Omega-3 polyunsaturated fatty acid supplementation during the pre and post-natal period: A meta-analysis and systematic review of randomized and semi-randomized controlled trials

•This meta-analysis evaluates the effects of n-3 PUFA supplementation on infant immunity and development.•The Comprehensive Meta-analysis Program used avoids nested multiplicity issues and use of the data without bias.•N-3 PUFA supplementation in infants does not improve visual acuity, language development, or cognition.•N-3 PUFA has targeted effects on cardiovascular and immunity differing between the breastfed and formula fed infants.•Overall, the evidence does not support the continued supplementation of infant formula with n-3 PUFA.

Background & AimsLong chain omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA) are widely considered beneficial for infant health and development. The aim of this meta-analysis was to summarize the evidence related to the clinical outcomes of long chain n-3 PUFA supplementation maternally and in fortified formula/taken directly. Additionally, we investigate if the addition of arachidonic acid (AA) alters the effects caused by n-3 PUFA supplements.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (1974 to June 2015) CINAHL (1990 to June 2015), PubMed (1966–2015), Web of Science (1864–2015), MEDLINE (1974 to June 2015), and hand searches for randomized and semi-randomized controlled trials on term infants evaluating the effects of long chain n-3 PUFA supplementation taken maternally and in milk based formula or directly.ResultsWe identified 39 formula and 39 breastmilk studies on the clinical outcomes of long chain n-3 PUFA supplementation, with or without AA, on infant immunity and development. Of these studies, 32 formula and 37 breastmilk studies were deemed appropriate resulting in a total of 2443 formula fed infants and 4553 breastfed infants exposed to n-3 PUFA supplementation. This meta-analysis shows that n-3 PUFA supplementation in infants delivered either maternally or in formula/directly, does not improve visual acuity, language development, or cognition. However, some aspects of growth, motor development, behavior and cardiovascular health are differentially altered in the summary effects of certain studies with the more desired effect occurring often in breastfed infants compared to formula fed infants. Moreover, this meta-analysis shows that n-3 PUFA supplements affects infant immune development and reduces pro-inflammatory responses in the supplemented breastfed and fortified formula fed/directly supplemented infants.ConclusionOverall, the evidence does not support the continued supplementation of infant formula with long chain n-3 PUFA considering the negative impact on the developing immune responses.