1. Omega-3 fatty acid supplements during pregnancy

2. Omega-3 fatty acids and pregnancy outcome
70 trials with 19,927 women. Each trial 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 the review. Most of the trials compared oral DHA and/or EPA (or mainly DHA/EPA) supplements with placebo or no omega-3 treatment.

3. Omega-3 fatty acids and pregnancy outcome
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; …with omega-3 LCPUFA

4. Omega-3 fatty acids and pregnancy outcome
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% CI ; 26 trials, 10,304 participants; high-quality evidence.

5. Omega-3 fatty acids and pregnancy outcome

6. Omega-3 fatty acids and pregnancy outcome

7. Omega-3 fatty acids and pregnancy outcome
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 ; 9 trials, 5204 participants; high-quality evidence.

8. Omega-3 fatty acids and pregnancy outcome
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.

9. Omega-3 fatty acids and pregnancy outcome
No differences were found in many secondary outcomes, e.g. maternal mortality; neonatal mortality; rate of eclampsia, pre-eclampsia or C-section; miscarriage; maternal blood loss; child neurodevelopment outcomes.

10. Omega-3 fatty acids and pregnancy outcome
“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…”

11. Omega-3 fatty acids and pregnancy outcome
What supplements were used?
DHA/largely DHA: 27 trials
Mixed EPA + DHA: 25 trials
Mixed DHA + EPA + other: 18 trials
Food (fish): 2 trials (about 300 patients)

12. Omega-3 fatty acids and pregnancy outcome
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.

13. Critically appraise the evidence
Is it unlikely that important, relevant studies were missed?
Thorough literature search was done (standard Cochrane search strategy).

14. Critically appraise the evidence
Were the included studies sufficiently valid for the type of question asked?
“We assessed most of the important perinatal outcomes as high-quality (e.g. preterm birth) or moderate-quality evidence (e.g. perinatal death).”

15. Critically appraise the evidence
Were the included studies sufficiently valid for the type of question asked?
“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 W.H.O. However, commercial organisations-mainly pharmaceutical companies-were reported as the only or main funding sources in 11 trials”

16. Dose of omega-3 LCPUFA
Subgroup analysis based on dose for low dose (≤ 500 mg/day) versus mid dose (500 mg to 1 g/day) versus high dose (>1g/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.

17. Applicability
The review found the optimum dose was a daily supplement containing between 500 and 1000 milligrams (mg) of long-chain omega-3 fats (containing at least 500mg of DHA) starting at 12 weeks of pregnancy

18. Applicability
The review found the optimum dose was a daily supplement containing between 500 and 1000 milligrams (mg) of long-chain omega-3 fats (containing at least 500mg of DHA) starting at 12 weeks of pregnancy

19. Safety
An independent lab contracted by Consumer Reports in 2012 tested three lots of each of 15 brands, bought in New York-area stores. All had their labeled amount of EPA and DHA. None exceeded limits for lead, mercury, dioxins, or polychlorinated biphenyls (PCBs) set by the U.S. Pharmacopeia (USP) or by the European Union.

20. Omega-3 fatty acids and pregnancy outcome
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.

21. Applicability