous: 3 (60%) in primrose oil group; 2 (40%) in placebo group

Makrides 2010

Primiparous: 471 (39.3%)

Primiparous: 474 (39.4%)

Malcolm 2003

Not reported

Mardones 2008

Mean (SD): 1.68 (0.90)

Mean (SD): 1.74 (0.91)

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

0: 18 (40%)

1‐3: 26 (57.8%)

> 4: 1 (2.2%)

0: 14 (35.0%)

1‐3: 23 (57.5%)

> 4: 2 (5.0%)

Min 2014 [diabetic women]

0: 10 (24%)

1‐3: 27 (65.9%)

> 4: 3 (7.3%)

0: 7 (14.9%)

1‐3: 32 (68.1%)

> 4: 6 (12.8%)

Min 2016

0: 33 (50%)

1‐3: 27 (41%)

≥ 4: 6 (9%)

0: 24 (35%)

1‐3: 40 (57%)

≥ 4: 5 (7%)

Mozurkewich 2013

Mean (SD):

0.87 (0.83) for EPA rich fish oil group;

1.08 (0.94) for DHA rich fish oil group

Mean (SD): 0.85 (1.2)

Mulder 2014

1: 60.6%

2: 30.8%

> 2: 8.6%

1: 47.7%

2: 36.7%

> 2: 15.6%

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Primiparous:

6 (35%) in advice group;

4 (24%) in advice + gift card group

Primiparous:

6 (30%) in control group

Olsen 1992

Primiparous:

Fish oil group: 56%

Primiparous:

Olive oil group: 61%

No oil group: 60%

Olsen 2000

Prophylactic trials: no nulliparous women except for:

Twins trial: 52.5% nulliparous

Therapeutic trials

Threat‐PE trial: 71.4% nulliparous

Susp‐IUGR trial: 52.0% nulliparous

Prophylactic trials: no nulliparous women except for:

Twins trial: 52.5% nulliparous

Therapeutic trials

Threat‐PE trial: 65.6% nulliparous

Susp‐IUGR trial: 51.9% nulliparous

Onwude 1995

Included primiparous and multiparous women

Otto 2000

Primiparous: 8 (67%)

Primiparous: 5 (42%)

Pietrantoni 2014

0: 46 (36%)

1: 83 (64%)

0: 50 (40%)

1: 76 (60%)

Ramakrishnan 2010

Not reported

Ranjkesh 2011

Mean (SD): 0.46 (0.50)

Mean (SD): 0.40 (0.49)

Razavi 2017

Not reported

Rees 2008

Mean (SD): 1.4 (0.9)

Mean (SD): 1.6 (1.2)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Excluded nulliparous women

Samimi 2015

Not reported

Sanjurjo 2004

Mean (SD): 1.63 (0.74)

Mean (SD): 1.38 (0.52)

Smuts 2003a

Nulliparous before study:

68%

Nulliparous before study:

58%

Smuts 2003b

Women were excluded if they had more than 4 previous pregnancies

Mean (SD): 1.9 (1.1)

Mean (SD): 2.3 (1.9)

Su 2008

Mean (SD): 1.7 (1.1)

Mean (SD): 1.8 (1.1)

Taghizadeh 2016

Not reported

Tofail 2006

Women with > 2 children: 16.8%

Women with > 2 children: 31.5%

Valenzuela 2015

Included women with 1‐4 prior births

Van Goor 2009

Included women with a first or second pregnancy

Van Winden 2017

Not reported

Vaz 2017

0‐1: 26 (81.2%)

≥ 2: 6 (18.8%)

0‐1: 18 (64.3%)

≥ 2: 10 (35.7%)
Eligibility criteria relating to omega‐3 intake

Forty of the 70 trials reported eligibility criteria relating to omega‐3 intake, such as excluding women with an allergy to fish or fish products and/or excluding women taking omega‐3, fish oil or DHA supplements or regular/any intake of fish. However in one case, women were required to be consuming fish at least twice a week to be eligible for inclusion in the trial in addition to either omega‐3 LCPUFA supplementation or placebo (Pietrantoni 2014). See Table 3 for further details for each relevant trial.

Open in table viewer
Table 3. Maternal omega‐3 intake criteria

Study

Eligibility criteria

Carlson 2013

Excluded women taking ≥ 300 mg DHA a day

Chase 2015

Excluded women planning to take DHA during pregnancy

de Groot 2004

Excluded women consuming fish more than twice a week

Dunstan 2008

Excluded women consuming fish more than twice a week

Freeman 2008

Excluded women with a previous intolerance to omega‐3 fatty acids

Furuhjelm 2009

Excluded women with an allergy to fish or undergoing treatment with omega‐3 fatty acid supplements

Giorlandino 2013

Excluded women with an allergy to fish or regular intake of fish oil

Gustafson 2013

Excluded women taking more than 200 mg DHA a day

Haghiac 2015

Excluded women with an allergy to fish or fish products; women who do not eat any fish; and women with a regular intake of fish oil (> 500 mg/week in the previous 4 weeks)

Harper 2010

Excluded women with an allergy to fish or fish products; and women with a regular intake of fish oil supplements (> 500 mg/week at any time during the preceding month)

Harris 2015

Excluded women with allergies to fish or consumption of salmon, mackerel, rainbow trout or sardines at least weekly

Hauner 2012

Excluded women taking omega‐3 supplementation before randomisation

Helland 2001

Excluded women already taking DHA

Hurtado 2015

Did not include women taking DHA supplements in pregnancy

Jamilian 2017

Excluded women taking omega‐3 fatty acid supplements

Kaviani 2014

Excluded women consuming fish more than twice a week

Keenan 2014

Excluded women consuming ≥ 2 servings of sea fish a week

Khalili 2016

Excluded women with an allergy to fish oil or fish products; and women consuming fish more than twice a week

Knudsen 2006

Included women with only limited fish intake and who did not use fish oil capsules during pregnancy

Krauss‐Etschmann 2007

Excluded women who had used fish oil supplements since the beginning of their pregnancy

Krummel 2016

Excluded women who consumed > 1 fish meal/week or who used DHA‐fortified foods or supplements

Makrides 2010

Excluded women who were already taking DHA supplements

Malcolm 2003

Excluded women with an allergy to fish products

Miller 2016

Excluded women with an allergy to seafood or fish oils

Min 2016

Excluded women taking fish oil supplements

Mozurkewich 2013

Excluded women taking omega‐3 fatty acid supplements and women consuming > 2 fish meals a week

Mulder 2014

Excluded women taking any lipid or fatty acid supplementation

Noakes 2012

included women with a diet low in oily fish (excluding canned tuna) ≤ twice per month

Ogundipe 2016

Excluded women with an allergy to fish and fish oil and women previously regularly taking a preconception fish oil supplement

Oken 2013

Excluded women consuming fish > 3 times a month; or with no contraindications to fish consumption such as allergy, or self‐restrictions such as a vegetarian diet

Olsen 1992

Excluded women with a fish allergy or regular intake of fish oil

Olsen 2000

Excluded women with a fish allergy or regular intake of fish oil

Pietrantoni 2014

Only included women who consumed fish at least twice a week (equivalent to 600 g fish a week)

Ramakrishnan 2010

Excluded women regularly taking fish oil or DHA supplements

Razavi 2017

Excluded women taking omega‐3 fatty acid supplements

Rees 2008

Excluded women taking fish oil supplements or eating more than 3 oily fish portions per week; not showing any signs of intolerance or allergy to fish

Ribeiro 2012

Excluded women with any signs of intolerance or allergy to fish or using dietary supplements containing omega‐3 and omega‐6 PUFA

Valenzuela 2015

Excluded women with a diet including polyunsaturated fatty acids (PUFA, ALA supplements) or LCPUFA (EPA and or DHA supplements)

Van Goor 2009

Excluded women who were vegetarians or vegans

Vaz 2017

Excluded women taking any oil supplementation (such as fish oil, flaxseed oil or cod liver oil)

Socioeconomic status

The socioeconomic status of women at baseline was reported by a range of measures including, education, employment, household income, socioeconomic index, and welfare/benefit dependence. Education measures were reported by 21 trials (Bergmann 2007; Bosaeus 2015; Carlson 2013; de Groot 2004; Dunstan 2008; Freeman 2008; Gustafson 2013; Harper 2010; Hauner 2012; Helland 2001; Judge 2007; Kaviani 2014; Khalili 2016; Krummel 2016; Makrides 2010; Mardones 2008; Pietrantoni 2014; Ramakrishnan 2010; Rees 2008; Tofail 2006; Vaz 2017), with all but seven of these trials suggesting that most women had at least 12 years education ‐ see Table 4. Five trials reported other measures of socio‐economic status ‐ Bisgaard 2016 reported that 10% of participants had low incomes; D'Almedia 1992 reported that 69% of women were employed; Krauss‐Etschmann 2007 stated that 40% of fathers had no training qualifications; Oken 2013 reported that 40% of women worked full‐time and Smuts 2003a reported that "most subjects received government assistance for medical aid". The remaining 42 trials did not report socioeconomic status of participants.

Open in table viewer
Table 4. Maternal socioeconomic status

Study ID

omega‐3

no omega‐3

Ali 2017

Not reported

Bergmann 2007

Employed: 31 (77.5%) in DHA/folate group

13 years of schooling: 32 (66.7%) in DHA/folate group

Employed: 35 (85.4%) in Vit/Min group; 30 (78.9%) in folate group

13 years of schooling: 28 (57.1%) in Vit/Min group; 32 (68.1%) in folate group

Bisgaard 2016;

Household annual income:

Low: 33 (9.6%)

Medium: 179 (51.9%)

High: 133 (38.6%)

Household annual income:

Low: 34 (9.7%)

Medium: 187 (53.6%)

High: 128 (36.7%)

Boris 2004

Not reported

Bosaeus 2015

15 or more years of education:

17 (94.4%)

15 or more years of education:

15 (88.2%)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

Maternal education:

Mean (SD): 13.69 years (2.67)

Maternal education:

Mean (SD): 13.36 years (2.72)

Chase 2015

Not reported

D'Almedia 1992

"Sixty‐nine percent were employed; ninety‐four percent of their husbands were employed".

de Groot 2004

Education measured on an 8‐point scale:

Mean (SD): 4.3 (1.4)

Education measured on an 8‐point scale:

Mean (SD): 3.9 (1.5)

Dunstan 2008

Maternal education:

10‐12 years: 10 (30.3%)

> 12 years: 23 (69.7%)

Maternal education:

10‐12 years: 9 (23.1%)

> 12 years: 30 (76.9%)

England 1989

Not reported

Freeman 2008

Maternal employment: 61.3% employed

Maternal education: Mean (SD): 15.5 years ((2.1)

Maternal employment: 60.7% employed

Maternal education, Mean (SD): 14.6 years (2.2)

Furuhjelm 2009

Not reported

Giorlandino 2013

Not reported

Gustafson 2013

Maternal education:

Mean (SD): 14.0 years (3.1)

Maternal education:

Mean (SD): 13.9 years (2.7)

Haghiac 2015

Not reported

Harper 2010

Maternal education:

Median (IQR): 13 years (12‐16)

Maternal education:

Median (IQR): 13 years (12‐16)

Harris 2015

Not reported

Hauner 2012

Maternal education:

63.8% attended ≥ 12 years of school

Maternal education:

69.9% attended ≥ 12 years of school

Helland 2001

Maternal education:

< 10 years: 2.9%

10‐12 years: 21.4%

> 12 years: 75.7%

Maternal education:

< 10 years: 1.8%

10‐12 years: 31.1%

> 12 years: 67.1%

Horvaticek 2017

Not reported

Hurtado 2015

Not reported

Ismail 2016

Not reported

Jamilian 2016

Not reported

Jamilian 2017

Not reported

Judge 2007

Maternal education:

Mean (SD): 12.8 years (2.2)

Maternal education;

Mean (SD): 12.2 years (1.5)

Judge 2014

Not reported

Kaviani 2014

Maternal education:

< 6 years: 7.5%

6 to 9 years: 12.5%

9 to 12 years: 20%

Maternal education:

< 6 years: 7.5 %

6 to 9 years: 15%

9 to 12 years: 10%

Keenan 2014

Not reported

Khalili 2016

Maternal education:

Primary school (1‐5 years): 14 (18.7%)

Seconday school (6‐8 years): 23 (30.7%)

High school (9‐12 years): 33 (44.0%)

University (> 12 years): 5 (6.7%)

Family income:

Adequate: 15 (20%)

Relatively adequate: 44 (58.7%)

Non adequate: 16 (21.3%)

Maternal education:

Primary school (1‐5 years): 15 (20.0%)

Seconday school (6‐8 years): 14 (18.7%)

High school (9‐12 years): 39 (52.0%)

University (> 12 years): 7 (9.3%)

Family income;

Adequate: 13 (17.3%)

Relatively adequate: 50 (66.7%)

Non adequate: 12 (16.0%)

Knudsen 2006

Not reported

Krauss‐Etschmann 2007

Job training of father:

None: 29 (45%) for DHA/EPA group; 17 (27%) for DHA/EPA+folate group

Apprenticeship: 14 (22%) for DHA/EPA group; 19 (31%) for DHA/EPA+folate group

University degree: 15 (23%) for DHA/EPA group; 21 (34%) for DHA/EPA+folate group

Job training of father:

None: 33 (47%) for folate group; 27 (40%) for placebo group

Apprenticeship: 10 (14%) for folate group; 14 (21%) for placebo group

University degree: 24 (34%) for folate group; 20 (29%) for placebo group

Krummel 2016

Education:

Mean (SD): 14.8 years (2.1)

Education:

Mean (SD): 14.9 years (3.2)

Laivuori 1993

Not reported

Makrides 2010

Mother completed secondary education: 755 (63.1%)

Mother completed further education: 816 (68.2%)

MSSI score: median 28.5, IQR (25.0 ‐ 31.0)

Mother completed secondary education: 760 (63.2%)

Mother completed further education: 824 (68.6%)

MSSI score: median 29.0, IQR (25.0 ‐ 31.0)

Malcolm 2003

Not reported

Mardones 2008

Education:

> 8 years: 82.1%

ESOMAR classification:

AB (high level): 0.5%

CA (medium level): 4.4%

CB (medium level): 34.9%

D (medium ‐ low level): 40.4%

E (low level): 19.8%

Education:

> 8 years: 80.7%

ESOMAR classification:

AB (high level): 0.3%

CA (medium level): 4.2%

CB (medium level): 33.4%

D (medium ‐ low level): 44.6%

E (low level): 17.5%

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

Not reported

Min 2014 [diabetic women]

Not reported

Min 2016

Not reported

Mozurkewich 2013

Not reported

Mulder 2014

Not reported

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Working full time: 6 (35%) for advice to eat fish group;

9 (50%) for advice to eat fish + gift card group

Working full time: 7 (35%) for control group

Olsen 1992

Not reported

Olsen 2000

Not reported

Olsen 2000 [twins]

see Olsen 2000

Onwude 1995

Not reported

Otto 2000

Not reported

Pietrantoni 2014

High school or university degree: 129 (100%)

Average socioeconomic status (not defined): 129 (100%)

High school or university degree: 126 (100%)

Average socioeconomic status (not defined): 126 (100%)

Ramakrishnan 2010

High school education or above: 56.6%

High school education or above: 59.5%

Ranjkesh 2011

Not reported

Razavi 2017

Not reported

Rees 2008

Maternal education:

Mean (SD): 14.5 years (3.5)

Maternal education:

Mean (SD): 15.3 (2.9)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Not reported

Sanjurjo 2004

Not reported

Smuts 2003a

"Most subjects received government assistance for medical care"

Smuts 2003b

Not reported

Su 2008

Not reported

Taghizadeh 2016

Not reported

Tofail 2006

Mostly low‐income participants

Mothers with > 5 years of schooling: 36.8%

Working mothers: 16.0

Fathers with stable job: 65.6

Family income (taka/month, 1 USD = 59 taka): 64.0

Mostly low‐income participants

Mothers with > 5 years of schooling: 32.3%

Working mothers: 12.1%

Fathers with stable job: 65.3%

Family income (taka/month, 1 USD = 59 taka): 54.0

Valenzuela 2015

SES assessed using the ESOMAR criteria:

High: 5.3%

Medium: 73.7%

Low: 21.1%

SES assessed using the ESOMAR criteria:

High: 19.0%

Medium: 66.7%

Low: 14.3%

Van Goor 2009

Not reported

Van Winden 2017

Not reported

Vaz 2017

Family income, not further defined:

US $263.2 (181.9‐383.0)

Maternal education:
Median (IQR): 11.0 years (7.0 ‐ 11)

Family income (US $) not further defined:

US $304.1 (180.7 ‐ 379.8)

Maternal education:

Median (IQR): 8.0 years (7.5 ‐ 10.5)

Abbreviations: DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; ESOMAR: European Society for Opinion and Marketing Research; IQR: interquartile range; MSSI: maternal social support index; SD: standard deviation; SES: socioeconomic status

Ethnicity or race

Most trials (46) reported no baseline information on ethnicity or race, though they did report the country where the study was conducted (with the exception of Van Winden 2017). Ten trials reported a mix of ethnicities, nine trials reported including only Caucasian women (understood to be white women) or women of similar ethnicities; two trials included African women, and one trial each reported including African‐American women or Hispanic women ‐ see Table 5.

Open in table viewer
Table 5. Maternal ethnicity

Study ID

Omega‐3

No omega‐3

Ali 2017

Not reported (study conducted in Egypt)

Bergmann 2007

"Caucasian women"

Bisgaard 2016

Caucasian:

333 (96.2%)

Caucasian:

332 (95.1%)

Boris 2004

Not reported (conducted in Denmark)

Bosaeus 2015

Women of European descent

Bulstra‐Ramakers 1994

Not reported (study conducted in the Netherlands)

Carlson 2013

Hispanic: 8%

Not Hispanic: 92%

Hispanic: 8%

Not Hispanic 92%

African‐American: 38%

Chase 2015

Maternal ethnicity not reported;

reported that 98% of included infants were white

Maternal ethnicity not reported;

reported that 93% of included infants were white

D'Almedia 1992

Not reported (conducted in Angola)

de Groot 2004

"White women"

Dunstan 2008

Caucasian women

England 1989

Not reported (conducted in South Africa)

Freeman 2008

Not reported (conducted in USA)

Furuhjelm 2009

Not reported (conducted in Sweden)

Giorlandino 2013

Not reported (conducted in Italy)

Gustafson 2013

28% African‐American (conducted in USA)

Haghiac 2015

African American: 11 (44%)

Caucasian: 10 (40%)

Other (e.g. Hispanic or Asian): 4 (16%)

African American: 6 (25%)

Caucasian: 11 (46%)

Other (e.g. Hispanic or Asian): 7 (29%)

Harper 2010

African American: 148 (34.1%)

White: 245 (56.5%)

Asian: 13 (3.0%)

Other: 28 (6.5%)

Hispanic/Latina ethnicity: 64 (14.7%)

African American: 145 (34.9%)

White: 240 (57.7%)

Asian: 5 (1.2%)

Other: 26 (6.3%)

Hispanic/Latina ethnicity: 57 (13.6%)

Harris 2015

Not reported (conducted in USA)

Hauner 2012

Not reported (conducted in Germany)

Helland 2001

Not reported (conducted in Norway)

Horvaticek 2017

Not reported (conducted in Croatia)

Hurtado 2015

Not reported (conducted in Spain)

Ismail 2016

Not reported (conducted in Egypt)

Jamilian 2016

Not reported (conducted in Iran)

Jamilian 2017

Not reported (conducted in Iran)

Judge 2007

Not reported (conducted in USA)

Judge 2014

Not reported (conducted in USA)

Kaviani 2014

Not reported (conducted in Iran)

Keenan 2014

African American women

Khalili 2016

Not reported (conducted in Iran)

Knudsen 2006

Not reported (conducted in Denmark)

Krauss‐Etschmann 2007

Not reported (conducted in Spain, Germany or Hungary)

Krummel 2016

African American: 12 (37.5%)

White: 20 (62.5%)

African American: 15 (53.6%)

White: 13 (46.4%)

Laivuori 1993

Not reported (conducted in Finland)

Makrides 2010

Not reported (conducted in Australia)

Malcolm 2003

Not reported (conducted in UK)

Mardones 2008

"mainly ethnically mixed (American and Hispanic)"

Martin‐Alvarez 2012

Not reported (conducted in Spain)

Miller 2016

African American: 1 (1.7%)

Caucasian: 55 (92%)

Hispanic: 2 (3%)

Asian: 1 (1.67%)

Other: 1 (1.67%)

African American: 0 (0%)

Caucasian: 52 (95%)

Hispanic: 2 (3%)

Asian: 1 (2%)

Other: 0 (0%)

Min 2014

Asian: 16 (35.6%)

African/Afro‐Caribbean: 10 (22.2%)

Caucasian: 13 (28.9%)

Others: 6 (13.3%)

Asian: 18 (45.0%)

African/Afro‐Caribbean: 14 (35.0%)

Caucasian: 6 (15.0%)

Others: 2 (5.0%)

Min 2014 [diabetic women]

Asian: 18 (43.9%)

African/Afro‐Caribbean: 15 (36.6%)

Caucasian: 5 (12.2%)

Others: 3 (7.3%)

Asian: 27 (57.5%)

African/Afro‐Caribbean: 10 (21.3%)

Caucasian: 5 (10.6%)

Others: 5 (10.6%)

Min 2016

Asian: 40 (60%)

African/Afro‐Caribbean: 18 (27%)

Caucasian: 5 (7%)

Others: 4 (7%)

Asian: 44 (62%)

African/Afro‐Caribbean: 18 (25%)

Caucasian: 5 (7%)

Others: 4 (6%)

Mozurkewich 2013

White: 33 (85%) for EPA‐rich group; 29 (76%) for DHA‐rich group

African‐American: 4 (10%) for EPA‐rich group; 4 (11%) for DHA‐rich group

Hispanic‐Latina: 0 (0%) for EPA‐rich group; 4 (11%) for DHA‐rich group

Asian: 1 (3%) for EPA‐rich group; 1 (3%) for DHA‐rich group

American Indian or Alaska Native: 0 (0%) for EPA‐rich group; 0 (0) for DHA‐rich group

Native Hawaiian or other Pacific ethnicity: 1 (3) for EPA‐rich group; 0 (0%) for DHA‐rich group

White: 34 (83%)

African‐American: 2 (5%)

Hispanic‐Latina: 3 (7%)

Asian: 1 (2%)

American Indian or Alaska Native: 1 (2%)

Native Hawaiian or other Pacific ethnicity: 0 (0%)

Mulder 2014

White: 73.1%

Non‐white: 26.9%

White: 73.9%

Non‐white: 26.1%

Noakes 2012

Not reported (conducted in UK)

Ogundipe 2016

Not reported (conducted in UK)

Oken 2013

White: 9 (50%) advice only group; 9 (53%) advice+voucher group

Black: 2 (11%) advice only group; 2 (12%) advice+voucher group

Asian: 2 (11%) advice only group; 1 (6%) advice+voucher group

Hispanic/other: 5 (28%) advice only group; 5 (29%) advice+voucher group

White: 9 (45%)

Black: 2 (10%)

Asian: 3 (15%)

Hispanic/other: 6 (30%)

Olsen 1992

Not reported (conducted in Denmark)

Olsen 2000

Not reported (conducted in Denmark, Scotland, Sweden, England, Italy, Netherlands, Norway, Belgium and Russia)

Olsen 2000 [twins]

See Olsen 2000

Onwude 1995

Not reported (conducted in UK)

Otto 2000

Not reported (conducted in the Netherlands)

Pietrantoni 2014

Caucasians

Ramakrishnan 2010

Not reported (conducted in Mexico)

Ranjkesh 2011

Not reported (conducted in Iran)

Razavi 2017

Not reported (conducted in Iran)

Rees 2008

Not reported (conducted in Australia)

Ribeiro 2012

Not reported (conducted in Brazil)

Rivas‐Echeverria 2000

Not reported (conducted in Venezuela)

Samimi 2015

Not reported (conducted in Iran)

Sanjurjo 2004

Not reported (conducted in Spain)

Smuts 2003a

African:104 (73%)

Other: 38 (27%)

African: 109 (73%)

Other: 40 (27%)

Smuts 2003b

African: 15 (83%)

Other: 3 (17%)

African: 15 (78%)

Other: 4 (22%)

Su 2008

Not reported (conducted in Taiwan)

Taghizadeh 2016

Not reported (conducted in Iran)

Tofail 2006

Not reported (conducted in India)

Valenzuela 2015

Hispanic: 19 (100%)

Hispanic: 21 (100%)

Van Goor 2009

Not reported (conducted in the Netherlands)

Van Winden 2017

Neither ethnicity, race or country where study conducted reported

Vaz 2017

White: 13 (40.6%)

Non‐white: 19 (59.4%)

White: 5 (17.9%)

Non‐white: 23 (82.1%)
Smoking

Thirteen trials reported excluding women who smoked. Twenty‐three trials reported smoking rates in pregnancy ranged from several per cent to nearly 50% in one trial. The remaining 35 trials did not report maternal smoking status, see Table 6.

Open in table viewer
Table 6. Maternal smoking status

Study ID

Omega‐3

No omega‐3

Ali 2017

Smokers were excluded

Bergmann 2007

Smokers were excluded

Bisgaard 2016

Smoking during pregnancy: 21 (6.1%)

Smoking during pregnancy: 33 (9.5%)

Boris 2004

"The three study groups were similar in baseline characteristics with regard to... percentage of smokers (data not shown)".

Bosaeus 2015

Not reported

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

History of smoking: 41%

Smoking during pregnancy: 30%

History of smoking: 45%

Smoking during pregnancy: 38%

Chase 2015

Not reported

D'Almedia 1992

Not reported

de Groot 2004

Smoking at 14 weeks GA:

Yes: 4 (14%)

Smoking at 14 weeks GA:

Yes: 10 (34%)

Dilli 2018

15 (28%)

24 (35%)

Dunstan 2008

Smokers were excluded

England 1989

Not reported

Freeman 2008

Not reported

Furuhjelm 2009

Exposure to smoke: (at least 1 of immediate family a smoker)

9 (17%)

Exposure to smoke: (at least 1 of immediate family a smoker)

11 (17%)

Giorlandino 2013

Maternal smoking at baseline: 50%

Maternal smoking at baseline: 48%

Gustafson 2013

Not reported

Haghiac 2015

Not reported

Harper 2010

Smoking during pregnancy: 64 (15%)

Smoking during pregnancy: 72 (17%)

Harris 2015

Not reported

Hauner 2012

Smoking before pregnancy: 16%

Smoking before pregnancy: 24%

Helland 2001

Smoking: 16%

Smoking: 22%

Horvaticek 2017

Not reported

Hurtado 2015

Not reported

Ismail 2016

Not reported

Jamilian 2016

Smokers were excluded

Jamilian 2017

Smokers were excluded

Judge 2007

Smokers were excluded

Judge 2014

Not reported

Kaviani 2014

Smokers were excluded

Keenan 2014

Regular smokers were excluded

Khalili 2016

Not reported

Knudsen 2006

Smoked during pregnancy

0.1 g/day EPA + DHA group: 79 (20.3%)

0.3 g/day EPA + DHA group: 78 (20.3%)

0.7 g/day EPA + DHA group: 78 (20.3%)

1.4 g/day EPA + DHA group: 79 (20.6%)

2.8 g/day EPA + DHA group: 78 (19.9%)

2.2g/day ALA group: 79 (20.3%)

Smoked during pregnancy

160 (20.7%)

Krauss‐Etschmann 2007

Smoking at study entry

Yes: 8 (12%) for DHA/EPA group; 9 (14%) for DHA/EPA + Folate group

Smoking at study entry

Yes: 5 (7%) for Folate group; 9 (13%) for placebo group

Krummel 2016

"Current or previous use of tobacco" an exclusion criteria

Laivuori 1993

Not reported

Makrides 2010

Smoking at trial entry or leading up to pregnancy

358 (29.9%)

Smoking at trial entry or leading up to pregnancy

407 (33.9%)

Malcolm 2003

Not reported

Mardones 2008

Not reported

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

Smoker

6 (13%)

Smoker

0 (0%)

Min 2014 [diabetic women]

Smoker

2 (4%)

Smoker

0 (0%)

Min 2016

Smoker

2 (3%)

Smoker

0 (0%)

Mozurkewich 2013

Not reported

Mulder 2014

Not reported

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Never smoker

14 (78%) in advice group; 12 (71%) in advice+gift card group

Never smoker

14 (70%) in control group

Olsen 1992

Smokers

Fish oil group: 33%

Smokers

Olive oil group: 29%

No oil group: 33%

Olsen 2000

Smoker

Prophylactic trials

Earl‐PD trial 45%

Earl‐IUGR trial 52%

Earl‐PIH trial 19%

Twins trial 33%

Therapeutic trials

Threat‐PE trial 18%

Susp‐IUGR trial 31%

Smoker

Prophylactic trials

Earl‐PD trial 41%

Earl‐IUGR 52%

Earl‐PIH trial 24%

Twins trial 29%

Therapeutic trials

Threat‐PE trial 21%

Susp‐IUGR trial 30%

Onwude 1995

Current smoker

42 (37%)

Current smoker

32 (27%)

Otto 2000

Not reported

Pietrantoni 2014

Smokers were excluded

Ramakrishnan 2010

Not reported

Ranjkesh 2011

Not reported

Razavi 2017

Smokers were excluded

Rees 2008

Smoker

0 (0%)

Smoker

3 (23%)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Smokers were excluded

Sanjurjo 2004

Smoker

1 (13%)

Smoker

2 (25%)

Smuts 2003a

Smoker before pregnancy: 46.8%

Smoker during pregnancy: 27.0%

Smoker before pregnancy: 38.2%

Smoker during pregnancy: 21.5%

Smuts 2003b

Not reported

Su 2008

Not reported

Taghizadeh 2016

Smokers were excluded

Tofail 2006

Not reported

Valenzuela 2015

Not reported

Van Goor 2009

Not reported

Van Winden 2017

Not reported

Vaz 2017

Not reported
Women at risk

We defined increased/high risk as any factors which might increase the risk of adverse maternal and birth outcomes; these baseline risks included being at risk of pre‐eclampsia, having a previous preterm birth, gestational diabetes mellitus (GDM), being overweight/obese or underweight, or being at risk of poor mental health ‐ see Table 7.We classified trials into increased/high risk (34 trials); any or mixed risk (8 trials) and low risk (29 trials). One trial reported women with GDM and low risk women separately (Min 2014). We also performed a subgroup analysis based on risk (see Analysis 6 and results text).

Open in table viewer
Table 7. Maternal risk

Study ID

All women included in the study

Ali 2017

Increased/high‐risk (pregnancy complicated with asymmetrical IUGR)

Bergmann 2007

Low‐risk (healthy women)

Bisgaard 2016

Any/mixed risk (not reported)

Boris 2004

Low‐risk (healthy women)

Bosaeus 2015

Low‐risk (healthy women)

Bulstra‐Ramakers 1994

Increased/high‐risk (women with a history of IUGR with or without PIH in the previous pregnancy)

Carlson 2013

Low‐risk (healthy women)

Chase 2015

Increased/high‐risk (Infants at risk of T1D (e.g. mothers with T1D)

D'Almedia 1992

Mixed risk (21% of all included women had a history of PIH, and 4% a history of preterm birth)

de Groot 2004

Low‐risk (healthy women)

Dilli 2018

Increased/high risk (women with GDM)

Dunstan 2008

Low‐risk (history of physician‐diagnosed allergic rhinitis and/or asthma and 1 or more positive skin prick test to common allergens, but who were otherwise healthy)

England 1989

Increased/high‐risk (women with severe gestational proteinuric hypertension

Freeman 2008

Increased/high‐risk (pregnant and postpartum women with a major depressive order)

Furuhjelm 2009

Low‐risk (pregnant women affected by allergy themselves, of having a husband or previous child with allergies, otherwise healthy)

Giorlandino 2013

Increased/high‐risk (pregnancy women with a history of IUGR, fetal demise or pre‐eclampsia)

Gustafson 2013

Low‐risk (healthy women)

Haghiac 2015

Increased/high‐risk: (overweight or obese (BMI ≥ 25)

Harper 2010

Increased/high‐risk (women with at least 1 prior spontaneous preterm birth)

Harris 2015

Low‐risk (healthy women)

Hauner 2012

Low‐risk (healthy women)

Helland 2001

Low‐risk (healthy women)

Horvaticek 2017

Increased/high‐risk (pregnant women with T1D)

Hurtado 2015

Low‐risk (healthy women)

Ismail 2016

Increased/high‐risk (oligohydramnios at 30‐34 weeks GA)

Jamilian 2016

Increased/high‐risk (women with GDM)

Jamilian 2017

Increased/high‐risk (women with GDM)

Judge 2007

Low‐risk (healthy women)

Judge 2014

Low‐risk (healthy women)

Kaviani 2014

Increased/high‐risk (women diagnosed with mild depression)

Keenan 2014

Increased/high‐risk (women living in urban low‐income environments)

Khalili 2016

Low‐risk (healthy women)

Knudsen 2006

Any/mixed risk (not reported)

Krauss‐Etschmann 2007

Low‐risk (healthy women)

Krummel 2016

Increased/high‐risk (all women overweight or obese)

Laivuori 1993

Increased/high‐risk (women with pre‐eclampsia)

Makrides 2010

Any/mixed risk

Malcolm 2003

Low‐risk (healthy women) for final outcomes (any/mixed risk for preterm birth outcome)

Mardones 2008

Increased/high‐risk (all included women underweight (BMI ≤ 21.2kg/m 2 at 10 weeks GA))

Martin‐Alvarez 2012

Any/mixed risk (not reported)

Miller 2016

Any/mixed risk

Min 2014

Low‐risk (healthy women)

Min 2014 [diabetic women]

Increased/high‐risk (women diagnosed with Type 2 diabetes)

Min 2016

Increased/high‐risk (women with GDM)

Mozurkewich 2013

Increased/high‐risk (women with a history of depression)

Mulder 2014

Low‐risk (healthy women)

Noakes 2012

Low‐risk (women with a history of allergy, atopy or asthma)

Ogundipe 2016

Increased/high‐risk: (women at risk of developing pre‐eclampsia, fetal growth restriction, gestational diabetes)

Oken 2013

Any/mixed risk

Olsen 1992

Low‐risk (healthy women)

Olsen 2000

Increased/high‐risk (previous preterm birth or IUGR in previous pregnancy or pregnancy‐induced hypertension or twins in current pregnancy; threatening pre‐eclampsia or ultrasonically estimated fetal weight below the 10th centile)

Olsen 2000 [twins]

See Olsen 2000

Onwude 1995

Increased/high‐risk (primigravida with abnormal Doppler blood flow, previous birthweight < 3rd centile, PIH, previous unexplained stillbirth)

Otto 2000

Low‐risk (healthy women)

Pietrantoni 2014

Low‐risk (healthy women)

Ramakrishnan 2010

Low‐risk (healthy women)

Ranjkesh 2011

Increased/high‐risk (women at high risk for pre‐eclampsia)

Razavi 2017

Increased/high‐risk (women diagnosed with GDM)

Rees 2008

Increased/high‐risk (current episode of major depression or dysthymia)

Ribeiro 2012

Any/mixed (not reported)

Rivas‐Echeverria 2000

Increased/high‐risk (women at risk of pre‐eclampsia)

Samimi 2015

Increased/high‐risk (women with GDM)

Sanjurjo 2004

Low‐risk (healthy women)

Smuts 2003a

Low‐risk (healthy women)

Smuts 2003b

Low‐risk (healthy women)

Su 2008

Increased/high‐risk (women diagnosed with major depressive disorder between 16 weeks and 32 weeks GA)

Taghizadeh 2016

Increased/high‐risk (women with GDM)

Tofail 2006

Increased/high‐risk (low income; 28% women undernourished)

Valenzuela 2015

Low‐risk ("women free from any known diseases that could affect fetal growth")

Van Goor 2009

Low‐risk (healthy women)

Van Winden 2017

Increased/high‐risk (women with GDM)

Vaz 2017

Increased/high‐risk (pregnant women classified at risk for postpartum depression)

Abbreviations: ADA: American Diabetes Association; BMI: body mass index; GA: gestational age; GDM: gestational diabetes mellitus; IUGR: intrauterine growth restriction; OGTT: oral glucose tolerance test; PIH: pregnancy‐induced hypertension; PPD: postpartum depression

Interventions
Overall analysis (Analysis 1)

Each of the 70 included trials compared an omega‐3 fatty acid intervention (stand‐alone or with a co‐intervention); including 10 trials with a food or dietary advice component), with placebo or no omega‐3 fatty acids, with 60 trials contributing data for this review.

