Background: Prenatal exposure to environmental adversities, including maternal overweight/obesity, diabetes/hypertensive or mood/anxiety disorders, increases the risk for adverse neurodevelopmental outcomes in children. However, the underlying biological mechanisms remain elusive. We tested whether maternal antenatal inflammation associated with the number of neurodevelopmental delay areas in children and mediated the association between exposure to any prenatal environmental adversity and child neurodevelopmental delay. Methods: Mother-child dyads (N=418) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up to 10.8 years. We analyzed maternal plasma high-sensitivity C-reactive-protein (hsCRP) and glycoprotein acetyls at three consecutive antenatal time points, extracted data on maternal body mass index in early pregnancy, and diabetes/hypertensive disorders in pregnancy from medical records, and mood/anxiety disorders until childbirth from the Care Register for Health Care (HILMO). To estimate the number of neurodevelopmental delay areas in children across cognitive, motor and social functioning, we pooled data from HILMO on psychological development disorders with mother-reported Ages and Stages Questionnaire data on developmental milestones.Results: Higher levels of maternal hsCRP and glycoprotein acetyls at and across all three antenatal time points were associated with 1.30 to 2.36-fold (p-values<0.02) increased relative risk for higher number of areas of child neurodevelopmental delay. Higher maternal inflammation across the three time points also mediated the effect of any prenatal environmental adversity on child neurodevelopmental delay.
Conclusions:Higher levels of maternal inflammation, especially when persisting throughout pregnancy, increase child's risk of neurodevelopmental delay and mediate the effect of prenatal environmental adversity on child neurodevelopmental delay.