Up-Regulation of Nfat5 mRNA and Fzd4 mRNA as a Marker of Poor Outcome in Neonatal Hypoxic-Ischemic Encephalopathy

Marc Paul O'Sullivan*, Sophie Casey, Mikael Finder, Caroline Ahearne, Gerard Clarke, Boubou Hallberg, Geraldine B. Boylan, Deirdre M. Murray

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Objective: To evaluate umbilical cord messenger RNA (mRNA) expression as biomarkers for the grade of hypoxic-ischemic encephalopathy (HIE) and long-term neurodevelopment outcome. Study design: Infants were recruited from the BiHiVE1 study, Ireland (2009-2011), and the BiHiVE2 study, Ireland, and Sweden (2013-2015). Infants with HIE were assigned modified Sarnat scores at 24 hours and followed at 18-36 months. mRNA expression from cord blood was measured using quantitative real-time polymerase chain reaction. Results: We studied 124 infants (controls, n = 37; perinatal asphyxia, n = 43; and HIE, n = 44). Fzd4 mRNA increased in severe HIE (median relative quantification, 2.98; IQR, 2.23-3.68) vs mild HIE (0.88; IQR, 0.46-1.37; P =.004), and in severe HIE vs moderate HIE (1.06; IQR, 0.81-1.20; P =.003). Fzd4 mRNA also increased in infants eligible for therapeutic hypothermia (1.20; IQR, 0.92-2.37) vs those who were ineligible for therapeutic hypothermia group (0.81; IQR, 0.46-1.53; P =.017). Neurodevelopmental outcome was analyzed for 56 infants. Nfat5 mRNA increased in infants with severely abnormal (1.26; IQR, 1.17-1.39) vs normal outcomes (0.97; IQR, 0.83-1.24; P =.036), and also in infants with severely abnormal vs mildly abnormal outcomes (0.96; IQR, 0.80-1.06; P =.013). Fzd4 mRNA increased in infants with severely abnormal (2.51; IQR, 1.60-3.56) vs normal outcomes (0.74; IQR, 0.48-1.49; P =.004) and in infants with severely abnormal vs mildly abnormal outcomes (0.97; IQR, 0.75-1.34; P =.026). Conclusions: Increased Fzd4 mRNA expression was observed in cord blood of infants with severe HIE; Nfat5 mRNA and Fzd4 mRNA expression were increased in infants with severely abnormal long-term outcomes. These mRNA may augment current measures as early objective markers of HIE severity at delivery.

Original languageEnglish
Pages (from-to)74-81.e2
JournalJournal of Pediatrics
Volume228
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

Keywords

  • biomarkers
  • hypoxic-ischemic encephalopathy
  • MIRA
  • MRNA
  • neonatal encephalopathy
  • neurodevelopmental outcome
  • perinatal asphyxia

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