Intervention type subgroup (Analysis 2)

As there was considerable variation between trials, we have subgrouped results by four main types of intervention (in addition to the overall analysis):

    • Most of these trials compared oral DHA and/or EPA (or mainly DHA/EPA) supplements with placebo or no omega‐3 treatment. Four trials compared unspecified or other oral omega‐3 fatty acid supplements with placebo or no omega‐3 (Laivuori 1993; Ribeiro 2012; Samimi 2015; Valenzuela 2015), and one trial compared vaginal omega‐3 supplementation with placebo (Giorlandino 2013). Some trials reported including small amounts of other agents in the intervention arm (e.g. vitamin E) but we judged these to have minimal effect on outcomes.

  • Intervention type 2: Omega‐3 supplements/enrichment plus food/dietary advice versus placebo or no omega‐3 fatty acids (7 trials) (de Groot 2004; Hauner 2012; Hurtado 2015; Martin‐Alvarez 2012; Pietrantoni 2014; Smuts 2003a; Smuts 2003b)

  • Intervention type 3: Omega‐3 food/dietary advice only versus placebo or no omega‐3 fatty acids (3 trials): (Bosaeus 2015; Noakes 2012; Oken 2013)

  • Intervention type 4: Omega‐3 supplements plus other agents versus placebo or no omega‐3 fatty acids (12 trials): the other agents used in these 12 trials were as follows.

Jamilian 2017* and Razavi 2017* are multi‐arm trials that span two of the above four intervention categories.

Multi‐arm trials

Ten trials had multi‐arm designs. We combined relevant groups in the multi‐arm trials to create appropriate single pair‐wise comparisons for inclusion in the main comparison, avoiding unit of analysis errors, specifically:

  • Bergmann 2007: three arms (DHA/EPA + prebiotic versus prebiotic + vitamin/mineral versus vitamin/mineral); analysed as DHA/EPA + prebiotic versus the other two arms combined (prebiotic/vitamin/mineral and vitamin/mineral) in the overall comparison (Analysis 1).

  • Harris 2015: three arms (300 g/day DHA versus 600 g/day DHA versus placebo); analysed as 300 g/day + 600 g/day combined versus placebo for the overall comparison (Analysis 1); we split doses in the dose subgroups (Analysis 3), and compared 300 g/day and 600 g/day directly in Analysis 8.

  • Krauss‐Etschmann 2007: four arms (DHA + EPA versus DHA + EPA + folate versus folate versus placebo, all using milk‐based sachets); analysed as DHA + EPA and DHA + EPA + folate groups combined, compared with placebo and folate only combined.

  • Jamilian 2017: four arms (DHA + EPA versus DHA + EPA + vitamin D versus vitamin D + placebo) ‐ data from this trial were not included (no review outcomes reported).

  • Knudsen 2006: seven arms (five different doses of DHA + EPA versus ALA versus no treatment/flax oil); analysed as six omega‐3 groups combined versus no treatment/flax oil for the overall comparison (Analysis 1); omega‐3 groups combined in two dose groups, < 1 g/day and ≥ 1 g/day in the direct dose comparison (Analysis 7); DHA + EPA versus ALA in the omega‐3 supplement type direct comparison (Analysis 8).

  • Laivuori 1993: three arms (DHA + EPA + other omega‐3 versus linoleic acid (LA)/GLA versus placebo) ‐ data from this trial were not included (no outcomes able to be used).

  • Mozurkewich 2013: three arms (mainly DPA versus mainly EPA versus placebo); DPA + EPA groups pooled in analysis 1; DPA versus mainly EPA groups included in omega‐3 supplement type comparison (Analysis 8).

  • Oken 2013: three arms (voucher to purchase fish plus advice on which fish to consume versus advice on fish consumption only versus generic dietary advice only); analysed as intervention arms pooled versus generic dietary advice only.

  • Razavi 2017 four arms (DHA + EPA versus DHA + EPA + vitamin D versus vitamin D versus placebo); two arms (DPA + EPA and DHA + EPA + vitamin D) pooled and compared with placebo in analysis.

  • Van Goor 2009: three arms (DHA + AA versus DHA versus placebo); intervention arms pooled and compared with placebo for overall comparison (Analysis 1) and other analyses except for DHA + AA versus DHA for direct omega‐3 supplement type comparison (Analysis 8).

For additional details on the omega‐3 fatty acid interventions and how they varied across the trials see Characteristics of included studies.

Comparisons

Most comparisons were between omega‐3 LCPUFA and placebo/no omega‐3. As well as contributing to the main omega‐3 versus no omega‐3 comparison in Analysis 1, five of the multi‐arm trials contributed outcomes from direct comparisons of omega‐3 supplement doses or omega‐3 supplements for inclusion in the meta‐analysis:

  • Omega‐3 supplement dose comparisons: two trials: Harris 2015 compared 600 mg versus 300 mg DHA/day; Knudsen 2006 compared six different doses which we collapsed into a comparison of < 1 g/day versus ≥ 1 g/day (see Analysis 7).

  • Omega‐3 supplements versus other omega‐3 supplements: three trials: Knudsen 2006 compared EPA/DHA (five doses combined) versus ALA; Mozurkewich 2013 compared DHA versus EPA; and Van Goor 2009 compared DHA versus DHA/AA combined (see Analysis 8).

Subgroup analyses
Dose subgroup ‐ DHA + EPA (Analysis 3)

*trials had more than one omega‐3 group with different doses

#only specified as omega‐3 and not DHA and/or EPA.

Timing subgroup ‐ gestational age when omega‐3 supplements commenced (Analysis 4)

DHA/mixed subgroup (Analysis 5)

Risk subgroup: women at increased/high risk, any/mixed risk or low risk (Analysis 6)

Increased or high baseline risk of adverse maternal and birth outcomes included being at risk of pre‐eclampsia, having a previous preterm birth, GDM, being overweight/obese or underweight, or being at risk of poor mental health ‐ see Table 7.

*Min 2014 reported diabetic women separately.

Outcomes

Primary outcomes were reported in a format suitable for meta‐analysis as follows:

  • preterm birth < 37 weeks reported by 26 trials;

  • preterm birth < 34 weeks reported by nine trials;

  • prolonged gestation > 42 weeks reported by six trials.

Most of our secondary outcomes were reported in at least some of the trials.

We were unable to include any outcomes from 10 trials in our meta‐analysis (Boris 2004; Bosaeus 2015; Chase 2015; Ismail 2016; Jamilian 2017; Laivuori 1993; Martin‐Alvarez 2012; Ogundipe 2016; Ribeiro 2012; Van Winden 2017). Of these, Boris 2004, Chase 2015, Ismail 2016, Jamilian 2017, Martin‐Alvarez 2012 and Ribeiro 2012 did not report on any of our prespecified review outcomes. Bosaeus 2015 and Laivuori 1993 reported review outcomes, however, the data were not suitable for inclusion in the meta‐analysis. Ogundipe 2016 only reported review outcomes overall, not separately by intervention and control group. Van Winden 2017 did report on maternal adverse effects, but narratively.

Sources of trial funding

Funding sources were reported by 56 of the 70 included trials (Bergmann 2007; Bisgaard 2016; Boris 2004; Bosaeus 2015; Carlson 2013; Chase 2015; D'Almedia 1992; de Groot 2004; Dilli 2018; Dunstan 2008; Freeman 2008; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Hauner 2012; Helland 2001; Hurtado 2015; Jamilian 2016; Jamilian 2017; Judge 2007; Judge 2014; Keenan 2014; Khalili 2016; Knudsen 2006; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Makrides 2010; Malcolm 2003; Mardones 2008; Min 2014; Min 2016; Mozurkewich 2013; Mulder 2014; Ogundipe 2016; Oken 2013; Olsen 1992; Olsen 2000; Otto 2000; Pietrantoni 2014; Ramakrishnan 2010; Razavi 2017; Rees 2008; Rivas‐Echeverria 2000; Samimi 2015; Sanjurjo 2004; Smuts 2003a; Smuts 2003b; Su 2008; Taghizadeh 2016; Tofail 2006; Van Goor 2009; Vaz 2017). Funding bodies listed by the trials were mostly non‐commercial organisations (e.g. government funding bodies, universities, health services and other not‐for‐profit foundations, including the World Health Organization). However, commercial organisations ‐ mainly pharmaceutical companies ‐ were reported as the only or main funding sources in 11 trials (Bergmann 2007; de Groot 2004; Giorlandino 2013; Helland 2001; Laivuori 1993; Mardones 2008; Otto 2000; Sanjurjo 2004; Smuts 2003a; Smuts 2003b; Van Goor 2009). Thirteen trials did not report any funding (Ali 2017; Bulstra‐Ramakers 1994; England 1989; Horvaticek 2017; Ismail 2016; Kaviani 2014; Martin‐Alvarez 2012; Miller 2016; Ranjkesh 2011; Ribeiro 2012; Rivas‐Echeverria 2000; Valenzuela 2015; Van Winden 2017).

Trial authors' declarations of interest

Eleven trials of the 70 trials reported information related to potential conflicts of interests for the trial authors, primarily related to income received from pharmaceutical and other commercial organisations (Carlson 2013; Freeman 2008; Harper 2010; Hauner 2012; Helland 2001; Hurtado 2015; Krauss‐Etschmann 2007; Makrides 2010; Mozurkewich 2013; Noakes 2012; Olsen 1992). A further 31 trials reported having no interests to declare (Ali 2017; Bergmann 2007; Bosaeus 2015; de Groot 2004; Dilli 2018; Dunstan 2008; Furuhjelm 2009; Haghiac 2015; Horvaticek 2017; Ismail 2016; Jamilian 2016; Jamilian 2017; Judge 2014; Kaviani 2014; Khalili 2016; Krummel 2016; Malcolm 2003; Mardones 2008; Min 2014; Min 2016; Mulder 2014; Oken 2013; Pietrantoni 2014; Ramakrishnan 2010; Razavi 2017; Ribeiro 2012; Taghizadeh 2016; Valenzuela 2015; Van Goor 2009; Van Winden 2017; Vaz 2017).

The remaining 28 trials did not report any information regarding declarations of interest (Bisgaard 2016; Boris 2004; Bulstra‐Ramakers 1994; Chase 2015; D'Almedia 1992; England 1989; Giorlandino 2013; Gustafson 2013; Harris 2015; Judge 2007; Keenan 2014; Knudsen 2006; Laivuori 1993; Martin‐Alvarez 2012; Miller 2016; Ogundipe 2016; Olsen 2000; Onwude 1995; Otto 2000; Ranjkesh 2011; Rees 2008; Rivas‐Echeverria 2000; Samimi 2015; Sanjurjo 2004; Smuts 2003a; Smuts 2003b; Su 2008; Tofail 2006). For further details of the reported declarations, see Characteristics of included studies.

Excluded studies

We excluded 15 studies (Escobar 2008; Fievet 1985; Gholami 2017; Herrera 1993; Herrera 1998; Herrera 2004; Lauritzen 2004; Marangell 2004; Morrison 1984; Morrison 1986; Nishi 2016; Starling 1990; Valentine 2013; Velzing‐Aarts 2001; Yelland 2016). Four trials assessed the effects of an omega‐6 fatty acid intervention (linoleic acid) (Herrera 1993; Herrera 1998; Herrera 2004; Morrison 1984), and one trial assessed evening primrose oil (Fievet 1985). In Escobar 2008, participants were registered, but none were recruited. In five trials participants were not randomised (Gholami 2017; Marangell 2004; Nishi 2016; Starling 1990; Velzing‐Aarts 2001), and in another it did not appear as if participants were randomised (Morrison 1986). In Lauritzen 2004 and Valentine 2013 women were supplemented with omega‐3 during lactation only. The remaining trial was a methodological study that assessed aspects of several trials (Yelland 2016).

Risk of bias in included studies

For a summary of the risk of bias across the included trials, see Figure 2 and Figure 3.

Figure 2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Figure 3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Allocation

Random sequence generation

We judged the methods used to generate the random sequence to be adequate in 37 of the 70 included trials (Ali 2017; Bergmann 2007; Bisgaard 2016; Bosaeus 2015; Carlson 2013; D'Almedia 1992; Giorlandino 2013; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Hauner 2012; Helland 2001; Hurtado 2015; Ismail 2016; Jamilian 2016; Jamilian 2017; Keenan 2014; Khalili 2016; Krummel 2016; Makrides 2010; Miller 2016; Min 2014; Min 2016; Mozurkewich 2013; Mulder 2014; Noakes 2012; Oken 2013; Olsen 2000; Onwude 1995; Ramakrishnan 2010; Razavi 2017; Rees 2008; Samimi 2015; Sanjurjo 2004; Smuts 2003a; Taghizadeh 2016), with all trials using computer‐generated methods or likely to have done so. We judged the risk of selection bias associated with sequence generation to be unclear in 32 trials, as many did not report how the random sequence was generated or provide sufficient information (Boris 2004; Bulstra‐Ramakers 1994; Chase 2015; de Groot 2004; Dilli 2018; Dunstan 2008; England 1989; Freeman 2008; Furuhjelm 2009; Horvaticek 2017; Judge 2007; Judge 2014; Kaviani 2014; Knudsen 2006; Krauss‐Etschmann 2007; Laivuori 1993; Malcolm 2003; Martin‐Alvarez 2012; Ogundipe 2016; Olsen 1992; Otto 2000; Pietrantoni 2014; Ranjkesh 2011; Ribeiro 2012; Rivas‐Echeverria 2000; Smuts 2003b; Su 2008; Tofail 2006; Valenzuela 2015; Van Goor 2009; Van Winden 2017; Vaz 2017). We judged one trial to be at high risk of selection bias, as alternation was used (odd and even numbers) (Mardones 2008).

Allocation concealment

We judged that 29 of the 70 trials had used adequate methods for allocation concealment (Ali 2017; Bisgaard 2016; Bulstra‐Ramakers 1994; Carlson 2013; D'Almedia 1992; Dunstan 2008; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Ismail 2016; Jamilian 2016; Judge 2014; Keenan 2014; Khalili 2016; Krummel 2016; Makrides 2010; Min 2014; Min 2016; Mozurkewich 2013; Oken 2013; Olsen 1992; Olsen 2000; Onwude 1995; Ramakrishnan 2010; Razavi 2017; Rees 2008; Samimi 2015; Taghizadeh 2016). Four of these reported using sequentially numbered, opaque sealed envelopes (Ali 2017; Ismail 2016; Oken 2013; Olsen 1992). Three reported computer driven telephone or centre based randomisation (Harper 2010; Makrides 2010; Olsen 2000); 21 reported third party (pharmacy, health provider, supplement provider or external investigator) controlled randomisation (Bisgaard 2016; Bulstra‐Ramakers 1994; Carlson 2013; D'Almedia 1992; Dunstan 2008; Gustafson 2013; Haghiac 2015; Harris 2015; Jamilian 2016; Judge 2014; Keenan 2014; Khalili 2016; Krummel 2016; Min 2014; Min 2016; Mozurkewich 2013; Ramakrishnan 2010; Razavi 2017; Rees 2008; Samimi 2015; Taghizadeh 2016), and one used sequentially numbered opaque sealed envelopes and third party (pharmacy) controlled randomisation (Onwude 1995).

Selection bias

We judged that the risk of selection bias associated with allocation concealment was unclear for 40 trials (Bergmann 2007; Boris 2004; Bosaeus 2015; Chase 2015; de Groot 2004; Dilli 2018; England 1989; Freeman 2008; Furuhjelm 2009; Giorlandino 2013; Hauner 2012; Helland 2001; Horvaticek 2017; Hurtado 2015; Jamilian 2017; Judge 2007; Kaviani 2014; Knudsen 2006; Krauss‐Etschmann 2007; Laivuori 1993; Malcolm 2003; Martin‐Alvarez 2012; Miller 2016; Mulder 2014; Noakes 2012; Ogundipe 2016; Otto 2000; Pietrantoni 2014; Ranjkesh 2011; Ribeiro 2012; Rivas‐Echeverria 2000; Sanjurjo 2004; Smuts 2003a; Smuts 2003b; Su 2008; Tofail 2006; Valenzuela 2015; Van Goor 2009; Van Winden 2017; Vaz 2017), with either no methods of concealment detailed, or the methods described lacking sufficient detail. We judged one trial to be at high risk of selection bias, as alternation was used (odd and even numbers) (Mardones 2008).

Blinding

Blinding of participants and personnel

We judged blinding of participants and personnel to be adequate in 52 of the 70 included trials (Bergmann 2007; Bisgaard 2016; Bulstra‐Ramakers 1994; Carlson 2013; D'Almedia 1992; Dilli 2018; Dunstan 2008; Freeman 2008; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Helland 2001; Horvaticek 2017; Hurtado 2015; Ismail 2016; Jamilian 2016; Jamilian 2017; Judge 2007; Judge 2014; Kaviani 2014; Keenan 2014; Khalili 2016; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Makrides 2010; Malcolm 2003; Miller 2016; Min 2014; Min 2016; Mozurkewich 2013; Mulder 2014; Oken 2013; Olsen 2000; Onwude 1995; Ramakrishnan 2010; Ranjkesh 2011; Razavi 2017; Rees 2008; Rivas‐Echeverria 2000; Samimi 2015; Sanjurjo 2004; Smuts 2003a; Su 2008; Taghizadeh 2016; Tofail 2006; Van Goor 2009; Van Winden 2017; Vaz 2017). We judged the risk of performance bias to be high in three trials, due to inadequate blinding of women and/or trial personnel (Bosaeus 2015; Hauner 2012; Otto 2000). For the remaining 15 trials, we judged the risk of performance bias to be unclear (Ali 2017; Boris 2004; Chase 2015; de Groot 2004; England 1989; Knudsen 2006; Mardones 2008; Martin‐Alvarez 2012; Noakes 2012; Ogundipe 2016; Olsen 1992; Pietrantoni 2014; Ribeiro 2012; Smuts 2003b; Valenzuela 2015). Eleven of these trials did not provide sufficient information to allow confident assessment of blinding (Ali 2017; Chase 2015; de Groot 2004; England 1989; Knudsen 2006; Martin‐Alvarez 2012; Noakes 2012; Ogundipe 2016; Pietrantoni 2014; Ribeiro 2012; Valenzuela 2015). Two trials reported that blinding of participants was partial (the no‐treatment groups were aware of this) (Boris 2004; Olsen 1992), and another two trials used food interventions which could not be fully blinded (Mardones 2008; Smuts 2003b).

Blinding of outcome assessors

Thirty‐nine trials clearly indicated that blinded trial personnel were involved in outcome assessment or data collection, and we judged them to be at low risk of detection bias (Bergmann 2007; Bisgaard 2016; Bulstra‐Ramakers 1994; Carlson 2013; D'Almedia 1992; Dunstan 2008; Freeman 2008; Furuhjelm 2009; Giorlandino 2013; Haghiac 2015; Harper 2010; Harris 2015; Helland 2001; Hurtado 2015; Ismail 2016; Jamilian 2016; Judge 2014; Keenan 2014; Khalili 2016; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Makrides 2010; Miller 2016; Min 2014; Min 2016; Mulder 2014; Noakes 2012; Oken 2013; Olsen 2000; Onwude 1995; Ramakrishnan 2010; Razavi 2017; Rees 2008; Samimi 2015; Smuts 2003a; Su 2008; Taghizadeh 2016; Tofail 2006). One trial reported that, except for ultrasound measurements (e.g. for fat mass measurements), assessors were not blinded and we judged to be at high risk of detection bias (Hauner 2012). For the remaining trials, we judged the risk of detection bias to be unclear, as most of them provided insufficient details about whether assessors and/or data collectors were blinded (Ali 2017; Boris 2004; Bosaeus 2015; Chase 2015; de Groot 2004; Dilli 2018; England 1989; Gustafson 2013; Horvaticek 2017; Jamilian 2017; Judge 2007; Kaviani 2014; Knudsen 2006; Malcolm 2003; Mardones 2008; Martin‐Alvarez 2012; Mozurkewich 2013; Ogundipe 2016; Olsen 1992; Otto 2000; Pietrantoni 2014; Ranjkesh 2011; Ribeiro 2012; Rivas‐Echeverria 2000; Sanjurjo 2004; Valenzuela 2015; Van Goor 2009; Van Winden 2017; Vaz 2017).

Incomplete outcome data

We judged 13 trials to be at low risk of attrition bias, with minimal losses to follow‐up, and similar numbers/reasons for losses to follow‐up in each group (Bisgaard 2016; Harper 2010; Jamilian 2017; Makrides 2010; Mozurkewich 2013; Olsen 1992; Olsen 2000; Onwude 1995; Otto 2000; Ranjkesh 2011; Razavi 2017; Samimi 2015; Valenzuela 2015).

We judged 27 trials to be at a high risk of attrition bias (Boris 2004; Bosaeus 2015; de Groot 2004; Dilli 2018; Freeman 2008; Haghiac 2015; Harris 2015; Hauner 2012; Helland 2001; Horvaticek 2017; Hurtado 2015; Judge 2007; Judge 2014; Knudsen 2006; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Malcolm 2003; Mardones 2008; Min 2014; Rees 2008; Smuts 2003b; Su 2008; Tofail 2006; Van Goor 2009; Van Winden 2017; Vaz 2017). See Characteristics of included studies for further details.

We judged the remaining 30 trials to be at an unclear risk of attrition bias, often due to incomplete or unclear reporting, and complexity in some of the trials with several periods of childhood follow‐up (Ali 2017; Bergmann 2007; Bulstra‐Ramakers 1994; Carlson 2013; Chase 2015; D'Almedia 1992; Dunstan 2008; England 1989; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Ismail 2016; Jamilian 2016; Judge 2007; Kaviani 2014; Keenan 2014; Khalili 2016; Martin‐Alvarez 2012; Miller 2016; Min 2016; Mulder 2014; Noakes 2012; Ogundipe 2016; Oken 2013; Pietrantoni 2014; Ramakrishnan 2010; Rivas‐Echeverria 2000; Smuts 2003a; Taghizadeh 2016; Van Goor 2009).

Selective reporting

We judged 13 trials to be at a low risk of reporting bias, as they provided data for the prespecified and/or expected outcomes (including from the published protocols) (Bergmann 2007; Bisgaard 2016; Carlson 2013; Harper 2010; Khalili 2016; Jamilian 2016; Makrides 2010; Mozurkewich 2013; Olsen 1992; Smuts 2003a; Taghizadeh 2016; Tofail 2006; Van Goor 2009). We judged 45 trials to be at an unclear risk of reporting bias (Ali 2017; Boris 2004; Bosaeus 2015; Bulstra‐Ramakers 1994; Chase 2015; D'Almedia 1992; de Groot 2004; Dilli 2018; Dunstan 2008; England 1989; Furuhjelm 2009; Giorlandino 2013; Haghiac 2015; Harris 2015; Hauner 2012; Helland 2001; Hurtado 2015; Ismail 2016; Jamilian 2017; Judge 2007; Keenan 2014; Krauss‐Etschmann 2007; Krummel 2016; Laivuori 1993; Malcolm 2003; Mardones 2008; Martin‐Alvarez 2012; Miller 2016; Min 2014; Min 2016; Mulder 2014; Noakes 2012; Ogundipe 2016; Oken 2013; Olsen 2000; Ramakrishnan 2010; Ranjkesh 2011; Razavi 2017; Ribeiro 2012; Samimi 2015; Sanjurjo 2004; Smuts 2003b; Valenzuela 2015; Van Winden 2017; Vaz 2017). For the majority of these trials there was insufficient information to permit us to assess selective reporting confidently (i.e. no access to a published trial protocol). We judged the remaining 12 trials to be at a high risk of reporting bias (Freeman 2008; Gustafson 2013; Horvaticek 2017; Judge 2014; Kaviani 2014; Knudsen 2006; Onwude 1995; Otto 2000; Pietrantoni 2014; Rees 2008; Rivas‐Echeverria 2000; Su 2008).

Kaviani 2014; Knudsen 2006; Pietrantoni 2014 and Rivas‐Echeverria 2000 each reported only one of the expected or prespecified outcomes. Freeman 2008, Gustafson 2013; Judge 2014; Otto 2000; and Rees 2008 reported few of the prespecified or expected outcomes. Onwude 1995 reported a limited range of expected outcomes and incomplete data (no standard deviations) for two of the continuous outcomes (length of gestation and birthweight). Su 2008 reported few of the expected outcomes, and data were incomplete for birth outcomes.

Other potential sources of bias

We judged 34 trials to be at a low risk of other potential sources of bias (Ali 2017; Bergmann 2007; Bisgaard 2016; Boris 2004; Carlson 2013; England 1989; Furuhjelm 2009; Giorlandino 2013; Gustafson 2013; Harper 2010; Harris 2015; Hurtado 2015; Ismail 2016; Jamilian 2016; Jamilian 2017; Khalili 2016; Knudsen 2006; Krauss‐Etschmann 2007; Makrides 2010; Mozurkewich 2013; Noakes 2012; Olsen 1992; Olsen 2000; Onwude 1995; Otto 2000; Pietrantoni 2014; Ramakrishnan 2010; Ranjkesh 2011; Razavi 2017; Samimi 2015; Smuts 2003a; Taghizadeh 2016; Valenzuela 2015; Van Goor 2009). We judged another 34 trials to be at an unclear risk of other potential sources of bias (Bosaeus 2015; Bulstra‐Ramakers 1994; Chase 2015; D'Almedia 1992; de Groot 2004; Dilli 2018; Dunstan 2008; Freeman 2008; Haghiac 2015; Hauner 2012; Helland 2001; Horvaticek 2017; Judge 2007; Judge 2014; Kaviani 2014; Keenan 2014; Krummel 2016; Malcolm 2003; Mardones 2008; Martin‐Alvarez 2012; Miller 2016; Min 2014; Min 2016; Mulder 2014; Ogundipe 2016; Oken 2013; Ribeiro 2012; Rivas‐Echeverria 2000; Sanjurjo 2004; Smuts 2003b; Su 2008; Tofail 2006; Van Winden 2017; Vaz 2017). We judged the remaining two trials, Laivuori 1993 and Rees 2008, to be at a high risk of other bias. In Laivuori 1993 there were substantial differences in the median length of supplementation between the three groups, which was a significant source of other bias, while in Rees 2008 women in the placebo group were more likely to have a co‐morbid anxiety disorder (9/13 versus 3/13), which introduced significant baseline imbalance between groups that was relevant to all reported outcomes.

Effects of interventions

See: Summary of findings for the main comparison Birth/infant outcomes; Summary of findings 2 Maternal outcomes; Summary of findings 3 Child/adult outcomes; Summary of findings 4 Health service outcomes

Omega‐3 supplementation versus no omega‐3

Primary outcomes
Preterm birth (< 37 weeks)

There was an 11% reduced risk of preterm birth (< 37 weeks) for omega‐3 LCPUFA compared with no omega‐3 (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 trials, 10,304 participants; high‐quality evidence; Analysis 1.1). Some asymmetry was observed on visual assessment of a funnel plot for this outcome, suggesting an absence of some small negative studies (Figure 4), with little likely impact on the overall result.

Figure 4
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.7 Preterm birth (< 37 weeks).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.7 Preterm birth (< 37 weeks).

Early preterm birth (< 34 weeks)

There was a 42% lower risk of early preterm birth (< 34 weeks) for omega‐3 LCPUFA compared with no omega‐3 (RR 0.58, 95% CI 0.44 to 0.77; 9 trials, 5204 participants; high‐quality evidence; Analysis 1.2).

Mother: secondary outcomes
Maternal death

Only four trials reported on maternal death (Bisgaard 2016; Makrides 2010; Oken 2013; Olsen 2000), with one maternal death reported in the omega‐3 group in Oken 2013. There was no evidence of a difference in the risk of maternal death for omega‐3 compared with no omega‐3 (RR 1.69, 95% CI 0.07 to 39.30; 4 trials, 4830 participants; Analysis 1.4).

Pre‐eclampsia (hypertension with proteinuria)

Pre‐eclampsia (hypertension with proteinuria) may be reduced for omega‐3 LCPUFA compared with no omega‐3 group (RR 0.84, 95% CI 0.69 to 1.01, 20 trials, 8306 participants; low‐quality evidence; Analysis 1.5). No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 5).

Figure 5
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.4 Pre‐eclampsia (hypertension with proteinuria).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.4 Pre‐eclampsia (hypertension with proteinuria).

High blood pressure (without proteinuria)

There was no evidence of a difference in the risk of high blood pressure (without proteinuria) for omega‐3 LCPUFA compared with no omega‐3 (RR 1.03, 95% CI 0.89 to 1.20; 7 trials, 4531 participants; Analysis 1.6).

Eclampsia

Only one trial reported on eclampsia (D'Almedia 1992), and indicated no clear difference between omega‐3 LCPUFA and no omega‐3 (RR 0.14, 95% CI 0.01 to 2.70; 1 trial; 100 participants; Analysis 1.7).

Maternal antepartum hospitalisation

There was no evidence of a difference in risk of maternal antepartum hospitalisation between omega‐3 LCPUFA and no omega‐3 overall (RR 0.92, 95% CI 0.81 to 1.04; 5 trials, 2876 participants; Analysis 1.8).

Mother's length of stay in hospital (days)

Bisgaard 2016 and Olsen 2000 were the only trials to report data on the mother's length of stay in hospital, and showed no clear differences between omega‐3 LCPUFA and no omega‐3 (MD 0.18 days, 95% CI ‐0.20 to 0.57; 2 trials, 2290 participants; Analysis 1.9).

Maternal anaemia

Only Olsen 2000 reported on maternal anaemia and no difference was seen between omega‐3 LCPUFA and no omega‐3 (RR 1.16, 95% CI 0.91 to 1.48; 846 participants; Analysis 1.10).

Miscarriage (< 24 weeks)

There was no clear difference in miscarriage risk (< 24 weeks) for omega‐3 LCPUFA compared with no omega‐3 (RR 1.07, 95% CI 0.80 to 1.43; 9 trials, 4190 participants; Analysis 1.11).

Antepartum vaginal bleeding

There was no evidence of a difference in risk of antepartum vaginal bleeding for omega‐3 LCPUFA compared with no omega‐3 overall (RR 1.01, 95% CI 0.69 to 1.48; 2 trials, 2151 participants; Analysis 1.12).

Rupture of membranes

Carlson 2013, Harris 2015, Pietrantoni 2014 and Smuts 2003a reported on rupture of membranes (prelabour and preterm prelabour), and showed a lower risk overall with omega‐3 LCPUFA compared with no omega‐3 (RR 0.46, 95% CI 0.28 to 0.76; 4 trials, 1281 participants. The separate results for prelabour and preterm prelabour rupture are shown in Analysis 1.13.

Maternal admission to intensive care

Two trials reported on maternal admission to intensive care (Makrides 2010; Taghizadeh 2016), and saw no evidence of a difference in risk between omega‐3 LCPUFA and no omega‐3 (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low‐quality evidence; Analysis 1.14).

Maternal adverse events

Overall 16 trials reported on one or more maternal adverse effects. Using a random‐effects model, there was no evidence of a difference in the risk of: severe adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low‐quality evidence), adverse events severe enough for cessation (RR 1.01, 95% CI 0.53 to 1.93; 6 trials, 1487 participants), any adverse effects (RR 1.38, 95% CI 1.16 to 1.65; I2 = 88%; 5 trials, 1480 participants), possibly due to higher reports of belching/burping in the omega‐3 LCPUFA group of Olsen 2000, and fewer reports of labour‐related complications in the omega‐3 LCPUFA group of Smuts 2003a (Analysis 1.15).

Very few differences were seen for individual adverse events, although unpleasant taste and belching/burping were more likely to be reported with omega‐3 LCPUFA than with no omega‐3 (Analysis 1.15).

Caesarean section

There was no evidence of a difference in the risk of caesarean section in omega‐3 LCPUFA compared with no omega‐3 (RR 0.97, 95% CI 0.91 to 1.03; 28 trials, 8481 participants; Analysis 1.16). No clear asymmetry was observed on visual assessment of a funnel plot for this outcome, although there was some indication that small negative trials may be missing (Figure 6). However this would be unlikely to affect the null findings.

Figure 6
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.16 Caesarean section.

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.16 Caesarean section.

Induction (post‐term)

Three trials reported on induction post‐term (Harris 2015; Hauner 2012; Makrides 2010). The effect of omega‐3 on post‐term induction is uncertain due to the wide confidence intervals and variation between the results of the studies (average RR 0.82, CI 0.22 to 2.98; 2900 participants, 3 trials; Tau2 = 0.70, P = 0.04, I2 = 77%; low‐quality evidence; Analysis 1.17).

Blood loss at birth (mL)

There was no evidence of a difference in maternal blood loss at birth between omega‐3 LCPUFA and no omega‐3 (MD 11.50 mL, 95% CI ‐6.75 to 29.76; 6 trials, 2776 participants; Analysis 1.18).

Postpartum haemorrhage

Four trials reported on postpartum haemorrhage (Carlson 2013;Harper 2010; Makrides 2010; Olsen 1992), and found no evidence of a difference between omega‐3 LCPUFA and no omega‐3 (RR 1.03, 95% CI 0.82 to 1.30; 4 trials, 4085 participants; Analysis 1.19).

Gestational diabetes

There was no evidence of a difference in the risk of GDM for omega‐3 LCPUFA compared with no omega‐3 (RR 1.02, 95% CI 0.83 to 1.26; 12 trials, 5235 participants; Analysis 1.20). No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 7).

Figure 7
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.20 Gestational diabetes.

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.20 Gestational diabetes.

Maternal insulin resistance (HOMA‐IR)

Only three trials reported on maternal insulin resistance (HOMA‐IR) (Krummel 2016; Samimi 2015; Taghizadeh 2016), and showed no clear differences overall for omega‐3 LCPUFA compared with no omega‐3 (average MD ‐0.85, 95% CI ‐2.50 to 0.80; Tau² = 1.82; P = 0.0008; I² = 86%; 176 participants; Analysis 1.21). The high statistical heterogeneity may be due to different populations (overweight/obese women in Krummel 2016 and women with GDM in the other two trials).

Excessive gestational weight gain

Only Carlson 2013 reported on excessive gestational weight gain, and observed no evidence of a difference in the risk between omega‐3 LCPUFA and no omega‐3 groups (RR 1.21, 95% CI 0.95 to 1.55; 350 participants; Analysis 1.22).

Gestational weight gain (kg)

There was no evidence of a difference in gestational weight gain for omega‐3 LCPUFA compared with no omega‐3 (MD ‐0.50 kg, 95% CI ‐0.68 to 0.59; 11 trials; random effects; Tau² = 0.60; P = 0.0006; I² = 59%; 2297 participants; Analysis 1.23). The funnel plot was not markedly asymmetric (Figure 8). Dilli 2018 contributed to the high statistical heterogeneity, with a 3 kg lower gain in the omega‐3 LCPUFA group compared with placebo.

