Abstract
BACKGROUND: Maternal immune activation, including inflammation and oxidative stress during pregnancy, has been linked to child neurodevelopmental problems (NDP) and emotional and behavioral problems (EBP). Polyunsaturated fatty acids (PUFAs) and their oxidized metabolites (oxylipins) are important bioactive lipids that modulate immune responses, inflammation, and oxidative stress. However, their roles in child NDP and EBP remain unclear. METHODS: This study included 259 mother-child pairs from the PROTECT birth cohort in Puerto Rico. Maternal plasma samples collected around 26 weeks' gestation were analyzed for bioactive lipid levels using high-performance liquid chromatography-tandem mass spectrometry. Child NDP and EBP were assessed at ages 1-3 using the Battelle Developmental Index, 2nd edition (BDI-2) and the Child Behavioral Checklist for ages 1.5-5 (CBCL/1.5-5). We evaluated associations between maternal bioactive lipid levels and child NDP or EBP outcomes and conducted sex-stratified analyses to examine effect modification by child sex. As a sensitivity analysis, we restricted analyses to term births to evaluate the associations independent of potential effects of preterm birth. RESULTS: Altered maternal bioactive lipid concentrations were associated with poorer neurodevelopmental and emotional/behavioral outcomes in children aged 1-3 years. The associations were modified by child sex and preterm birth status. CONCLUSION: These findings underscore the need for further research into bioactive-lipid-related maternal mechanisms that may influence early childhood neurodevelopment and behavior. IMPACT: Previous studies suggest potential roles of maternal PUFAs and oxylipins during pregnancy on child NDP and EBP, as these bioactive lipids play crucial roles in immune response, inflammation, and oxidative stress. In this cohort study, we found several associations between maternal bioactive lipid levels during pregnancy and child neurodevelopment and behavior from 1 to 3 years of age. The associations were attenuated after excluding preterm children, suggesting a potential mediating role of preterm birth. Additionally, distinct patterns emerged based on both the inflammatory properties of the bioactive lipids and child sex.