Fish Oil-Derived Fatty Acids in Pregnancy and Brain Metabolism in Middle Childhood: Results From a Randomized Controlled Trial

Maternal blood levels of polyunsaturated fatty acids (PUFA) during pregnancy have been associated with brain health outcomes in offspring, but causal effects of PUFA on brain metabolism is unexplored. We examined the effect of maternal PUFA supplementation on brain metabolism in children at age 10, measured as cerebral blood flow (CBF), oxygen consumption (CMRO₂), and brain lactate concentration. We used data from the COPSAC2010 cohort (n = 700), where pregnant women were randomized to PUFA supplementation or placebo. At age 10, the children underwent psychopathological and cognitive assessments as well as MRI scans to obtain CBF, CMRO₂, and brain lactate. We estimated the effect of maternal PUFA intake on brain metabolism and examined the associations between those metabolic measurements with psychopathological symptoms and cognitive outcomes in the offspring. Lastly, we investigated the association of age with brain metabolic outcomes by comparing with data from adult participants from five previous studies. 487 children (51.7% male, 10.3 ± 0.32 years old) underwent 3 Tesla MRI scan. Children whose mothers received PUFA supplementation exhibited significantly lower CBF and CMRO₂; however, these parameters were not associated with psychopathology or cognition. The age-related analysis, with additional data of 248 adults, showed that higher age was associated with lower CBF, CMRO₂, and lactate concentration. Our findings suggest that maternal PUFA supplementation influences brain maturation in the offspring at age 10, although PUFA supplementation does not directly translate into psychopathological status and cognitive performance. Our results highlight the need for further large-scale studies on maternal nutrition and brain development.