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

Acknowledgments

We would like to thank Francesca de Vries and the Ottawa medical editor Joan Ramsay for their help in reviewing this article and Tim Ramsay for his constructive comments.

Disclosure statement

No potential conflict of interest was reported by the authors. The authors have no financial relationships relevant to this article to disclose.

Additional information

Funding

Gillian MacLean under the supervision of Thierry Daboval received funding from the Children’s Hospital of Eastern Ontario Research Institute—Resident Grant.

Notes on contributors

Thierry Daboval

Pr. Daboval conceptualized and designed the study, oversaw the methodology, reviewed all analyzed data, contributed to drafting the original manuscript, and approved the final manuscript as submitted.

Paul Ouellet

Pr. Ouellet conceptualized and designed the study, oversaw the methodology, reviewed all analyzed data, contributed to drafting the original manuscript, and approved the final manuscript as submitted.

François Charles

Dr. Charles participated in the concept and design, oversaw the methodology, reviewed all analyzed data, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Ronald A. Booth

Dr. Booth participated in the concept and design, oversaw the methodology, reviewed all analyzed data, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Gillian MacLean

Dr. MacLean participated in the concept and design, collected the data, reviewed all analyzed data, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Rhiana Roeper

Dr. Roeper participated in the concept and design, collected the data, reviewed all analyzed data, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Claude Racinet

Pr. Racinet conceptualized and designed the study, oversaw the methodology, reviewed all analyzed data, contributed to drafting the original manuscript, and approved the final manuscript as submitted.