Supplementary Material for: Investigating the value of umbilical artery eucapnic pH as a biomarker for adverse neonatal outcomes: A systematic review

Introduction: Metabolic acidosis at birth is associated with severe neonatal outcomes, making umbilical artery gas analysis crucial for management. However, conventional potential of hydrogen (pH) and base deficit (BD) methods have limitations in neonates. Neonatal eucapnic pH (pH-euc-n), derived from the pH and partial pressure of carbon dioxide, reflects neonatal metabolic acidosis more accurately, potentially providing a better assessment than conventional biomarkers. This study aimed to assess the utility of pH-euc-n for predicting adverse neonatal outcomes.
Methods: A systematic search was conducted of PubMed, Web of Sciences, Scopus, and Embase on September 24, 2024. Articles comparing pH-euc-n with standard umbilical artery pH and BD for detecting neonates with hypoxic-ischemic encephalopathy (HIE) or neonatal intensive care unit (NICU) admissions were included. Data on the predictive ability of each biomarker for neonatal HIE/NICU admission were collected. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.
Results: Five retrospective cohort studies were included. We found very little evidence supporting the superiority of pH-euc-n over the standard pH for predicting HIE/NICU admission. Moderate evidence supported pH-euc-n for predicting HIE/NICU admissions in neonates with pH 7.00–7.15, the evidence was very low for pH≤7.00. Similarly, low evidence favored pH-euc-n over BD and retained pH (combined pH-euc-n and standard pH) over standard pH for predicting these outcomes.
Conclusions: pH-euc-n is a calculated value derived from an algorithm applied to measured pH (rather than a direct measurement), designed to eliminate the respiratory component and isolate the metabolic component of acidemia. While hypercapnia present at birth typically resolves rapidly after stabilization of breathing, the metabolic component persists, offering valuable insight into neonatal acidemia. This method serves as a complement to, rather than a replacement for, standard pH assessment, particularly in cases of significant respiratory acidosis. Importantly, its calculation entails no additional risks, constraints, or costs. Despite its theoretical advantages, this review found limited evidence that pH-euc-n outperforms standard pH or BD in identifying the risk of HIE, although moderate evidence supports its diagnostic accuracy in high-risk cases (pH=7.00–7.15). Consequently, further research is warranted to clarify its clinical utility and establish its role in neonatal care.