Fish oil-derived fatty acids during pregnancy and risk of neurodevelopmental disorders in children at age 10 - A randomized controlled trial.

Fish oil-derived omega-3 fatty acids (ꙍ-3 FA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are critical for early brain development, but evidence of causal effects from supplementation during pregnancy is limited. In the prospective COPSAC2010 cohort of 700 mother-child pairs, we investigated whether i) maternal DHA + EPA blood concentrations in mid-pregnancy and ii) fish oil supplementation in a randomized trial in late pregnancy influence neurodevelopmental outcomes at age 10. Maternal blood DHA + EPA concentrations were measured at 24 weeks gestation, followed by randomization to 2.4 g daily fish oil (37% DHA, 55% EPA) or placebo until one-week postpartum. Psychopathology was assessed in the children at age 10 using the Kiddie Schedule for Affective Disorders and Schizophrenia -Present and Lifetime version and parental-rated questionnaires Statistical analyses included logistic and linear regression models. Higher maternal DHA + EPA concentrations were associated with reduced ADHD risk (OR 0.71, p = 0.03) and ADHD symptom load (β = -1.14, p < 0.001) in unadjusted analyses but not after confounder adjustment (OR 0.82, p = 0.24; β = -0.49, p = 0.21). Similar trends were observed for autistic traits (β = -1.96, [-1.11; -0.24] p = 0.01), but not significant after confounder adjustment. Fish oil supplementation showed no significant reduction in ADHD (OR 0.79, p = 0.37) or ASD risk (OR 0.56, p = 0.42). A secondary analysis suggested a protective effect for ADHD Predominantly Inattentive Presentation, although it did not hold significance after correction for multiple testing (OR 0.41; p = 0.03; FDRp=0.12). Thus, potential effects on inattentive ADHD symptoms should be explored in future studies.