Comparisons between umbilical cord biomarkers for newborn hypoxic-ischemic encephalopathy

Abstract

Background: Cord blood umbilical artery (Ua) pH, base deficit (BD), and pH eucapnic Blickstein/Green-50 may mislead clinicians to identify newborns at risk for hypoxic-ischemic encephalopathy. Neonatal eucapnic pH (pH euc-n Racinet-54) may be a comprehensive alternative. The goal of the study is to compare the predictive performance of these four biomarkers for the combined primary outcome of hypoxic-ischemic encephalopathy/death.

Methods: This retrospective cohort study includes newborns ≥35 weeks gestational age. Receiver operating characteristics curves analysis was performed for Ua cord pH, BD, pH euc-n Racinet-54, and pH eucapnic Blickstein/Green-50 for the global cohort and for two subgroups of newborns with Ua cord pH ≤ 7.15. Cutoff values were derived for all four markers.

Results: From the original cohort of 61,037 newborns born between 1 January 2007 and 31 December 2016, we excluded cases with major congenital malformations and missing/incomplete data. The global cohort includes 51,286 newborns and 60 newborns afflicted with hypoxic-ischemic encephalopathy (HIE)/death. The area under the curves (AUC) derived from the global cohort were comparable between Ua cord pH (0.95; 95%CI = 0.94-0.95), BD (0.93; 95%CI = 0.93-0.93), pH euc-n Racinet-54 (0.93; 95% CI = 0.93-0.93), and lower for pH Blickstein/Green-50 (0.78; 95% CI = 0.77-0.78) (p < .05). Within newborn with severe acidemia (pH ≤ 7.00) and moderate acidemia (7.00 ≤ pH ≤ 7.15), pH euc-n Racinet-54 had the largest AUC and best positive likelihood ratios especially for sensitivity ≥ 0.80 to minimize false negative cases.

Conclusion: In this large retrospective study, predictive performance for Ua cord pH, BD, and pH euc-n Racinet-54 are comparable when applied to the global group. For newborns with Ua cord pH ≤ 7.00 and Ua cord 7.00 ≤ pH ≤ 7.15, pH euc-n Racinet-54 appears better to identify those with HIE/death, especially when the target is sensitivity > 80%. Prospective studies will confirm if pH euc-n Racinet-54 is a better alternative to Ua cord pH and BD to evaluate newborn acid-base physiology.

Keywords: Base deficit; fetal acid–base status; fetal physiology; hypoxic–ischemic encephalopathy; neonatal death; neonatal eucapnic pH; neonatal metabolic acidosis; umbilical artery cord gas.