MATERNAL INTERLEUKIN-6 CONCENTRATION DURING PREGNANCY IS ASSOCIATED WITH VARIATION IN FRONTOLIMBIC WHITE MATTER AND COGNITIVE DEVELOPMENT IN EARLY LIFE

All Authors:
Jerod M. Rasmussen, UC Irvine, Irvine, CA, United States (Primary Presenter)
Alice Graham, Oregon Health and Science University, Portland, United States
Sonja Entringer, University of California, Irvine, Orange, CA
John H Gilmore, University of North Carolina, Chapel Hill, United States
Martin Styner, University of North Carolina, Chapel Hill, United States
Damien Fair, Oregon Health and Science University, Portland, United States
Pathik Wadhwa, University of California Irvine, Irvine, United States
Claudia Buss, University of California Irvine, Orange, C

The majority of research related to prenatal maternal inflammation has been conducted in animal models. We test the hypothesis, in humans, that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in white matter microstructural properties in neonates. Participants were recruited in early pregnancy and maternal blood sampled in each trimester. Neonates underwent brain MRI (N=86, gestational age at birth=39.3+/-1.7 weeks, scan age=26.1+/-12.1 days) and again at age 12-months (N=32, scan age=54.0±3.1 weeks). Diffusion Tensor Imaging (DTI) focused on characterization of diffusion properties along the fronto-limbic white matter pathway (uncinate fasciculus, UF). A subset of infants’ cognitive and socioemotional development was characterized using the Bayley Scales of Infant Development. Principal component analysis and tract-based linear regression were used to test the association between average (across pregnancy) maternal IL-6 and neonatal fractional anisotropy (FA). Confounding factors were tested in post-hoc analyses. Maternal IL-6 concentration was inversely associated with neonatal FA (bi-lateral, p<0.01) in the central isthmus portion of the UF proximal to the amygdala. Maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p<0.05), and inversely associated with offspring cognition at age 12-months. The latter association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context.