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

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 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 mRNA were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.

RESULTS

Activin A analysis included 101 infants (controls,  = 50, perinatal asphyxia,  = 28, HIE,  = 23). No differences were detected across groups ( = 0.69). No differences were detected across HIE grades ( = 0.12). mRNA analysis included 67 infants (controls,  = 22, perinatal asphyxia,  = 23, and HIE,  = 22), and no differences were observed across groups ( = 0.75). No differences were detected across HIE grades ( = 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 mRNA ( = 0.55 and  = 0.90, respectively).

CONCLUSION

UCB Activin A and 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.