Figure 8
Funnel plot of comparison: 1 Overall: omega‐3 versus no omega‐3, outcome: 1.23 Gestational weight gain (kg).

Funnel plot of comparison: 1 Overall: omega‐3 versus no omega‐3, outcome: 1.23 Gestational weight gain (kg).

Depression during pregnancy: thresholds

Carlson 2013, Su 2008 and Vaz 2017 reported on different thresholds for depression during pregnancy (using the Hamilton Rating Scale for Depression (HAM‐D), Edinburgh Postnatal Depression Scale (EPDS) and not specified), and showed no evidence of a difference between omega‐3 LCPUFA and no omega‐3 for each trial (Analysis 1.24).

Depression during pregnancy: scores

Depression scores during pregnancy were reported by five trials using four different methods (Beck Depression Inventory (BDI), HAM‐D, EPDS and the Montgomery–Åsberg Depression Rating Scale (MADRS)). Only BDI showed a result favouring omega‐3 LCPUFA over no omega‐3 (MD ‐5.86 points 95% CI ‐8.32 to ‐3.39; 2 trials, 104 participants) with the other three comparisons showing no evidence of an effect (Analysis 1.25).

Anxiety during pregnancy

Only Carlson 2013 reported on anxiety during pregnancy, and observed no evidence of a difference between omega‐3 LCPUFA and no omega‐3 (RR 0.95, 95% CI 0.06 to 15.12; 301 participants; Analysis 1.26).

Difficult life circumstances (maternal)

Only Keenan 2014 reported on difficult life circumstances (maternal), indicating no evidence of a difference between omega‐3 LCPUFA and no omega‐3 (MD 0.32, 95% CI ‐0.15 to 0.79; 51 participants; Analysis 1.27).

Stress (maternal)

Keenan 2014 was also the only trial to report on maternal stress, showing no important difference between omega‐3 LCPUFA and no omega‐3 as measured by the perceived stress scale (MD ‐1.82 points, 95% CI ‐3.68 to 0.04; 51 participants; Analysis 1.28).

Depressive symptoms postpartum: thresholds

Postpartum depression scores were reported by four trials using three different methods (Postpartum Depression Screening Scale (PDSS) ≥ 80, EPDS, and major depressive disorder), with none of the trials showing clear differences between omega‐3 LCPUFA and no omega‐3 (Analysis 1.29).

Depressive symptoms postpartum: scores

Only two trials reported on scores for postpartum depressive symptoms (Judge 2014; Mozurkewich 2013), and found no clear differences between omega‐3 LCPUFA and no omega‐3 for either BDI, PDSS overall or components of PDSS up to six months postpartum (Analysis 1.30).

Length of gestation (days)

There was an increase in length of gestation with omega‐3 LCPUFA compared with no omega‐3 (average MD 1.67 days, 95% CI 0.95 to 2.39; Tau² = 2.33; P < 0.0001; I² = 52%; 41 trials, 12,517 participants; moderate‐quality evidence; Analysis 1.31). Reasons for the high statistical heterogeneity are not readily apparent, although there were wide variations in populations, inclusion criteria and doses of omega‐3. Additionally, it was not always clear how length of gestation was determined and this may have varied across studies. No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 9).

Figure 9
Funnel plot of comparison: 1 OVERALL omega‐3 versus placebo/no omega‐3, outcome: 1.31 Length of gestation (days).

Funnel plot of comparison: 1 OVERALL omega‐3 versus placebo/no omega‐3, outcome: 1.31 Length of gestation (days).

Baby/infant/child
Perinatal death

There were fewer perinatal deaths in the omega‐3 LCPUFA groups than the no omega‐3 groups, though this did not reach conventional statistical significance (RR 0.75, 95% CI 0.54 to 1.03; 10 trials, 7416 participants; moderate‐quality evidence; Analysis 1.32). No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 10).

Figure 10
Funnel plot of comparison: 1 OVERALL omega‐3 versus no omega‐3, outcome: 1.32 Perinatal death.

Funnel plot of comparison: 1 OVERALL omega‐3 versus no omega‐3, outcome: 1.32 Perinatal death.

Stillbirth

No clear differences in stillbirth were seen between omega‐3 LCPUFA and no omega‐3 (RR 0.94, 95% CI 0.62 to 1.42; 16 trials, 7880 participants; Analysis 1.33). No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 11).

Figure 11
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.32 Stillbirth.

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.32 Stillbirth.

Neonatal death

No clear difference between omega‐3 LCPUFA and no omega‐3 was seen for neonatal death (RR 0.61, 95% CI 0.34 to 1.11; 9 trials, 7448 participants; Analysis 1.34).

Infant death

Four trials reported on infant death (Carlson 2013; Makrides 2010; Mulder 2014; Tofail 2006), and observed no evidence of a difference in risk between the omega‐3 LCPUFA and no omega‐3 groups (RR 0.74, 95% CI 0.25 to 2.19; 3239 participants; Analysis 1.35).

Large‐for‐gestational age

Six trials reported on large‐for‐gestational age (generally defined as greater than the 90th percentile) (Dilli 2018; Harper 2010; Hauner 2012; Makrides 2010; Min 2014; Taghizadeh 2016), with a possible small increase in risk with omega‐3 LCPUFA than no omega‐3 (RR 1.15, 95% CI 0.97 to 1.03; 3722 participants; moderate‐quality evidence; Analysis 1.36). This outcome was not prespecified in the protocol.

Macrosomia

For macrosomia (generally defined as birthweight < 4000 g), no clear differences were seen between omega‐3 LCPUFA and no omega‐3 (RR 0.69, 95% CI 0.43 to 1.13; 6 trials, 2008 participants; Analysis 1.37). This outcome was not prespecified in the protocol.

Low birthweight (< 2500 g)

Rates of low birthweight (< 2500 g) showed a 10% relative risk reduction with omega‐3 LCPUFA compared with no omega‐3 (RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high‐quality evidence Analysis 1.38). No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 12).

Figure 12
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.38 Low birthweight (< 2500 g).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.38 Low birthweight (< 2500 g).

Small‐for‐gestational age or intrauterine growth restriction (IUGR)

There was little or no evidence of a difference in risk of small‐for‐gestational age or IUGR between omega‐3 LCPUFA and no omega‐3 (RR 1.01, 95% CI 0.90 to 1.13; 8 trials, 6907 participants; moderate‐quality evidence; Analysis 1.39).

Birthweight (g)

Birthweight was higher in the omega‐3 LCPUFA group than the no omega‐3 group (average MD 75.74 g, 95% CI 38.05 to 113.43; Tau² = 7943.10; P < 0.00001; I² = 66%; 42 trials, 11,584 participants; Analysis 1.40). Reasons for the high statistical heterogeneity were not readily apparent, although there was a wide variation in birthweights between studies and inclusion criteria. No obvious asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 13).

Figure 13
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.41 Birthweight (g).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.41 Birthweight (g).

Birthweight Z score

Four trials reported on birthweight Z score (Bergmann 2007; Krummel 2016; Makrides 2010; Mulder 2014), and there was no evidence of a difference between omega‐3 LCPUFA and no omega‐3 (MD 0.06, 95% CI ‐0.02 to 0.13; 2792 participants; Analysis 1.41).

Birth length (cm)

There was no evidence of a difference in birth length for omega‐3 LCPUFA compared with no omega‐3 (MD 0.11 cm, 95% CI ‐0.10 to 0.31; Tau² = 0.13; P = 0.0001, I² = 57%; 28 trials, 8128 participants; Analysis 1.42). No clear asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 14).

Figure 14
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.43 Birth length (cm).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.43 Birth length (cm).

Head circumference at birth (cm)

There was no evidence of a difference in head circumference at birth for omega‐3 LCPUFA compared with no omega‐3 (average MD 0.07 cm, 95% CI ‐0.05 to 0.19; 22 trials, 7161 participants; Tau² 0.02, P = 0.06, I² = 33%, Analysis 1.43). No clear asymmetry was observed on visual assessment of a funnel plot for this outcome (Figure 15).

Figure 15
Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.45 Head circumference at birth (cm).

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.45 Head circumference at birth (cm).

Head circumference at birth Z score

Only two trials reported on head circumference at birth Z score (Krummel 2016; Makrides 2010), and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups (MD ‐0.03, 95% CI ‐0.14 to 0.07; 2462 participants; Analysis 1.44).

Length at birth Z score

Only two trials reported on length at birth Z score (Krummel 2016; Makrides 2010), and observed no clear difference between omega‐3 LCPUFA and no omega‐3 (average MD 0.18, 95% CI ‐0.18 to 0.54; Tau² = 0.05; P = 0.12; I² = 59%; 2462 participants; Analysis 1.45).

Baby admitted to neonatal care

There was an 8% relative reduced risk of a baby being admitted to neonatal care with omega‐3 LCPUFA compared with no omega‐3, although this did not reach conventional statistical significance (RR 0.92, 95% CI 0.83 to 1.03; 9 trials, 6920 participants; Analysis 1.46).

Infant length of stay in hospital (days)

Only Olsen 2000 reported on infant length of stay in hospital and observed no evidence of a difference in length between the omega‐3 LCPUFA and no omega‐3 groups (MD 0.11 days, 95% CI ‐1.40 to 1.62; 2014 participants; Analysis 1.47).

Congenital anomalies

Three trials reported on congenital anomalies (Carlson 2013; Olsen 1992; Ramakrishnan 2010), and observed no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (RR 1.08, 95% CI 0.61 to 1.92; 1807 participants; Analysis 1.48).

Retinopathy of prematurity

Only one trial reported on retinopathy of prematurity (Harper 2010), and there was no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (RR 1.20, 95% CI 0.32 to 4.44; 837 participants; Analysis 1.49).

Bronchopulmonary dysplasia

Only Harper 2010 and Makrides 2010 reported on bronchopulmonary dysplasia, and there was no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (RR 1.06, 95% CI 0.45 to 2.48; 3191 participants; Analysis 1.50).

Respiratory distress syndrome

Two trials reported on respiratory distress syndrome (Carlson 2013; Harper 2010), and found no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (average RR 1.17, 95% CI 0.54 to 2.52; Tau² = 0.21; P = 0.09; I² = 66%; 1129 participants; Analysis 1.51). Reasons for the statistical heterogeneity were not readily apparent although all the women in Harper 2010 had experienced a previous preterm birth and were treated with weekly intramuscular progesterone injections.

Necrotising enterocolitis (NEC)

Only Harper 2010 and Makrides 2010 reported on NEC, and found no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (RR 0.97, 95% CI 0.26 to 3.55; 3198 participants; Analysis 1.52).

Neonatal sepsis (proven)

Harper 2010, Helland 2001 and Makrides 2010 reported on proven neonatal sepsis, and found no evidence of a difference in risk between the omega‐3 LCPUFA and no omega‐3 groups (RR 0.97, 95% CI 0.44 to 2.14; 3788 participants; Analysis 1.53).

Convulsion

Only Makrides 2010 reported on convulsion, and observed no clear difference between the omega‐3 LCPUFA and no omega‐3 groups (RR 0.09, 95% CI 0.01 to 1.63; 2361 participants; Analysis 1.54).

Intraventricular haemorrhage

Three trials reported on intraventricular haemorrhage (Harper 2010; Makrides 2010; Olsen 2000), and found no evidence of a difference in risk between the omega‐3 LCPUFA and no omega‐3 groups in any intraventricular haemorrhage (RR 1.00, 95% CI 0.29 to 3.49; random effects; Tau² = 0.63; P = 0.12, I² = 53%; 5423 participants). Although Makrides 2010 showed a marked reduction in intraventricular haemorrhage, reasons for the statistical heterogeneity were not clear. Harper 2010 also reported Grade 3 or 4 intraventricular haemorrhage, finding no clear differences between omega‐3 LCPUFA and no omega‐3 (RR 1.60, 95% CI 0.38 to 6.65; 837 participants; Analysis 1.55).

Neonatal/infant adverse events

There was possibly a small decrease for any adverse events in neonates/infants with omega‐3 LCPUFA compared with no omega‐3 (RR 0.92, 95% CI 0.82 to 1.02; 2 trials, 592 participants; Analysis 1.56). For serious neonatal/infant adverse events, there was a reduced risk with omega‐3 LCPUFA compared with no omega‐3 (RR 0.72, 95% CI 0.53 to 0.99; 2 trials, 2690 participants; low‐quality evidence; Analysis 1.56).

Neonatal/infant morbidity

One trial of 291 infants reported on neonatal/infant cardiovascular, respiratory or morbidity caused by pregnancy/birth (Smuts 2003a), and found no evidence of difference between omega‐3 LCPUFA and no omega‐3 (Analysis 1.57; Analysis 1.58 and Analysis 1.59 respectively).

Another trial with 834 participants reported on neonatal/infant morbidity (Ramakrishnan 2010), and found no important differences in rates between omega‐3 LCPUFA and no omega‐3 for colds, fevers, rash, respiratory illnesses, vomiting, diarrhoea or other illnesses up to six months of age (Analysis 1.60).

Infant/child morbidity

Makrides 2010 reported on infant/child morbidity, and found a potentially reduced risk of ICU admissions for omega‐3 LCPUFA compared with no omega‐3 (RR 0.58, 95% CI 0.31 to 1.06; 1396 participants, but no clear differences for medical diagnosis of attention deficit hyperactivity disorder; autism spectrum disorder; other learning/behavioural disorders or other chronic health conditions; Analysis 1.61).

Ponderal index (g/m³ x 100)

There was no evidence of a difference in ponderal index between the omega‐3 LCPUFA and no omega‐3 groups (MD 0.05 g/m³ x 100, 95% CI ‐0.01 to 0.11; random effects, Tau² = 0.00, P = 0.07, I² = 50%, 6 trials, 887 participants; Analysis 1.62).

Infant/child weight (kg)

A total of 10 trials reported on infant/child weight at various time points, and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from six weeks to seven years of age (Analysis 1.63).

Infant/child length/height (cm)

Ten trials reported on length/height at various time points, and there was no evidence of a difference between the omega‐3 and no omega‐3 groups from six weeks to five years. However there was evidence of child height being lower in the omega‐3 LCPUFA compared with no omega‐3 groups at seven years (MD ‐1.22 cm 95% CI ‐2.29 to ‐0.16; 2 trials, 393 participants; Analysis 1.64).

Infant/child head circumference (cm)

A total of 10 trials reported on infant/child head circumference at various time points, and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from six weeks to six years of age (Analysis 1.65).

Infant/child length/height for age Z score (LAZ/HAZ)

Three trials reported on infant/child length/height for age Z score (LAZ/HAZ) at various time points (Mulder 2014; Ramakrishnan 2010; Tofail 2006), and observed no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from two months to five years (Analysis 1.66).

Infant/child waist circumference (cm)

Hauner 2012 and Makrides 2010 reported on infant/child waist circumference at various time points, and observed no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from two to five years (Analysis 1.67).

Infant/child weight‐for‐age Z score (WAZ)

Mulder 2014 and Ramakrishnan 2010 reported on infant/child weight‐for‐age Z score (WAZ) at various time points, and observed no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from one month to five years (Analysis 1.68).

Infant/child BMI Z score

Five trials reported on infant/child BMI Z score at various time points (Bergmann 2007; Carlson 2013; Ramakrishnan 2010; Krummel 2016; Makrides 2010), and found no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups between any of the time points from 18 months to seven years of age (Analysis 1.69).

Infant/child weight for length/height Z score (WHZ)

Mulder 2014, Ramakrishnan 2010 and Tofail 2006 reported on infant/child weight for length/height Z score (WHZ) at various time points and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from two months to 18 months old (Analysis 1.70).

Infant/child BMI percentile

Only Hauner 2012 reported on infant/child BMI percentile and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at two, three and five years of age. However a higher infant/child BMI percentile was observed in the omega‐3 LCPUFA compared with the no omega‐3 group at 48 months (MD 13.00%; 95% CI 3.19 to 22.81; 107 participants; Analysis 1.71).

Child/adult BMI

Helland 2001, Makrides 2010; and Olsen 1992 reported on child/adult BMI at various time points and there was no evidence of a difference between the omega‐3 LCPUFA and no omega‐3 groups at any of the time points from three to 19 years of age (Analysis 1.72).

Infant/child body fat (%)

Carlson 2013, Hauner 2012 and Makrides 2010 reported on infant/child body fat at various time points, and found no evidence of differences at any points from one to seven years of age between the omega‐3 LCPUFA and no omega‐3 groups (Analysis 1.73).

Infant/child total fat mass (kg)

Hauner 2012 and Makrides 2010 reported on infant/child total fat mass at various time points, and found no evidence of differences at any points from one to seven years of age between the omega‐3 LCPUFA and no omega‐3 groups (Analysis 1.74).

Cognition: thresholds

Makrides 2010, Mulder 2014 and Ramakrishnan 2010 reported Bayley Scales of Infant Development (BSID) II or III cognition thresholds at 18 months, and found no evidence of differences between the omega‐3 LCPUFA and no omega‐3 groups, except for BSID III < 85, which favoured omega‐3 LCPUFA, in Makrides 2010 (RR 0.49, 95% CI 0.24 to 0.98; 726 participants; Analysis 1.75).

Cognition: scores

Nine trials reported cognition scores at various time points. There was no evidence of a difference in cognition scores between the omega‐3 LCPUFA and no omega‐3 groups at any time point from nine months to 12 years of age, as measured by BSID II or III, Fagan novelty preference, Kaufman Assessment Battery for Children (K‐ABC) mental processing composite, Griffith Mental Development Scale (GMDS) general quotient score, Differential Ability Scales (DAS) II, Wechsler Abbreviated Scale of Intelligence (WASI) full‐scale intelligence quotient (IQ) or Wechsler Intelligence Scale for Children (WISC) IV full scale IQ (Analysis 1.76).

Attention: scores

Three trials reported on attention scores at various time points and used different assessment measures (Krauss‐Etschmann 2007, Makrides 2010; Ramakrishnan 2010). There was no evidence of a difference between omega‐3 LCPUFA and no omega‐3 groups at any time point or with any measure from 27 months to 8.5 years except in Ramakrishnan 2010, where lower attention scores were seen at five years as measured by K‐CPT omissions (MD ‐1.90, 95% CI ‐3.39 to ‐0.41; 797 participants; Analysis 1.77).

Motor: thresholds

Two trials reported thresholds for motor scores (Mulder 2014; Ramakrishnan 2010), and observed no differences between omega‐3 LCPUFA and no omega‐3 groups at 18 months of age (Analysis 1.78).

Motor: scores

No difference was observed in motor scores between the omega‐3 LCPUFA and no omega‐3 groups, as measured by BSID III or II at 4 to 18 months of age across six trials (Analysis 1.79).

Language: thresholds

In one trial with 726 participants there was no evidence of a difference in BSID III language score thresholds between the omega‐3 LCPUFA and no omega‐3 groups at 18 months (Makrides 2010). Howevever in Mulder 2014 (154 participants), most Communicative Development Inventories (CDI) language thresholds were higher with omega‐3 LCPUFA in children at 14 and 18 months (Analysis 1.80).

Language: scores

No differences between omega‐3 LCPUFA and no omega‐3 were seen in any communication or language scores in children from four months to seven years of age, across four trials (Analysis 1.81).

Behaviour: thresholds

In one trial with 730 participants no differences between omega‐3 LCPUFA and no omega‐3 were seen in behaviour thresholds for children at 18 months of age (Analysis 1.82) (Ramakrishnan 2010).

Behaviour: scores

There were few differences between omega‐3 LCPUFA and no omega‐3 in behaviour scores in children measured with different tools and over different time points from birth to 12 years. However, there was evidence of less difficult behaviour in the placebo compared with the omega‐3 LCPUFA group as measured by the Strengths and Difficulties Questionnaire (SDQ) Total Difficulties at six to nine years in Makrides 2010 (MD 1.08, 95% CI 0.18 to 1.98; 543 participants; Analysis 1.83).

Vision: visual acuity (cycles/degree)

Only Mulder 2014 and Judge 2007 reported on visual acuity, observing no evidence of a difference between groups at two, four or six months (Analysis 1.84).

Vision: visual evoked potential

Three trials reported visual evoked potential at various time points from birth to six months, with no important differences seen between omega‐3 and no omega‐3 (Analysis 1.85).

Hearing: brainstem auditory‐evoked responses

Only one trial reported on various ways of measuring brainstem auditory‐evoked responses from one to three months (Ramakrishnan 2010), and found no evidence of differences between the omega‐3 LCPUFA and no omega‐3 groups (Analysis 1.87).

Neurodevelopment (overall): thresholds

Three trials reported various measures of overall neurodevelopment from six months to five years, and observed no clear differences between the omega‐3 LCPUFA and no omega‐3 groups (Analysis 1.88).

Neurodevelopment (overall): scores

One trial reported components of the Ages and Stages Questionnaire (ASQ) at four and six months (Khalili 2016), and found no clear differences except for improved communication with omega‐3 LCPUFA at four months (MD 2.70 95% CI 0.41 to 4.99; 148 participants; Analysis 1.89).

Child Development Inventory

Only Hauner 2012 reported on the child development inventory (parent‐reported), and observed no clear differences between the omega‐3 LCPUFA and no omega‐3 groups, across a range of measures when children were five years old (Analysis 1.90).

Infant sleep behaviour

Only Judge 2007 reported on infant sleep behaviour, and found fewer arousals in quiet and active sleep with omega‐3 LCPUFA compared with no omega, but with no other differences between groups; 39 participants (Analysis 1.91).

Cerebral palsy

A single trial with 114 participants reported no cases of cerebral palsy in either the omega‐3 LCPUFA or the placebo group (Van Goor 2009) (Analysis 1.92).

None of the trials reported caesarean section (post‐term), jaundice, or use of community health services.

Subgroup analyses
By intervention type (Analysis 2)

Analyses were performed (where possible) based on type of omega‐3 intervention (omega‐3 LCPUFA supplements only; omega‐3 LCPUFA supplements, omega‐3 rich food and/or dietary advice; omega‐3 LCPUFA supplements and other agents; and omega‐3 supplements, omega‐3 LCPUFA rich food and other agents). No clear or important subgroup differences were revealed for any outcome except for:

  • birth length, where birth length was higher with omega‐3 LCPUFA supplements alone, or with omega‐3 rich food and/or diet advice; and lower when the intervention was omega‐3 LCPUFA combined with another non‐omega‐3 agent (Analysis 2.40).

However the small increase is not likely to be clinically meaningful.

By dose of DHA and EPA supplements (Analysis 3)

Subgroup analysis based on dose of omega‐3 supplements for low dose (≤ 500 mg/day) versus mid dose (500 mg to 1 g/day) versus high dose (> 1 g/day) revealed no clear or important difference for any of the 12 prespecified outcomes except for:

  • low birthweight, where the effect of low and mid doses of omega‐3 LCPUFA (500 mg to 1 g/day) appeared more pronounced in reducing low birthweight than high dose (Analysis 3.10); Chi² 6.17, P = 0.05, I² 67.6%; and

  • birthweight (Analysis 3.12); Chi² 8.34, P = 0.04, I² 64%, which appears to be driven by a single trial of flaxseed oil. When this trial is omitted, the subgroup analysis is no longer statistically significant.

Timing of intervention: gestational age when omega‐3 supplements commenced (Analysis 4)

Subgroup analysis based on the time when omega‐3 LCPUFA supplements started (≤ 20 weeks' gestation or > 20 weeks' gestation) revealed no clear or important differences for any of the 12 prespecified outcomes except for pre‐eclampsia (Analysis 4.4). However as the single trial contributing to the heterogeneity did not report timing of intervention (Rivas‐Echeverria 2000), this does not help elucidate the influence of timing start of supplement on this outcome.

Type of supplements (Analysis 5)

Subgroup analysis based on type of supplements (DHA/largely DHA versus mixed DHA/EPA versus mixed DHA/EPA/other) revealed no clear subgroup differences for the outcomes, except for:

  • pre‐eclampsia (likely due to the influence of a single study, Rivas‐Echeverria 2000), in the mixed DHA/EPA/other subgroup (Analysis 5.4); Chi² 7.58, P = 0.02, I² = 73.6%; and

  • caesarean section where incidence was higher in the mixed DHA/EPA subgroup (Analysis 5.5); Chi² 6.29, P = 0.04, I² = 68.2% than for the other DHA or EPA subgroups.

Risk (Analysis 6)

Analyses were performed based on risk of women ‐ low risk (healthy women or health condition unlikely to affect birth outcomes, e.g. allergy) versus increased/high risk (e.g. women with hypertension, gestational diabetes mellitus, depression, a history of preterm birth) versus mixed risk (no inclusion criteria related to maternal health risk, or health risk not reported). No clear or important subgroup differences were seen for any of the outcomes except low birthweight where studies with women at low or any risk showed a reduction compared with the studies involving women at increased or higher risk (Analysis 6.10); Chi² 6.24, P = 0.04, I² 67.9%.

Omega‐3 dose direct comparisons (Analysis 7)

One trial reported outcomes in 224 participants from a direct comparison of 600 mg and 300 mg DHA a day (Harris 2015); and another trial reported five different doses of DHA/EPA from 0.1 g/day to 2.8 g/day (which we collapsed into ≤ 1 g/day and > 1 g/day DHA/EPA) (Knudsen 2006). Knudsen 2006 only reported gestational length.

Primary outcomes

In one trial, no difference between doses was seen for:

  • early preterm birth (< 34 weeks) (RR 0.91, 95% CI 0.13 to 6.38; Analysis 7.1); or

  • prolonged gestation (> 42 weeks) (RR 0.91, 95% CI 0.06 to 14.44; Analysis 7.2) (Harris 2015).

Mother: secondary outcomes

One trial (Harris 2015), observed no evidence of a difference between women who received 600 mg DHA/day compared with 300 mg DHA/day for:

  • pre‐eclampsia (RR 0.91, 95% CI 0.06 to 14.44; Analysis 7.3);

  • induction post term (RR 0.10; 95% CI 0.01 to 1.87; Analysis 7.4);

  • premature rupture of membranes (RR 0.30, 95% CI 0.03 to 2.89; Analysis 7.5); or

  • premature prelabour rupture of membranes (RR 1.22, 95% CI 0.28 to 5.32; Analysis 7.6).

Two trials (Harris 2015; Knudsen 2006), observed no difference in length of gestation between women who received higher and lower doses of omega‐3 LCPUFA daily (MD 0.24 days, 95% CI ‐1.16 to 1.64; 1475 participants; Analysis 7.7).

Baby/infant/child

Harris 2015 observed no difference in women who received 600 mg DHA/day versus 300 mg DHA/day for:

  • birthweight (‐110.35 g, 95% CI ‐242.80 to 22.10; Analysis 7.8);

  • length at birth (MD 0.05 cm, 95% CI ‐0.80 to 0.90; Analysis 7.9); or

  • head circumference at birth (‐0.24 cm, 95% CI 0.87 to 0.39) (Analysis 7.10).

Omega‐3 type direct comparisons (Analysis 8)

Three trials reported direct comparisons of different types of omega‐3 supplements (Knudsen 2006; Mozurkewich 2013; Van Goor 2009).

Primary outcomes

None of the three trials reported any of the review's primary outcomes.

Mother: secondary outcomes

Mozurkewich 2013 observed no evidence of a difference between women who received DHA compared with EPA for:

  • caesarean section (RR 1.23, 95% CI 0.61 to 2.51; 77 participants; Analysis 8.2);

  • cessation due to adverse events (RR 0.82, 95% CI 0.24 to 2.83; 77 participants; Analysis 8.3).

  • blood loss at birth (MD 1.00 mL, 95% CI ‐181.94 to 183.94; 77 participants; Analysis 8.5);

  • major depressive disorder at six to eight weeks postpartum (RR 0.68, 95% CI 0.12 to 3.87; Analysis 8.6); or in

  • depressive symptoms postpartum as measured by the BDI at six to eight weeks (MD ‐1.40, 95% CI ‐3.75 to 0.95; Analysis 8.7).

In Mozurkewich 2013, there was a reduction in pre‐eclampsia in women who received DHA compared with EPA (RR 0.26, 95% CI 0.06 to 1.13; 77 participants; Analysis 8.4), though this did not reach statistical significance.

Two trials reported on gestational diabetes (Mozurkewich 2013; Van Goor 2009); in Mozurkewich 2013 there was a reduction in gestational diabetes when women received DHA compared with EPA (RR 0.15, 95% CI 0.02 to 1.14; 77 participants), though this did not reach statistical significance. Van Goor 2009 observed no evidence of difference between women who received DHA versus DHA/AA (RR 0.33, 95% CI 0.01 to 7.96; 86 participants; Analysis 8.1).

Length of gestation was reported by three trials, two of which found no difference between different types of omega‐3 supplements. Knudsen 2006 observed no evidence of a difference in length of gestation between women who received EPA/DHA compared with ALA (MD ‐0.29 days, 95% CI ‐2.33 to 1.75; 1250 participants). Van Goor 2009 found no evidence of a difference in this outcome between women who received DHA compared with DHA/AA (MD 0.00, 95% CI ‐3.31 to 3.31; 83 participants). However, Mozurkewich 2013 observed a greater length of gestation in women who received DHA compared with EPA (MD 9.10 days, 95% CI 5.24 to 12.96; 77 participants; Analysis 8.8).

Baby/infant/child

Mozurkewich 2013 observed no evidence of a difference between infants of women who received DHA and EPA in admission to neonatal care (RR 0.35, 95% CI 0.08 to 1.63; 78 participants; Analysis 8.9).

In Van Goor 2009, there was no evidence of a difference in birthweight between infants of women who received DHA compared with DHA/AA (MD ‐79.00 g, 95% CI ‐260.22 to 102.22; 83 participants). However, in Mozurkewich 2013 there was evidence of a higher birthweight in infants of mothers who received DHA compared with EPA (MD 372.00 g, 95% CI 151.90 to 592.10; 78 participants; Analysis 8.10).

Van Goor 2009 observed no evidence of a difference in infants of women who received DHA compared with infants of women who received DHA/AA for:

  • weight (MD ‐0.20 kg, 95% CI ‐0.79 to 0.39; 80 participants; Analysis 8.11);

  • height (MD ‐0.80 cm, 95% CI ‐2.50 to 0.90; 80 participants; Analysis 8.12);

  • infant head circumference (MD 0.10, 95% CI ‐0.45 to 0.65; 80 participants; Analysis 8.13).

  • cognition as measured by the BSID II (MD 0.90, 95% CI ‐4.71 to 6.51; 80 participants; Analysis 8.14); or

  • motor development as measured by the BSID II (MD 3.40, 95% CI ‐1.07 to 7.87; 79 participants; Analysis 8.15).

One trial, Van Goor 2009, reported on neurodevelopment from a direct comparison of omega‐3 (DHA versus DHA/AA). No differences between infants of mothers assigned to the two groups were observed for the neonatal neurological classification of mildly/definitely abnormal at two weeks (RR 0.73 95% CI 0.28 to 1.87; 67 participants), or for general movement quality that was mildly/definitely abnormal at two weeks (RR 1.08 95% CI 0.68 to 1.72; 67 participants), However, there was a higher risk of general movement quality being mildly or definitely abnormal at 12 weeks in infants of mothers in the DHA group (RR 1.81 95% CI 1.11 to 2.95; 83 participants; Analysis 8.16).

Van Goor 2009 observed no evidence of any difference between the infants of women who received DHA and infants of women who received DHA/AA in cerebral palsy (not estimable) (Analysis 8.17).

Sensitivity analyses (Analysis 9)

We included just over a third of the trials (24/70) that we considered to be at low risk of selection and performance bias in sensitivity analyses (Bisgaard 2016; Carlson 2013; D'Almedia 1992; Gustafson 2013; Haghiac 2015; Harper 2010; Harris 2015; Ismail 2016; Jamilian 2016; Keenan 2014; Khalili 2016; Krummel 2016; Makrides 2010; Min 2014; Min 2016; Mozurkewich 2013; Oken 2013; Olsen 2000; Onwude 1995; Ramakrishnan 2010; Razavi 2017; Rees 2008; Samimi 2015; Taghizadeh 2016). The 12 outcomes assessed in subgroup analyses 3 to 6 were included in these sensitivity analyses.

For preterm birth (< 37 weeks), the sensitivity analysis was similar to the overall analysis, although it lost conventional statistical significance (RR 0.92 95% CI 0.83 to 1.02; Analysis 9.1). Sensitivity analyses for early preterm birth (< 34 weeks) (RR 0.61 95% CI 0.46 to 0.82; Analysis 9.2) and prolonged pregnancy (> 42 weeks) (RR 2.32, 95% CI 1.26 to 4.28; Analysis 9.3) were very similar to the overall analyses.

The sensitivity analysis for pre‐eclampsia indicated a null result (RR 1.00 95% CI 0.81 to 1.25; Analysis 9.4), in contrast to a possible benefit seen with omega‐3 LCPUFA in the overall analysis.

For caesarean section, there was very little difference between the sensitivity analysis (RR 0.96 95% CI 0.89 to 1.04; Analysis 9.5) and the overall analysis. Length of gestation also showed similar results in the sensitivity analysis (1.42 more days with omega‐3, 95% CI 0.73 to 2.11; Analysis 9.6, now as a fixed‐effect model due to much lower statistical heterogeneity) and the overall findings.

The sensitivity analysis for perinatal death (RR 0.60, 95% CI 0.37 to 0.97; Analysis 9.7) now reached conventional statistical significance, but had a similar magnitude to the overall borderline analysis (Analysis 1.32).

In contrast, the sensitivity analysis for low birthweight lost statistical significance (RR 0.85 95% CI 0.68 to 1.06; Analysis 9.10) but was similar to the overall analysis which reached conventional statistical significance.

The sensitivity analyses for stillbirth (RR 0.72, 95% CI 0.35 to 1.52; Analysis 9.8), neonatal death (RR 0.56, 95% CI 0.25 to 1.27; Analysis 9.9), and small‐for‐gestational age (RR 0.94, 95% CI 0.78 to 1.12; Analysis 9.11) showed similar findings to their corresponding overall analyses (Analysis 1.33; Analysis 1.34; Analysis 1.39).

The sensitivity analysis for birthweight (MD 48.84 g; 95% CI 22.93 to 74.76; 17 trials, 7382 participants; Analysis 9.12) also showed a similar (but lower) result to the overall analysis (Analysis 1.40) (and had lower statistical heterogeneity).

Discussion

available in

Summary of main results

In this update we have included 70 trials with 19,927 women. Most of the trials evaluated omega‐3 long‐chain polyunsaturated fatty acids (LCPUFA) interventions compared with placebo or no omega‐3. We grouped these as: omega‐3 LCPUFA supplements (50 trials); omega‐3 LCPUFA supplements combined with food or dietary additions (seven trials); food/dietary additions (three trials); and omega‐3 fatty acid interventions combined with other agents (12 trials).

For our primary review outcomes, there was an 11% reduced risk (95% confidence interval (CI) 3% to 19%) of preterm birth < 37 weeks (high‐quality evidence) and a 42% reduced risk (95% CI 23% to 56%) of early preterm birth < 34 weeks (high‐quality evidence) for women receiving omega‐3 LCPUFA compared with no omega‐3. The number needed to treat for an additional beneficial outcome (NNTB) to prevent one preterm birth < 37 weeks is 68 (95% CI 39 to 238), and the NNTB to prevent a preterm birth < 34 weeks is 52 (95% CI 39 to 95). Conversely for prolonged gestation there was a probable 61% increase (95% CI 11% to 233%) with omega‐3 LCPUFA (moderate‐quality evidence) and the number needed to treat for an additional harmful outcome (NNTH) for an additional pregnancy prolonged beyond 42 weeks is 102 (95% CI 47 to 568). In the sensitivity analysis for preterm birth < 37 weeks, conventional statistical significance was lost, although results were similar. Sensitivity analyses for early preterm birth < 34 weeks and prolonged pregnancy > 42 weeks were very close to the overall analyses.

