Middleton · The Cochrane database of systematic reviews 2018 · Systematic review and meta-analysis of RCTs · n=70 studies (19,927 participants)

Omega-3 fatty acid addition during pregnancy.

Cited 446 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 30480773 · doi:10.1002/14651858.CD003402.pub3 · record verified 2026-08-30

What was done

This Cochrane systematic review assessed 70 randomized controlled trials (RCTs) involving 19,927 women comparing omega-3 long-chain polyunsaturated fatty acid (LCPUFA) interventions (supplements or dietary additions) to placebo or no omega-3 during pregnancy. Two review authors independently selected trials, extracted data, assessed risk of bias, and evaluated the certainty of evidence for maternal, perinatal, neonatal, and child outcomes using the GRADE approach.

What was found

Omega-3 LCPUFA supplementation reduced preterm birth < 37 weeks (11.9% vs. 13.4%; RR 0.89, 95% CI 0.81 to 0.97; 26 RCTs, n = 10,304; high-quality evidence), early preterm birth < 34 weeks (2.7% vs. 4.6%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, n = 5,204; high-quality evidence), and low birthweight babies (14.0% vs. 15.6%; RR 0.90, 95% CI 0.82 to 0.99; 15 RCTs, n = 8,449; high-quality evidence). Prolonged gestation > 42 weeks increased with omega-3 supplementation (2.6% vs. 1.6%; RR 1.61, 95% CI 1.11 to 2.33; 6 RCTs, n = 5,141; moderate-quality evidence), and mean gestational length increased (mean difference 1.67 days, 95% CI 0.95 to 2.39; 41 RCTs, n = 12,517; moderate-quality evidence). Non-significant reductions were observed for perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, n = 7,416; moderate-quality) and neonatal care admission (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, n = 6,920; moderate-quality). No clear effects were identified for small-for-gestational age (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, n = 6,907; moderate-quality), pre-eclampsia (RR 0.84, 95% CI 0.69 to 1.01; 20 RCTs, n = 8,306; low-quality), postnatal depression (RR 0.99, 95% CI 0.56 to 1.77; 2 RCTs, n = 2,431; low-quality), or child neurodevelopment and growth outcomes.

Why it matters

Omega-3 LCPUFA supplementation in pregnancy is an effective intervention to lower the incidence of preterm and early preterm birth and reduce low birthweight, though it moderately increases the likelihood of post-term pregnancy.

Limits

Most trials were conducted in upper-middle or high-income countries, limiting generalizability to low-income settings. There was a high risk of attrition bias in some included trials. Data regarding maternal adverse events, postnatal depression, and long-term child cognitive, visual, and metabolic outcomes were under-reported, imprecise, and of low to very low quality.

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