Long-term effects of LCPUFA supplementation on childhood cognitive outcomes

Abstract

Background: The effect of long-chain polyunsaturated fatty acid (LCPUFA) intake on cognitive development is controversial. Most randomized trials have assessed cognition at 18 mo, although significant development of cognitive abilities (early executive function) emerge later.

Objective: The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid (0.32%, 0.64%, and 0.96% of total fatty acids) and arachidonic acid (ARA; 0.64%) compared with children who were not fed LCPUFA as infants.

Design: Eighty-one children (19 placebo, 62 LCPUFA) who participated in a double-blind, randomized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate standardized and specific cognitive tests.

Results: LCPUFA supplementation did not influence performance on standardized tests of language and performance at 18 mo; however, significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks, the Peabody Picture Vocabulary Test at 5 y, and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory, simple inhibition, or advanced problem solving.

Conclusions: The data from this relatively small trial suggest that, although the effects of LCPUFAs may not always be evident on standardized developmental tasks at 18 mo, significant effects may emerge later on more specific or fine-grained tasks. The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood. This parent trial was registered at clinicaltrials.gov as NCT00266825.

FIGURE 1.

Participant flow in the follow-up study. The primary study (26) followed children to 18 mo. The current study reports on measures taken from 18 to 72 mo of age. ARA, arachidonic acid; CNS, central nervous system.

FIGURE 2.

Mean (±SE) scores for the BSID-2 subscales and MBCDI productive vocabulary test (adjusted for covariates) at 18 mo as a function of group assignment. Neither ANOVA nor ANCOVA showed any significant differences as a function of formula on these measures. ARA, arachidonic acid; BSID, Bayley Scales of Infant Development; MBCDI, MacArthur-Bates Communicative Development Inventory; MDI, Mental Developmental Index; PDI, Psychomotor Development Index.

FIGURE 3.

Mean (±SE) overall DCCS scores as a function of group assignment and age at assessment. Infants who received supplemented formula had accelerated developmental improvement on this task compared with the control group. Mixed-model analyses showed positive effects of diet on this task, which were most evident in the comparison of controls with the 0.32% DHA and 0.64% DHA groups at 48 and 60 mo. ARA, arachidonic acid; DCCS, Dimensional Change Card Sort.

FIGURE 4.

Mean (±SE) overall Stroop task scores as a function of group assignment, collapsed across all ages of testing and across the 2 different Stroop variants. Omnibus statistical tests were carried out with mixed-model analyses; the P values represent differences between each long-chain PUFA group and the control group. Infants who received 0.64% DHA and 0.96% DHA performed better than did the control group; the 0.32% group was intermediate between these groups and the control group. ARA, arachidonic acid.

FIGURE 5.

Mean (±SE) PPVT-III standard scores, adjusted for covariates, at age 5 y as a function of group assignment. Both one-factor ANOVA and ANCOVA analyses showed that infants who received the long-chain PUFA formula performed better on the PPVT-III. The effects were most evident in the 0.32% DHA and 0.64% DHA groups; the P values represent statistical test results against control group values; the numbers within the bars are means. ARA, arachidonic acid; PPVT-III, Peabody Picture Vocabulary Test, 3rd edition.

FIGURE 6.

Mean (±SE) WPPSI-III standard scores, adjusted for covariates, at age 6 y as a function of assignment to LCPUFA or control formula. Both ANOVA and ANCOVA analyses showed that infants who received the LCPUFA formula performed significantly better on the Verbal IQ subscale, and the differences were nearly significant for Full-Scale IQ. The numbers within the bars are means. The P values represent the results of ANCOVAs that compared values from the 3 LCPUFA groups (collapsed) with the control group; the d values represent the effect size for each comparison and were adjusted for covariates. IQ, intelligence quotient; LCPUFA, long-chain PUFA; WPPSI-III, Weschler Primary Preschool Scale of Intelligence, 3rd edition.