Activin A and Acvr2b mRNA from Umbilical Cord Blood Are Not Reliable Markers of Mild or Moderate Neonatal Hypoxic-Ischemic Encephalopathy

Neuropediatrics. 2021 Aug;52(4):261-267. doi: 10.1055/s-0041-1725012. Epub 2021 Mar 11.

Abstract

Background: Activin A protein and its receptor ACVR2B have been considered viable biomarkers for the diagnosis of hypoxic-ischemic encephalopathy (HIE). This study aimed to assess umbilical cord blood (UCB) levels of Activin A and Acvr2b messenger RNA (mRNA) as early biomarkers of mild and moderate HIE and long-term neurodevelopmental outcome.

Methods: One-hundred and twenty-six infants were included in the analyses from the BiHiVE2 cohort, a multi-center study, recruited in Ireland and Sweden (2013 to 2015). UCB serum Activin A and whole blood Acvr2b mRNA were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.

Results: Activin A analysis included 101 infants (controls, n = 50, perinatal asphyxia, n = 28, HIE, n = 23). No differences were detected across groups (p = 0.69). No differences were detected across HIE grades (p = 0.12). Acvr2b mRNA analysis included 67 infants (controls, n = 22, perinatal asphyxia, n = 23, and HIE, n = 22), and no differences were observed across groups (p = 0.75). No differences were detected across HIE grades (p = 0.58). No differences were detected in neurodevelopmental outcome in infants followed up to 18 to 36 months in serum Activin A or in whole blood Acvr2b mRNA (p = 0.55 and p = 0.90, respectively).

Conclusion: UCB Activin A and Acvr2b mRNA are not valid biomarkers of infants with mild or moderate HIE; they are unable to distinguish infants with HIE or infants with poor neurodevelopmental outcomes.

Publication types

  • Multicenter Study

MeSH terms

  • Activin Receptors, Type II* / genetics
  • Activin Receptors, Type II* / metabolism
  • Activins* / genetics
  • Activins* / metabolism
  • Biomarkers / metabolism
  • Female
  • Fetal Blood* / metabolism
  • Humans
  • Hypoxia-Ischemia, Brain*
  • Infant
  • Infant, Newborn
  • Pregnancy
  • RNA, Messenger* / blood
  • RNA, Messenger* / metabolism

Substances

  • Biomarkers
  • RNA, Messenger
  • activin A
  • Activins
  • ACVR2B protein, human
  • Activin Receptors, Type II