Omega‐3 LCPUFA probably reduces the risk of both perinatal death (moderate‐quality evidence) and neonatal care admission (moderate‐quality evidence); and reduces the risk of low birthweight babies (high‐quality evidence). Little or no difference in small for gestational age (SGA) or intrauterine growth restriction (moderate‐quality evidence) with a possible small increase in large for gestational age babies (moderate‐quality evidence) was seen. For most maternal outcomes, we observed no differences between groups. Mean gestational length was greater in women who received omega‐3 LCPUFA and pre‐eclampsia may also have been reduced (low‐quality evidence). For child/adult outcomes, very few differences between the antenatal omega‐3 LCPUFA and no omega‐3 groups were observed, indicating that there is uncertainty regarding the impact of omega‐3 LCPUFA on child development and growth.

Subgroup analyses (based on type of intervention (e.g. supplementation, food or advice), dose of docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), timing, type of omega‐3 LCPUFA, and degree of risk for women) revealed few differences. In the subgroup analyses by intervention, omega‐3 LCPUFA supplements and/or omega‐3 rich food and dietary advice indicated a greater positive effect on birth length than for the other intervention types. In the dose subgroup analysis, there was a positive effect from the lower doses (< 1 g/day) for low birthweight. For the risk subgroup analysis, studies with low or any risk women showed a greater reduction in low birthweight compared with the studies involving women at increased or higher risk.

Direct comparisons of doses and types of omega‐3 LCPUFA showed longer gestation and higher birthweight for DHA compared with EPA. There were few other differences apart from a possible reduction in pre‐eclampsia and in gestational diabetes mellitus for DHA compared with EPA.

Sensitivity analysis (restricted to trials at low risk of selection and performance bias) largely supported the findings observed in the main analyses, except for pre‐eclampsia (which no longer showed a reduction for omega‐3 LCPUFA compared with no omega‐3).

Overall completeness and applicability of evidence

Of the 70 trials included in this update, our three primary outcomes (preterm birth, early preterm birth and prolonged pregnancy) were reported by only 26, nine and six trials respectively, even though these could have been reported by most trials (e.g. as part of routine perinatal data collection). Birthweight was the most comprehensively reported outcome (41 trials). Longer‐term childhood outcomes were sparsely reported and many different assessment measures were used, for example, in neurodevelopment.

Generally the larger trials reported most of the outcomes that we had prespecified as being important, and so the body of evidence in this review is reasonably complete. However, some trials were conducted for specific reasons, such as assessing the effects of omega‐3 LCPUFA supplementation on allergy outcomes, and these trials did not always report other perinatal outcomes extensively. (Allergy outcomes from these trials are included in a separate review (Gunaratne 2015).) Some trials even excluded preterm births altogether, which may have underestimated the differences seen in preterm birth in this review. For some of these trials we were able to deduce outcomes such as preterm birth from trial flow diagrams. Exclusion of preterm births may have also led to incomplete reporting of linked outcomes, such as gestational age.

In this update we broadened the scope of the review to ensure that we could track the evolution of the perceived benefits of omega‐3 and present a single comprehensive review of the effects of omega‐3 LCPUFA during pregnancy. For example, in the 2006 version of this review, the major benefit of omega‐3 LCPUFA was thought to be in preventing pre‐eclampsia and increasing the duration of gestation. In the next decade, there was an emphasis on assessing the role of omega‐3 LCPUFA supplementation on child cognition and growth. More recently, there has been renewed interest in the role of omega‐3 LCPUFA in preventing preterm birth.

We also included trials assessing omega‐3 LCPUFA from food sources and omega‐3 LCPUFA with co‐interventions, although most of the 63 trials we have added in this update compare omega‐3 supplementation (largely DHA and EPA) with placebo. We have presented overall analyses as well as analyses of the different comparisons. While trials were conducted in a broad range of countries, most were from high‐income settings (although some of these studies recruited only disadvantaged women). Reporting of characteristics of women was both limited and variable, for example for baseline omega‐3 LCPUFA concentrations, which may influence pregnancy and longer term outcomes.

Quality of the evidence

Overall study‐level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials at some time points.

Most of the important perinatal outcomes assessed using GRADE had a rating of high‐quality (e.g. preterm birth) or moderate‐quality evidence (e.g. perinatal death) (summary of findings Table for the main comparison). For birth outcomes, we only downgraded for attrition bias if substantial losses happened around the time of birth, as later losses were not relevant here. For the other outcome domains GRADE ratings ranged from moderate to very low, with over half rated as low (maternal summary of findings Table 2, child/adult summary of findings Table 3, and health service summary of findings Table 4, outcomes). Reasons for downgrading were mostly due to design limitations (largely due to high risk of attrition bias and selection bias; and unclear randomisation and blinding) and imprecision. Particularly for the longer‐term child outcomes (summary of findings Table 3), there were often low numbers of studies and thus imprecision. Due to the large number of studies following up participants or subsets of participants, often for quite lengthy periods, attrition bias was commonly evident for these longer‐term outcomes.

Potential biases in the review process

Due to the rigorous methods we used (comprehensive searching, double screening and data extraction, and careful appraisal and analysis), biases are likely to be low. We were able to include 12 funnel plots, most of which did not indicate evidence of publication bias.

While we applied wide inclusion criteria at the review level, some studies had quite restrictive criteria (e.g. excluding preterm births, as discussed above) and some reported small numbers of outcomes although potentially more (e.g. perinatal death) would have been readily available and could have been reported by the trial authors.

Agreements and disagreements with other studies or reviews

A large systematic review from the US Agency for Healthcare Research and Quality (AHRQ) on the effects of omega‐3 fatty acids on child and maternal health concluded that, except for small beneficial effects on infant randomised controlled trials (RCTs) reporting preterm birth < 37 weeks and found no significant difference between omega‐3 and no omega‐3 (odds ratio (OR) 0.87 95% CI 0.66 to 1.15 for DHA and OR 0.86, 95% CI 0.65 to 1.15 for DHA/EPA, random‐effects). We included 26 RCTs for this outcome and found a clear result in favour of omega‐3 (risk ratio (RR) 0.89, 95% 0.81 to 0.97, fixed‐effect). For comparison, our result converts to OR 0.85 95% CI 0.74 to 0.99, random‐effects. The AHRQ review did not report on early preterm birth, which in our review showed a clear reduction with omega‐3 LCPUFA (RR 0.58, 95% CI 0.44 to 0.77).

Imhoff‐Kunsch 2012 reviewed 15 RCTs, finding like us, a clear reduction in early preterm birth, but only a suggestion of a reduction in preterm birth overall. In the Kar 2016 systematic review of nine included studies, a clear reduction was seen in both preterm and early preterm birth. Another systematic review of omega‐3 LCPUFA concentrating on birth outcomes was also largely consistent with our findings (e.g. reduced risk of early preterm birth and preterm birth (though the authors used a broader definition of early preterm birth and used a fixed‐effect model throughout the review) (Chen 2016). The same authors conducted a review of omega‐3 LCPUFA addressing gestational diabetes, pregnancy hypertension and pre‐eclampsia and found no evidence of differences (Chen 2015). Again their findings were largely consistent with ours, although we found a possible decrease in pre‐eclampsia with omega‐3 LCPUFA.

The Saccone 2016 systematic review included 34 studies, which comprised 17 omega‐3 LCPUFA trials. They found no clear differences in preterm birth in seven trials including 3493 asymptomatic singleton pregnancies (RR 0.90, 95% CI 0.72 to 1.11) whereas we found an 11% decrease in preterm birth < 37 weeks (RR 0.89, 95% CI 0.81 to 0.97; 24 trials, 10,121 participants). (Saccone 2016 excluded trials of women who had experienced previous preterm birth. When we omitted these two trials, it made minimal difference to our results.) For perinatal death, Saccone 2016 found no differences overall between omega‐3 LCPUFA and no omega‐3 LCPUFA in six trials (RR 0.61, 95% CI 0.30 to 1.24) whereas we found a possible reduction (RR 0.75, 95% CI 0.54 to 1.03; 10 trials, 7416 women). Saccone 2016 also stated that when omega‐3 LCPUFA supplementation started at 20 weeks' or less gestation this showed a large (73%) decrease in perinatal death with omega‐3 LCPUFA compared with placebo in singleton pregnancies, but the authors did not use accepted subgroup interaction methods to test this (Higgins 2011). Our subgroup interaction test for perinatal death did not show a difference in timing of gestation ‐ perinatal death was reduced at any time that supplementation started (≤ 20 weeks' gestation or later) (Analysis 4.7).

Saccone and colleagues have also published three prior systematic reviews focusing on specific outcomes: Saccone 2015a: recurrent intrauterine growth (three trials); Saccone 2015b: prior preterm birth (two trials); and Saccone 2015c: preterm birth prevention (nine trials). The Saccone 2016 review includes all studies from Saccone 2015a and Saccone 2015c, but not Saccone 2015b, which included two trials in women with prior preterm birth. All relevant studies in the four Saccone reviews are included in our review (Saccone 2015a; Saccone 2015b; Saccone 2015c; Saccone 2016).

Gould and colleagues reviewed 11 RCTs involving 5272 participants and concluded that this body of evidence did not conclusively support or refute the role of omega‐3 LCPUFA supplementation in pregnancy for improving cognitive or visual development (Gould 2013). Other recent reviews of child growth and development are consistent with our findings of little impact from omega‐3 LCPUFA supplementation during pregnancy (Campoy 2012; Li 2017; Rangel‐Huerta 2018).

Study flow diagram.
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Figure 1

Study flow diagram.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.7 Preterm birth (< 37 weeks).
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Figure 4

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.7 Preterm birth (< 37 weeks).

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.4 Pre‐eclampsia (hypertension with proteinuria).
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Figure 5

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.4 Pre‐eclampsia (hypertension with proteinuria).

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.16 Caesarean section.
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Figure 6

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.16 Caesarean section.

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.20 Gestational diabetes.
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Figure 7

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.20 Gestational diabetes.

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Funnel plot of comparison: 1 Overall: omega‐3 versus no omega‐3, outcome: 1.23 Gestational weight gain (kg).
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Figure 8

Funnel plot of comparison: 1 Overall: omega‐3 versus no omega‐3, outcome: 1.23 Gestational weight gain (kg).

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Funnel plot of comparison: 1 OVERALL omega‐3 versus placebo/no omega‐3, outcome: 1.31 Length of gestation (days).
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Figure 9

Funnel plot of comparison: 1 OVERALL omega‐3 versus placebo/no omega‐3, outcome: 1.31 Length of gestation (days).

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Funnel plot of comparison: 1 OVERALL omega‐3 versus no omega‐3, outcome: 1.32 Perinatal death.
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Figure 10

Funnel plot of comparison: 1 OVERALL omega‐3 versus no omega‐3, outcome: 1.32 Perinatal death.

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.32 Stillbirth.
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Figure 11

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.32 Stillbirth.

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.38 Low birthweight (< 2500 g).
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Figure 12

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.38 Low birthweight (< 2500 g).

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.41 Birthweight (g).
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Figure 13

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.41 Birthweight (g).

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.43 Birth length (cm).
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Figure 14

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.43 Birth length (cm).

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Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.45 Head circumference at birth (cm).
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Figure 15

Funnel plot of comparison: 1 Omega‐3 versus placebo/no omega‐3: OVERALL, outcome: 1.45 Head circumference at birth (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 1 Preterm birth (< 37 weeks).
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Analysis 1.1

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 2 Early preterm birth (< 34 weeks).
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Analysis 1.2

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 3 Prolonged gestation (> 42 weeks).
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Analysis 1.3

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 4 Maternal death.
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Analysis 1.4

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 4 Maternal death.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 5 Pre‐eclampsia (hypertension with proteinuria).
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Analysis 1.5

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 5 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 6 High blood pressure (without proteinuria).
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Analysis 1.6

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 6 High blood pressure (without proteinuria).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 7 Eclampsia.
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Analysis 1.7

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 7 Eclampsia.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 8 Maternal antepartum hospitalisation.
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Analysis 1.8

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 8 Maternal antepartum hospitalisation.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 9 Mother's length of stay in hospital (days).
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Analysis 1.9

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 9 Mother's length of stay in hospital (days).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 10 Maternal anaemia.
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Analysis 1.10

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 10 Maternal anaemia.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 11 Miscarriage (< 24 weeks).
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Analysis 1.11

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 11 Miscarriage (< 24 weeks).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 12 Antepartum vaginal bleeding.
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Analysis 1.12

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 12 Antepartum vaginal bleeding.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 13 Rupture of membranes (PPROM; PROM).
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Analysis 1.13

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 13 Rupture of membranes (PPROM; PROM).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 14 Maternal admission to intensive care.
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Analysis 1.14

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 14 Maternal admission to intensive care.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 15 Maternal adverse events.
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Analysis 1.15

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 15 Maternal adverse events.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 16 Caesarean section.
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Analysis 1.16

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 16 Caesarean section.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 17 Induction (post‐term).
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Analysis 1.17

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 17 Induction (post‐term).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 18 Blood loss at birth (mL).
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Analysis 1.18

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 18 Blood loss at birth (mL).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 19 Postpartum haemorrhage.
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Analysis 1.19

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 19 Postpartum haemorrhage.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 20 Gestational diabetes.
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Analysis 1.20

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 20 Gestational diabetes.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 21 Maternal insulin resistance (HOMA‐IR).
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Analysis 1.21

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 21 Maternal insulin resistance (HOMA‐IR).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 22 Excessive gestational weight gain.
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Analysis 1.22

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 22 Excessive gestational weight gain.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 23 Gestational weight gain (kg).
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Analysis 1.23

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 23 Gestational weight gain (kg).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 24 Depression during pregnancy: thresholds.
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Analysis 1.24

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 24 Depression during pregnancy: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 25 Depression during pregnancy: scores.
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Analysis 1.25

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 25 Depression during pregnancy: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 26 Anxiety during pregnancy.
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Analysis 1.26

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 26 Anxiety during pregnancy.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 27 Difficult life circumstances (maternal).
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Analysis 1.27

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 27 Difficult life circumstances (maternal).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 28 Stress (maternal).
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Analysis 1.28

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 28 Stress (maternal).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 29 Depressive symptoms postpartum: threshold.
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Analysis 1.29

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 29 Depressive symptoms postpartum: threshold.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 30 Depressive symptoms postpartum: scores.
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Analysis 1.30

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 30 Depressive symptoms postpartum: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 31 Gestational length (days).
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Analysis 1.31

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 31 Gestational length (days).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 32 Perinatal death.
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Analysis 1.32

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 32 Perinatal death.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 33 Stillbirth.
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Analysis 1.33

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 33 Stillbirth.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 34 Neonatal death.
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Analysis 1.34

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 34 Neonatal death.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 35 Infant death.
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Analysis 1.35

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 35 Infant death.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 36 Large‐for‐gestational age.
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Analysis 1.36

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 36 Large‐for‐gestational age.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 37 Macrosomia.
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Analysis 1.37

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 37 Macrosomia.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 38 Low birthweight (< 2500 g).
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Analysis 1.38

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 38 Low birthweight (< 2500 g).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 39 Small‐for‐gestational age/IUGR.
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Analysis 1.39

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 39 Small‐for‐gestational age/IUGR.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 40 Birthweight (g).
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Analysis 1.40

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 40 Birthweight (g).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 41 Birthweight Z score.
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Analysis 1.41

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 41 Birthweight Z score.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 42 Birth length (cm).
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Analysis 1.42

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 42 Birth length (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 43 Head circumference at birth (cm).
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Analysis 1.43

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 43 Head circumference at birth (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 44 Head circumference at birth Z score.
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Analysis 1.44

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 44 Head circumference at birth Z score.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 45 Length at birth Z score.
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Analysis 1.45

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 45 Length at birth Z score.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 46 Baby admitted to neonatal care.
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Analysis 1.46

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 46 Baby admitted to neonatal care.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 47 Infant length of stay in hospital (days).
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Analysis 1.47

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 47 Infant length of stay in hospital (days).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 48 Congenital anomalies.
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Analysis 1.48

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 48 Congenital anomalies.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 49 Retinopathy of prematurity.
Figures and Tables -
Analysis 1.49

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 49 Retinopathy of prematurity.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 50 Bronchopulmonary dysplasia.
Figures and Tables -
Analysis 1.50

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 50 Bronchopulmonary dysplasia.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 51 Respiratory distress syndrome.
Figures and Tables -
Analysis 1.51

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 51 Respiratory distress syndrome.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 52 Necrotising enterocolitis (NEC).
Figures and Tables -
Analysis 1.52

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 52 Necrotising enterocolitis (NEC).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 53 Neonatal sepsis (proven).
Figures and Tables -
Analysis 1.53

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 53 Neonatal sepsis (proven).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 54 Convulsion.
Figures and Tables -
Analysis 1.54

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 54 Convulsion.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 55 Intraventricular haemorrhage.
Figures and Tables -
Analysis 1.55

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 55 Intraventricular haemorrhage.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 56 Neonatal/infant adverse events.
Figures and Tables -
Analysis 1.56

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 56 Neonatal/infant adverse events.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 57 Neonatal/infant morbidity: cardiovascular.
Figures and Tables -
Analysis 1.57

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 57 Neonatal/infant morbidity: cardiovascular.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 58 Neonatal/infant morbidity: respiratory.
Figures and Tables -
Analysis 1.58

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 58 Neonatal/infant morbidity: respiratory.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 59 Neonatal/infant morbidity: due to pregnancy/birth events.
Figures and Tables -
Analysis 1.59

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 59 Neonatal/infant morbidity: due to pregnancy/birth events.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 60 Neonatal/infant morbidity: other.
Figures and Tables -
Analysis 1.60

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 60 Neonatal/infant morbidity: other.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 61 Infant/child morbidity.
Figures and Tables -
Analysis 1.61

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 61 Infant/child morbidity.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 62 Ponderal index.
Figures and Tables -
Analysis 1.62

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 62 Ponderal index.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 63 Infant/child weight (kg).
Figures and Tables -
Analysis 1.63

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 63 Infant/child weight (kg).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 64 Infant/child length/height (cm).
Figures and Tables -
Analysis 1.64

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 64 Infant/child length/height (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 65 Infant/child head circumference (cm).
Figures and Tables -
Analysis 1.65

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 65 Infant/child head circumference (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 66 Infant/child length/height for age Z score (LAZ/HAZ).
Figures and Tables -
Analysis 1.66

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 66 Infant/child length/height for age Z score (LAZ/HAZ).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 67 Infant/child waist circumference (cm).
Figures and Tables -
Analysis 1.67

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 67 Infant/child waist circumference (cm).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 68 Infant/child weight‐for‐age Z score (WAZ).
Figures and Tables -
Analysis 1.68

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 68 Infant/child weight‐for‐age Z score (WAZ).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 69 Infant/child BMI Z score.
Figures and Tables -
Analysis 1.69

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 69 Infant/child BMI Z score.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 70 Infant/child weight for length/height Z score (WHZ).
Figures and Tables -
Analysis 1.70

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 70 Infant/child weight for length/height Z score (WHZ).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 71 Infant/child BMI percentile.
Figures and Tables -
Analysis 1.71

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 71 Infant/child BMI percentile.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 72 Child/adult BMI.
Figures and Tables -
Analysis 1.72

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 72 Child/adult BMI.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 73 Infant/child body fat (%).
Figures and Tables -
Analysis 1.73

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 73 Infant/child body fat (%).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 74 Infant/child total fat mass (kg).
Figures and Tables -
Analysis 1.74

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 74 Infant/child total fat mass (kg).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 75 Cognition: thresholds.
Figures and Tables -
Analysis 1.75

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 75 Cognition: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 76 Cognition: scores.
Figures and Tables -
Analysis 1.76

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 76 Cognition: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 77 Attention: scores.
Figures and Tables -
Analysis 1.77

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 77 Attention: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 78 Motor: thresholds.
Figures and Tables -
Analysis 1.78

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 78 Motor: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 79 Motor: scores.
Figures and Tables -
Analysis 1.79

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 79 Motor: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 80 Language: thresholds.
Figures and Tables -
Analysis 1.80

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 80 Language: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 81 Language: scores.
Figures and Tables -
Analysis 1.81

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 81 Language: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 82 Behaviour: thresholds.
Figures and Tables -
Analysis 1.82

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 82 Behaviour: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 83 Behaviour: scores.
Figures and Tables -
Analysis 1.83

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 83 Behaviour: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 84 Vision: visual acuity (cycles/degree).
Figures and Tables -
Analysis 1.84

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 84 Vision: visual acuity (cycles/degree).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 85 Vision: VEP acuity.
Figures and Tables -
Analysis 1.85

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 85 Vision: VEP acuity.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 86 Vision: VEP latency.
Figures and Tables -
Analysis 1.86

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 86 Vision: VEP latency.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 87 Hearing: brainstem auditory‐evoked responses.
Figures and Tables -
Analysis 1.87

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 87 Hearing: brainstem auditory‐evoked responses.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 88 Neurodevelopment: thresholds.
Figures and Tables -
Analysis 1.88

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 88 Neurodevelopment: thresholds.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 89 Neurodevelopment: scores.
Figures and Tables -
Analysis 1.89

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 89 Neurodevelopment: scores.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 90 Child Development Inventory.
Figures and Tables -
Analysis 1.90

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 90 Child Development Inventory.

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 91 Infant sleep behaviour (%).
Figures and Tables -
Analysis 1.91

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 91 Infant sleep behaviour (%).

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Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 92 Cerebral palsy.
Figures and Tables -
Analysis 1.92

Comparison 1 Overall: omega‐3 versus no omega‐3, Outcome 92 Cerebral palsy.

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Comparison 2 Type of omega‐3 intervention, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 2.1

Comparison 2 Type of omega‐3 intervention, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 2 Type of omega‐3 intervention, Outcome 2 Early preterm birth (< 34 weeks).
Figures and Tables -
Analysis 2.2

Comparison 2 Type of omega‐3 intervention, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 2 Type of omega‐3 intervention, Outcome 3 Prolonged gestation (> 42 weeks).
Figures and Tables -
Analysis 2.3

Comparison 2 Type of omega‐3 intervention, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 2 Type of omega‐3 intervention, Outcome 4 Maternal death.
Figures and Tables -
Analysis 2.4

Comparison 2 Type of omega‐3 intervention, Outcome 4 Maternal death.

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Comparison 2 Type of omega‐3 intervention, Outcome 5 Pre‐eclampsia (hypertension with proteinuria).
Figures and Tables -
Analysis 2.5

Comparison 2 Type of omega‐3 intervention, Outcome 5 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 2 Type of omega‐3 intervention, Outcome 6 High blood pressure (without proteinuria).
Figures and Tables -
Analysis 2.6

Comparison 2 Type of omega‐3 intervention, Outcome 6 High blood pressure (without proteinuria).

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Comparison 2 Type of omega‐3 intervention, Outcome 7 Eclampsia.
Figures and Tables -
Analysis 2.7

Comparison 2 Type of omega‐3 intervention, Outcome 7 Eclampsia.

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Comparison 2 Type of omega‐3 intervention, Outcome 8 Maternal antepartum hospitalisation.
Figures and Tables -
Analysis 2.8

Comparison 2 Type of omega‐3 intervention, Outcome 8 Maternal antepartum hospitalisation.

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Comparison 2 Type of omega‐3 intervention, Outcome 9 Mother's length of stay in hospital (days).
Figures and Tables -
Analysis 2.9

Comparison 2 Type of omega‐3 intervention, Outcome 9 Mother's length of stay in hospital (days).

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Comparison 2 Type of omega‐3 intervention, Outcome 10 Maternal anaemia.
Figures and Tables -
Analysis 2.10

Comparison 2 Type of omega‐3 intervention, Outcome 10 Maternal anaemia.

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Comparison 2 Type of omega‐3 intervention, Outcome 11 Miscarriage (< 24 weeks).
Figures and Tables -
Analysis 2.11

Comparison 2 Type of omega‐3 intervention, Outcome 11 Miscarriage (< 24 weeks).

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Comparison 2 Type of omega‐3 intervention, Outcome 12 Antepartum vaginal bleeding.
Figures and Tables -
Analysis 2.12

Comparison 2 Type of omega‐3 intervention, Outcome 12 Antepartum vaginal bleeding.

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Comparison 2 Type of omega‐3 intervention, Outcome 13 Preterm prelabour rupture of membranes.
Figures and Tables -
Analysis 2.13

Comparison 2 Type of omega‐3 intervention, Outcome 13 Preterm prelabour rupture of membranes.

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Comparison 2 Type of omega‐3 intervention, Outcome 14 Prelabour rupture of membranes.
Figures and Tables -
Analysis 2.14

Comparison 2 Type of omega‐3 intervention, Outcome 14 Prelabour rupture of membranes.

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Comparison 2 Type of omega‐3 intervention, Outcome 15 Maternal admission to intensive care.
Figures and Tables -
Analysis 2.15

Comparison 2 Type of omega‐3 intervention, Outcome 15 Maternal admission to intensive care.

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Comparison 2 Type of omega‐3 intervention, Outcome 16 Maternal severe adverse effects (including cessation).
Figures and Tables -
Analysis 2.16

Comparison 2 Type of omega‐3 intervention, Outcome 16 Maternal severe adverse effects (including cessation).

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Comparison 2 Type of omega‐3 intervention, Outcome 17 Caesarean section.
Figures and Tables -
Analysis 2.17

Comparison 2 Type of omega‐3 intervention, Outcome 17 Caesarean section.

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Comparison 2 Type of omega‐3 intervention, Outcome 18 Induction (post‐term).
Figures and Tables -
Analysis 2.18

Comparison 2 Type of omega‐3 intervention, Outcome 18 Induction (post‐term).

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Comparison 2 Type of omega‐3 intervention, Outcome 19 Blood loss at birth (mL).
Figures and Tables -
Analysis 2.19

Comparison 2 Type of omega‐3 intervention, Outcome 19 Blood loss at birth (mL).

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Comparison 2 Type of omega‐3 intervention, Outcome 20 Postpartum haemorrhage.
Figures and Tables -
Analysis 2.20

Comparison 2 Type of omega‐3 intervention, Outcome 20 Postpartum haemorrhage.

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Comparison 2 Type of omega‐3 intervention, Outcome 21 Gestational diabetes.
Figures and Tables -
Analysis 2.21

Comparison 2 Type of omega‐3 intervention, Outcome 21 Gestational diabetes.

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Comparison 2 Type of omega‐3 intervention, Outcome 22 Maternal insulin resistance (HOMA‐IR).
Figures and Tables -
Analysis 2.22

Comparison 2 Type of omega‐3 intervention, Outcome 22 Maternal insulin resistance (HOMA‐IR).

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Comparison 2 Type of omega‐3 intervention, Outcome 23 Excessive gestational weight gain.
Figures and Tables -
Analysis 2.23

Comparison 2 Type of omega‐3 intervention, Outcome 23 Excessive gestational weight gain.

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Comparison 2 Type of omega‐3 intervention, Outcome 24 Gestational weight gain (kg).
Figures and Tables -
Analysis 2.24

Comparison 2 Type of omega‐3 intervention, Outcome 24 Gestational weight gain (kg).

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Comparison 2 Type of omega‐3 intervention, Outcome 25 Depression during pregnancy: scores.
Figures and Tables -
Analysis 2.25

Comparison 2 Type of omega‐3 intervention, Outcome 25 Depression during pregnancy: scores.

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Comparison 2 Type of omega‐3 intervention, Outcome 26 Depression during pregnancy: thresholds.
Figures and Tables -
Analysis 2.26

Comparison 2 Type of omega‐3 intervention, Outcome 26 Depression during pregnancy: thresholds.

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Comparison 2 Type of omega‐3 intervention, Outcome 27 Depressive symptoms postpartum: thresholds.
Figures and Tables -
Analysis 2.27

Comparison 2 Type of omega‐3 intervention, Outcome 27 Depressive symptoms postpartum: thresholds.

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Comparison 2 Type of omega‐3 intervention, Outcome 28 Depressive symptoms postpartum: scores.
Figures and Tables -
Analysis 2.28

Comparison 2 Type of omega‐3 intervention, Outcome 28 Depressive symptoms postpartum: scores.

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Comparison 2 Type of omega‐3 intervention, Outcome 29 Length of gestation (days).
Figures and Tables -
Analysis 2.29

Comparison 2 Type of omega‐3 intervention, Outcome 29 Length of gestation (days).

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Comparison 2 Type of omega‐3 intervention, Outcome 30 Perinatal death.
Figures and Tables -
Analysis 2.30

Comparison 2 Type of omega‐3 intervention, Outcome 30 Perinatal death.

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Comparison 2 Type of omega‐3 intervention, Outcome 31 Stillbirth.
Figures and Tables -
Analysis 2.31

Comparison 2 Type of omega‐3 intervention, Outcome 31 Stillbirth.

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Comparison 2 Type of omega‐3 intervention, Outcome 32 Neonatal death.
Figures and Tables -
Analysis 2.32

Comparison 2 Type of omega‐3 intervention, Outcome 32 Neonatal death.

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Comparison 2 Type of omega‐3 intervention, Outcome 33 Infant death.
Figures and Tables -
Analysis 2.33

Comparison 2 Type of omega‐3 intervention, Outcome 33 Infant death.

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Comparison 2 Type of omega‐3 intervention, Outcome 34 Large‐for‐gestational age.
Figures and Tables -
Analysis 2.34

Comparison 2 Type of omega‐3 intervention, Outcome 34 Large‐for‐gestational age.

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Comparison 2 Type of omega‐3 intervention, Outcome 35 Macrosomia.
Figures and Tables -
Analysis 2.35

Comparison 2 Type of omega‐3 intervention, Outcome 35 Macrosomia.

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Comparison 2 Type of omega‐3 intervention, Outcome 36 Low birthweight (< 2500 g).
Figures and Tables -
Analysis 2.36

Comparison 2 Type of omega‐3 intervention, Outcome 36 Low birthweight (< 2500 g).

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Comparison 2 Type of omega‐3 intervention, Outcome 37 Small‐for‐gestational age/IUGR.
Figures and Tables -
Analysis 2.37

Comparison 2 Type of omega‐3 intervention, Outcome 37 Small‐for‐gestational age/IUGR.

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Comparison 2 Type of omega‐3 intervention, Outcome 38 Birthweight (g).
Figures and Tables -
Analysis 2.38

Comparison 2 Type of omega‐3 intervention, Outcome 38 Birthweight (g).

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Comparison 2 Type of omega‐3 intervention, Outcome 39 Birthweight Z score.
Figures and Tables -
Analysis 2.39

Comparison 2 Type of omega‐3 intervention, Outcome 39 Birthweight Z score.

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Comparison 2 Type of omega‐3 intervention, Outcome 40 Birth length (cm).
Figures and Tables -
Analysis 2.40

Comparison 2 Type of omega‐3 intervention, Outcome 40 Birth length (cm).

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Comparison 2 Type of omega‐3 intervention, Outcome 41 Length at birth Z score.
Figures and Tables -
Analysis 2.41

Comparison 2 Type of omega‐3 intervention, Outcome 41 Length at birth Z score.

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Comparison 2 Type of omega‐3 intervention, Outcome 42 Head circumference at birth (cm).
Figures and Tables -
Analysis 2.42

Comparison 2 Type of omega‐3 intervention, Outcome 42 Head circumference at birth (cm).

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Comparison 2 Type of omega‐3 intervention, Outcome 43 Head circumference at birth Z score.
Figures and Tables -
Analysis 2.43

Comparison 2 Type of omega‐3 intervention, Outcome 43 Head circumference at birth Z score.

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Comparison 2 Type of omega‐3 intervention, Outcome 44 Baby admitted to neonatal care.
Figures and Tables -
Analysis 2.44

Comparison 2 Type of omega‐3 intervention, Outcome 44 Baby admitted to neonatal care.

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Comparison 2 Type of omega‐3 intervention, Outcome 45 Infant length of stay in hospital (days).
Figures and Tables -
Analysis 2.45

Comparison 2 Type of omega‐3 intervention, Outcome 45 Infant length of stay in hospital (days).

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Comparison 2 Type of omega‐3 intervention, Outcome 46 Congenital anomalies.
Figures and Tables -
Analysis 2.46

Comparison 2 Type of omega‐3 intervention, Outcome 46 Congenital anomalies.

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Comparison 2 Type of omega‐3 intervention, Outcome 47 Retinopathy of prematurity.
Figures and Tables -
Analysis 2.47

Comparison 2 Type of omega‐3 intervention, Outcome 47 Retinopathy of prematurity.

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Comparison 2 Type of omega‐3 intervention, Outcome 48 Bronchopulmonary dysplasia.
Figures and Tables -
Analysis 2.48

Comparison 2 Type of omega‐3 intervention, Outcome 48 Bronchopulmonary dysplasia.

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Comparison 2 Type of omega‐3 intervention, Outcome 49 Respiratory distress syndrome.
Figures and Tables -
Analysis 2.49

Comparison 2 Type of omega‐3 intervention, Outcome 49 Respiratory distress syndrome.

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Comparison 2 Type of omega‐3 intervention, Outcome 50 Necrotising enterocolitis (NEC).
Figures and Tables -
Analysis 2.50

Comparison 2 Type of omega‐3 intervention, Outcome 50 Necrotising enterocolitis (NEC).

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Comparison 2 Type of omega‐3 intervention, Outcome 51 Neonatal sepsis (proven).
Figures and Tables -
Analysis 2.51

Comparison 2 Type of omega‐3 intervention, Outcome 51 Neonatal sepsis (proven).

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Comparison 2 Type of omega‐3 intervention, Outcome 52 Convulsion.
Figures and Tables -
Analysis 2.52

Comparison 2 Type of omega‐3 intervention, Outcome 52 Convulsion.

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Comparison 2 Type of omega‐3 intervention, Outcome 53 Intraventricular haemorrhage.
Figures and Tables -
Analysis 2.53

Comparison 2 Type of omega‐3 intervention, Outcome 53 Intraventricular haemorrhage.

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Comparison 2 Type of omega‐3 intervention, Outcome 54 Neonatal/infant serious adverse events.
Figures and Tables -
Analysis 2.54

Comparison 2 Type of omega‐3 intervention, Outcome 54 Neonatal/infant serious adverse events.

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Comparison 2 Type of omega‐3 intervention, Outcome 55 Neonatal/infant morbidity: cardiovascular.
Figures and Tables -
Analysis 2.55

Comparison 2 Type of omega‐3 intervention, Outcome 55 Neonatal/infant morbidity: cardiovascular.

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Comparison 2 Type of omega‐3 intervention, Outcome 56 Neonatal/infant morbidity: respiratory.
Figures and Tables -
Analysis 2.56

Comparison 2 Type of omega‐3 intervention, Outcome 56 Neonatal/infant morbidity: respiratory.

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Comparison 2 Type of omega‐3 intervention, Outcome 57 Neonatal/infant morbidity: caused by pregnancy/birth.
Figures and Tables -
Analysis 2.57

Comparison 2 Type of omega‐3 intervention, Outcome 57 Neonatal/infant morbidity: caused by pregnancy/birth.

