Neuroanatomical Correlates Underlying the Association Between Maternal Interleukin 6 Concentration During Pregnancy and Offspring Fluid Reasoning Performance in Early Childhood

Abstract

Background: Maternal inflammation during pregnancy can alter offspring brain development and influence risk for disorders commonly accompanied by deficits in cognitive functioning. We therefore examined associations between maternal interleukin 6 (IL-6) concentrations during pregnancy and offspring cognitive ability and concurrent magnetic resonance imaging-based measures of brain anatomy in early childhood. We further examined newborn brain anatomy in secondary analyses to consider whether effects are evident soon after birth and to increase capacity to differentiate effects of pre- versus postnatal exposures.

Methods: IL-6 concentrations were quantified in early (12.6 ± 2.8 weeks), mid (20.4 ± 1.5 weeks), and late (30.3 ± 1.3 weeks) pregnancy. Offspring nonverbal fluid intelligence (Gf) was assessed at 5.2 ± 0.6 years using a spatial reasoning task (Wechsler Preschool and Primary Scale of Intelligence-Matrix) (n = 49). T1-weighted magnetic resonance imaging scans were acquired at birth (n = 89, postmenstrual age = 42.9 ± 2.0 weeks) and in early childhood (n = 42, scan age = 5.1 ± 1.0 years). Regional cortical volumes were examined for a joint association between maternal IL-6 and offspring Gf performance.

Results: Average maternal IL-6 concentration during pregnancy was inversely associated with offspring Gf performance after adjusting for socioeconomic status and the quality of the caregiving and learning environment (R² = 13%; p = .02). Early-childhood pars triangularis volume was jointly associated with maternal IL-6 and childhood Gf (p_corrected < .001). An association also was observed between maternal IL-6 and newborn pars triangularis volume (R² = 6%; p = .02).

Conclusions: These findings suggest that the origins of variation in child cognitive ability can, in part, trace back to maternal conditions during the intrauterine period of life and support the role of inflammation as an important component of this putative biological pathway.

Keywords: Fluid intelligence; Fluid reasoning; Inferior frontal gyrus; Inflammation; Interleukin 6; Longitudinal MRI; Newborn; Pars triangularis.

Figure 1.. Maternal IL-6 Concentration During Pregnancy is Associated with Early Childhood Fluid Reasoning Performance (Gf).

Scatter plot of the negative association between maternal IL-6 concentration during pregnancy and offspring Gf.

Figure 2.. ROI-Based Cortical Volume Associations: Maternal IL-6 Concentration During Pregnancy and Early Childhood Fluid Reasoning Performance (Gf).

Left column depicts ROI-based gray matter volumes associated with Gf, middle column depicts ROI-based associations between maternal IL-6 concentration during pregnancy and gray matter volumes, right column depicts multiple comparisons corrected bi-lateral joint significance (maternal IL-6 and Gf performance associated with gray matter volume).

Figure 3.. Pars Triangularis (PT) Volume in Early Childhood Mediates the Association Between Maternal IL-6 Concentration During Pregnancy and Early Childhood Fluid Reasoning Performance (Gf).

Maternal IL-6 concentration during pregnancy is positively associated with early childhood PT volume and negatively associated with early childhood Gf. Early childhood PT volume is negatively associated with early childhood Gf. Early childhood PT volume mediates the association between maternal IL-6 concentration during pregnancy and early childhood Gf (p<0.05).

Figure 4.. Maternal IL-6 Concentrations During Pregnancy, Offspring Pars Triangularis Volume, and Early Childhood Fluid Reasoning Performance (Gf).

Scatter plots depicting bi-variate associations between newborn (top row) and early childhood (bottom row) pars triangularis gray matter volume, and maternal IL-6 concentration during pregnancy (left column) and Gf (right column).