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Neuropediatrics 2021; 52(04): 261-267
DOI: 10.1055/s-0041-1725012
Original Article

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

Marc Paul O'Sullivan 
1   INFANT Research Centre, Ireland
2   Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
3   National Children's Research Centre, Crumlin, Dublin 12, Ireland
,
Niamh Denihan
1   INFANT Research Centre, Ireland
2   Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
,
Klaudia Sikora
1   INFANT Research Centre, Ireland
,
Mikael Finder
4   Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
5   Neonatal Department, Karolinska University Hospital, Stockholm, Sweden
,
Caroline Ahearne
1   INFANT Research Centre, Ireland
2   Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
,
Gerard Clarke
1   INFANT Research Centre, Ireland
6   Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
7   APC Microbiome Ireland, University College Cork, Cork, Ireland
,
Boubou Hallberg
4   Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
5   Neonatal Department, Karolinska University Hospital, Stockholm, Sweden
,
Geraldine B. Boylan
1   INFANT Research Centre, Ireland
2   Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
,
Deirdre M. Murray
1   INFANT Research Centre, Ireland
2   Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
3   National Children's Research Centre, Crumlin, Dublin 12, Ireland
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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.

Keywords

biomarkers - Activin A - perinatal asphyxia - hypoxic–ischemic encephalopathy - neonatal encephalopathy - long-term outcome

Statement of Financial Support

The research was funded by the National Children's Research Centre, Crumlin (NCRC; B/14/1), the Health Research Board (HRB; CSA/2012/40), and a Science Foundation Research Centre Award (INFANT; 12/RC/2272). GC is also funded by Science Foundation Ireland (SFI) grant number 12/RC/2273 P2.




Publication History

Received: 31 August 2020

Accepted: 19 January 2021

Article published online:
11 March 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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