Keim SA, et al. - This study was undertaken to determine if 6 months of daily docosahexaenoic acid (DHA) supplementation improves developmental outcomes in a randomized clinical trial of 377 US children aged 1 year who were born preterm. Daily supplementation of 200 mg DHA and 200 mg arachidonic acid (AA) for 6 months resulted in no improvement in the cognitive development and early measurements of executive function vs placebo. They observed small to medium negative effects for language ability among children of lower birth weight and for effortful control for children from all but the very lowest income strata. For children who were born preterm, these findings did not support DHA supplementation in the second year of life.

Methods

• It was a randomized, fully masked, placebo-controlled trial.
• This trial was conducted from April 26, 2012, to March 24, 2017 at a large US pediatric academic center with 9 neonatal intensive care units.
• Children born under 35 weeks of gestation, aged 10 to 16 months, underwent 6 months of intervention.
• Out of 2363 children evaluated, 982 were eligible, 605 declined, and 377 enrolled and were randomized.
• Analyses were according to intent to treat.
• Intervention included one-to-one allocation to receive daily microencapsulated DHA, 200 mg, and AA, 200 mg (DHA+AA), or microencapsulated corn oil (placebo).
• The primary outcome specified a priori was Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive composite score at 16 to 22 months corrected age.
• Bayley-III language and motor composite scores and Infant Behavior Questionnaire–Revised and Early Childhood Behavior Questionnaire effortful control and activity level scores were included secondary outcomes.
• By income, sex, and birth weight, subgroup analyses defined a priori.

Results

• Of the 377 children randomized and included (182 girls and 195 boys; median corrected age, 15.7 months), 338 children (89.7%) had complete primary outcome data.
• Between the DHA+AA and placebo groups (difference in change, 0.5 [95% CI, –1.8 to 2.8]; effect size, 0.05; P=.66), Bayley-III cognitive scores did not vary.
• Among children with lower birth weights (eg, a child with a birth weight of 1000 g assigned to receive DHA+AA experienced a 4.1-point relative decrease, while a child assigned to placebo did not; P=.03 for interaction), assignment to the DHA+AA group had a small to medium negative effect on Bayley-III language scores.
• Similarly, supplementation had a negative impact on effortful control scores among children with annual household incomes greater than $35,000 (difference in change, –0.3 [95% CI, –0.4 to –0.1]; effect size, –0.37; P=.01).
• It was noted that Bayley-III motor scores and activity level scores were not affected.