Gene expression in archived newborn blood spots distinguishes infants who will later develop cerebral palsy from matched controls

Abstract

BackgroundGene expression in archived newborn blood spots remaining from newborn screening may reflect pathophysiological disturbances useful in understanding the etiology of cerebral palsy (CP).MethodsWe quantified the expression of gene sets representing four physiological pathways hypothesized to contribute to CP in archived unfrozen residual newborn blood spot specimens from 53 children with CP and 53 age, gender, and gestational-age–matched controls. We selected four empirical and three canonical gene sets representing inflammatory, hypoxic, coagulative, and thyroidal pathways, and examined mRNA expression using an 8×60K oligonucleotide microarray. The log2 fold change of gene expression between matched cases and controls were analyzed using the Generally Applicable Gene Set Enrichment (GAGE) method.ResultsThe empirical inflammatory and empirical hypoxic gene sets were significantly down-regulated in term-born CP cases (N = 33) as compared to matched controls (P = 0.0007 and 0.0009, respectively), while both gene sets were significantly up-regulated (P = 0.0055 and 0.0223, respectively) in preterm-born CP cases (N = 20). The empirical thyroidal gene set was significantly up-regulated in preterm-born CP (P = 0.0023).ConclusionThe newborn blood spot transcriptome can serve as a platform for investigating distinctive gene expression patterns in children who later develop CP.