Maternal Immune Activation and Fetal-Infant Neurobehavioral Development

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An estimated 1 in 5 children are diagnosed with a neurodevelopmental disorder. Neurodevelopmental disorders increase the likelihood of poor academic performance and social challenges. Although there has been some research on early risk for later neurodevelopmental disorders, there are few studies in the first years of life. Maternal immune activation (MIA) to infectious and inflammatory agents raises the risk of neurodevelopmental disorders, such as intellectual disabilities and autism. The overarching purpose of the Career Development Award (K23) is for the candidate, Marisa Spann, a clinical child neuropsychologist, to gain training and mentored research experience on prenatal immunological antecedents of infant brain and behavioral development. With mentorship from Drs. Catherine Monk, Alan Brown, and R. Todd Constable, the application includes training activities for the candidate to achieve the following career goals: 1) develop knowledge of developmental and maternal-fetal immunology; (2) develop skills in perinatal biobehavioral study design and methods; and (3) develop skills in functional neuroimaging and longitudinal statistical modeling. The training and mentored research will occur at Columbia University Medical Center (CUMC)—a top research institution with multi-disciplinary research programs. The research plan will capitalize on a cross-disciplinary model that combines the strengths of a population-based Finnish birth cohort from an extant dataset, and new data collection with a clinical sample of pregnant women recruited from CUMC. The primary goal of the study is to detect associations between prenatal MIA and early brain (head circumference, brain morphometry and connectivity) and behavioral development. In the population-based birth cohort, the candidate will investigate the associations between prenatal maternal influenza infection (influenza immunoglobulin G) and an inflammatory (C-reactive protein) marker, and growth velocity of head circumference from birth to one year. The new data collection will include the recruitment of a new hospital-based sample of pregnant women. In the newly established clinical cohort from CUMC, the candidate will detect associations of maternal influenza and inflammatory markers with neonatal brain morphometry and functional connectivity indices and behavioral reactivity in 3rd trimester fetuses and 4 month old infants. With the well-integrated training and research plans, the K23 award will ensure that the candidate develops the skills necessary to achieve independence in a novel interdisciplinary career area as a perinatal–developmental neuroscience researcher. The candidate will be uniquely positioned to discover distinct and common neurobiological and behavioral trajectories of neurobehavioral health prior to age one, in the service of determining risks for neurodevelopmental disorders, and its early identification.