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

• Published in: The Journal of nutrition 2018-03, Vol.148 (3), p.409-418
• Main Authors: Shulkin, Masha, Pimpin, Laura, Bellinger, David, Kranz, Sarah, Fawzi, Wafaie, Duggan, Christopher, Mozaffarian, Dariush
• Format: Article
• Language: English
• Subjects: Acuity; Adolescent; Adult; Age; Bayley Scales of Infant Development; Child; Child development; Child Development - drug effects; Childhood; Children; cognition; Cognition & reasoning; Cognition - drug effects; Cognitive ability; development; Dietary Supplements; Epidemiology; Evidence-based medicine; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Female; Gestational Age; Heterogeneity; Humans; Infant; infant formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infants; Intelligence; long-chain n–3 polyunsaturated fatty acids; Male; Maternal Nutritional Physiological Phenomena; Meta-analysis; Mothers; Nutrition; Nutritional Epidemiology; Polyunsaturated fatty acids; Premature babies; prenatal; Psychomotor Performance - drug effects; Regression analysis; Seafood; Statistical analysis; Subgroups; supplementation trials; Supplements; Systematic review; Visual acuity; Visual Acuity - drug effects; Visual effects; Young Adult
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxx031

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