Maternal interleukin 6 in pregnancy is associated with everyday, but not test-based executive functioning in 10-year-old children

Background Elevated maternal interleukin 6 (IL-6) during pregnancy has been associated with adverse fetal brain development and neurodevelopmental disorders, which often involve executive functioning (EF) impairments. However, the association between maternal IL-6 levels during pregnancy and EF remains largely unexplored. Methods The COPSYCH study is based on the prospective COPSAC2010 birth cohort of 700 mother-child pairs, recruited during pregnancy. The children's executive functioning was assessed at age 10 using: (i) the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) parental questionnaire, and (ii) a comprehensive neuropsychological test battery. Maternal blood levels of IL-6 and hs-CRP were measured at gestational week 24. Associations between IL-6 (main analysis) and hs-CRP (secondary analysis) and EF in children at age 10 were investigated with regression models with extensive confounder adjustment. Results Six hundred and four children (86% of the cohort) completed the 10-year follow-up. Higher maternal IL-6 levels were significantly associated with less efficient parental-rated executive functioning in the children: BRIEF-2 Global Executive Composite score (p = 0.003), Behavior Regulation Index (p = 0.005), Emotion Regulation Index (p=0.04), and Cognitive Regulation Index (p=0.007). Interaction analysis with sex was significant (p-value=0.01) and exploratory analyses showed that IL-6 associations to BRIEF-2 were solely driven by boys. Associations between IL-6 and neuropsychological tests, as well as associations between hs-CRP and EF outcomes, were non-significant. Conclusion IL-6 during pregnancy was associated with less efficient everyday EF in children at age 10. If replicated, preventive strategies targeting inflammation in pregnancy may ameliorate adverse cognitive outcomes in offspring.