High dose arachidonic and docosahexaenoic acid in very preterm infants and neurodevelopment at 2 years - A double-blind randomized controlled trial

BACKGROUND AND AIMS: The fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) accumulate in neural tissue in the last trimester, thus preterm infants have lower levels compared to their term-born peers. Our aim was to evaluate the impact of ARA and DHA supplementation in very preterm infants on neurodevelopmental outcomes at two years corrected age (CA). We also wanted to study the effect of in-hospital growth, socioeconomic factors and other possible covariates on neurodevelopmental outcomes for the entire study population. METHODS: This is a follow-up study of the ImNuT-trial (NCT03555019); a randomized controlled trial (RCT), where 120 infants born before 29 weeks of gestational age (GA) were randomized to receive an enteral supplement of both ARA and DHA (ARA:DHA group) or medium chain triglycerides (control group). The infants received supplementation from the second day of life until 36 weeks postmenstrual age (PMA). At two years CA, the children underwent neurodevelopmental assessment using Bayley Scales of Infant and Toddler Development, third edition (BSID-III) and Peabody Developmental Motor Scales second edition (PDMS-2). RESULTS: Mean (SD) GA at birth was 26.4 (1.7) weeks. The mean (SD) corrected age at follow-up was 24 months + 7 days (17 days). There were no significant differences in neurodevelopmental outcomes between the treatment groups. The multivariable regression model showed a positive association between female sex and motor scores as well as maternal education level and language scores. Faster linear growth from day 28-36 weeks PMA was associated with higher cognitive scores. Non-Scandinavian family language was negatively associated with all three BSID-scores. CONCLUSION: Supplementation with ARA and DHA in very preterm children did not result in significant differences in neurodevelopmental outcomes assessed with BSID-III and PDMS-2 at 2 years corrected age. Higher maternal education level, female sex, faster linear growth during hospitalization and Scandinavian family language were predictive of neurodevelopmental outcome. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT03555019.