N–3 Fatty Acid Supplementation in Mothers, Preterm Infants, and Term Infants and Childhood Psychomotor and Visual Development: A Systematic Review and Meta-Analysis

Abstract

Epidemiologic studies link maternal seafood and n-3 (ω-3) polyunsaturated fatty acid (PUFA) consumption with improved childhood cognitive development; trials show mixed results. We investigated effects of n-3 PUFA supplementation on child cognitive and visual outcomes. We systematically reviewed and meta-analyzed randomized controlled trials of n-3 PUFA supplementation in mothers or infants (age≤2 y) and evaluated standardized measures of cognitive or visual development up to age 18 y. Of 6286 abstracts and 669 full-text articles, 38 trials with 53 intervention arms were included. Data were extracted independently in duplicate. Findings were pooled using random-effects meta-analysis across supplementation periods (maternal, preterm, term infant); we also explored subgroup analyses stratified by supplementation period. Heterogeneity was explored using I2, stratified analysis, and meta-regression. Cognitive development was assessed by Bayley Scales of Infant Development mental and psychomotor developmental indexes (MDI, PDI) and intelligence quotient (IQ); visual acuity was assessed by electrophysiological or behavioral measures. The 38 trials (mothers: n=13; preterm infants: n=7; term infants: n=18) included 5541 participants. When we explored effects during different periods of supplementation, n-3 PUFA supplementation improved MDI in preterm infants (3.33; 95% CI: 0.72, 5.93), without statistically significant effects on PDI or IQ in different intervention period subgroups. Visual acuity [measured as the logarithm of the minimum angle of resolution (logMAR)] was improved by supplementation in preterm (-0.08 logMAR; 95% CI: -0.14, -0.01 logMAR) and term infants (-0.08 logMAR; 95% CI: -0.11, -0.05 logMAR), with a nonsignificant trend for maternal supplementation (-0.02 logMAR; 95% CI: -0.04, 0.00 logMAR). In main analyses pooling all supplementation periods, compared with placebo, n-3 PUFA supplementation improved MDI (n=21 trials; 0.91; 95% CI: 0.005, 1.81; P=0.049), PDI (n=21 trials; 1.06 higher index; 95% CI: 0.10, 2.03; P=0.031), and visual acuity (n=24; -0.063 logMAR; 95% CI: -0.084, -0.041 logMAR; P<0.001) but not IQ (n=7; 0.20; 95% CI: -1.56, 1.96, P=0.83), although few studies assessed this endpoint. Potential publication bias was identified for MDI (Eggers P=0.005), but not other endpoints. Significant differences in findings were not identified by world region, race, maternal education, age at outcome assessment, supplementation duration, DHA or EPA dose, DHA:AA ratio, or study quality score (P-interaction>0.05 each). n-3 PUFA supplementation improves childhood psychomotor and visual development, without significant effects on global IQ later in childhood, although the latter conclusion is based on fewer studies.