Maternal high-dose docosahexaenoic acid supplementation and neurodevelopment at 5 Years of preterm children

Background & aims: Docosahexaenoic acid (DHA) is the most abundant omega-3 fatty acid in the brain and is accumulated by the fetal brain during the last trimester of pregnancy. Our objective was to determine whether high-dose DHA supplementation during the neonatal period, vs. placebo, improves behavioral functioning at 5 years in children born very preterm.

Methods: This is a follow-up at 5 years corrected age of a subset of children who participated in a multicenter randomized controlled trial. The participants received a high-dose DHA supplementation, or a placebo, through maternal breastmilk until 36 weeks' postmenstrual age. Primary outcome was child behavioral functioning, assessed by the Total Difficulties Score from the Strengths and Difficulties Questionnaire (SDQ). Secondary outcomes included behavioral scores from the SDQ, executive functions assessment and global developmental performance. Neurodevelopmental outcomes were assessed through interviews with parents. Mean differences between DHA and placebo groups were estimated using mixed linear models. Subgroup analyses were conducted for sex and gestational age (GA) at birth.

Results: Among 177 eligible children, 132 (74.6 %) completed neurodevelopmental assessment at 5 years (DHA, N = 64, placebo, N = 68). Total Difficulties Score did not differ between the DHA and placebo groups (mean differences, -0.9 [95 % confidence interval, -2.7 to 0.8], P = 0.30), nor any of the secondary outcomes. There was no significant interaction between treatment groups and sex, nor GA, for the primary outcome. However, significant interactions between treatment groups and sex or GA were found for some secondary outcomes.

Conclusions: In very preterm infants, high-dose DHA supplementation did not improve behavioral functioning at 5 years.

Clinical trial registration: ClinicalTrials.gov, NCT02371460, https://clinicaltrials.gov/study/NCT02371460.