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Comparison 2 Type of omega‐3 intervention, Outcome 58 Ponderal index.
Figures and Tables -
Analysis 2.58

Comparison 2 Type of omega‐3 intervention, Outcome 58 Ponderal index.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 3.1

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 2 Early preterm birth (< 34 weeks).
Figures and Tables -
Analysis 3.2

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 3 Prolonged gestation (> 42 weeks).
Figures and Tables -
Analysis 3.3

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).
Figures and Tables -
Analysis 3.4

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 5 Caesarean section.
Figures and Tables -
Analysis 3.5

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 5 Caesarean section.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 6 Length of gestation (days).
Figures and Tables -
Analysis 3.6

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 6 Length of gestation (days).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 7 Perinatal death.
Figures and Tables -
Analysis 3.7

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 7 Perinatal death.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 8 Stillbirth.
Figures and Tables -
Analysis 3.8

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 8 Stillbirth.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 9 Neonatal death.
Figures and Tables -
Analysis 3.9

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 9 Neonatal death.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 10 Low birthweight (< 2500 g).
Figures and Tables -
Analysis 3.10

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 10 Low birthweight (< 2500 g).

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 11 Small‐for‐gestational age/IUGR.
Figures and Tables -
Analysis 3.11

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 11 Small‐for‐gestational age/IUGR.

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Comparison 3 Dose (DHA/EPA) subgroups, Outcome 12 Birthweight (g).
Figures and Tables -
Analysis 3.12

Comparison 3 Dose (DHA/EPA) subgroups, Outcome 12 Birthweight (g).

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Comparison 4 Timing subgroups, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 4.1

Comparison 4 Timing subgroups, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 4 Timing subgroups, Outcome 2 Early preterm birth (< 34 weeks).
Figures and Tables -
Analysis 4.2

Comparison 4 Timing subgroups, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 4 Timing subgroups, Outcome 3 Prolonged gestation (> 42 weeks).
Figures and Tables -
Analysis 4.3

Comparison 4 Timing subgroups, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 4 Timing subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).
Figures and Tables -
Analysis 4.4

Comparison 4 Timing subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 4 Timing subgroups, Outcome 5 Caesarean section.
Figures and Tables -
Analysis 4.5

Comparison 4 Timing subgroups, Outcome 5 Caesarean section.

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Comparison 4 Timing subgroups, Outcome 6 Length of gestation (days).
Figures and Tables -
Analysis 4.6

Comparison 4 Timing subgroups, Outcome 6 Length of gestation (days).

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Comparison 4 Timing subgroups, Outcome 7 Perinatal death.
Figures and Tables -
Analysis 4.7

Comparison 4 Timing subgroups, Outcome 7 Perinatal death.

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Comparison 4 Timing subgroups, Outcome 8 Stillbirth.
Figures and Tables -
Analysis 4.8

Comparison 4 Timing subgroups, Outcome 8 Stillbirth.

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Comparison 4 Timing subgroups, Outcome 9 Neonatal death.
Figures and Tables -
Analysis 4.9

Comparison 4 Timing subgroups, Outcome 9 Neonatal death.

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Comparison 4 Timing subgroups, Outcome 10 Low birthweight (< 2500 g).
Figures and Tables -
Analysis 4.10

Comparison 4 Timing subgroups, Outcome 10 Low birthweight (< 2500 g).

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Comparison 4 Timing subgroups, Outcome 11 Small‐for‐gestational age/IUGR.
Figures and Tables -
Analysis 4.11

Comparison 4 Timing subgroups, Outcome 11 Small‐for‐gestational age/IUGR.

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Comparison 4 Timing subgroups, Outcome 12 Birthweight (g).
Figures and Tables -
Analysis 4.12

Comparison 4 Timing subgroups, Outcome 12 Birthweight (g).

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Comparison 5 DHA/mixed subgroups, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 5.1

Comparison 5 DHA/mixed subgroups, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 5 DHA/mixed subgroups, Outcome 2 Early preterm birth (< 34 weeks).
Figures and Tables -
Analysis 5.2

Comparison 5 DHA/mixed subgroups, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 5 DHA/mixed subgroups, Outcome 3 Prolonged gestation (> 42 weeks).
Figures and Tables -
Analysis 5.3

Comparison 5 DHA/mixed subgroups, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 5 DHA/mixed subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).
Figures and Tables -
Analysis 5.4

Comparison 5 DHA/mixed subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 5 DHA/mixed subgroups, Outcome 5 Caesarean section.
Figures and Tables -
Analysis 5.5

Comparison 5 DHA/mixed subgroups, Outcome 5 Caesarean section.

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Comparison 5 DHA/mixed subgroups, Outcome 6 Gestational length (days).
Figures and Tables -
Analysis 5.6

Comparison 5 DHA/mixed subgroups, Outcome 6 Gestational length (days).

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Comparison 5 DHA/mixed subgroups, Outcome 7 Perinatal death.
Figures and Tables -
Analysis 5.7

Comparison 5 DHA/mixed subgroups, Outcome 7 Perinatal death.

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Comparison 5 DHA/mixed subgroups, Outcome 8 Stillbirth.
Figures and Tables -
Analysis 5.8

Comparison 5 DHA/mixed subgroups, Outcome 8 Stillbirth.

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Comparison 5 DHA/mixed subgroups, Outcome 9 Neonatal death.
Figures and Tables -
Analysis 5.9

Comparison 5 DHA/mixed subgroups, Outcome 9 Neonatal death.

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Comparison 5 DHA/mixed subgroups, Outcome 10 Low birthweight (< 2500 g).
Figures and Tables -
Analysis 5.10

Comparison 5 DHA/mixed subgroups, Outcome 10 Low birthweight (< 2500 g).

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Comparison 5 DHA/mixed subgroups, Outcome 11 Small‐for‐gestational age/IUGR.
Figures and Tables -
Analysis 5.11

Comparison 5 DHA/mixed subgroups, Outcome 11 Small‐for‐gestational age/IUGR.

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Comparison 5 DHA/mixed subgroups, Outcome 12 Birthweight (g).
Figures and Tables -
Analysis 5.12

Comparison 5 DHA/mixed subgroups, Outcome 12 Birthweight (g).

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Comparison 6 Risk subgroups, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 6.1

Comparison 6 Risk subgroups, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 6 Risk subgroups, Outcome 2 Early preterm birth (< 34 weeks).
Figures and Tables -
Analysis 6.2

Comparison 6 Risk subgroups, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 6 Risk subgroups, Outcome 3 Prolonged gestation (> 42 weeks).
Figures and Tables -
Analysis 6.3

Comparison 6 Risk subgroups, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 6 Risk subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).
Figures and Tables -
Analysis 6.4

Comparison 6 Risk subgroups, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 6 Risk subgroups, Outcome 5 Caesarean section.
Figures and Tables -
Analysis 6.5

Comparison 6 Risk subgroups, Outcome 5 Caesarean section.

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Comparison 6 Risk subgroups, Outcome 6 Length of gestation (days).
Figures and Tables -
Analysis 6.6

Comparison 6 Risk subgroups, Outcome 6 Length of gestation (days).

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Comparison 6 Risk subgroups, Outcome 7 Perinatal death.
Figures and Tables -
Analysis 6.7

Comparison 6 Risk subgroups, Outcome 7 Perinatal death.

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Comparison 6 Risk subgroups, Outcome 8 Stillbirth.
Figures and Tables -
Analysis 6.8

Comparison 6 Risk subgroups, Outcome 8 Stillbirth.

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Comparison 6 Risk subgroups, Outcome 9 Neonatal death.
Figures and Tables -
Analysis 6.9

Comparison 6 Risk subgroups, Outcome 9 Neonatal death.

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Comparison 6 Risk subgroups, Outcome 10 Low birthweight (< 2500 g).
Figures and Tables -
Analysis 6.10

Comparison 6 Risk subgroups, Outcome 10 Low birthweight (< 2500 g).

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Comparison 6 Risk subgroups, Outcome 11 Small‐for‐gestational age/IUGR.
Figures and Tables -
Analysis 6.11

Comparison 6 Risk subgroups, Outcome 11 Small‐for‐gestational age/IUGR.

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Comparison 6 Risk subgroups, Outcome 12 Birthweight (g).
Figures and Tables -
Analysis 6.12

Comparison 6 Risk subgroups, Outcome 12 Birthweight (g).

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 1 Early preterm birth < 34 weeks.
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Analysis 7.1

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 1 Early preterm birth < 34 weeks.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 2 Prolonged gestation > 42 weeks.
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Analysis 7.2

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 2 Prolonged gestation > 42 weeks.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 3 Pre‐eclampsia.
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Analysis 7.3

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 3 Pre‐eclampsia.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 4 Induction (post‐term).
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Analysis 7.4

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 4 Induction (post‐term).

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 5 PROM.
Figures and Tables -
Analysis 7.5

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 5 PROM.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 6 PPROM.
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Analysis 7.6

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 6 PPROM.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 7 Length of gestation.
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Analysis 7.7

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 7 Length of gestation.

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 8 Birthweight (g).
Figures and Tables -
Analysis 7.8

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 8 Birthweight (g).

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 9 Length at birth (cm).
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Analysis 7.9

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 9 Length at birth (cm).

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Comparison 7 Omega‐3 doses: direct comparisons, Outcome 10 Head circumference at birth (cm).
Figures and Tables -
Analysis 7.10

Comparison 7 Omega‐3 doses: direct comparisons, Outcome 10 Head circumference at birth (cm).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 1 Gestational diabetes.
Figures and Tables -
Analysis 8.1

Comparison 8 Omega‐3 type: direct comparisons, Outcome 1 Gestational diabetes.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 2 Caesarean section.
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Analysis 8.2

Comparison 8 Omega‐3 type: direct comparisons, Outcome 2 Caesarean section.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 3 Adverse events: cessation.
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Analysis 8.3

Comparison 8 Omega‐3 type: direct comparisons, Outcome 3 Adverse events: cessation.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 4 Pre‐eclampsia.
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Analysis 8.4

Comparison 8 Omega‐3 type: direct comparisons, Outcome 4 Pre‐eclampsia.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 5 Blood loss at birth (mL).
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Analysis 8.5

Comparison 8 Omega‐3 type: direct comparisons, Outcome 5 Blood loss at birth (mL).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 6 Depressive symptoms postpartum: thresholds.
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Analysis 8.6

Comparison 8 Omega‐3 type: direct comparisons, Outcome 6 Depressive symptoms postpartum: thresholds.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 7 Depressive symptoms postpartum: scores.
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Analysis 8.7

Comparison 8 Omega‐3 type: direct comparisons, Outcome 7 Depressive symptoms postpartum: scores.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 8 Length of gestation (days).
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Analysis 8.8

Comparison 8 Omega‐3 type: direct comparisons, Outcome 8 Length of gestation (days).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 9 Baby admitted to neonatal care.
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Analysis 8.9

Comparison 8 Omega‐3 type: direct comparisons, Outcome 9 Baby admitted to neonatal care.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 10 Birthweight (g).
Figures and Tables -
Analysis 8.10

Comparison 8 Omega‐3 type: direct comparisons, Outcome 10 Birthweight (g).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 11 Infant weight (kg).
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Analysis 8.11

Comparison 8 Omega‐3 type: direct comparisons, Outcome 11 Infant weight (kg).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 12 Infant height (cm).
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Analysis 8.12

Comparison 8 Omega‐3 type: direct comparisons, Outcome 12 Infant height (cm).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 13 Infant head circumference (cm).
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Analysis 8.13

Comparison 8 Omega‐3 type: direct comparisons, Outcome 13 Infant head circumference (cm).

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 14 Cognition: Scores.
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Analysis 8.14

Comparison 8 Omega‐3 type: direct comparisons, Outcome 14 Cognition: Scores.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 15 Motor: Scores.
Figures and Tables -
Analysis 8.15

Comparison 8 Omega‐3 type: direct comparisons, Outcome 15 Motor: Scores.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 16 Neurodevelopment.
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Analysis 8.16

Comparison 8 Omega‐3 type: direct comparisons, Outcome 16 Neurodevelopment.

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Comparison 8 Omega‐3 type: direct comparisons, Outcome 17 Cerebral palsy.
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Analysis 8.17

Comparison 8 Omega‐3 type: direct comparisons, Outcome 17 Cerebral palsy.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 1 Preterm birth (< 37 weeks).
Figures and Tables -
Analysis 9.1

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 1 Preterm birth (< 37 weeks).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 2 Early preterm birth (< 34 weeks).
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Analysis 9.2

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 2 Early preterm birth (< 34 weeks).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 3 Prolonged gestation (> 42 weeks).
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Analysis 9.3

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 3 Prolonged gestation (> 42 weeks).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).
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Analysis 9.4

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 4 Pre‐eclampsia (hypertension with proteinuria).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 5 Caesarean section.
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Analysis 9.5

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 5 Caesarean section.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 6 Length of gestation (days).
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Analysis 9.6

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 6 Length of gestation (days).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 7 Perinatal death.
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Analysis 9.7

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 7 Perinatal death.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 8 Stillbirth.
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Analysis 9.8

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 8 Stillbirth.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 9 Neonatal death.
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Analysis 9.9

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 9 Neonatal death.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 10 Low birthweight (< 2500 g).
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Analysis 9.10

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 10 Low birthweight (< 2500 g).

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 11 Small‐for‐gestational age/IUGR.
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Analysis 9.11

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 11 Small‐for‐gestational age/IUGR.

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Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 12 Birthweight (g).
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Analysis 9.12

Comparison 9 Sensitivity analysis: omega‐3 versus no omega‐3, Outcome 12 Birthweight (g).

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Summary of findings for the main comparison. Birth/infant outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: birth/infant outcomes

Population: pregnant women and their babies

Settings: Angola (1 RCT), Australia (1 RCT), Belgium (1 RCT), Canada (1 RCT), Chile (1 RCT), Croatia (1 RCT), Chile (1 RCT), Denmark (3 RCTs), Egypt (1 RCT), Germany (2 RCTs), India (1 RCT), Iran (3 RCTs), Italy (1 RCT), Mexico (1 RCT), Netherlands (3 RCTs), Norway (1 RCT), Russia (1 RCT), Sweden (1 RCT), Turkey (1 RCT), UK (4 RCTs), USA (8 RCTs)

Intervention: omega 3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Preterm birth < 37 weeks

134/1000

119 per 1000

(109 to 130)

RR 0.89 (0.81 to 0.97)

10,304 (26 RCTs)

⊕⊕⊕⊕

HIGH1

Early preterm birth < 34 weeks

46/1000

27 per 1000

(20 to 35)

RR 0.58 (0.44 to 0.77)

5204 (9 RCTs)

⊕⊕⊕⊕

HIGH2

Perinatal death

20/1000

15 per 1000

(11 to 21)

RR 0.75 (0.54 to 1.03)

7416 (10 RCTs)

⊕⊕⊕⊝

MODERATE3

SGA/IUGR

129/1000

130 per 1000

(116 to 146)

RR 1.01 (0.90 to 1.13)

6907 (8 RCTs)

⊕⊕⊕⊝

MODERATE3

LBW

156/1000

140

(128 to 154)

RR 0.90 (0.82 to 0.99)

8449 (15 RCTs)

⊕⊕⊕⊕

HIGH

LGA

117/1000

134 per 1000

(113 to 159)

RR 1.15 (0.97 to 1.36)

3722 (6 RCTs)

⊕⊕⊕⊝

MODERATE4

Serious adverse events for neonate/infant

63/1000

45 per 1000 (37 to 62)

RR 0.72 (0.53 to 0.99)

2690 (2 RCTs)

⊕⊕⊝⊝

low:5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; LBW: low birth weight LGA: large‐for‐gestational age;RCT: randomised controlled trial; RR: risk ratio; SGA/IUGR: small‐for‐gestational age/intrauterine growth restriction

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

1 Design limitations: larger studies of high quality, but some smaller studies with unclear risk of selective reporting and some smaller studies with unclear or high attrition bias at the time of birth (not downgraded for study limitations)

2 Design limitations: larger studies of higher quality, but several studies with unclear or high attrition bias at the time of birth, or baseline imbalances (not downgraded for study limitations)

3 Imprecision (‐1): downgraded one level due to crossing line of no effect and/or wide confidence intervals

4 Imprecision (‐1): downgraded one level due to wide confidence intervals

5 Design limitations (‐2): downgraded two levels; one study with unclear allocation concealment and attrition bias; specific adverse events not detailed in this study

Figures and Tables -
Summary of findings for the main comparison. Birth/infant outcomes
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Summary of findings 2. Maternal outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: maternal outcomes

Population: pregnant women

Settings: Angola (1 RCT), Australia (2 RCTs), Belgium (1 RCT), Brazil (1 RCT), Chile (1 RCT), Croatia (1 RCT), Denmark (3 RCTs), Egypt (1 RCT), Germany (3 RCTs), Hungary (1 RCT), Iran (5 RCTs), India (1 RCT), Italy (2 RCTs), Mexico (1 RCT), Netherlands (4 RCTs), Norway (2 RCTs), Russia (1 RCT), Scotland (2 RCTs), Spain (4 RCTs) Sweden (2 RCTs), Turkey (1 RCT), UK (3 RCTs) USA (12 RCTs), Venezuela (1 RCT)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Prolonged gestation > 42 weeks

16/1000

26/1000

(18 to 37)

RR 1.61 (1.11 to 2.33)

5141 (6)

⊕⊕⊕⊝

MODERATE6

Induction post‐term

83/1000

68/1000

(18 to 247)

Average RR 0.82 (0.22 to 2.98)

2900 (3)

⊕⊕⊝⊝

LOW7

Pre‐eclampsia

53/1000

44/1000

(37 to 53)

RR 0.84 (0.69 to 1.01)

8306 (20)

⊕⊕⊝⊝

LOW7

Defined as hypertension with proteinuria

Gestational length

The mean gestational age in the intervention group was 1.67 days greater (0.95 greater to 2.39 days greater)

Average MD 1.67 days (0.95 to 2.39)

12,517 (41)

⊕⊕⊕⊝

MODERATE8

Maternal serious adverse events

6/1000

6/1000

(2 to 16)

RR 1.04 (0.40 to 2.72)

2690 (2)

⊕⊕⊝⊝

LOW9

Maternal admission to intensive care

1/1000

1/1000

(0 to 3)

RR 0.56 (0.12 to 2.63)

2458 (2)

⊕⊕⊝⊝

LOW9

Postnatal depression

112/1000

100

(80 to 125)

Average RR 0.99 (0.56 to 1.77)

2431 (2)

⊕⊕⊝⊝

LOW10

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

6 Design limitations (‐1): downgraded one level due to some studies with attrition bias and some selective reporting bias; and some imprecision (not downgraded)

7 Design limitations (‐1): downgraded one level for combined study limitations (mostly attrition bias and selective reporting bias); Imprecision (‐1): downgraded one level due to confidence intervals including line of no effect

8 Design limitations (‐1): downgraded one level for study limitations (mainly attrition bias): heterogeneity I2 = 54%, but not downgraded due to use of a random‐effects model

9 Imprecision (‐2): downgraded two levels for wide confidence intervals and only 2 studies

10 Design limitations (‐1): downgraded one level for study limitations (unclear randomisation in 1 study); downgraded one level for imprecision (wide confidence intervals; 2 studies only)

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Summary of findings 2. Maternal outcomes
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Summary of findings 3. Child/adult outcomes

Omega‐3 LCPUFA compared with no omega‐3 during pregnancy: child/adult outcomes

Population: children of women randomised to omega‐3 or no omega‐3 during pregnancy

Settings: Australia (2 RCTs), Bangladesh (1 RCT), Canada (1 RCT), Denmark (1 RCT), Hungary (1 RCT), Germany (1 RCT), Spain (2 RCTs), Mexico (1 RCT), Netherlands (1 RCT)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Risk with no omega‐3

Risk with omega‐3

Cognition:

BSID II score at < 24 months

The mean BSID II score at 24 months in the intervention group was 0.37 points lower in the intervention group (1.47 lower to 0.76 higher)

MD ‐0.37 (‐1.49 to 0.76)

1154 (4)

⊕⊕⊝⊝

LOW11

Cognition:

BSID III score at < 24 months

The mean BSID III score at 24 months in the intervention group was 0.04 points higher (1.59 lower to 1.68 higher)

MD 0.04 (‐1.59 to 1.68)

809 (2)

⊕⊕⊝⊝

LOW12

IQ: WASI at 7 years

The mean WASI at 7 years in the intervention group was identical to the mean in the control group (0.79 points lower to 2.79 higher)

MD 1.00 (‐0.79 to 2.79)

543 (1)

⊕⊕⊝⊝

LOW12

IQ: WISC‐IV at 12 years

The WISC‐IV at 12 years in the intervention group was identical to in the control group (5.16 points lower to 7.16 higher)

MD 1.00 (‐5.16 to 7.16)

50 (1)

⊕⊝⊝⊝

VERY LOW13

Behaviour: BSID III adaptive behaviour score at 12‐18 months

The mean BSID III adaptive behaviour score in the intervention group at 12‐18 months was 1.20 points lower (3.12 lower to 0.72 higher)

MD ‐1.20 (‐3.12 to 0.72)

809 (2)

⊕⊕⊝⊝

LOW14

At 12 months (one study), 18 months (one study)

Behaviour: SDQ Total Difficulties at 7 years

The mean SDQ total difficulties score at 7 years in the intervention group was 1.08 higher (0.18 higher to 1.98 higher)

MD 1.08 (0.18 to 1.98)

543 (1)

⊕⊕⊝⊝

LOW12

BMI at 19 years

The mean BMI at 19 years in the intervention group was identical to that in the control group (0.83 lower to 0.83 higher)

MD 0 (‐0.83 to 0.83)

243 (1)

⊕⊝⊝⊝

VERY LOW15

Diabetes

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
BMI: body mass index; BSID: Bayley Scales of Infant Development; CI: confidence interval; IQ: Intelligence Quotient; MD: mean difference; SDQ: Strengths and Difficulties Questionnaire; WASI: Weschler Abbreviated Scale of Intelligence; WISC: Weschler Intelligence Scale for Children

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

11 Design limitations (‐1): downgraded one level due to unclear randomisation in 3 studies (that contributed 40% to meta‐analysis) and some studies at high risk of attrition bias; Imprecision (‐1): downgraded one level for wide confidence intervals including line of no effect

12 Imprecision (‐2): downgraded one level for confidence intervals including line of no effect; and one level for small number of studies/single study

13 Design limitations (‐1): downgraded one level for unclear selection bias (not clear if random sequence generated), possible attrition and/or reporting bias; Imprecision (‐2): downgraded two levels for wide confidence intervals including line of no effect and 1 study with small number of participants

14 Design limitations (‐1): downgraded one level for unclear randomisation (possible lack of allocation concealment), possible attrition and/or selective bias in 1 of the trials (contributing 15% to analysis); Imprecision (‐1): downgraded one level for confidence intervals including line of no effect and few studies

Design limitations (‐1): downgraded one level for unclear sequence generation and unclear blinding: Imprecision (‐2): downgraded two levels for confidence intervals including line of no effect and 1 study with small number of participants

Figures and Tables -
Summary of findings 3. Child/adult outcomes
Navigate to table in Review
Summary of findings 4. Health service outcomes

Omega‐3 compared with no omega‐3 during pregnancy: health services outcomes

Population: pregnant women and their infants

Settings: Australia (1 RCT), Belgium (1 RCT), Denmark (2 RCTs), Egypt (1), Iran (2 RCTs), Italy (1 RCT), Netherlands (1 RCT), Norway (1 RCT), Russia (1 RCT), Scotland (1 RCT), UK (1 RCT), USA (5 RCTs)

Intervention: omega‐3

Comparison: no omega‐3

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

no omega‐3

omega‐3

Maternal hospital admission (antenatal)

273/1000

251/1000

(221 to 284)

RR 0.92 (0.81 to 1.04)

2876 (5)

⊕⊕⊝⊝

LOW 16

Infant admission to neonatal care

151/1000

139/1000

(125 to 156)

RR 0.92 (0.83 to 1.03)

6920 (9)

⊕⊕⊕⊝

MODERATE 17

Maternal length of hospital stay (days)

The mean length of stay in the intervention group was 0.18 days greater (0.20 less to 0.57 days greater)

MD 0.18 (‐0.20 to 0.57)

2290 (2)

⊕⊕⊝⊝

LOW 8

Infant length of hospital stay (days)

The mean length of stay in the intervention group was 0.11 days greater (1.40 less to 1.62 days greater)

MD 0.11 (‐1.40 to 1.62)

2041 (1)

⊕⊕⊝⊝

LOW 8

Costs

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; MD: mean difference; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

16 Design limitations (‐1): downgraded one level due to some studies with possible risk of attrition bias; Imprecision (‐1): downgraded one level for confidence intervals including line of no effect

17 Imprecision (‐1): downgraded one level for confidence intervals including line of no effect

18 Imprecision (‐2): downgraded one level for confidence intervals including line of no effect and once for small number of studies

Figures and Tables -
Summary of findings 4. Health service outcomes
Navigate to table in Review
Table 1. Maternal age (years)

Study ID

Omega‐3 (mean (SD)unless otherwise reported)

No omega‐3 (mean (SD)unless otherwise reported)

Ali 2017

27 (4.3)

27 (4.8)

Bergmann 2007

30.9 (4.6) for DHA/FOS group

30.0 (4.62) in vitamin/mineral group; 31 (4.71) for FOS group

Bisgaard 2016;

32.3 (4.3)

32.2 (4.5)

Boris 2004

"The three study groups were similar in baseline characteristics with regard to maternal age at delivery (data not shown)".

Bosaeus 2015

31.4 (3.9)

31.2 (4.0)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

25.3 (4.9)

24.8 (4.7)

Chase 2015

Not reported

D'Almedia 1992

"Ages ranged from 14‐40 years"

de Groot 2004

30.0 (3.3)

29.2 (3.8)

Dilli 2018

30.9 (5.3)

32.7 (5.9)

Dunstan 2008

30.9 (3.7)

32.6 (3.6)

England 1989

Not reported

Freeman 2008

31.0 (5.8)

29.7 (6.2)

Furuhjelm 2009

31.1 (4.1)

31.7 (3.9)

Giorlandino 2013

32.6 (4.6)

32.2 (4.8)

Gustafson 2013

25.5 (4.3)

25.6 (4.8)

Haghiac 2015

27 (5)

27 (5)

Harper 2010

Median (interquartile range): 28 (23 ‐ 32)

Median (interquartile range): 27 (24‐32)

Harris 2015

In high‐dose group 24.5 (12.72);

In low‐dose group 24.3 (12.72)

27.0 (9.05)

Hauner 2012

31.9 (4.9)

31.6 (4.5)

Helland 2001

28.6 (3.4)

27.6 (3.2)

Horvaticek 2017

29.8 (5.5)

29.6 (4.8)

Hurtado 2015

30.5 (4.8)

29.9 (4.7)

Ismail 2016

27.17 (6.34)

26.71 (5.66)

Jamilian 2016

30.1 (5.3)

30.0 (5.5)

Jamilian 2017

30.7 (3.5) for omega‐3 group

31.2 (4.3) for omega‐3 + vitamin D group

30.7 (4.1) for placebo group

31.5 (7.0) for vitamin D group

Judge 2007

23.9 (4.3)

24.7 (4.8)

Judge 2014

Not reported

Kaviani 2014

26.33 (4.2)

25.15 (4.2)

Keenan 2014

Not reported

Khalili 2016

25.9 (4.8)

26.9 (4.5)

Knudsen 2006

28.4 for 0.1 g/day EPA + DHA group

28.7 for 0.3 g/day EPA + DHA group

28.4 for 0.7 g/day EPA + DHA group

28.9 for 1.4 g/day EPA + DHA group

28.8 for 2.8 g/day EPA + DHA group

28.8 for 2.2g/day ALA group

28.5 for no treatment group

Krauss‐Etschmann 2007

Median (range): 30.6 (20.1 ‐ 41.1) for DHA/EPA group

Median (range): 31.1 (21.5 ‐ 40.1) for DHA/EPA+folate group

Median (range): 31.1 (18.8 ‐ 40.8) for folate group

Median (range): 31.1 (18.4 ‐ 40.3) for no treatment (placebo) group

Krummel 2016

27.9 (4.6)

26.3 (5.0)

Laivuori 1993

Median (IQR): 30.3 (24‐40)

Median (IQR): 30.2 (26‐32) in placebo group; 32.0 (23‐40) in primrose oil group

Makrides 2010

28.9 (5.7)

28.9 (5.6)

Malcolm 2003

Not reported

Mardones 2008

25.06 (5.73)

25.11 (7.45)

Martin‐Alvarez 2012

Not reported

Miller 2016

31.7 (4.4)

31.2 (4.4)

Min 2014

Median (range): 29 (18 ‐ 42)

Median (range): 29 (18 ‐ 44)

Min 2014 [diabetic women]

Median (range): 34 (20 ‐ 45)

Median (range): 37 (27‐45)

Min 2016

Median (range): 31.0 (21.0 ‐ 41.0)

Median (range): 32.0 (21.0 ‐ 44.0)

Mozurkewich 2013

30.6 (4.5) in DHA rich fish oil group; 29.9 (5.0) in EPA rich fish oil group

30.4 (5.9)

Mulder 2014

32.6 (4.04)

33.4 (3.61)

Noakes 2012

29.5 (3.94)

28.4 (4.69)

Ogundipe 2016

Not reported

Oken 2013

Median (IQR): 32.6 (27.9 ‐ 35.9) advice group;

27.6 (24.5 ‐ 32.0) advice + gift card group

Median (IQR): 32.4 (27.7 to 34.3)

Olsen 1992

29.4 (4.4)

olive oil group 29.7 (4.3); placebo/no oil group 29.1 (4.1)

Olsen 2000

Prophylactic trials

PD trial 29.3 (4.87)

IUGR trial 30 (4.64)

PIH trial 30.3 (7.01)

Twins trial 30.2 (6.18)

Therapeutic trials

Threat‐PE trial 32.1 (11.7)

Susp‐IUGR trial 29.3 (7.88)

Prophylactic trials

PD trial 30.0 (6.22)

IUGR trial 29.0 (3.93)

PIH trial 28.9 (5.32)

Twins trial 30.2 (6.35)

Therapeutic trials

Threat‐PE trial 32.9 (14.6)

Susp‐IUGR trial 29.8 (10.3)

Olsen 2000 [twins]

see Olsen 2000

Onwude 1995

Mean (range): 26.6 (18‐39)

Mean (range): 26.1 (16‐40)

Otto 2000

30.3 (5.2)

28.3 (4.85)

Pietrantoni 2014

30.86 (4.18)

29.92 (4.80)

Ramakrishnan 2010

26.2 (4.6)

26.3 (4.8)

Ranjkesh 2011

30.06 (7.59)

28.96 (6.40)

Razavi 2017

29.7 (3.6) for omega‐3 group

29.9 (4.0) for omega‐3 + vitamin D group

29.2 (3.4) for placebo group

29.9 (5.0) for vitamin D group

Rees 2008

31.2 (4.4)

34.5 (3.8)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Median (range): 26.8 (18‐39)

Median (range): 26.1 (16‐40)

Sanjurjo 2004

34.5 (7.41)

31.25 (5.18)

Smuts 2003a

21.7 (4.3)

21.6 (4.2)

Smuts 2003b

High DHA egg group 19.9 (4.1)

Ordinary egg group 24.8 (7.8)

Su 2008

30.9 (3.9)

31.3 (5.7)

Taghizadeh 2016

28.6 (6.3)

29.4 (4.4)

Tofail 2006

22.1 (4.2)

23.4 (4.5)

Valenzuela 2015

29 (4.7)

28.3 (6.7)

Van Goor 2009

Median (range): 32.3 (22.3 ‐ 43.3) in DHA group;

31.5 (24.8 ‐ 41.4) in DHA + AA group

Median (range): 33.5 (26.0 ‐ 40.3)

Van Winden 2017

Not reported

Vaz 2017

Median (IQR): 25.5 (22.0‐34.5)

Median (IQR): 27.0 (21.0 ‐ 31.0)

Abbreviations: IQR (interquartile range)

Figures and Tables -
Table 1. Maternal age (years)
Navigate to table in Review
Table 2. Maternal parity

Study ID

Omega‐3

No omega‐3

Ali 2017

Mean (SD): 2.9 (4.8)

Mean (SD): 2.8 (1.6)

Bergmann 2007

> 1: 22 (45.8%) in DHA/FOS group

> 1: 28 (57.1%) in vitamin/mineral group

24 (51.1%) in FOS group

Bisgaard 2016;

1: 155 (44.8%)

1: 166 (47.6%)

Boris 2004

Not reported

Bosaeus 2015

Median (IQR): 0.5 (0,1)

Median (IQR): 0 (0,1)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

Prior pregnancies, N

Mean (SD): 1.2 (1.3)

Prior pregnancies, N

Mean (SD): 1.3 (1.4)

Chase 2015

Not reported

D'Almedia 1992

Not reported

de Groot 2004

0: 11 (38%)

1: 15 (52%)

2: 3 (10%)

3: 0 (0%)

0: 12 (41%)

1: 11 (38%)

2: 5 (17%)

3: 1 (3%)

Dunstan 2008

≥ 1: 15 (45.5%)

≥ 1: 21 (53.8%)

England 1989

Not reported

Freeman 2008

Primiparous: 24 (77.4%)

Primiparous: 22 (78.6%)

Furuhjelm 2009

Not reported

Giorlandino 2013

Not reported

Gustafson 2013

Not reported

Haghiac 2015

0: 7 (28%)

1:18 (72%)

0: 5 (21%)

1: 19 (79%)

Harper 2010

Not reported

Harris 2015

Not reported

Hauner 2012

Primiparous: 55.8%

Primiparous: 61.2%

Helland 2001

Mean (SD): 0.3 (0.5)

Mean (SD): 0.3 (0.5)

Horvaticek 2017

Nulliparous: 25 (53%)

Primiparous: 22 (47%)

Nulliparous: 26 (60%)

Primiparous: 17 (40%)

Hurtado 2015

Multiparous: 35.6%

Multiparous: 31.8%

Ismail 2016

Mean (SD): 1.38 (1.67)

Mean (SD): 1.53 (1.55)

Jamilian 2016

Not reported

Jamilian 2017

Not reported

Judge 2007

Mean (SD): 1.5 (0.8)

Mean (SD): 1.8 (0.8)

Judge 2014

Not reported

Kaviani 2014

Not reported

Keenan 2014

Not reported

Khalili 2016

1: 38 (50.7%)

2: 28 (37.3%)

≥ 3: 9 (12.0%)

1: 37 (49.3%)

2: 27 (36%)

≥ 3: 11 (14.7%)

Knudsen 2006

Primiparous women

0.1 g/day EPA + DHA group: 257 (66.2%)

0.3 g/day EPA + DHA group: 267 (69.5%)

0.7 g/day EPA + DHA group: 244 (63.5%)

1.4 g/day EPA + DHA group: 247 (64.7%)

2.8 g/day EPA + DHA group: 246 (62.9%)

2.2 g/day ALA group: 258 (66.3%)

Primiparous women

No treatment group: 513 (66.4%)

Krauss‐Etschmann 2007

< 2: 56 (86%) for DHA/EPA group; 56 (88%) for DHA/EPA+folate group

2: 7 (11%) for DHA/EPA group; 6 (9%) for DHA/EPA+folate group

> 2: 2 (3%) for DHA/EPA group; 2 (3%) for DHA/EPA+folate group

< 2: 65 (90%) for folate group; 61 (88%) for placebo group

2: 7 (10%).for folate group; 7 (10%) for placebo group

> 2: 0 (0) for folate group; 1 (1%) for placebo group

Krummel 2016

Not reported

Laivuori 1993

Nulliparous: 2 (66%) in fish oil group

Primiparous: 1 in (33%) fish oil group

Nulliparous: 1 (25%) in primrose oil group; 3 (75%) in placebo group

Primiparous: 3 (60%) in primrose oil group; 2 (40%) in placebo group

Makrides 2010

Primiparous: 471 (39.3%)

