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

Pediatr Res. 2013 Apr;73(4 Pt 1):450-6. doi: 10.1038/pr.2012.200. Epub 2012 Dec 26.

Abstract

Background: Gene expression in archived newborn blood spots remaining from newborn screening may reflect pathophysiological disturbances useful in understanding the etiology of cerebral palsy (CP).

Methods: We 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 the inflammatory, hypoxic, coagulative, and thyroidal pathways and examined mRNA expression using an 8 × 60,000 oligonucleotide microarray. The log2 fold change of gene expression between matched cases and controls was analyzed using the generally applicable gene set enrichment method.

Results: The empirical inflammatory and empirical hypoxic gene sets were significantly downregulated in term-born CP cases (n = 33) as compared with matched controls (P = 0.0007 and 0.0009, respectively), whereas both gene sets were significantly upregulated (P =0.0055 and 0.0223, respectively) in preterm-born CP cases (n = 20). The empirical thyroidal gene set was significantly upregulated in preterm-born CP cases (P = 0.0023).

Conclusion: The newborn blood spot transcriptome can serve as a platform for investigating distinctive gene expression patterns in children who later develop CP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Cerebral Palsy / blood
  • Cerebral Palsy / diagnosis
  • Cerebral Palsy / genetics*
  • Child
  • Child, Preschool
  • Dried Blood Spot Testing*
  • Female
  • Gene Expression Profiling*
  • Gene Regulatory Networks
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Male
  • Neonatal Screening / methods*
  • Phenotype
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Reproducibility of Results

Substances

  • Genetic Markers