Background Hypoxicischaemic encephalopathy (HIE) remains one of the leading causes of neonatal morbidity and mortality. Therapeutic hypothermia may improve the outcome of infants with moderate/severe encephalopathy but only if initiated within six hours of the initial insult. The aim of our study was to determine if umbilical cord blood (UCB) levels of Activin-A, a glycoprotein previously implicated in neuronal brain injury, could identify infants with moderate/severe encephalopathy at birth.

Methods Full term infants with perinatal asphyxia (PA) were identified by a cord pH < 7.1 and/or five minute Apgar score ≤ 6 and/or requirement for intubation/CPR at birth. Following diagnosis at delivery, UCB was drawn, processed and bio-banked. HIE grade was confirmed with early continuous EEG monitoring and modified Sarnat score. Activin-A analysis was carried out using ELISA (R&D Systems).

Results In total 156 infants (controls = 78, cases = 78) were included in the study. Cases included 56 infants with PA (non-HIE) and 24 infants with HIE (mild = 14, moderate = 6, severe = 4). Following analysis, a significant increase in Activin-A expression was observed between the control and severe HIE groups, and between the perinatal asphyxia and severe HIE groups (median (SD) = 487.48 (470.21) vs 911.54(594.1) p = 0.032 and 487.95 (384.1) vs 911.54 (594.1), p = 0.035, respectively). No significant difference was seen between PA and mild or moderate HIE. Using a cut-off value of 724.5 pg/ml we report Activin-A has a 100% negative predicitive value, with a sensitivity and specificity of 100% and 70% respectively.

Conclusion Our study supports the use of Activin-A as a biomarker of severe encephalopathy.