Primiparous: 474 (39.4%)

Malcolm 2003

Not reported

Mardones 2008

Mean (SD): 1.68 (0.90)

Mean (SD): 1.74 (0.91)

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

0: 18 (40%)

1‐3: 26 (57.8%)

> 4: 1 (2.2%)

0: 14 (35.0%)

1‐3: 23 (57.5%)

> 4: 2 (5.0%)

Min 2014 [diabetic women]

0: 10 (24%)

1‐3: 27 (65.9%)

> 4: 3 (7.3%)

0: 7 (14.9%)

1‐3: 32 (68.1%)

> 4: 6 (12.8%)

Min 2016

0: 33 (50%)

1‐3: 27 (41%)

≥ 4: 6 (9%)

0: 24 (35%)

1‐3: 40 (57%)

≥ 4: 5 (7%)

Mozurkewich 2013

Mean (SD):

0.87 (0.83) for EPA rich fish oil group;

1.08 (0.94) for DHA rich fish oil group

Mean (SD): 0.85 (1.2)

Mulder 2014

1: 60.6%

2: 30.8%

> 2: 8.6%

1: 47.7%

2: 36.7%

> 2: 15.6%

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Primiparous:

6 (35%) in advice group;

4 (24%) in advice + gift card group

Primiparous:

6 (30%) in control group

Olsen 1992

Primiparous:

Fish oil group: 56%

Primiparous:

Olive oil group: 61%

No oil group: 60%

Olsen 2000

Prophylactic trials: no nulliparous women except for:

Twins trial: 52.5% nulliparous

Therapeutic trials

Threat‐PE trial: 71.4% nulliparous

Susp‐IUGR trial: 52.0% nulliparous

Prophylactic trials: no nulliparous women except for:

Twins trial: 52.5% nulliparous

Therapeutic trials

Threat‐PE trial: 65.6% nulliparous

Susp‐IUGR trial: 51.9% nulliparous

Onwude 1995

Included primiparous and multiparous women

Otto 2000

Primiparous: 8 (67%)

Primiparous: 5 (42%)

Pietrantoni 2014

0: 46 (36%)

1: 83 (64%)

0: 50 (40%)

1: 76 (60%)

Ramakrishnan 2010

Not reported

Ranjkesh 2011

Mean (SD): 0.46 (0.50)

Mean (SD): 0.40 (0.49)

Razavi 2017

Not reported

Rees 2008

Mean (SD): 1.4 (0.9)

Mean (SD): 1.6 (1.2)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Excluded nulliparous women

Samimi 2015

Not reported

Sanjurjo 2004

Mean (SD): 1.63 (0.74)

Mean (SD): 1.38 (0.52)

Smuts 2003a

Nulliparous before study:

68%

Nulliparous before study:

58%

Smuts 2003b

Women were excluded if they had more than 4 previous pregnancies

Mean (SD): 1.9 (1.1)

Mean (SD): 2.3 (1.9)

Su 2008

Mean (SD): 1.7 (1.1)

Mean (SD): 1.8 (1.1)

Taghizadeh 2016

Not reported

Tofail 2006

Women with > 2 children: 16.8%

Women with > 2 children: 31.5%

Valenzuela 2015

Included women with 1‐4 prior births

Van Goor 2009

Included women with a first or second pregnancy

Van Winden 2017

Not reported

Vaz 2017

0‐1: 26 (81.2%)

≥ 2: 6 (18.8%)

0‐1: 18 (64.3%)

≥ 2: 10 (35.7%)
Figures and Tables -
Table 2. Maternal parity
Navigate to table in Review
Table 3. Maternal omega‐3 intake criteria

Study

Eligibility criteria

Carlson 2013

Excluded women taking ≥ 300 mg DHA a day

Chase 2015

Excluded women planning to take DHA during pregnancy

de Groot 2004

Excluded women consuming fish more than twice a week

Dunstan 2008

Excluded women consuming fish more than twice a week

Freeman 2008

Excluded women with a previous intolerance to omega‐3 fatty acids

Furuhjelm 2009

Excluded women with an allergy to fish or undergoing treatment with omega‐3 fatty acid supplements

Giorlandino 2013

Excluded women with an allergy to fish or regular intake of fish oil

Gustafson 2013

Excluded women taking more than 200 mg DHA a day

Haghiac 2015

Excluded women with an allergy to fish or fish products; women who do not eat any fish; and women with a regular intake of fish oil (> 500 mg/week in the previous 4 weeks)

Harper 2010

Excluded women with an allergy to fish or fish products; and women with a regular intake of fish oil supplements (> 500 mg/week at any time during the preceding month)

Harris 2015

Excluded women with allergies to fish or consumption of salmon, mackerel, rainbow trout or sardines at least weekly

Hauner 2012

Excluded women taking omega‐3 supplementation before randomisation

Helland 2001

Excluded women already taking DHA

Hurtado 2015

Did not include women taking DHA supplements in pregnancy

Jamilian 2017

Excluded women taking omega‐3 fatty acid supplements

Kaviani 2014

Excluded women consuming fish more than twice a week

Keenan 2014

Excluded women consuming ≥ 2 servings of sea fish a week

Khalili 2016

Excluded women with an allergy to fish oil or fish products; and women consuming fish more than twice a week

Knudsen 2006

Included women with only limited fish intake and who did not use fish oil capsules during pregnancy

Krauss‐Etschmann 2007

Excluded women who had used fish oil supplements since the beginning of their pregnancy

Krummel 2016

Excluded women who consumed > 1 fish meal/week or who used DHA‐fortified foods or supplements

Makrides 2010

Excluded women who were already taking DHA supplements

Malcolm 2003

Excluded women with an allergy to fish products

Miller 2016

Excluded women with an allergy to seafood or fish oils

Min 2016

Excluded women taking fish oil supplements

Mozurkewich 2013

Excluded women taking omega‐3 fatty acid supplements and women consuming > 2 fish meals a week

Mulder 2014

Excluded women taking any lipid or fatty acid supplementation

Noakes 2012

included women with a diet low in oily fish (excluding canned tuna) ≤ twice per month

Ogundipe 2016

Excluded women with an allergy to fish and fish oil and women previously regularly taking a preconception fish oil supplement

Oken 2013

Excluded women consuming fish > 3 times a month; or with no contraindications to fish consumption such as allergy, or self‐restrictions such as a vegetarian diet

Olsen 1992

Excluded women with a fish allergy or regular intake of fish oil

Olsen 2000

Excluded women with a fish allergy or regular intake of fish oil

Pietrantoni 2014

Only included women who consumed fish at least twice a week (equivalent to 600 g fish a week)

Ramakrishnan 2010

Excluded women regularly taking fish oil or DHA supplements

Razavi 2017

Excluded women taking omega‐3 fatty acid supplements

Rees 2008

Excluded women taking fish oil supplements or eating more than 3 oily fish portions per week; not showing any signs of intolerance or allergy to fish

Ribeiro 2012

Excluded women with any signs of intolerance or allergy to fish or using dietary supplements containing omega‐3 and omega‐6 PUFA

Valenzuela 2015

Excluded women with a diet including polyunsaturated fatty acids (PUFA, ALA supplements) or LCPUFA (EPA and or DHA supplements)

Van Goor 2009

Excluded women who were vegetarians or vegans

Vaz 2017

Excluded women taking any oil supplementation (such as fish oil, flaxseed oil or cod liver oil)

Figures and Tables -
Table 3. Maternal omega‐3 intake criteria
Navigate to table in Review
Table 4. Maternal socioeconomic status

Study ID

omega‐3

no omega‐3

Ali 2017

Not reported

Bergmann 2007

Employed: 31 (77.5%) in DHA/folate group

13 years of schooling: 32 (66.7%) in DHA/folate group

Employed: 35 (85.4%) in Vit/Min group; 30 (78.9%) in folate group

13 years of schooling: 28 (57.1%) in Vit/Min group; 32 (68.1%) in folate group

Bisgaard 2016;

Household annual income:

Low: 33 (9.6%)

Medium: 179 (51.9%)

High: 133 (38.6%)

Household annual income:

Low: 34 (9.7%)

Medium: 187 (53.6%)

High: 128 (36.7%)

Boris 2004

Not reported

Bosaeus 2015

15 or more years of education:

17 (94.4%)

15 or more years of education:

15 (88.2%)

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

Maternal education:

Mean (SD): 13.69 years (2.67)

Maternal education:

Mean (SD): 13.36 years (2.72)

Chase 2015

Not reported

D'Almedia 1992

"Sixty‐nine percent were employed; ninety‐four percent of their husbands were employed".

de Groot 2004

Education measured on an 8‐point scale:

Mean (SD): 4.3 (1.4)

Education measured on an 8‐point scale:

Mean (SD): 3.9 (1.5)

Dunstan 2008

Maternal education:

10‐12 years: 10 (30.3%)

> 12 years: 23 (69.7%)

Maternal education:

10‐12 years: 9 (23.1%)

> 12 years: 30 (76.9%)

England 1989

Not reported

Freeman 2008

Maternal employment: 61.3% employed

Maternal education: Mean (SD): 15.5 years ((2.1)

Maternal employment: 60.7% employed

Maternal education, Mean (SD): 14.6 years (2.2)

Furuhjelm 2009

Not reported

Giorlandino 2013

Not reported

Gustafson 2013

Maternal education:

Mean (SD): 14.0 years (3.1)

Maternal education:

Mean (SD): 13.9 years (2.7)

Haghiac 2015

Not reported

Harper 2010

Maternal education:

Median (IQR): 13 years (12‐16)

Maternal education:

Median (IQR): 13 years (12‐16)

Harris 2015

Not reported

Hauner 2012

Maternal education:

63.8% attended ≥ 12 years of school

Maternal education:

69.9% attended ≥ 12 years of school

Helland 2001

Maternal education:

< 10 years: 2.9%

10‐12 years: 21.4%

> 12 years: 75.7%

Maternal education:

< 10 years: 1.8%

10‐12 years: 31.1%

> 12 years: 67.1%

Horvaticek 2017

Not reported

Hurtado 2015

Not reported

Ismail 2016

Not reported

Jamilian 2016

Not reported

Jamilian 2017

Not reported

Judge 2007

Maternal education:

Mean (SD): 12.8 years (2.2)

Maternal education;

Mean (SD): 12.2 years (1.5)

Judge 2014

Not reported

Kaviani 2014

Maternal education:

< 6 years: 7.5%

6 to 9 years: 12.5%

9 to 12 years: 20%

Maternal education:

< 6 years: 7.5 %

6 to 9 years: 15%

9 to 12 years: 10%

Keenan 2014

Not reported

Khalili 2016

Maternal education:

Primary school (1‐5 years): 14 (18.7%)

Seconday school (6‐8 years): 23 (30.7%)

High school (9‐12 years): 33 (44.0%)

University (> 12 years): 5 (6.7%)

Family income:

Adequate: 15 (20%)

Relatively adequate: 44 (58.7%)

Non adequate: 16 (21.3%)

Maternal education:

Primary school (1‐5 years): 15 (20.0%)

Seconday school (6‐8 years): 14 (18.7%)

High school (9‐12 years): 39 (52.0%)

University (> 12 years): 7 (9.3%)

Family income;

Adequate: 13 (17.3%)

Relatively adequate: 50 (66.7%)

Non adequate: 12 (16.0%)

Knudsen 2006

Not reported

Krauss‐Etschmann 2007

Job training of father:

None: 29 (45%) for DHA/EPA group; 17 (27%) for DHA/EPA+folate group

Apprenticeship: 14 (22%) for DHA/EPA group; 19 (31%) for DHA/EPA+folate group

University degree: 15 (23%) for DHA/EPA group; 21 (34%) for DHA/EPA+folate group

Job training of father:

None: 33 (47%) for folate group; 27 (40%) for placebo group

Apprenticeship: 10 (14%) for folate group; 14 (21%) for placebo group

University degree: 24 (34%) for folate group; 20 (29%) for placebo group

Krummel 2016

Education:

Mean (SD): 14.8 years (2.1)

Education:

Mean (SD): 14.9 years (3.2)

Laivuori 1993

Not reported

Makrides 2010

Mother completed secondary education: 755 (63.1%)

Mother completed further education: 816 (68.2%)

MSSI score: median 28.5, IQR (25.0 ‐ 31.0)

Mother completed secondary education: 760 (63.2%)

Mother completed further education: 824 (68.6%)

MSSI score: median 29.0, IQR (25.0 ‐ 31.0)

Malcolm 2003

Not reported

Mardones 2008

Education:

> 8 years: 82.1%

ESOMAR classification:

AB (high level): 0.5%

CA (medium level): 4.4%

CB (medium level): 34.9%

D (medium ‐ low level): 40.4%

E (low level): 19.8%

Education:

> 8 years: 80.7%

ESOMAR classification:

AB (high level): 0.3%

CA (medium level): 4.2%

CB (medium level): 33.4%

D (medium ‐ low level): 44.6%

E (low level): 17.5%

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

Not reported

Min 2014 [diabetic women]

Not reported

Min 2016

Not reported

Mozurkewich 2013

Not reported

Mulder 2014

Not reported

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Working full time: 6 (35%) for advice to eat fish group;

9 (50%) for advice to eat fish + gift card group

Working full time: 7 (35%) for control group

Olsen 1992

Not reported

Olsen 2000

Not reported

Olsen 2000 [twins]

see Olsen 2000

Onwude 1995

Not reported

Otto 2000

Not reported

Pietrantoni 2014

High school or university degree: 129 (100%)

Average socioeconomic status (not defined): 129 (100%)

High school or university degree: 126 (100%)

Average socioeconomic status (not defined): 126 (100%)

Ramakrishnan 2010

High school education or above: 56.6%

High school education or above: 59.5%

Ranjkesh 2011

Not reported

Razavi 2017

Not reported

Rees 2008

Maternal education:

Mean (SD): 14.5 years (3.5)

Maternal education:

Mean (SD): 15.3 (2.9)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Not reported

Sanjurjo 2004

Not reported

Smuts 2003a

"Most subjects received government assistance for medical care"

Smuts 2003b

Not reported

Su 2008

Not reported

Taghizadeh 2016

Not reported

Tofail 2006

Mostly low‐income participants

Mothers with > 5 years of schooling: 36.8%

Working mothers: 16.0

Fathers with stable job: 65.6

Family income (taka/month, 1 USD = 59 taka): 64.0

Mostly low‐income participants

Mothers with > 5 years of schooling: 32.3%

Working mothers: 12.1%

Fathers with stable job: 65.3%

Family income (taka/month, 1 USD = 59 taka): 54.0

Valenzuela 2015

SES assessed using the ESOMAR criteria:

High: 5.3%

Medium: 73.7%

Low: 21.1%

SES assessed using the ESOMAR criteria:

High: 19.0%

Medium: 66.7%

Low: 14.3%

Van Goor 2009

Not reported

Van Winden 2017

Not reported

Vaz 2017

Family income, not further defined:

US $263.2 (181.9‐383.0)

Maternal education:
Median (IQR): 11.0 years (7.0 ‐ 11)

Family income (US $) not further defined:

US $304.1 (180.7 ‐ 379.8)

Maternal education:

Median (IQR): 8.0 years (7.5 ‐ 10.5)

Abbreviations: DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; ESOMAR: European Society for Opinion and Marketing Research; IQR: interquartile range; MSSI: maternal social support index; SD: standard deviation; SES: socioeconomic status

Figures and Tables -
Table 4. Maternal socioeconomic status
Navigate to table in Review
Table 5. Maternal ethnicity

Study ID

Omega‐3

No omega‐3

Ali 2017

Not reported (study conducted in Egypt)

Bergmann 2007

"Caucasian women"

Bisgaard 2016

Caucasian:

333 (96.2%)

Caucasian:

332 (95.1%)

Boris 2004

Not reported (conducted in Denmark)

Bosaeus 2015

Women of European descent

Bulstra‐Ramakers 1994

Not reported (study conducted in the Netherlands)

Carlson 2013

Hispanic: 8%

Not Hispanic: 92%

Hispanic: 8%

Not Hispanic 92%

African‐American: 38%

Chase 2015

Maternal ethnicity not reported;

reported that 98% of included infants were white

Maternal ethnicity not reported;

reported that 93% of included infants were white

D'Almedia 1992

Not reported (conducted in Angola)

de Groot 2004

"White women"

Dunstan 2008

Caucasian women

England 1989

Not reported (conducted in South Africa)

Freeman 2008

Not reported (conducted in USA)

Furuhjelm 2009

Not reported (conducted in Sweden)

Giorlandino 2013

Not reported (conducted in Italy)

Gustafson 2013

28% African‐American (conducted in USA)

Haghiac 2015

African American: 11 (44%)

Caucasian: 10 (40%)

Other (e.g. Hispanic or Asian): 4 (16%)

African American: 6 (25%)

Caucasian: 11 (46%)

Other (e.g. Hispanic or Asian): 7 (29%)

Harper 2010

African American: 148 (34.1%)

White: 245 (56.5%)

Asian: 13 (3.0%)

Other: 28 (6.5%)

Hispanic/Latina ethnicity: 64 (14.7%)

African American: 145 (34.9%)

White: 240 (57.7%)

Asian: 5 (1.2%)

Other: 26 (6.3%)

Hispanic/Latina ethnicity: 57 (13.6%)

Harris 2015

Not reported (conducted in USA)

Hauner 2012

Not reported (conducted in Germany)

Helland 2001

Not reported (conducted in Norway)

Horvaticek 2017

Not reported (conducted in Croatia)

Hurtado 2015

Not reported (conducted in Spain)

Ismail 2016

Not reported (conducted in Egypt)

Jamilian 2016

Not reported (conducted in Iran)

Jamilian 2017

Not reported (conducted in Iran)

Judge 2007

Not reported (conducted in USA)

Judge 2014

Not reported (conducted in USA)

Kaviani 2014

Not reported (conducted in Iran)

Keenan 2014

African American women

Khalili 2016

Not reported (conducted in Iran)

Knudsen 2006

Not reported (conducted in Denmark)

Krauss‐Etschmann 2007

Not reported (conducted in Spain, Germany or Hungary)

Krummel 2016

African American: 12 (37.5%)

White: 20 (62.5%)

African American: 15 (53.6%)

White: 13 (46.4%)

Laivuori 1993

Not reported (conducted in Finland)

Makrides 2010

Not reported (conducted in Australia)

Malcolm 2003

Not reported (conducted in UK)

Mardones 2008

"mainly ethnically mixed (American and Hispanic)"

Martin‐Alvarez 2012

Not reported (conducted in Spain)

Miller 2016

African American: 1 (1.7%)

Caucasian: 55 (92%)

Hispanic: 2 (3%)

Asian: 1 (1.67%)

Other: 1 (1.67%)

African American: 0 (0%)

Caucasian: 52 (95%)

Hispanic: 2 (3%)

Asian: 1 (2%)

Other: 0 (0%)

Min 2014

Asian: 16 (35.6%)

African/Afro‐Caribbean: 10 (22.2%)

Caucasian: 13 (28.9%)

Others: 6 (13.3%)

Asian: 18 (45.0%)

African/Afro‐Caribbean: 14 (35.0%)

Caucasian: 6 (15.0%)

Others: 2 (5.0%)

Min 2014 [diabetic women]

Asian: 18 (43.9%)

African/Afro‐Caribbean: 15 (36.6%)

Caucasian: 5 (12.2%)

Others: 3 (7.3%)

Asian: 27 (57.5%)

African/Afro‐Caribbean: 10 (21.3%)

Caucasian: 5 (10.6%)

Others: 5 (10.6%)

Min 2016

Asian: 40 (60%)

African/Afro‐Caribbean: 18 (27%)

Caucasian: 5 (7%)

Others: 4 (7%)

Asian: 44 (62%)

African/Afro‐Caribbean: 18 (25%)

Caucasian: 5 (7%)

Others: 4 (6%)

Mozurkewich 2013

White: 33 (85%) for EPA‐rich group; 29 (76%) for DHA‐rich group

African‐American: 4 (10%) for EPA‐rich group; 4 (11%) for DHA‐rich group

Hispanic‐Latina: 0 (0%) for EPA‐rich group; 4 (11%) for DHA‐rich group

Asian: 1 (3%) for EPA‐rich group; 1 (3%) for DHA‐rich group

American Indian or Alaska Native: 0 (0%) for EPA‐rich group; 0 (0) for DHA‐rich group

Native Hawaiian or other Pacific ethnicity: 1 (3) for EPA‐rich group; 0 (0%) for DHA‐rich group

White: 34 (83%)

African‐American: 2 (5%)

Hispanic‐Latina: 3 (7%)

Asian: 1 (2%)

American Indian or Alaska Native: 1 (2%)

Native Hawaiian or other Pacific ethnicity: 0 (0%)

Mulder 2014

White: 73.1%

Non‐white: 26.9%

White: 73.9%

Non‐white: 26.1%

Noakes 2012

Not reported (conducted in UK)

Ogundipe 2016

Not reported (conducted in UK)

Oken 2013

White: 9 (50%) advice only group; 9 (53%) advice+voucher group

Black: 2 (11%) advice only group; 2 (12%) advice+voucher group

Asian: 2 (11%) advice only group; 1 (6%) advice+voucher group

Hispanic/other: 5 (28%) advice only group; 5 (29%) advice+voucher group

White: 9 (45%)

Black: 2 (10%)

Asian: 3 (15%)

Hispanic/other: 6 (30%)

Olsen 1992

Not reported (conducted in Denmark)

Olsen 2000

Not reported (conducted in Denmark, Scotland, Sweden, England, Italy, Netherlands, Norway, Belgium and Russia)

Olsen 2000 [twins]

See Olsen 2000

Onwude 1995

Not reported (conducted in UK)

Otto 2000

Not reported (conducted in the Netherlands)

Pietrantoni 2014

Caucasians

Ramakrishnan 2010

Not reported (conducted in Mexico)

Ranjkesh 2011

Not reported (conducted in Iran)

Razavi 2017

Not reported (conducted in Iran)

Rees 2008

Not reported (conducted in Australia)

Ribeiro 2012

Not reported (conducted in Brazil)

Rivas‐Echeverria 2000

Not reported (conducted in Venezuela)

Samimi 2015

Not reported (conducted in Iran)

Sanjurjo 2004

Not reported (conducted in Spain)

Smuts 2003a

African:104 (73%)

Other: 38 (27%)

African: 109 (73%)

Other: 40 (27%)

Smuts 2003b

African: 15 (83%)

Other: 3 (17%)

African: 15 (78%)

Other: 4 (22%)

Su 2008

Not reported (conducted in Taiwan)

Taghizadeh 2016

Not reported (conducted in Iran)

Tofail 2006

Not reported (conducted in India)

Valenzuela 2015

Hispanic: 19 (100%)

Hispanic: 21 (100%)

Van Goor 2009

Not reported (conducted in the Netherlands)

Van Winden 2017

Neither ethnicity, race or country where study conducted reported

Vaz 2017

White: 13 (40.6%)

Non‐white: 19 (59.4%)

White: 5 (17.9%)

Non‐white: 23 (82.1%)
Figures and Tables -
Table 5. Maternal ethnicity
Navigate to table in Review
Table 6. Maternal smoking status

Study ID

Omega‐3

No omega‐3

Ali 2017

Smokers were excluded

Bergmann 2007

Smokers were excluded

Bisgaard 2016

Smoking during pregnancy: 21 (6.1%)

Smoking during pregnancy: 33 (9.5%)

Boris 2004

"The three study groups were similar in baseline characteristics with regard to... percentage of smokers (data not shown)".

Bosaeus 2015

Not reported

Bulstra‐Ramakers 1994

Not reported

Carlson 2013

History of smoking: 41%

Smoking during pregnancy: 30%

History of smoking: 45%

Smoking during pregnancy: 38%

Chase 2015

Not reported

D'Almedia 1992

Not reported

de Groot 2004

Smoking at 14 weeks GA:

Yes: 4 (14%)

Smoking at 14 weeks GA:

Yes: 10 (34%)

Dilli 2018

15 (28%)

24 (35%)

Dunstan 2008

Smokers were excluded

England 1989

Not reported

Freeman 2008

Not reported

Furuhjelm 2009

Exposure to smoke: (at least 1 of immediate family a smoker)

9 (17%)

Exposure to smoke: (at least 1 of immediate family a smoker)

11 (17%)

Giorlandino 2013

Maternal smoking at baseline: 50%

Maternal smoking at baseline: 48%

Gustafson 2013

Not reported

Haghiac 2015

Not reported

Harper 2010

Smoking during pregnancy: 64 (15%)

Smoking during pregnancy: 72 (17%)

Harris 2015

Not reported

Hauner 2012

Smoking before pregnancy: 16%

Smoking before pregnancy: 24%

Helland 2001

Smoking: 16%

Smoking: 22%

Horvaticek 2017

Not reported

Hurtado 2015

Not reported

Ismail 2016

Not reported

Jamilian 2016

Smokers were excluded

Jamilian 2017

Smokers were excluded

Judge 2007

Smokers were excluded

Judge 2014

Not reported

Kaviani 2014

Smokers were excluded

Keenan 2014

Regular smokers were excluded

Khalili 2016

Not reported

Knudsen 2006

Smoked during pregnancy

0.1 g/day EPA + DHA group: 79 (20.3%)

0.3 g/day EPA + DHA group: 78 (20.3%)

0.7 g/day EPA + DHA group: 78 (20.3%)

1.4 g/day EPA + DHA group: 79 (20.6%)

2.8 g/day EPA + DHA group: 78 (19.9%)

2.2g/day ALA group: 79 (20.3%)

Smoked during pregnancy

160 (20.7%)

Krauss‐Etschmann 2007

Smoking at study entry

Yes: 8 (12%) for DHA/EPA group; 9 (14%) for DHA/EPA + Folate group

Smoking at study entry

Yes: 5 (7%) for Folate group; 9 (13%) for placebo group

Krummel 2016

"Current or previous use of tobacco" an exclusion criteria

Laivuori 1993

Not reported

Makrides 2010

Smoking at trial entry or leading up to pregnancy

358 (29.9%)

Smoking at trial entry or leading up to pregnancy

407 (33.9%)

Malcolm 2003

Not reported

Mardones 2008

Not reported

Martin‐Alvarez 2012

Not reported

Miller 2016

Not reported

Min 2014

Smoker

6 (13%)

Smoker

0 (0%)

Min 2014 [diabetic women]

Smoker

2 (4%)

Smoker

0 (0%)

Min 2016

Smoker

2 (3%)

Smoker

0 (0%)

Mozurkewich 2013

Not reported

Mulder 2014

Not reported

Noakes 2012

Not reported

Ogundipe 2016

Not reported

Oken 2013

Never smoker

14 (78%) in advice group; 12 (71%) in advice+gift card group

Never smoker

14 (70%) in control group

Olsen 1992

Smokers

Fish oil group: 33%

Smokers

Olive oil group: 29%

No oil group: 33%

Olsen 2000

Smoker

Prophylactic trials

Earl‐PD trial 45%

Earl‐IUGR trial 52%

Earl‐PIH trial 19%

Twins trial 33%

Therapeutic trials

Threat‐PE trial 18%

Susp‐IUGR trial 31%

Smoker

Prophylactic trials

Earl‐PD trial 41%

Earl‐IUGR 52%

Earl‐PIH trial 24%

Twins trial 29%

Therapeutic trials

Threat‐PE trial 21%

Susp‐IUGR trial 30%

Onwude 1995

Current smoker

42 (37%)

Current smoker

32 (27%)

Otto 2000

Not reported

Pietrantoni 2014

Smokers were excluded

Ramakrishnan 2010

Not reported

Ranjkesh 2011

Not reported

Razavi 2017

Smokers were excluded

Rees 2008

Smoker

0 (0%)

Smoker

3 (23%)

Ribeiro 2012

Not reported

Rivas‐Echeverria 2000

Not reported

Samimi 2015

Smokers were excluded

Sanjurjo 2004

Smoker

1 (13%)

Smoker

2 (25%)

Smuts 2003a

Smoker before pregnancy: 46.8%

Smoker during pregnancy: 27.0%

Smoker before pregnancy: 38.2%

Smoker during pregnancy: 21.5%

Smuts 2003b

Not reported

Su 2008

Not reported

Taghizadeh 2016

Smokers were excluded

Tofail 2006

Not reported

Valenzuela 2015

Not reported

Van Goor 2009

Not reported

Van Winden 2017

Not reported

Vaz 2017

Not reported
Figures and Tables -
Table 6. Maternal smoking status
Navigate to table in Review
Table 7. Maternal risk

Study ID

All women included in the study

Ali 2017

Increased/high‐risk (pregnancy complicated with asymmetrical IUGR)

Bergmann 2007

Low‐risk (healthy women)

Bisgaard 2016

Any/mixed risk (not reported)

Boris 2004

Low‐risk (healthy women)

Bosaeus 2015

Low‐risk (healthy women)

Bulstra‐Ramakers 1994

Increased/high‐risk (women with a history of IUGR with or without PIH in the previous pregnancy)

Carlson 2013

Low‐risk (healthy women)

Chase 2015

Increased/high‐risk (Infants at risk of T1D (e.g. mothers with T1D)

D'Almedia 1992

Mixed risk (21% of all included women had a history of PIH, and 4% a history of preterm birth)

de Groot 2004

Low‐risk (healthy women)

Dilli 2018

Increased/high risk (women with GDM)

Dunstan 2008

Low‐risk (history of physician‐diagnosed allergic rhinitis and/or asthma and 1 or more positive skin prick test to common allergens, but who were otherwise healthy)

England 1989

Increased/high‐risk (women with severe gestational proteinuric hypertension

Freeman 2008

Increased/high‐risk (pregnant and postpartum women with a major depressive order)

Furuhjelm 2009

Low‐risk (pregnant women affected by allergy themselves, of having a husband or previous child with allergies, otherwise healthy)

Giorlandino 2013

Increased/high‐risk (pregnancy women with a history of IUGR, fetal demise or pre‐eclampsia)

Gustafson 2013

Low‐risk (healthy women)

Haghiac 2015

Increased/high‐risk: (overweight or obese (BMI ≥ 25)

Harper 2010

Increased/high‐risk (women with at least 1 prior spontaneous preterm birth)

Harris 2015

Low‐risk (healthy women)

Hauner 2012

Low‐risk (healthy women)

Helland 2001

Low‐risk (healthy women)

Horvaticek 2017

Increased/high‐risk (pregnant women with T1D)

Hurtado 2015

Low‐risk (healthy women)

Ismail 2016

Increased/high‐risk (oligohydramnios at 30‐34 weeks GA)

Jamilian 2016

Increased/high‐risk (women with GDM)

Jamilian 2017

Increased/high‐risk (women with GDM)

Judge 2007

Low‐risk (healthy women)

Judge 2014

Low‐risk (healthy women)

Kaviani 2014

Increased/high‐risk (women diagnosed with mild depression)

Keenan 2014

Increased/high‐risk (women living in urban low‐income environments)

Khalili 2016

Low‐risk (healthy women)

Knudsen 2006

Any/mixed risk (not reported)

Krauss‐Etschmann 2007

Low‐risk (healthy women)

Krummel 2016

Increased/high‐risk (all women overweight or obese)

Laivuori 1993

Increased/high‐risk (women with pre‐eclampsia)

Makrides 2010

Any/mixed risk

Malcolm 2003

Low‐risk (healthy women) for final outcomes (any/mixed risk for preterm birth outcome)

Mardones 2008

Increased/high‐risk (all included women underweight (BMI ≤ 21.2kg/m 2 at 10 weeks GA))

Martin‐Alvarez 2012

Any/mixed risk (not reported)

Miller 2016

Any/mixed risk

Min 2014

Low‐risk (healthy women)

Min 2014 [diabetic women]

Increased/high‐risk (women diagnosed with Type 2 diabetes)

Min 2016

Increased/high‐risk (women with GDM)

Mozurkewich 2013

Increased/high‐risk (women with a history of depression)

Mulder 2014

Low‐risk (healthy women)

Noakes 2012

Low‐risk (women with a history of allergy, atopy or asthma)

Ogundipe 2016

Increased/high‐risk: (women at risk of developing pre‐eclampsia, fetal growth restriction, gestational diabetes)

Oken 2013

Any/mixed risk

Olsen 1992

Low‐risk (healthy women)

Olsen 2000

Increased/high‐risk (previous preterm birth or IUGR in previous pregnancy or pregnancy‐induced hypertension or twins in current pregnancy; threatening pre‐eclampsia or ultrasonically estimated fetal weight below the 10th centile)

Olsen 2000 [twins]

See Olsen 2000

Onwude 1995

Increased/high‐risk (primigravida with abnormal Doppler blood flow, previous birthweight < 3rd centile, PIH, previous unexplained stillbirth)

Otto 2000

Low‐risk (healthy women)

Pietrantoni 2014

Low‐risk (healthy women)

Ramakrishnan 2010

Low‐risk (healthy women)

Ranjkesh 2011

Increased/high‐risk (women at high risk for pre‐eclampsia)

Razavi 2017

Increased/high‐risk (women diagnosed with GDM)

Rees 2008

Increased/high‐risk (current episode of major depression or dysthymia)

Ribeiro 2012

Any/mixed (not reported)

Rivas‐Echeverria 2000

Increased/high‐risk (women at risk of pre‐eclampsia)

Samimi 2015

Increased/high‐risk (women with GDM)

Sanjurjo 2004

Low‐risk (healthy women)

Smuts 2003a

Low‐risk (healthy women)

Smuts 2003b

Low‐risk (healthy women)

Su 2008

Increased/high‐risk (women diagnosed with major depressive disorder between 16 weeks and 32 weeks GA)

Taghizadeh 2016

Increased/high‐risk (women with GDM)

Tofail 2006

Increased/high‐risk (low income; 28% women undernourished)

Valenzuela 2015

Low‐risk ("women free from any known diseases that could affect fetal growth")

Van Goor 2009

Low‐risk (healthy women)

Van Winden 2017

Increased/high‐risk (women with GDM)

Vaz 2017

Increased/high‐risk (pregnant women classified at risk for postpartum depression)

Abbreviations: ADA: American Diabetes Association; BMI: body mass index; GA: gestational age; GDM: gestational diabetes mellitus; IUGR: intrauterine growth restriction; OGTT: oral glucose tolerance test; PIH: pregnancy‐induced hypertension; PPD: postpartum depression

Figures and Tables -
Table 7. Maternal risk
Navigate to table in Review
Comparison 1. Overall: omega‐3 versus no omega‐3

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

26

10304

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.81, 0.97]

2 Early preterm birth (< 34 weeks) Show forest plot

9

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [1.11, 2.33]

4 Maternal death Show forest plot

4

4830

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.07, 39.30]

5 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

20

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.01]

6 High blood pressure (without proteinuria) Show forest plot

7

4531

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.89, 1.20]

7 Eclampsia Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.70]

8 Maternal antepartum hospitalisation Show forest plot

5

2876

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.81, 1.04]

8.1 Any

4

2813

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.80, 1.03]

8.2 Due to PIH or IUGR

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.67, 2.28]

9 Mother's length of stay in hospital (days) Show forest plot

2

2290

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.20, 0.57]

10 Maternal anaemia Show forest plot

1

846

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.91, 1.48]

11 Miscarriage (< 24 weeks) Show forest plot

9

4190

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.80, 1.43]

12 Antepartum vaginal bleeding Show forest plot

2

2151

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.69, 1.48]

13 Rupture of membranes (PPROM; PROM) Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Preterm prelabour rupture of membranes (PPROM)

3

925

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.25, 1.10]

13.2 Premature rupture of membranes (PROM)

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.21, 0.82]

