Impact of prenatal omega-3 fatty acids supplementation on cognitive outcomes: A systematic review with meta-analysis

The beneficial effects of omega-3 polyunsaturated fatty acids (PUFA) supplementation during pregnancy have been associated with reduced risk of preterm birth and low birthweight. However, inconsistent findings have been reported regarding their impact on children's neurodevelopmental trajectories. We performed a comprehensive systematic review with meta-analysis of preclinical studies to assess the effects of prenatal omega-3 supplementation on long-term outcomes in offspring and to identify key relevant neurodevelopmental domains to guide the design and prioritization of future clinical follow-up studies. The databases consulted included PubMed/Medline, Scopus and Web of Science. Thirty-five studies were included in the systematic review, and 19 studies were included in the meta-analysis. Relevant information such as characteristics of nutritional interventions, maternal conditions, offspring characteristics and article attributes were extracted. Sample sizes, means, and standard deviation or standard error for the outcome measures were also extracted. The search yielded 3198 articles; 35 met inclusion criteria, with 11 included in a random-effects meta-analysis of memory retention, and 8 in a meta-analysis of brain-derived neurotrophic factor (BDNF) levels. Our findings show that maternal omega-3 PUFA supplementation during pregnancy improves memory retention (SMD=0.671; CI 95 %: 0.163-1.179; p = 0.010) and increases levels of BDNF (SMD=0.838; CI 95 %: 0.369-1.307; p = 0.000) in the offspring. These effects are more pronounced in offspring exposed to prenatal adversities. Maternal omega-3 supplementation shows promise in mitigating oxidative stress and inflammation, although findings remain heterogeneous. Maternal omega-3 supplementation appears as a safe and effective means to improve offspring neurodevelopment, with stronger effects under adverse gestational conditions, highlighting its potential for at-risk populations.