Meta-Analysis of Maternal DHA Supplementation During Pregnancy on Neurodevelopmental Outcomes in Preterm Infants

Background Docosahexaenoic acid (DHA), an essential n-3 polyunsaturated fatty acid, plays a critical role in fetal brain development. Preterm infants are at risk of DHA deficiency due to interrupted intrauterine accumulation, which may impair neurodevelopment. However, the effects of maternal DHA supplementation during pregnancy on neurodevelopmental outcomes in preterm infants remain controversial. This meta-analysis aimed to systematically evaluate the efficacy of maternal DHA supplementation in improving neurodevelopmental outcomes in preterm infants. Methods PubMed, Embase, Cochrane Library, Web of Science, and CINAHL databases were searched from inception to October 2025 for randomized controlled trials (RCTs) comparing maternal DHA supplementation during pregnancy with placebo or standard care on neurodevelopmental outcomes in preterm infants (gestational age < 37 weeks). Two reviewers independently performed literature screening, data extraction, and risk of bias assessment using the Cochrane Collaboration’s tool. Meta-analysis was conducted with RevMan5.4 software. Primary outcomes included cognitive development, motor development, and language development assessed by standardized scales with Bayley Scales of Infant and Toddler Development( BSID). Secondary outcomes included the incidence of neurodevelopmental disorders and adverse events. Results A total of 10 RCTs involving 4,048 participants (2,034 in the DHA group and 2,014 in the control group) were included. Maternal DHA supplementation during pregnancy significantly improved cognitive development scores in preterm infants at 12–24 months of corrected age (mean difference [MD] = 3.36, 95% confidence interval [CI]: 2.88–3.84, P < 0.00001, I² = 0%), motor development scores (MD = 2.96, 95% CI: 2.49–3.43, P < 0.00001, I² = 0%). and language development scores (MD = 2.85, 95% CI: 2.32–3.38, P < 0.00001, I² = 0%) ; No significant difference was observed in the incidence of neurodevelopmental disorders (relative risk [RR] = 0.81, 95% CI: 0.56–1.17, P = 0.26, I² = 0%) and adverse events (RR = 0.94, 95% CI: 0.72–1.23,P = 0.67, I² = 0% ). Subgroup analysis showed that supplementation with DHA ≥ 800 mg/day and initiation before 20 weeks of gestation yielded more pronounced benefits on cognitive and motor development. Conclusion Maternal DHA supplementation during pregnancy may improve cognitive and motor development in preterm infants, especially with higher doses (≥ 800 mg/day) and early initiation. However, evidence for effects on language development and neurodevelopmental disorders remains insufficient. Further large-scale, long-term RCTs are needed to confirm these findings and optimize supplementation strategies.