We aimed to perform an umbrella review of systematic reviews and meta-analyses (SRMAs) of randomized clinical trials (RCT) of the effects of long-chain omega-3 fatty acid supplementation in pregnancy, lactation, and infancy. We searched PubMed, Scopus, and Web of Science to November 2020. Two independent investigators extracted the information, evaluated the methodological quality of SRMAs using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR2), and rated the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Either a fixed-effects or a random-effects model was used to recalculate the effect sizes and 95%CIs, depending on the number of trials. Overall, 28 SRMAs of RCTs, reporting 124 outcomes from 672 RCTs with 273,523 participants were considered eligible for the present umbrella review. Our results demonstrated evidence of moderate to high certainty that omega-3 supplementation reduced the risk of pre-eclampsia and low-birth weight and improved head circumference when used in pregnant women, and reduced severe retinopathy of prematurity and cholestasis when used in infancy. There were also favorable effects on preterm delivery, pre-natal and post-partum depression, glycemic control and inflammation markers in pregnant women, and sensitization to peanuts, positive skin prick tests, anthropometric measures, language development, visual acuity, and duration of ventilation in infants (GRADE = low). Our findings suggested that omega-3 supplementation during pregnancy can exert favorable effects against pre-eclampsia, low-birth weight, pre-term delivery, and post-partum depression, and can improve anthropometric measures, immune system, and visual activity in infants and cardiometabolic risk factors in pregnant mothers.
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