Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial

Follow-up of a randomized controlled trial in very preterm infants born before 33 weeks' gestation at five Australian tertiary hospitals. Baseline arm sizes were high-DHA n=291 and standard-DHA n=313; 657 infants were randomized overall, 626 were eligible for 7-year follow-up, 604 families consented, and the primary outcome was analyzed in 286 high-DHA and 296 standard-DHA children. Children were assessed at a mean of 7.2 years' corrected age.

The high-DHA arm received enteral DHA from the first week of life until 40 weeks' corrected age, with infant feeds providing about 50 mg/kg/day of DHA and preterm formula containing approximately 1.0% DHA and 0.6% AA. Lactating mothers in the high-DHA arm took DHA-rich tuna oil capsules daily to target a breast milk DHA concentration of about 1% of total fatty acids; the standard-DHA arm received about 20 mg/kg/day of DHA, standard preterm formula containing approximately 0.35% DHA, and placebo soy oil capsules.

High-DHA feeding did not improve IQ or other neurodevelopmental outcomes at 7 years' corrected age compared with standard-DHA feeding. For the primary outcome, Full Scale IQ was 98.3 (14.0) in the high-DHA group and 98.5 (14.9) in the standard-DHA group, with an adjusted treatment effect of -0.3 (95% CI -2.9 to 2.2; p=0.79). There were no significant differences in verbal IQ, performance IQ, attention, memory, executive function, behavior, visual perception, educational progress, or quality of life. Parent-reported ADHD, autism spectrum disorder, and cerebral palsy outcomes also did not differ significantly between groups.

Follow-up was incomplete relative to the original randomized cohort, with attrition from 657 randomized to 604 consenting and fewer children analyzed for the primary outcome. The trial was conducted in Australian tertiary centers, which may limit generalizability, and some sex-specific behavioral signals were reported but may reflect chance. The absence of benefit was based on a single long-term follow-up after early-life supplementation, so smaller effects or effects in subgroups could have been missed.