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

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.

• Authors: Marc Paul O'Sullivan, Sophie Casey, Mikael Finder, Caroline Ahearne, Gerard Clarke, Boubou Hallberg, Geraldine B Boylan, Deirdre M Murray
• Journal: The Journal of pediatrics (J Pediatr) Vol. 228 Pg. 74-81.e2 (01 2021) ISSN: 1097-6833 [Electronic] United States
• PMID: 32828883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• FZD4 protein, human
• Frizzled Receptors
• NFAT5 protein, human
• RNA, Messenger
• Transcription Factors

Topics

• Asphyxia Neonatorum (blood, diagnosis, genetics)
• Biomarkers (blood)
• Electroencephalography
• Female
• Follow-Up Studies
• Frizzled Receptors (genetics, metabolism)
• Humans
• Hypoxia-Ischemia, Brain (blood, genetics)
• Infant, Newborn
• Male
• Prognosis
• RNA, Messenger (blood, genetics)
• Retrospective Studies
• Severity of Illness Index
• Transcription Factors (blood, genetics)
• Up-Regulation