Previous research has indicated that maternal prenatal infection and immune reaction are associated with increased risk of neurodevelopmental disorders including ADHD. Most of these studies have, however, been hampered by retrospective designs, inadequate sample size and lack of biological data to define individual variation in responses to infection or confirm exposure through serology. Leveraging the unique properties of data sources and biological samples now available in Norway through the Norwegian Mother and Child Cohort Study (MoBa), we propose to address these methodological limitations. MoBa is a nationwide, prospective pregnancy cohort that now includes 114,516 children and 95,278 mothers. The mean age of the children is now 8.5 years (range, 5 - 15). Through linkage of MoBa with the Norwegian Patient Registry, we have identified 1549 children (73% boys) with two or more registrations with a main diagnosis of ADHD. Longitudinally collected questionnaire data on types and timing of exposures will allow us to examine the relationship of prenatal infection to child ADHD, controlling for the potential relationship between prolonged fever and comorbid autoimmune and allergic conditions, and also provide means of evaluating additional factors that may influence the effect of early childhood infection. We will also investigate whether specific immunological signatures are associated with ADHD risk by comparing levels of 61 immune/inflammatory molecules in plasma of mothers (mid-gestation, birth) and children with or without ADHD using multiplexed, magnetic bead-based immunoassays employed in the Center for Infection and Immunity laboratory at Columbia University over the last decade. Finally, we will examine the association between ADHD and specific infectious agents commonly implicated in neurodevelopmental disorders: influenza viruses and the pathogens Toxoplasma gondii, rubellavirus, cytomegalovirus and herpes simplex viruses 1 and 2.