14 Maternal admission to intensive care Show forest plot

2

2458

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.12, 2.63]

15 Maternal adverse events Show forest plot

17

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 Severe adverse event

2

2690

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.40, 2.72]

15.2 Severe enough for cessation

6

1487

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.53, 1.93]

15.3 Any

5

1480

Risk Ratio (M‐H, Fixed, 95% CI)

1.38 [1.16, 1.65]

15.4 Nausea

9

2929

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.90, 1.22]

15.5 Unpleasant taste

5

2356

Risk Ratio (M‐H, Fixed, 95% CI)

4.82 [3.35, 6.92]

15.6 Vomiting

7

3640

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.95, 1.37]

15.7 Stomach pain

4

928

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [0.62, 3.59]

15.8 Reflux

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.16, 6.07]

15.9 Belching or burping

5

2262

Risk Ratio (M‐H, Fixed, 95% CI)

3.52 [2.86, 4.34]

15.10 Diarrhoea

6

1764

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.52, 1.24]

15.11 Constipation

1

1077

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.08, 2.15]

15.12 Nasal bleeding

2

1506

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.24]

15.13 Swelling/other reaction at injection site

1

852

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.99, 1.22]

15.14 Insomnia

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.28, 7.93]

15.15 Headache

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [0.91, 2.86]

15.16 Gynaecological infections

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.45, 1.55]

15.17 Labour related

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.27, 0.88]

15.18 Urinary tract infection

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.06, 1.42]

16 Caesarean section Show forest plot

28

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

17 Induction (post‐term) Show forest plot

3

2900

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.22, 2.98]

18 Blood loss at birth (mL) Show forest plot

6

2776

Mean Difference (IV, Fixed, 95% CI)

11.50 [‐6.75, 29.76]

19 Postpartum haemorrhage Show forest plot

4

4085

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.82, 1.30]

20 Gestational diabetes Show forest plot

12

5235

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.26]

21 Maternal insulin resistance (HOMA‐IR) Show forest plot

3

176

Mean Difference (IV, Random, 95% CI)

‐0.85 [‐2.50, 0.80]

22 Excessive gestational weight gain Show forest plot

1

350

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.95, 1.55]

23 Gestational weight gain (kg) Show forest plot

11

2297

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.68, 0.59]

24 Depression during pregnancy: thresholds Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

24.1 HAMD 50% reduction (after 8 weeks)

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

2.26 [0.78, 6.49]

24.2 HAMD ≤ 7

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

2.12 [0.51, 8.84]

24.3 Unspecified

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.39 [0.47, 12.11]

24.4 EPDS ≥ 11

1

34

Risk Ratio (M‐H, Fixed, 95% CI)

1.4 [0.55, 3.55]

25 Depression during pregnancy: scores Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

25.1 BDI

2

104

Mean Difference (IV, Random, 95% CI)

‐5.86 [‐8.32, ‐3.39]

25.2 HAMD

3

71

Mean Difference (IV, Random, 95% CI)

‐0.92 [‐5.91, 4.06]

25.3 EPDS

4

122

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐3.70, 2.89]

25.4 MADRS

1

26

Mean Difference (IV, Random, 95% CI)

‐1.60 [‐7.80, 4.60]

26 Anxiety during pregnancy Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.06, 15.12]

27 Difficult life circumstances (maternal) Show forest plot

1

51

Mean Difference (IV, Fixed, 95% CI)

0.32 [‐0.15, 0.79]

28 Stress (maternal) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

28.1 Perceived Stress Scale (scores)

1

51

Mean Difference (IV, Fixed, 95% CI)

‐1.82 [‐3.68, 0.04]

29 Depressive symptoms postpartum: threshold Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

29.1 PDSS ≥ 80

1

42

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.04, 3.25]

29.2 EPDS

2

2431

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.56, 1.77]

29.3 Major depressive disorder

1

118

Risk Ratio (M‐H, Random, 95% CI)

1.33 [0.27, 6.56]

30 Depressive symptoms postpartum: scores Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

30.1 BDI: 6‐8 weeks postpartum

1

118

Mean Difference (IV, Fixed, 95% CI)

0.25 [‐1.93, 2.43]

30.2 PDSS total (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐6.08 [‐12.42, 0.26]

30.3 Disturbances sleep/eating (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐2.66, 0.66]

30.4 Anxiety/insecurity (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐1.30 [‐2.96, 0.36]

30.5 Emotional lability (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐1.29 [‐3.10, 0.52]

30.6 Mental confusion (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐1.30 [‐2.92, 0.32]

30.7 Loss of self (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.90 [‐1.80, 0.00]

30.8 Guilt (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐1.13, 0.53]

30.9 Suicide (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.35, 0.21]

30.10 PDSS total at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐2.87 [‐12.17, 6.43]

30.11 Disturbances sleep/eating at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐2.08, 1.68]

30.12 Anxiety/insecurity at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.46 [‐2.65, 1.73]

30.13 Emotional lability at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.96 [‐3.32, 1.40]

30.14 Mental confusion at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐2.15, 1.89]

30.15 Loss of self at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.97 [‐2.18, 0.24]

30.16 Guilt at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.69, 1.11]

30.17 Suicide at 6 months

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.52 [‐1.13, 0.09]

31 Gestational length (days) Show forest plot

43

12517

Mean Difference (IV, Random, 95% CI)

1.67 [0.95, 2.39]

32 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

33 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

34 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

35 Infant death Show forest plot

4

3239

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.25, 2.19]

36 Large‐for‐gestational age Show forest plot

6

3722

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.97, 1.36]

37 Macrosomia Show forest plot

6

2008

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.43, 1.13]

38 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

39 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

40 Birthweight (g) Show forest plot

44

11584

Mean Difference (IV, Random, 95% CI)

75.74 [38.05, 113.43]

41 Birthweight Z score Show forest plot

4

2792

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.02, 0.13]

42 Birth length (cm) Show forest plot

29

8128

Mean Difference (IV, Random, 95% CI)

0.11 [‐0.10, 0.31]

43 Head circumference at birth (cm) Show forest plot

24

7161

Mean Difference (IV, Random, 95% CI)

0.07 [‐0.05, 0.19]

44 Head circumference at birth Z score Show forest plot

2

2462

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.14, 0.07]

45 Length at birth Z score Show forest plot

2

2462

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.18, 0.54]

46 Baby admitted to neonatal care Show forest plot

9

6920

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.03]

47 Infant length of stay in hospital (days) Show forest plot

1

2041

Mean Difference (IV, Fixed, 95% CI)

0.11 [‐1.40, 1.62]

48 Congenital anomalies Show forest plot

3

1807

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.61, 1.92]

49 Retinopathy of prematurity Show forest plot

1

837

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.32, 4.44]

50 Bronchopulmonary dysplasia Show forest plot

2

3191

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.45, 2.48]

51 Respiratory distress syndrome Show forest plot

2

1129

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.54, 2.52]

52 Necrotising enterocolitis (NEC) Show forest plot

2

3198

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.26, 3.55]

53 Neonatal sepsis (proven) Show forest plot

3

3788

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.44, 2.14]

54 Convulsion Show forest plot

1

2361

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 1.63]

55 Intraventricular haemorrhage Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

55.1 Any

3

5423

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.29, 3.49]

55.2 Grade 3 or 4

1

837

Risk Ratio (M‐H, Random, 95% CI)

1.60 [0.38, 6.65]

56 Neonatal/infant adverse events Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

56.1 Any adverse event

2

592

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.82, 1.02]

56.2 Serious adverse events

2

2690

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.53, 0.99]

57 Neonatal/infant morbidity: cardiovascular Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

58 Neonatal/infant morbidity: respiratory Show forest plot

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.66, 1.57]

59 Neonatal/infant morbidity: due to pregnancy/birth events Show forest plot

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.67, 1.55]

60 Neonatal/infant morbidity: other Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

60.1 Colds in past 15 days: at 1 month of age

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.72, 1.00]

60.2 Colds in past 15 days: at 3 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.73, 1.01]

60.3 Colds in past 15 days: at 6 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.86, 1.15]

60.4 Fever in past 15 days: at 1 month of age

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.53, 2.22]

60.5 Fever in past 15 days: at 3 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.53, 1.23]

60.6 Fever in past 15 days: at 6 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.74, 1.31]

60.7 Rash in past 15 days: at 1 month of age

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.89, 1.38]

60.8 Rash in past 15 days: at 3 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.54, 1.26]

60.9 Rash in past 15 days: at 6 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.76, 1.71]

60.10 Vomiting in past 15 days: at 1 month of age

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

1.55 [0.82, 2.93]

60.11 Vomiting in past 15 days: at 3 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

1.43 [0.69, 2.96]

60.12 Vomiting in past 15 days: at 6 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.72, 2.46]

60.13 Diarrhoea in past 15 days: at 1 month of age

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.42, 1.67]

60.14 Diarrhoea in past 15 days: at 3 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.46, 1.51]

60.15 Diarrhoea in past 15 days: at 6 months of age

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.63, 1.64]

60.16 Other illness in the past 15 days: at 1 month

1

849

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [0.81, 2.41]

60.17 Other illness in the past 15 days: at 3 months

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.54, 1.73]

60.18 Other illness in the past 15 days: at 6 months

1

834

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.68, 1.95]

61 Infant/child morbidity Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

61.1 ICU admissions

1

1396

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.31, 1.06]

61.2 Medical diagnosis of attention deficit hyperactivity disorder (ADHD)

1

1526

Risk Ratio (M‐H, Fixed, 95% CI)

2.96 [0.31, 28.40]

61.3 Medical diagnosis of autism spectrum disorder

1

1526

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.54, 2.47]

61.4 Medical diagnosis of other learning/behavioural disorders

1

1526

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.78, 1.60]

61.5 Medical diagnosis of other chronic health conditions

1

1526

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.65, 1.44]

62 Ponderal index Show forest plot

6

887

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.01, 0.11]

63 Infant/child weight (kg) Show forest plot

11

Mean Difference (IV, Random, 95% CI)

Subtotals only

63.1 At < 3 months

2

863

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.07, 0.09]

63.2 At 3 to < 12 months

4

1028

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.18, 0.20]

63.3 At 1 to < 2 years

4

1084

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.19, 0.21]

63.4 At 2 to < 3 years

2

182

Mean Difference (IV, Random, 95% CI)

0.24 [‐0.20, 0.68]

63.5 At 3 to < 4 years

2

1651

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.20, 0.57]

63.6 At 4 to < 5 years

2

631

Mean Difference (IV, Random, 95% CI)

0.38 [‐0.29, 1.05]

63.7 At 5 to < 6 years

4

2618

Mean Difference (IV, Random, 95% CI)

0.23 [‐0.18, 0.63]

63.8 At ≥ 6 years

3

508

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐0.79, 0.64]

64 Infant/child length/height (cm) Show forest plot

11

Mean Difference (IV, Random, 95% CI)

Subtotals only

64.1 < 3 months

2

861

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.69, 0.66]

64.2 3 to < 12 months

4

1115

Mean Difference (IV, Random, 95% CI)

0.11 [‐0.20, 0.42]

64.3 1 to < 2 years

4

998

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.45, 0.48]

64.4 2 to < 3 years

2

182

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.73, 1.08]

64.5 3 to < 4 years

2

1651

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.21, 0.58]

64.6 4 to < 5 years

2

631

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.36, 0.95]

64.7 5 to < 6 years

5

2733

Mean Difference (IV, Random, 95% CI)

0.20 [‐0.17, 0.57]

64.8 At ≥ 6 years

2

393

Mean Difference (IV, Random, 95% CI)

‐1.22 [‐2.29, ‐0.16]

65 Infant/child head circumference (cm) Show forest plot

10

Mean Difference (IV, Random, 95% CI)

Subtotals only

65.1 At < 3 months

2

863

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.22, 0.14]

65.2 At 3 to < 12 months

5

1309

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.19, 0.12]

65.3 At 1 to < 2 years

4

1084

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.18, 0.30]

65.4 At 2 to < 3 years

2

182

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.47, 0.40]

65.5 At 3 to < 4 years

2

1651

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.16, 0.14]

65.6 At 4 to < 5 years

1

107

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.47, 0.47]

65.7 At ≥ 5 years

3

1760

Mean Difference (IV, Random, 95% CI)

0.02 [‐0.13, 0.17]

66 Infant/child length/height for age Z score (LAZ/HAZ) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

66.1 At < 3 months

2

875

Mean Difference (IV, Random, 95% CI)

‐0.13 [‐0.27, 0.02]

66.2 At 3 to < 12 months

3

1085

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.19, 0.09]

66.3 At 12 to < 24 months

2

897

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.31, 0.18]

66.4 At 4 to < 5 years

1

524

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.15, 0.15]

66.5 At ≥ 5 years

1

802

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.12, 0.12]

67 Infant/child waist circumference (cm) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

67.1 At 2 to < 3 years

1

101

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.29, 0.89]

67.2 At 3 to < 4 years

2

1651

Mean Difference (IV, Fixed, 95% CI)

0.28 [‐0.05, 0.60]

67.3 At 4 to < 5 years

1

106

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐0.40, 1.80]

67.4 At ≥ 5 years

2

1645

Mean Difference (IV, Fixed, 95% CI)

0.15 [‐0.24, 0.55]

68 Infant/child weight‐for‐age Z score (WAZ) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

68.1 At < 3 months

2

874

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.30, 0.12]

68.2 At 3 to < 12 months

2

834

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.18, 0.08]

68.3 At 12 to < 24 months

2

883

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.13, 0.12]

68.4 At ≥ 60 months

1

802

Mean Difference (IV, Random, 95% CI)

‐0.1 [‐0.25, 0.05]

69 Infant/child BMI Z score Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

69.1 At 1 to < 2 years

2

801

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.09, 0.00]

69.2 At 2 to < 3 years

1

63

Mean Difference (IV, Random, 95% CI)

‐0.07 [‐0.25, 0.11]

69.3 At 3 to < 4 years

1

1531

Mean Difference (IV, Random, 95% CI)

0.02 [‐0.08, 0.12]

69.4 At 4 to < 5 years

2

587

Mean Difference (IV, Random, 95% CI)

0.15 [‐0.16, 0.47]

69.5 At 5 to < 6 years

3

2504

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.05, 0.11]

69.6 At 6 to < 7 years

1

115

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.02, 0.05]

69.7 At ≥ 7 years

1

250

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.10, 0.46]

70 Infant/child weight for length/height Z score (WHZ) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

70.1 At < 3 months

2

860

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.41, 0.34]

70.2 At 3 to < 12 months

3

1083

Mean Difference (IV, Random, 95% CI)

‐0.00 [‐0.14, 0.14]

70.3 At 12 to < 24 months

2

883

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.14, 0.10]

71 Infant/child BMI percentile Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

71.1 At 24 months

1

118

Mean Difference (IV, Fixed, 95% CI)

4.5 [‐5.50, 14.50]

71.2 At 36 months

1

120

Mean Difference (IV, Fixed, 95% CI)

8.0 [‐1.09, 17.09]

71.3 At 48 months

1

107

Mean Difference (IV, Fixed, 95% CI)

13.0 [3.19, 22.81]

71.4 At 60 months

1

114

Mean Difference (IV, Fixed, 95% CI)

4.80 [‐4.70, 14.30]

72 Child/adult BMI Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

72.1 At 3 to 4 years

1

1531

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.14, 0.16]

72.2 At 5 to 6 years

1

1531

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.18, 0.16]

72.3 At 7 to 9 years

2

393

Mean Difference (IV, Fixed, 95% CI)

0.16 [‐0.25, 0.57]

72.4 At 19 years

1

243

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.83, 0.83]

73 Infant/child body fat (%) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

73.1 At 1 year

1

165

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.88, 0.88]

73.2 At 2 to < 3 years

1

110

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.68, 1.08]

73.3 At 3 to < 4 years

2

1644

Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.74, 0.38]

73.4 At 4 to < 5 years

1

102

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.79, 1.39]

73.5 At 5 to < 6 years

3

1797

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.56, 0.58]

73.6 At ≥ 7 years: BIS

1

250

Mean Difference (IV, Fixed, 95% CI)

1.44 [‐0.31, 3.19]

73.7 At ≥ 7 years: BOD POD

1

250

Mean Difference (IV, Fixed, 95% CI)

‐0.42 [‐2.23, 1.39]

74 Infant/child total fat mass (kg) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

74.1 At 1 year

1

164

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.07, 0.07]

74.2 At 2 to < 3 years

1

110

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.09, 0.29]

74.3 At 3 to < 4 years

2

1644

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.10]

74.4 At 4 to < 5 years

1

102

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.05, 0.45]

74.5 At 5 to < 6 years

3

1797

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.10, 0.21]

74.6 Up to 8 years: BOD POD

1

250

Mean Difference (IV, Fixed, 95% CI)

0.08 [‐0.71, 0.87]

74.7 Up to 8 years: BIS

1

250

Mean Difference (IV, Fixed, 95% CI)

0.29 [‐0.47, 1.05]

75 Cognition: thresholds Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

75.1 BSID III < 85 at 18 months

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.24, 0.98]

75.2 BSID III > 115 at 18 months

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.49, 1.44]

75.3 BSID II < 85 at 18 months

1

730

Risk Ratio (M‐H, Fixed, 95% CI)

1.43 [0.97, 2.12]

75.4 BSID III cognitive score (highest quartile): at 18 months

1

154

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.49, 1.65]

76 Cognition: scores Show forest plot

10

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

76.1 BSID II score < 24 months

4

1154

Mean Difference (IV, Fixed, 95% CI)

‐0.37 [‐1.49, 0.76]

76.2 BSID III score < 24 months

2

809

Mean Difference (IV, Fixed, 95% CI)

0.04 [‐1.59, 1.68]

76.3 Fagan novelty preference < 24 months

2

274

Mean Difference (IV, Fixed, 95% CI)

‐0.79 [‐1.68, 0.11]

76.4 K‐ABC mental processing composite at 2 to 5 years

1

84

Mean Difference (IV, Fixed, 95% CI)

4.10 [‐0.14, 8.34]

76.5 K‐ABC sequential processing at 5 to 6 years

1

96

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐1.80, 1.80]

76.6 GMDS general quotient score at 2 to 5 years

1

72

Mean Difference (IV, Fixed, 95% CI)

3.70 [‐1.02, 8.42]

76.7 DAS II: General Conceptual Ability Scale at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

0.13 [‐1.53, 1.79]

76.8 DAS II: Non‐verbal Reasoning Scale at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

‐0.35 [‐2.04, 1.34]

76.9 DAS II: Verbal Scale at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

‐0.35 [‐1.74, 1.04]

76.10 DAS II: Spatial Scale at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

0.96 [‐0.77, 2.69]

76.11 MCDS: scale index general cognitive at 5 years

1

797

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐2.35, 1.35]

76.12 WASI full‐scale IQ at 6 to 9 years

1

543

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐0.79, 2.79]

76.13 WISC‐IV full scale IQ at > 12 years

1

50

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐5.16, 7.16]

77 Attention: scores Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

77.1 K‐CPT omissions at 5 years

1

797

Mean Difference (IV, Fixed, 95% CI)

‐1.90 [‐3.39, ‐0.41]

77.2 K‐CPT commissions at 5 years

1

797

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐1.37, 1.57]

77.3 K‐CPT hit response time at 5 years

1

797

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐2.06, 0.86]

77.4 Attention: single‐object task: total time looking at toy(s) at 2 to 5 years

1

150

Mean Difference (IV, Fixed, 95% CI)

‐7.80 [‐22.59, 6.99]

77.5 Attention: multiple‐object task; # times shifted looks between toys at 2 to 5 years

1

150

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐4.28, 3.48]

77.6 Attention: distractibility: av latency to look when attention focused (s) at 2 to 5 years

1

150

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.86, 0.26]

77.7 Attention: global speed (ms) at 8.5 years

1

130

Mean Difference (IV, Fixed, 95% CI)

‐5.5 [‐47.16, 36.16]

77.8 Attention: interference (ms) at 8.5 years

1

130

Mean Difference (IV, Fixed, 95% CI)

6.97 [‐16.42, 30.36]

77.9 Attention: orienting (ms) at 8.5 years

1

130

Mean Difference (IV, Fixed, 95% CI)

3.99 [‐16.90, 24.88]

77.10 Attention: alertness (ms) at 8.5 years

1

130

Mean Difference (IV, Fixed, 95% CI)

‐5.69 [‐27.88, 16.50]

78 Motor: thresholds Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

78.1 BSID II score < 85 at 18 months

1

730

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.65, 1.19]

78.2 Fine motor (highest quartile): at 18 months

1

154

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.71, 1.99]

78.3 Gross motor (highest quartile): at 18 months

1

154

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.68, 1.88]

79 Motor: scores Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

79.1 BSID II at < 24 months

4

1153

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐0.90, 1.36]

79.2 BSID III at < 24 months

1

726

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐1.52, 1.64]

79.3 BSID III fine motor score at < 24 months

1

49

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐1.20, 1.30]

79.4 BSID III gross motor score at < 24 months

1

49

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.68, 0.78]

80 Language: thresholds Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

80.1 BSID III < 85

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.74, 1.40]

80.2 BSID III > 115

1

726

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.52, 1.29]

80.3 Receptive language (highest quartile)

1

154

Risk Ratio (M‐H, Fixed, 95% CI)

1.82 [1.07, 3.10]

80.4 Expressive language (highest quartile)

1

154

Risk Ratio (M‐H, Fixed, 95% CI)

1.65 [1.02, 2.68]

80.5 Infant CDI: words understood (highest quartile)

1

159

Risk Ratio (M‐H, Fixed, 95% CI)

2.42 [1.33, 4.42]

80.6 Infant CDI: words produced (highest quartile)

1

159

Risk Ratio (M‐H, Fixed, 95% CI)

2.08 [1.15, 3.74]

80.7 Infant CDI: words understood (highest quartile)

1

134

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.11, 3.48]

80.8 Infant CDI: words produced (highest quartile)

1

134

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [1.11, 3.48]

80.9 Toddler CDI: words produced (highest quartile)

1

134

Risk Ratio (M‐H, Fixed, 95% CI)

2.09 [1.12, 3.90]

80.10 Non‐native constant contrast discrimination

1

144

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.68, 1.40]

81 Language: scores Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

81.1 Receptive communication at < 24 months

1

49

Mean Difference (IV, Fixed, 95% CI)

0.55 [‐0.77, 1.87]

81.2 Receptive language (Peabody Picture Vocabulary Test IIIA) at 2 to 5 years

1

70

Mean Difference (IV, Fixed, 95% CI)

3.90 [‐0.73, 8.53]

81.3 Expressive communication at < 24 months

1

49

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.86, 1.28]

81.4 BSID III at < 24 months

2

809

Mean Difference (IV, Fixed, 95% CI)

‐0.84 [‐2.77, 1.09]

81.5 CELF‐P2 Core Language Score at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

‐0.93 [‐2.92, 1.06]

81.6 CELF‐P2 Core Language Score at 6 to 9 years

1

543

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐2.51, 2.09]

81.7 Peabody Picture Vocabulary Test

1

97

Mean Difference (IV, Fixed, 95% CI)

4.0 [‐3.11, 11.11]

82 Behaviour: thresholds Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

82.1 Behaviour Rating Scale scores < 26: at < 24 months

1

730

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.24, 103.79]

83 Behaviour: scores Show forest plot

6

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

83.1 NBAS habituation

1

27

Mean Difference (IV, Fixed, 95% CI)

‐1.45 [‐8.49, 5.59]

83.2 NBAS orienting

1

27

Mean Difference (IV, Fixed, 95% CI)

3.65 [‐9.09, 16.39]

83.3 NBAS motor

1

27

Mean Difference (IV, Fixed, 95% CI)

2.99 [‐8.23, 14.21]

83.4 NBAS state organisation

1

27

Mean Difference (IV, Fixed, 95% CI)

1.63 [‐7.21, 10.47]

83.5 NBAS state regulation

1

27

Mean Difference (IV, Fixed, 95% CI)

0.51 [‐14.70, 15.72]

83.6 NBAS autonomic

1

27

Mean Difference (IV, Fixed, 95% CI)

3.30 [‐8.75, 15.35]

83.7 NBAS reflexes

1

27

Mean Difference (IV, Fixed, 95% CI)

0.68 [‐10.28, 11.64]

83.8 BehavioUr Rating Scale score 12 to < 24 months

1

730

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.94, 0.94]

83.9 Wolke: approach at < 12 months

1

249

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.42, 0.22]

83.10 Wolke: activity at < 12 months

1

249

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.45, 0.25]

83.11 Wolke: co‐operation at < 12 months

1

249

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.39, 0.39]

83.12 Wolke: emotional tone at < 12 months

1

249

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.49, 0.29]

83.13 Wolke: vocalisation at < 12 months

1

249

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.52, 0.32]

83.14 BSID III social‐emotional score at < 24 months

2

809

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐3.04, 1.64]

83.15 BSID III adaptive behaviour score at < 24 months

2

809

Mean Difference (IV, Fixed, 95% CI)

‐1.20 [‐3.12, 0.72]

83.16 SDQ Total Difficulties at 2 to 5 years

1

646

Mean Difference (IV, Fixed, 95% CI)

0.62 [‐0.00, 1.24]

83.17 SDQ Total Difficulties at 6 to 9 years

1

543

Mean Difference (IV, Fixed, 95% CI)

1.08 [0.18, 1.98]

83.18 BASC‐2: Behavioral Symptoms Index (%) at 5 years

1

797

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐4.54, 3.54]

83.19 CBCL total problem behaviour at 2 ‐ 5 years

1

72

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐3.41, 1.41]

83.20 CBCL parent report: total behaviours score at 12+ years

1

48

Mean Difference (IV, Fixed, 95% CI)

‐0.80 [‐5.23, 3.63]

83.21 CBCL parent report: total competence score at > 12 years

1

48

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐6.36, 5.96]

84 Vision: visual acuity (cycles/degree) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

84.1 At 2 months

1

135

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.01, 0.37]

84.2 At 4 months

1

30

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.43, 1.43]

84.3 At 6 months

1

26

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐0.48, 1.48]

85 Vision: VEP acuity Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

85.1 Adjusted VEP acuity at 4 months (cpd)

1

182

Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.75, 0.39]

85.2 Unadjusted VEP acuity at 4 months (cpd)

1

182

Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.76, 0.40]

86 Vision: VEP latency Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

86.1 Peak latency N1 at birth

1

9

Mean Difference (IV, Fixed, 95% CI)

‐12.60 [‐29.40, 4.20]

86.2 Peak latency P1 at birth

1

14

Mean Difference (IV, Fixed, 95% CI)

‐6.80 [‐20.44, 6.84]

86.3 Peak latency N2 at birth

1

49

Mean Difference (IV, Fixed, 95% CI)

3.60 [‐12.39, 19.59]

86.4 Peak latency P2 at birth

1

55

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐16.28, 16.48]

86.5 Peak latency N3 at birth

1

53

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐36.15, 23.75]

86.6 Latency N1 (ms) at 3 months

1

679

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐2.21, 2.81]

86.7 Latency P1 (ms) at 3 months

1

679

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐3.19, 2.19]

86.8 Latency N3 (ms) at 3 months

1

679

Mean Difference (IV, Fixed, 95% CI)

‐2.30 [‐5.91, 1.31]

86.9 Latency (69 min of arc) at 4 months (ms)

1

182

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐3.47, 1.47]

86.10 Latency (48 min of arc) at 4 months (ms)

1

182

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐3.20, 3.20]

86.11 Latency (20 min of arc) at 4 months (ms)

1

182

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐4.22, 4.22]

86.12 Latency N1 (ms) at 6 months

1

817

Mean Difference (IV, Fixed, 95% CI)

‐1.40 [‐3.44, 0.64]

86.13 Latency P1 (ms) at 6 months

1

817

Mean Difference (IV, Fixed, 95% CI)

‐0.80 [‐2.78, 1.18]

86.14 Latency N3 (ms) at 6 months

1

817

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐3.45, 2.05]

87 Hearing: brainstem auditory‐evoked responses Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

87.1 Latency 1 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.03, 0.01]

87.2 Latency 3 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.06, 0.04]

87.3 Latency 5 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.09, 0.03]

87.4 Interpeak latency 1‐3 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.06, 0.04]

87.5 Interpeak latency 3‐5 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.05, 0.05]

87.6 Interpeak latency 1‐5 (ms) at 1 month

1

749

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.07, 0.03]

87.7 Latency 1 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.02, 0.02]

87.8 Latency 3 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.04, 0.06]

87.9 Latency 5 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.10, 0.02]

87.10 Interpeak latency 1‐3 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.03, 0.05]

87.11 Interpeak latency 3‐5 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.08, 0.02]

87.12 Interpeak latency 1‐5 (ms) at 3 months

1

664

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.09, 0.03]

88 Neurodevelopment: thresholds Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

88.1 Hempel: simple minor neurological dysfunction at 18 months

1

114

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.80, 1.53]

88.2 Hempel: simple and complex minor neurological dysfunction at 4 years

1

167

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.37, 3.23]

88.3 Hempel: complex minor neurological dysfunction at 18 months

1

114

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.24, 1.93]

88.4 ASQ total at 6 months (subnormal ‐ below 2 SD less than mean scores)

1

146

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.17, 1.77]

88.5 Touwen: simple and complex minor neurological dysfunction at 5.5 years

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.61, 1.63]

88.6 Neonatal neurological classification: mildly/definitely abnormal at 2 weeks

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.38, 1.97]

88.7 General movements: mildly/definitely abnormal at 2 weeks

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.27 [0.75, 2.14]

88.8 General movements: mildly/definitely abnormal at 12 weeks

1

119

Risk Ratio (M‐H, Fixed, 95% CI)

1.54 [0.89, 2.65]

89 Neurodevelopment: scores Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

89.1 ASQ gross motor at 4 months

1

148

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐2.38, 2.98]

89.2 ASQ gross motor at 6 months

1

146

Mean Difference (IV, Fixed, 95% CI)

1.20 [‐2.31, 4.71]

89.3 ASQ fine motor at 4 months

1

148

Mean Difference (IV, Fixed, 95% CI)

1.10 [‐2.03, 4.23]

89.4 ASQ fine motor at 6 months

1

146

Mean Difference (IV, Fixed, 95% CI)

1.20 [‐1.59, 3.99]

89.5 ASQ problem solving at 4 months

1

148

Mean Difference (IV, Fixed, 95% CI)

1.60 [‐0.99, 4.19]

89.6 ASQ problem solving at 6 months

1

146

Mean Difference (IV, Fixed, 95% CI)

0.5 [‐1.95, 2.95]

89.7 ASQ personal‐social at 4 months

1

148

Mean Difference (IV, Fixed, 95% CI)

1.10 [‐1.64, 3.84]

89.8 ASQ personal‐social at 6 months

1

146

Mean Difference (IV, Fixed, 95% CI)

0.80 [‐2.61, 4.21]

89.9 ASQ communication at 4 months

1

148

Mean Difference (IV, Fixed, 95% CI)

2.70 [0.41, 4.99]

89.10 ASQ communication at 6 months

1

146

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐1.55, 2.35]

90 Child Development Inventory Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

90.1 Social

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

90.2 Self help

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.01, 6.90]

90.3 Gross motor

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

4.30 [0.21, 87.76]

90.4 Fine motor

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

4.30 [0.21, 87.76]

90.5 Expressive language

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.05, 13.41]

90.6 Language comprehension

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

90.7 Letters

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.17 [0.01, 3.51]

90.8 Numbers

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.05, 13.41]

90.9 General development

1

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.13, 2.06]

91 Infant sleep behaviour (%) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

91.1 Arousals in quiet sleep: day 1

1

46

Mean Difference (IV, Fixed, 95% CI)

‐3.19 [‐6.07, ‐0.31]

91.2 Arousals in quiet sleep: day 2

1

39

Mean Difference (IV, Fixed, 95% CI)

‐1.89 [‐4.49, 0.71]

91.3 Quiet sleep: day 1

1

46

Mean Difference (IV, Fixed, 95% CI)

0.74 [‐1.97, 3.45]

91.4 Quiet sleep: day 2

1

39

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐4.36, 2.36]

91.5 Active sleep: day 1

1

46

Mean Difference (IV, Fixed, 95% CI)

‐2.42 [‐8.51, 3.67]

91.6 Active sleep: day 2

1

39

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐8.23, 7.97]

91.7 Arousals in active sleep: day 1

1

46

Mean Difference (IV, Fixed, 95% CI)

‐3.0 [‐5.66, ‐0.34]

91.8 Arousals in active sleep: day 2

1

46

Mean Difference (IV, Fixed, 95% CI)

‐0.63 [‐4.12, 2.86]

92 Cerebral palsy Show forest plot

1

114

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figures and Tables -
Comparison 1. Overall: omega‐3 versus no omega‐3
Navigate to table in Review
Comparison 2. Type of omega‐3 intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

27

10304

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.81, 0.97]

1.1 Omega‐3 supplements only

18

7608

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.80, 1.01]

1.2 Omega‐3 supplements/enrichment + food/diet advice

3

516

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.41, 1.29]

1.3 Omega‐3 food/diet advice

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 2.22]

1.4 Omega‐3 supplements + other agents

6

2132

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.76, 1.04]

2 Early preterm birth (< 34 weeks) Show forest plot

9

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

2.1 Omega‐3 supplements only

8

4234

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.46, 0.82]

2.2 Omega‐3 supplements + other agents

1

970

Risk Ratio (M‐H, Fixed, 95% CI)

0.19 [0.04, 0.88]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [1.11, 2.33]

3.1 Omega‐3 supplements only

5

4953

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [1.09, 2.31]

3.2 Omega‐3 supplements + food/diet advice

1

188

Risk Ratio (M‐H, Fixed, 95% CI)

3.13 [0.13, 75.84]

4 Maternal death Show forest plot

4

4830

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.07, 39.30]

4.1 Omega‐3 supplements only

3

4782

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Omega‐3 food/diet advice

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.07, 39.30]

5 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

21

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.01]

5.1 Omega‐3 supplements only

13

5825

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.76, 1.19]

5.2 Omega‐3 supplements/enrichment + food/dietary advice

2

328

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.25, 1.69]

5.3 Omega‐3 supplements + other agents

6

2153

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.39, 0.88]

6 High blood pressure (without proteinuria) Show forest plot

7

4531

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.89, 1.20]

6.1 Omega‐3 supplements only

6

4431

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.90, 1.22]

6.2 Omega‐3 supplements + other agents

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.33, 1.47]

7 Eclampsia Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.70]

7.1 Omega‐3 supplements + other agents

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.70]

8 Maternal antepartum hospitalisation Show forest plot

5

2876

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.81, 1.04]

8.1 Omega‐3 supplements only

4

2817

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.82, 1.04]

8.2 Omega‐3 supplementation + other agents

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.01, 4.13]

9 Mother's length of stay in hospital (days) Show forest plot

2

2290

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.20, 0.57]

9.1 Omega‐3 supplements only

2

2290

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.20, 0.57]

10 Maternal anaemia Show forest plot

1

846

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.91, 1.48]

10.1 Omega‐3 supplements only

1

846

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.91, 1.48]

11 Miscarriage (< 24 weeks) Show forest plot

9

4190

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.80, 1.43]

11.1 Omega‐3 supplements only

8

3049

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.56, 1.60]

11.2 Omega‐3 supplements + other agents

1

1141

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.80, 1.61]

12 Antepartum vaginal bleeding Show forest plot

2

2151

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.69, 1.48]

12.1 Omega‐3 supplements only

2

2151

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.69, 1.48]

13 Preterm prelabour rupture of membranes Show forest plot

3

925

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.25, 1.10]

13.1 Omega‐3 supplements only

2

670

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.28, 1.34]

13.2 Omega‐3 supplementation/enrichment + food/diet advice

1

255

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.03, 2.15]

