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

Background: Epidemiologic studies link maternal seafood and n-3 (ω-3) polyunsaturated fatty acid (PUFA) consumption with improved childhood cognitive development; trials show mixed results.

Objective: We investigated effects of n-3 PUFA supplementation on child cognitive and visual outcomes.

Methods: 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.

Results: 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).

Conclusions: 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.

FIGURE 1

Effects of n–3 PUFA supplementation on Bayley Scales of Infant Development mental developmental index (weighted mean difference) in randomized controlled trials. These analyses included 32 intervention arms from 21 trials, with an overall pooled result across all supplementation periods of 0.91 (95%CI: 0.00, 1.81; I² = 27.0%). Significant differences were seen by intervention period, with stronger effects for supplementation in preterm infants, compared with maternal supplementation (P-interaction = 0.018). Findings were pooled using random-effects meta-analysis. Shaded squares represent the weight of each study, and dotted vertical lines and diamonds represent the pooled central estimate and its 95% CI, respectively, for each group. AA, arachidonic acid.

FIGURE 2

Effects of n–3 PUFA supplementation on Bayley Scales of Infant Development psychomotor developmental index (weighted mean difference) in randomized controlled trials. These analyses included 32 intervention arms from 21 trials, with an overall pooled result across all supplementation periods of 1.06 (95%CI: 0.10, 2.03; I² = 42.3%). Observed potential differences by intervention period did not achieve statistical significance (P-interaction > 0.05). Findings were pooled using random-effects meta-analysis. Shaded squares represent the weight of each study, and dotted vertical lines and diamonds represent the pooled central estimate and its 95% CI, respectively, for each group. AA, arachidonic acid.

FIGURE 3

Effects of n–3 PUFA supplementation on intelligence quotient (weighted mean difference) in randomized controlled trials. These analyses included 9 intervention arms from 7 trials, with an overall pooled result across all supplementation periods of 0.20 (95%CI: –1.56, 1.96; I² = 0.0%). No statistically significant differences were identified by intervention period (P-interaction > 0.05 each). Subgroup meta-analysis was not performed for preterm infants given that only one trial was identified, shown here. Other findings were pooled using random-effects meta-analysis. Shaded squares represent the weight of each study, and dotted vertical lines and diamonds represent the pooled central estimate and its 95% CI, respectively, for each group. AA, arachidonic acid; K-ABC, Kaufman Assessment Battery for Children; WASI, Wechsler Abbreviated Scale of Intelligence; WISC, Wechsler Intelligence Scale for Children; WPPSI, Wechsler Preschool and Primary Scale of Intelligence.

FIGURE 4

Effects of n–3 PUFA supplementation on visual acuity (weighted mean difference) in randomized controlled trials. These analyses included 35 intervention arms from 24 trials, with an overall pooled result across all supplementation periods of –0.06 (95%CI: –0.08, –0.04; I² = 81.6%). Stronger effects were identified for supplementation in term infants, compared with maternal supplementation (P-interaction = 0.022), but were not significantly higher in preterm infants (P-interaction = 0.115). Findings were pooled using random-effects meta-analysis. AA, arachidonic acid; HOTV, distance visual acuity testing using HOTV optotypes chart; TAC, Teller Acuity Card; VEP, Visual Evoked Potential.