This proposal is a revised version of an R01 application for a comprehensive five-year case-control study of CP (New Paradigms of CP Etiology 1R01NS055101). We now propose to perform a two year case-control study that focuses centrally on one rich source of exposure information, the newborn blood spot, which is available on all MI births since 1986, supplemented with a maternal interview about pregnancy exposures, birth certificate data, newborn thyroid hormone screening data, and, when available, maternal serum assays. We will collect and store (but not assay) salivary-based genetic material from enrolled subjects and their parents. The overall aim of the project is to assess the extent to which children with CP and matched controls differ in newborn expression of genes relating to inflammation, hypoxia, coagulation and thyroid hormone production, as well as presence of viruses in blood at birth. Through collaborations with the University of Michigan and the DeVos Children's Hospital, we will expand our enrollment from Central Michigan to West and Southeast Michigan, enrolling the same number of cases and controls (440) in two years as we had originally planned in five years. The blood spot material will be assessed in three laboratories: mRNA expression will be assessed in triplicate at the Van Andel Research Institute (Grand Rapids, MI);key mRNA species will be further assessed by qPCR at MSU;viral genomic markers will be examined at the University of Minnesota. Maternal antenatal specimens will be assessed at MSU. We will extend these hypotheses to include maternal exposures in pregnancy in the fraction of subjects for whom maternal serum can be retrieved. Maternal interviews and birth certificates will inform the above analyses by linking molecular information to self-reported and recorded clinical events and conditions.