14 Prelabour rupture of membranes Show forest plot

3

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.21, 0.82]

14.1 Omega‐3 supplements only

1

369

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.14, 2.11]

14.2 Omega‐3 supplementation/enrichment + food/diet advice

2

546

Risk Ratio (M‐H, Fixed, 95% CI)

0.38 [0.17, 0.85]

15 Maternal admission to intensive care Show forest plot

2

2458

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.12, 2.63]

15.1 Omega‐3 supplements only

1

2399

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.14, 7.12]

15.2 Omega‐3 supplements + other agent

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.01, 4.13]

16 Maternal severe adverse effects (including cessation) Show forest plot

8

4177

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.59, 1.75]

16.1 Omega‐3 supplements only

7

3886

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.54, 1.87]

16.2 Omega‐3 supplementation/enrichment + food/diet advice

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.35, 3.18]

17 Caesarean section Show forest plot

29

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

17.1 Omega‐3 supplements only

19

6537

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.92, 1.06]

17.2 Omega‐3 supplements/enrichment +food/diet advice

4

574

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.63, 1.19]

17.3 Omega‐3 food/diet advice

1

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.38, 2.17]

17.4 Omega‐3 supplements + other agents

5

1263

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.72, 1.08]

18 Induction (post‐term) Show forest plot

3

2900

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.22, 2.98]

18.1 Omega‐3 supplements only

2

2712

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.22, 2.98]

18.2 Omega‐3 supplements + food/diet advice

1

188

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Blood loss at birth (mL) Show forest plot

6

2776

Mean Difference (IV, Fixed, 95% CI)

11.50 [‐6.75, 29.76]

19.1 Omega‐3 supplements only

5

2588

Mean Difference (IV, Fixed, 95% CI)

11.64 [‐8.89, 32.17]

19.2 Omega‐3 supplements + food/diet advice

1

188

Mean Difference (IV, Fixed, 95% CI)

11.0 [‐28.91, 50.91]

20 Postpartum haemorrhage Show forest plot

4

4085

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.82, 1.30]

20.1 Omega‐3 supplements only

3

3233

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.71, 1.34]

20.2 Omega‐3 supplements + other agent

1

852

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.79, 1.57]

21 Gestational diabetes Show forest plot

12

5235

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.83, 1.26]

21.1 Omega‐3 supplements only

7

3726

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.80, 1.30]

21.2 Omega‐3 supplements/enrichment + food/diet advice

4

595

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.33, 1.34]

21.3 Omega‐3 supplements + other agents

2

914

Risk Ratio (M‐H, Fixed, 95% CI)

1.34 [0.80, 2.24]

22 Maternal insulin resistance (HOMA‐IR) Show forest plot

3

176

Mean Difference (IV, Random, 95% CI)

‐0.85 [‐2.50, 0.80]

22.1 Omega‐3 supplements only

2

116

Mean Difference (IV, Random, 95% CI)

‐0.25 [‐1.94, 1.44]

22.2 Omega‐3 supplements + other agents

1

60

Mean Difference (IV, Random, 95% CI)

‐2.0 [‐3.10, ‐0.90]

23 Excessive gestational weight gain Show forest plot

1

350

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.95, 1.55]

23.1 Omega‐3 supplements only

1

350

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.95, 1.55]

24 Gestational weight gain (kg) Show forest plot

11

2297

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.68, 0.59]

24.1 Omega‐3 supplements only

6

955

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐1.47, 1.03]

24.2 Omega‐3 supplements/enrichment + food/diet advice

3

313

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.99, 0.78]

24.3 Omega‐3 supplements + other agents

2

1029

Mean Difference (IV, Random, 95% CI)

0.43 [‐0.08, 0.95]

25 Depression during pregnancy: scores Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

25.1 Omega‐3 supplements only: BDI

2

104

Mean Difference (IV, Fixed, 95% CI)

‐5.86 [‐8.32, ‐3.39]

25.2 Omega‐3 supplements only: HAMD

3

71

Mean Difference (IV, Fixed, 95% CI)

‐1.08 [‐3.35, 1.19]

25.3 Omega‐3 supplements only: EPDS

4

122

Mean Difference (IV, Fixed, 95% CI)

‐0.15 [‐2.09, 1.79]

25.4 Omega‐3 supplements only: MADRS

1

26

Mean Difference (IV, Fixed, 95% CI)

‐1.60 [‐7.80, 4.60]

26 Depression during pregnancy: thresholds Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

26.1 Omega‐3 supplements only: HAMD 50% reduction (after 8 weeks)

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

2.26 [0.78, 6.49]

26.2 Omega‐3 supplements only: HAMD ≤ 7

1

24

Risk Ratio (M‐H, Fixed, 95% CI)

2.12 [0.51, 8.84]

26.3 Omega‐3 supplements only: unspecified

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.39 [0.47, 12.11]

26.4 Omega‐3 supplements only: EPDS ≥ 11

1

34

Risk Ratio (M‐H, Fixed, 95% CI)

1.4 [0.55, 3.55]

27 Depressive symptoms postpartum: thresholds Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

27.1 Omega‐3 supplements only: PDSS ≥80

1

42

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.04, 3.25]

27.2 Omega‐3 supplements only: EPDS

2

2431

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.71, 1.12]

27.3 Omega‐3 supplements only: major depressive disorder

1

118

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.27, 6.56]

28 Depressive symptoms postpartum: scores Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

28.1 Omega‐3 supplements only: BD: 6‐8 weeks postpartum

1

118

Mean Difference (IV, Fixed, 95% CI)

0.25 [‐1.93, 2.43]

28.2 Omega‐3 supplements only: PDSS total (LS over 6 months)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐6.08 [‐12.42, 0.26]

29 Length of gestation (days) Show forest plot

43

12517

Mean Difference (IV, Random, 95% CI)

1.65 [0.94, 2.37]

29.1 Omega‐3 supplements only

29

9290

Mean Difference (IV, Random, 95% CI)

1.67 [0.76, 2.59]

29.2 Omega‐3 supplements/enrichment + food/diet advice

6

680

Mean Difference (IV, Random, 95% CI)

2.45 [‐0.14, 5.04]

29.3 Omega‐3 food/diet advice

1

107

Mean Difference (IV, Random, 95% CI)

5.00 [0.64, 9.36]

29.4 Omega‐3 supplements + other agents

8

2440

Mean Difference (IV, Random, 95% CI)

1.04 [0.05, 2.03]

30 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

30.1 Omega‐3 supplements only

8

6496

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.48, 1.03]

30.2 Omega‐3 supplements + other agents

2

920

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.47, 1.62]

31 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

31.1 Omega‐3 supplements only

13

7693

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.60, 1.42]

31.2 Omega‐3 supplements + food/diet advice

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.75]

31.3 Omega‐3 food/diet advice

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.07, 39.30]

31.4 Omega‐3 supplements + other agents

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 70.83]

32 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

32.1 Omega‐3 supplements only

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

33 Infant death Show forest plot

4

3239

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.25, 2.19]

33.1 Omega‐3 supplements only

4

3239

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.25, 2.19]

34 Large‐for‐gestational age Show forest plot

5

3602

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [1.01, 1.43]

34.1 Omega‐3 supplements only

2

2518

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.99, 1.43]

34.2 Omega‐3 supplements + food/diet advice

1

188

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.48, 3.17]

34.3 Omega‐3 supplements + other agent

2

896

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.72, 2.29]

35 Macrosomia Show forest plot

7

2008

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.43, 1.13]

35.1 Omega‐3 supplements only

5

1904

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.47, 1.36]

35.2 Omega‐3 supplements + other agent

2

104

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.08, 1.23]

36 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

36.1 Omega‐3 supplements only

10

6214

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.86, 1.07]

36.2 Omega‐3 supplements/enrichment + food/diet advice

2

328

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.34, 1.26]

36.3 Omega‐3 supplements + other agents

3

1907

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.62, 0.95]

37 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

37.1 Omega‐3 supplements only

5

5041

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.93, 1.20]

37.2 Omega‐3 supplements + other agents

3

1866

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.59, 1.09]

38 Birthweight (g) Show forest plot

44

11584

Mean Difference (IV, Random, 95% CI)

75.74 [38.05, 113.43]

38.1 Omega‐3 supplements only

31

8522

Mean Difference (IV, Random, 95% CI)

59.41 [23.23, 95.59]

38.2 Omega‐3 supplements/enrichment + food/diet advice

6

859

Mean Difference (IV, Random, 95% CI)

129.42 [49.52, 209.31]

38.3 Omega‐3 food/diet advice

1

107

Mean Difference (IV, Random, 95% CI)

‐17.0 [‐190.97, 156.97]

38.4 Omega‐3 supplements + other agents

6

2096

Mean Difference (IV, Random, 95% CI)

69.14 [‐72.81, 211.10]

39 Birthweight Z score Show forest plot

4

2792

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.02, 0.13]

39.1 Omega‐3 supplements only

3

2677

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.01, 0.14]

39.2 Omega‐3 supplements + other agent

1

115

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.21, 0.21]

40 Birth length (cm) Show forest plot

29

8008

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.08, 0.34]

40.1 Omega‐3 supplements only

20

6010

Mean Difference (IV, Random, 95% CI)

0.21 [‐0.03, 0.45]

40.2 Omega‐3 supplements/enrichment + food/diet advice

4

606

Mean Difference (IV, Random, 95% CI)

0.42 [‐0.01, 0.85]

40.3 Omega‐3 food/diet advice

1

123

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.56, 0.36]

40.4 Omega‐3 supplements + other agent

4

1269

Mean Difference (IV, Random, 95% CI)

‐0.51 [‐0.78, ‐0.23]

41 Length at birth Z score Show forest plot

2

2462

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.18, 0.54]

41.1 Omega‐3 supplements only

2

2462

Mean Difference (IV, Random, 95% CI)

0.18 [‐0.18, 0.54]

42 Head circumference at birth (cm) Show forest plot

23

7041

Mean Difference (IV, Fixed, 95% CI)

0.10 [0.01, 0.18]

42.1 Omega‐3 supplements only

16

5442

Mean Difference (IV, Fixed, 95% CI)

0.07 [‐0.03, 0.17]

42.2 Omega‐3 supplements/enrichment + food/diet advice

3

418

Mean Difference (IV, Fixed, 95% CI)

0.34 [0.03, 0.65]

42.3 Omega‐3 food/diet advice only

1

107

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.75, 0.35]

42.4 Omega‐3 supplements + other agent

3

1074

Mean Difference (IV, Fixed, 95% CI)

0.15 [‐0.06, 0.35]

43 Head circumference at birth Z score Show forest plot

2

2462

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.14, 0.07]

43.1 Omega‐3 supplementation only

2

2462

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.14, 0.07]

44 Baby admitted to neonatal care Show forest plot

9

6920

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.03]

44.1 Omega‐3 supplements only

5

5692

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.79, 1.02]

44.2 Omega‐3 supplements/enrichment + food/diet advice

2

328

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.54, 1.50]

44.3 Omega‐3 supplements + other agents

2

900

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.81, 1.26]

45 Infant length of stay in hospital (days) Show forest plot

1

2041

Mean Difference (IV, Fixed, 95% CI)

0.11 [‐1.40, 1.62]

45.1 Omega‐3 supplementation only

1

2041

Mean Difference (IV, Fixed, 95% CI)

0.11 [‐1.40, 1.62]

46 Congenital anomalies Show forest plot

3

1807

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.61, 1.92]

46.1 Omega‐3 supplements only

3

1807

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.61, 1.92]

47 Retinopathy of prematurity Show forest plot

1

837

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.32, 4.44]

47.1 Omega‐3 supplementation + other agent only

1

837

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.32, 4.44]

48 Bronchopulmonary dysplasia Show forest plot

2

3191

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.45, 2.48]

48.1 Omega‐3 supplementation only

1

2363

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.09, 2.71]

48.2 Omega‐3 supplementation + other agent

1

828

Risk Ratio (M‐H, Fixed, 95% CI)

1.42 [0.51, 3.96]

49 Respiratory distress syndrome Show forest plot

2

1129

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.54, 2.52]

49.1 Omega‐3 supplementation only

1

301

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.31, 1.65]

49.2 Omega‐3 supplementation + other agent

1

828

Risk Ratio (M‐H, Random, 95% CI)

1.60 [1.08, 2.37]

50 Necrotising enterocolitis (NEC) Show forest plot

2

3198

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.26, 3.55]

50.1 Omega‐3 supplementation only

1

2361

Risk Ratio (M‐H, Fixed, 95% CI)

2.98 [0.12, 73.13]

50.2 Omega‐3 supplementation + other agent

1

837

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.16, 3.20]

51 Neonatal sepsis (proven) Show forest plot

3

3788

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.44, 2.14]

51.1 Omega‐3 supplements only

3

3788

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.44, 2.14]

52 Convulsion Show forest plot

1

2361

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 1.63]

52.1 Omega‐3 supplementation only

1

2361

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 1.63]

53 Intraventricular haemorrhage Show forest plot

3

5423

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.29, 3.49]

53.1 Omega‐3 supplements only

2

4586

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.02, 16.16]

53.2 Omega‐3 supplementation + other agent

1

837

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.44, 2.60]

54 Neonatal/infant serious adverse events Show forest plot

2

2690

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.53, 0.99]

54.1 Omega‐3 supplementation

1

2399

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.44, 1.01]

54.2 Omega‐3 supplements/enrichment + food/diet advice

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.50, 1.31]

55 Neonatal/infant morbidity: cardiovascular Show forest plot

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.85, 1.69]

55.1 Omega‐3 supplements/enrichment + food/diet advice

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.85, 1.69]

56 Neonatal/infant morbidity: respiratory Show forest plot

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.66, 1.57]

56.1 Omega‐3 supplements/enrichment + food/diet advice

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.66, 1.57]

57 Neonatal/infant morbidity: caused by pregnancy/birth Show forest plot

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.67, 1.55]

57.1 Omega‐3 supplements/enrichment + food/diet advice

1

291

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.67, 1.55]

58 Ponderal index Show forest plot

6

887

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.01, 0.11]

58.1 Omega‐3 supplements only

5

699

Mean Difference (IV, Random, 95% CI)

0.04 [‐0.04, 0.11]

58.2 Omega‐3 supplements + food/diet advice

1

188

Mean Difference (IV, Random, 95% CI)

0.08 [0.01, 0.15]
Figures and Tables -
Comparison 2. Type of omega‐3 intervention
Navigate to table in Review
Comparison 3. Dose (DHA/EPA) subgroups

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

26

10294

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.80, 0.97]

1.1 Low: < 500 mg/day

6

1604

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.65, 1.20]

1.2 Mid: 500 mg‐1 g/day

9

4343

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.64, 0.98]

1.3 High: > 1 g/day

9

4240

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.03]

1.4 Other

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.19, 2.32]

2 Early preterm birth (< 34 weeks) Show forest plot

9

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

2.1 Low: < 500 mg/day

1

168

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.05, 1.51]

2.2 Mid: 500 mg‐1 g/day

7

4176

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.30, 0.75]

2.3 High: > 1 g/day

2

860

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.49, 0.99]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [1.10, 2.30]

3.1 Low: < 500 mg/day

2

303

Risk Ratio (M‐H, Fixed, 95% CI)

1.72 [0.07, 41.64]

3.2 Mid: 500 mg‐1 g/day

2

2544

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [0.54, 6.81]

3.3 High: > 1 g/day

3

2294

Risk Ratio (M‐H, Fixed, 95% CI)

1.56 [1.05, 2.30]

4 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

20

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.69, 1.01]

4.1 Low: < 500 mg/day

5

650

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.28, 1.26]

4.2 Mid: 500 mg‐1 g/day

7

4118

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.62, 1.11]

4.3 High: > 1 g/day

8

3479

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.66, 1.14]

4.4 Other

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

2.07 [0.20, 21.60]

5 Caesarean section Show forest plot

28

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

5.1 Low: < 500 g/day

8

1670

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.84, 1.06]

5.2 Mid: 500 mg‐1 g/day

10

4399

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.85, 1.02]

5.3 High: > 1 g/day

8

2294

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.97, 1.37]

5.4 Other

2

118

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.30, 1.15]

6 Length of gestation (days) Show forest plot

42

12517

Mean Difference (IV, Random, 95% CI)

1.67 [0.95, 2.39]

6.1 Low: < 500 mg/day

12

2117

Mean Difference (IV, Random, 95% CI)

1.05 [0.07, 2.03]

6.2 Mid: 500 mg‐1 g/day

15

4881

Mean Difference (IV, Random, 95% CI)

1.97 [0.56, 3.38]

6.3 High: > 1 g/day

12

3364

Mean Difference (IV, Random, 95% CI)

1.86 [0.45, 3.27]

6.4 Mixed

1

1998

Mean Difference (IV, Random, 95% CI)

0.10 [‐1.00, 1.20]

6.5 Other

3

157

Mean Difference (IV, Random, 95% CI)

2.24 [‐0.83, 5.31]

7 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

7.1 Low: < 500 mg/day

2

1127

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.20, 1.33]

7.2 Mid: 500 mg‐1 g/day

3

2566

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.16, 1.02]

7.3 High: > 1 g/day

5

3723

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.61, 1.29]

8 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

8.1 Low: < 500 mg/day

1

977

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.11, 3.96]

8.2 Mid: 500 mg/day‐1 g/day

5

2783

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.27, 1.83]

8.3 High: > 1 g/day

7

3933

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.62, 1.69]

8.4 Other

3

187

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.23, 5.94]

9 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

9.1 Low: < 500 mg/day

2

1123

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.15, 1.44]

9.2 Mid: 500 mg/day‐1 g/day

2

2700

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.12, 1.98]

9.3 High: > 1 g/day

5

3625

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.34, 1.78]

10 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

10.1 Low: < 500 mg/day

5

1551

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.51, 1.08]

10.2 Mid: 500 mg‐1 g/day

5

3901

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.54, 0.92]

10.3 High: > 1 g/day

5

2997

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.88, 1.08]

11 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

11.1 Low: < 500 mg/day

1

973

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.73, 1.48]

11.2 Mid: 500 mg‐1 g/day

2

3369

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.66, 1.09]

11.3 High: > 1 g/day

4

2506

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.93, 1.23]

11.4 Other

1

59

Risk Ratio (M‐H, Fixed, 95% CI)

2.07 [0.20, 21.60]

12 Birthweight (g) Show forest plot

44

11584

Mean Difference (IV, Random, 95% CI)

75.30 [38.09, 112.50]

12.1 Low: < 500 mg/day

12

2220

Mean Difference (IV, Random, 95% CI)

26.32 [‐12.74, 65.39]

12.2 Mid: 500 mg‐1 g/day

18

5007

Mean Difference (IV, Random, 95% CI)

91.49 [24.34, 158.64]

12.3 High: > 1 g/day

14

4298

Mean Difference (IV, Random, 95% CI)

88.31 [29.61, 147.01]

12.4 Other

1

59

Mean Difference (IV, Random, 95% CI)

‐203.20 [‐456.97, 50.57]
Figures and Tables -
Comparison 3. Dose (DHA/EPA) subgroups
Navigate to table in Review
Comparison 4. Timing subgroups

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

26

10304

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.81, 0.97]

1.1 ≤ 20 weeks GA start

12

6563

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.76, 0.95]

1.2 > 20 weeks GA start

13

3693

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.82, 1.23]

1.3 Mixed

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 2.22]

2 Early preterm birth (< 34 weeks) Show forest plot

9

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

2.1 ≤ 20 weeks GA start

8

5090

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.43, 0.75]

2.2 > 20 weeks GA start

1

114

Risk Ratio (M‐H, Fixed, 95% CI)

4.83 [0.24, 98.44]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [1.11, 2.33]

3.1 ≤ 20 weeks GA start

5

4608

Risk Ratio (M‐H, Fixed, 95% CI)

2.35 [1.29, 4.28]

3.2 > 20 weeks GA start

1

533

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.73, 1.93]

4 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

20

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.01]

4.1 ≤ 20 weeks GA start

13

6296

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.74, 1.15]

4.2 > 20 weeks GA start

6

1883

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.53, 1.18]

4.3 Not reported

1

127

Risk Ratio (M‐H, Fixed, 95% CI)

0.07 [0.01, 0.54]

5 Caesarean section Show forest plot

28

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

5.1 ≤ 20 weeks GA start

13

4995

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.88, 1.07]

5.2 > 20 weeks GA start

14

2617

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.87, 1.10]

5.3 Mixed

1

869

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.83, 1.08]

6 Length of gestation (days) Show forest plot

43

12517

Mean Difference (IV, Random, 95% CI)

1.67 [0.95, 2.39]

6.1 ≤ 20 weeks GA start

23

9396

Mean Difference (IV, Random, 95% CI)

1.99 [1.08, 2.90]

6.2 > 20 weeks GA start

20

3121

Mean Difference (IV, Random, 95% CI)

1.18 [‐0.05, 2.40]

7 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

7.1 ≤ 20 weeks GA start

6

5815

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.49, 1.07]

7.2 > 20 weeks GA start

4

1601

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.46, 1.38]

8 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

8.1 ≤ 20 weeks GA start

8

5537

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.52, 1.48]

8.2 > 20 weeks GA start

7

2295

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.50, 2.07]

8.3 Mixed

1

48

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.07, 39.30]

9 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

9.1 ≤ 20 weeks GA start

6

5415

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.26, 1.36]

9.2 > 20 weeks GA start

3

2033

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.26, 1.49]

10 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

10.1 ≤ 20 weeks GA start

9

6553

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.79, 0.97]

10.2 > 20 weeks GA start

6

1896

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.81, 1.28]

11 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

11.1 ≤ 20 weeks GA start

5

5643

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.88, 1.14]

11.2 > 20 weeks GA start

3

1264

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.79, 1.34]

12 Birthweight (g) Show forest plot

43

11584

Mean Difference (IV, Random, 95% CI)

75.69 [37.84, 113.55]

12.1 ≤ 20 weeks GA start

25

7802

Mean Difference (IV, Random, 95% CI)

83.26 [44.09, 122.43]

12.2 > 20 weeks GA start

17

3747

Mean Difference (IV, Random, 95% CI)

42.96 [‐34.14, 120.06]

12.3 Not reported

1

35

Mean Difference (IV, Random, 95% CI)

200.0 [‐205.07, 605.07]
Figures and Tables -
Comparison 4. Timing subgroups
Navigate to table in Review
Comparison 5. DHA/mixed subgroups

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

26

10304

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.81, 0.97]

1.1 DHA/largely DHA

12

4744

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.02]

1.2 Mixed DHA/EPA

9

4172

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.03]

1.3 Mixed DHA/EPA/other

5

1388

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.45, 1.11]

2 Early preterm birth (< 34 weeks) Show forest plot

9

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

2.1 DHA/largely DHA

5

3260

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.28, 0.76]

2.2 Mixed DHA/EPA

2

860

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.49, 0.99]

2.3 Mixed DHA/EPA/other

2

1084

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.14, 1.25]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [1.11, 2.33]

3.1 DHA/largely DHA

3

2847

Risk Ratio (M‐H, Fixed, 95% CI)

2.12 [0.60, 7.49]

3.2 Mixed DHA/EPA

2

2106

Risk Ratio (M‐H, Fixed, 95% CI)

1.54 [1.04, 2.28]

3.3 Mixed DHA/EPA/other

1

188

Risk Ratio (M‐H, Fixed, 95% CI)

3.13 [0.13, 75.84]

4 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

20

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.01]

4.1 DHA/largely DHA

6

3454

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.71, 1.33]

4.2 Mixed DHA/EPA

9

3506

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.69, 1.18]

4.3 Mixed DHA/EPA/other

5

1346

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.23, 0.71]

5 Caesarean section Show forest plot

28

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

5.1 DHA/largely DHA

9

4327

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.87, 1.03]

5.2 Mixed DHA/EPA

10

2433

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.95, 1.27]

5.3 Mixed DHA/EPA/other

9

1721

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.75, 1.02]

6 Gestational length (days) Show forest plot

43

12517

Mean Difference (IV, Random, 95% CI)

1.67 [0.95, 2.39]

6.1 DHA/largely DHA

14

4791

Mean Difference (IV, Random, 95% CI)

2.44 [0.91, 3.98]

6.2 Mixed DHA/EPA

17

5760

Mean Difference (IV, Random, 95% CI)

1.23 [0.21, 2.24]

6.3 Mixed DHA/EPA/other

12

1966

Mean Difference (IV, Random, 95% CI)

1.42 [0.33, 2.50]

7 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

7.1 DHA/largely DHA

3

3475

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.21, 0.91]

7.2 Mixed DHA/EPA

6

3873

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.60, 1.27]

7.3 Mixed DHA/EPA/other

1

68

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.74]

8 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

8.1 DHA/largely DHA

5

3639

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.28, 1.70]

8.2 Mixed DHA/EPA

8

3987

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.65, 1.73]

8.3 Mixed DHA/EPA/other

3

254

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.14, 3.51]

9 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

9.1 DHA/largely DHA

3

3673

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.20, 1.23]

9.2 Mixed DHA/EPA

6

3775

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.33, 1.62]

10 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

10.1 DHA/largely DHA

6

4118

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.56, 0.93]

10.2 Mixed DHA/EPA

6

3147

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.87, 1.07]

10.3 Mixed DHA/EPA/other

3

1184

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.51, 1.18]

11 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

11.1 DHA/largely DHA

2

3372

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.75, 1.20]

11.2 Mixed DHA/EPA

4

2506

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.93, 1.23]

11.3 Mixed EPA/DHA/other

2

1029

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.50, 1.22]

12 Birthweight (g) Show forest plot

43

11584

Mean Difference (IV, Random, 95% CI)

75.69 [37.84, 113.55]

12.1 DHA/largely DHA

17

6121

Mean Difference (IV, Random, 95% CI)

52.60 [26.96, 78.23]

12.2 Mixed DHA/EPA

15

4429

Mean Difference (IV, Random, 95% CI)

72.72 [6.67, 138.78]

12.3 Mixed DHA/EPA/other

11

1034

Mean Difference (IV, Random, 95% CI)

113.65 [12.54, 214.75]
Figures and Tables -
Comparison 5. DHA/mixed subgroups
Navigate to table in Review
Comparison 6. Risk subgroups

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

27

10304

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.81, 0.97]

1.1 Increased/high risk

12

3702

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.03]

1.2 Low risk

10

3241

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.71, 1.20]

1.3 Any/mixed risk

5

3361

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.54, 0.93]

2 Early preterm birth (< 34 weeks) Show forest plot

10

5204

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.44, 0.77]

2.1 Increased/high risk

6

2104

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.49, 0.93]

2.2 Low risk

3

701

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.12, 0.79]

2.3 Any/mixed risk

1

2399

Risk Ratio (M‐H, Fixed, 95% CI)

0.48 [0.25, 0.93]

3 Prolonged gestation (> 42 weeks) Show forest plot

6

5141

Risk Ratio (M‐H, Fixed, 95% CI)

1.61 [1.11, 2.33]

3.1 Increased/high risk

1

1573

Risk Ratio (M‐H, Fixed, 95% CI)

2.39 [1.19, 4.80]

3.2 Low risk

4

1201

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.79, 2.01]

3.3 Any/mixed risk

1

2367

Risk Ratio (M‐H, Fixed, 95% CI)

2.00 [0.50, 7.97]

4 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

20

8306

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.69, 1.01]

4.1 Increased/high risk

12

3564

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.59, 0.99]

4.2 Low risk

5

1507

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.28, 1.24]

4.3 Any/mixed risk

3

3235

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.74, 1.37]

5 Caesarean section Show forest plot

29

8481

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.91, 1.03]

5.1 Increased/high risk

12

2046

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.80, 1.05]

5.2 Low risk

14

3185

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.89, 1.09]

5.3 Any/mixed risk

3

3250

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.87, 1.10]

6 Length of gestation (days) Show forest plot

43

12517

Mean Difference (IV, Random, 95% CI)

1.67 [0.95, 2.39]

6.1 Increased/high risk

18

3707

Mean Difference (IV, Random, 95% CI)

2.17 [0.65, 3.68]

6.2 Low risk

22

4330

Mean Difference (IV, Random, 95% CI)

1.41 [0.52, 2.29]

6.3 Any/mixed group

3

4480

Mean Difference (IV, Random, 95% CI)

1.27 [‐0.36, 2.91]

7 Perinatal death Show forest plot

10

7416

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.03]

7.1 Increased/high risk

6

3566

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.56, 1.26]

7.2 Low risk

2

1127

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.20, 1.33]

7.3 Any/mixed risk

2

2723

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.35, 1.26]

8 Stillbirth Show forest plot

16

7880

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.62, 1.42]

8.1 Increased/high risk

9

3137

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.65, 1.72]

8.2 Low risk

5

2296

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.40, 3.23]

8.3 Any/mixed risk

2

2447

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.06, 1.27]

9 Neonatal death Show forest plot

9

7448

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.34, 1.11]

9.1 Increased/high risk

4

2889

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.34, 1.78]

9.2 Low risk

3

1424

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.19, 1.45]

9.3 Any/mixed risk

2

3135

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.08, 2.07]

10 Low birthweight (< 2500 g) Show forest plot

15

8449

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

10.1 Increased/high risk

7

4081

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.87, 1.07]

10.2 Low risk

6

1869

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.52, 1.02]

10.3 Any/mixed risk

2

2499

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.44, 0.92]

11 Small‐for‐gestational age/IUGR Show forest plot

8

6907

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.90, 1.13]

11.1 Increased/high risk

6

3535

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.90, 1.18]

11.2 Low risk

1

973

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.73, 1.48]

11.3 Any/mixed risk

1

2399

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.66, 1.21]

12 Birthweight (g) Show forest plot

43

11584

Mean Difference (IV, Random, 95% CI)

75.69 [37.84, 113.55]

12.1 Increased/high risk

19

4848

Mean Difference (IV, Random, 95% CI)

105.52 [30.84, 180.21]

12.2 Low risk

23

4337

Mean Difference (IV, Random, 95% CI)

46.63 [13.90, 79.36]

12.3 Any/mixed group

1

2399

Mean Difference (IV, Random, 95% CI)

68.0 [22.38, 113.62]
Figures and Tables -
Comparison 6. Risk subgroups
Navigate to table in Review
Comparison 7. Omega‐3 doses: direct comparisons

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Early preterm birth < 34 weeks Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.13, 6.38]

2 Prolonged gestation > 42 weeks Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.06, 14.44]

3 Pre‐eclampsia Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.06, 14.44]

4 Induction (post‐term) Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.01, 1.87]

5 PROM Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.03, 2.89]

6 PPROM Show forest plot

1

224

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.28, 5.32]

7 Length of gestation Show forest plot

2

1474

Mean Difference (IV, Fixed, 95% CI)

0.24 [‐1.16, 1.64]

8 Birthweight (g) Show forest plot

1

224

Mean Difference (IV, Fixed, 95% CI)

‐110.35 [‐242.80, 22.10]

9 Length at birth (cm) Show forest plot

1

224

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.80, 0.90]

10 Head circumference at birth (cm) Show forest plot

1

224

Mean Difference (IV, Fixed, 95% CI)

‐0.24 [‐0.87, 0.39]
Figures and Tables -
Comparison 7. Omega‐3 doses: direct comparisons
Navigate to table in Review
Comparison 8. Omega‐3 type: direct comparisons

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Gestational diabetes Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 DHA versus EPA

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.02, 1.14]

1.2 DHA versus DHA/AA

1

86

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.96]

2 Caesarean section Show forest plot

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.61, 2.51]

2.1 DHA versus EPA

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.61, 2.51]

3 Adverse events: cessation Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 DHA versus EPA

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.24, 2.83]

4 Pre‐eclampsia Show forest plot

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.06, 1.13]

4.1 DHA versus EPA

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.06, 1.13]

5 Blood loss at birth (mL) Show forest plot

1

77

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐181.94, 183.94]

5.1 DHA versus EPA

1

77

Mean Difference (IV, Fixed, 95% CI)

1.0 [‐181.94, 183.94]

6 Depressive symptoms postpartum: thresholds Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Major depressive disorder at 6‐8 weeks

1

77

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.12, 3.87]

7 Depressive symptoms postpartum: scores Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 BDI: 6‐8 weeks postpartum

1

77

Mean Difference (IV, Fixed, 95% CI)

‐1.40 [‐3.75, 0.95]

8 Length of gestation (days) Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 DHA versus EPA

1

77

Mean Difference (IV, Fixed, 95% CI)

9.10 [5.24, 12.96]

8.2 EPA/DHA vs ALA

1

1250

Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐2.33, 1.75]

8.3 DHA versus DHA/AA

1

83

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐3.31, 3.31]

9 Baby admitted to neonatal care Show forest plot

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.08, 1.63]

9.1 DHA versus EPA

1

78

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.08, 1.63]

10 Birthweight (g) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

10.1 DHA versus EPA

1

78

Mean Difference (IV, Fixed, 95% CI)

372.0 [151.90, 592.10]

10.2 DHA versus DHA/AA

1

83

Mean Difference (IV, Fixed, 95% CI)

‐79.0 [‐260.22, 102.22]

11 Infant weight (kg) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 DHA versus DHA/AA

1

80

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.79, 0.39]

12 Infant height (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

12.1 DHA versus DHA/AA

1

80

Mean Difference (IV, Fixed, 95% CI)

‐0.80 [‐2.50, 0.90]

13 Infant head circumference (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

13.1 At 18 months

1

80

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.45, 0.65]

14 Cognition: Scores Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

14.1 DHA versus DHA/AA: BSID II

1

80

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐4.71, 6.51]

15 Motor: Scores Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

15.1 DHA versus DHA/AA: BSID II

1

79

Mean Difference (IV, Fixed, 95% CI)

3.40 [‐1.07, 7.87]

16 Neurodevelopment Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

16.1 DHA versus DHA/AA: neonatal neurological classification: mildly/definitely abnormal at 2 weeks

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.28, 1.87]

16.2 DHA versus DHA/AA: general movement quality: mildly/definitely abnormal at 2 weeks

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.68, 1.72]

16.3 DHA versus DHA/AA: general movement quality: mildly/definitely abnormal at 12 weeks

1

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.11, 2.95]

17 Cerebral palsy Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

17.1 DHA versus DHA/AA

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figures and Tables -
Comparison 8. Omega‐3 type: direct comparisons
Navigate to table in Review
Comparison 9. Sensitivity analysis: omega‐3 versus no omega‐3

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Preterm birth (< 37 weeks) Show forest plot

12

6718

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.83, 1.02]

2 Early preterm birth (< 34 weeks) Show forest plot

6

4073

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.46, 0.82]

3 Prolonged gestation (> 42 weeks) Show forest plot

3

4285

Risk Ratio (M‐H, Fixed, 95% CI)

2.32 [1.26, 4.28]

4 Pre‐eclampsia (hypertension with proteinuria) Show forest plot

12

6104

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.81, 1.25]

5 Caesarean section Show forest plot

12

5239

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.89, 1.04]

6 Length of gestation (days) Show forest plot

16

6313

Mean Difference (IV, Fixed, 95% CI)

1.42 [0.73, 2.11]

7 Perinatal death Show forest plot

5

4610

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.37, 0.97]

8 Stillbirth Show forest plot

10

6193

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.49, 1.31]

9 Neonatal death Show forest plot

6

4791

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.25, 1.27]

10 Low birthweight (< 2500 g) Show forest plot

10

6839

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.73, 1.04]

11 Small‐for‐gestational age/IUGR Show forest plot

6

5874

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.91, 1.16]

12 Birthweight (g) Show forest plot

18

7382

Mean Difference (IV, Fixed, 95% CI)

48.84 [22.93, 74.76]
Figures and Tables -
Comparison 9. Sensitivity analysis: omega‐3 versus no omega‐3
Navigate to table in Review