Associations between maternal cytokine levels during gestation and measures of child cognitive abilities and executive functioning

Abstract

Preclinical studies demonstrate that environmentally-induced alterations in inflammatory cytokines generated by the maternal and fetal immune system can significantly impact fetal brain development. Yet, the relationship between maternal cytokines during gestation and later cognitive ability and executive function remains understudied. Children (n = 246) were born of mothers enrolled in the Newborn Epigenetic Study - a prospective pre-birth cohort in the Southeastern US. We characterized seven cytokines [IL-1β, IL-4,IL-6, IL-12p70, IL-17A, tumor necrosis factor-α (TNFα), and interferon-γ (IFNγ)] and one chemokine (IL-8) from maternal plasma collected during pregnancy. We assessed children's cognitive abilities and executive functioning at a mean age of 4.5 (SD = 1.1) years. Children's DAS-II and NIH toolbox scores were regressed on cytokines and the chemokine, controlling for maternal age, race, education, body mass index, IQ, parity, smoking status, delivery type, gestational weeks, and child birth weight and sex. Higher IL-12p70 (β_IL-12p70 = 4.26, p = 0.023) and IL-17A (β_IL-17A = 3.70, p = 0.042) levels were related to higher DAS-II GCA score, whereas higher IL-1β (β_IL-1B = -6.07, p = 0.003) was related to lower GCA score. Higher IL-12p70 was related to higher performance on NIH toolbox measures of executive functions related to inhibitory control and attention (β_IL-12p70 = 5.20, p = 0.046) and cognitive flexibility (β_IL-12p70 = 5.10, p = 0.047). Results suggest that dysregulation in gestational immune activity are associated with child cognitive ability and executive functioning.

Keywords: Chemokine; Cognitive abilities; Executive function; NIH toolbox; Proinflammatory cytokines.