Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem Neuroapoptosis in newborns with respiratory acidosis at birth José D. Santotoribio a,b, ⁎ , Consuelo Cañavate-Solano a , Rocío Quintero-Prado c , Carmen González-Macías c,d , Estefanía Soto-Pazos c , Ángel Vilar-Sanchez c , Pablo Mesa-Suárez e , Victoria Ramos-Ramos f , Juan F. Cuadros-Muñoz a , María Mayor-Reyes a , Santiago Pérez-Ramos a,b , Juan J. Fernández-Alba c,d a Department of Laboratory Medicine, Puerto Real University Hospital, Cadiz, Spain b Department of Biomedicine, Biotechnology and Public Health, Cadiz University School of Medicine, Cadiz, Spain c Department of Obstetrics and Gynecology. Puerto Real University Hospital, Cadiz, Spain d Department of Mother-Child and Radiology, Cadiz University School of Medicine, Cadiz, Spain e Department of Anesthesiology, Puerto Real University Hospital, Cadiz, Spain f Department of Pediatrics, Jerez de la Frontera Hospital, Cadiz. Spain ABSTRACT Background: S100B protein is one of the most accurate biomarkers for diagnosis of neuroapoptosis and brain damage. The aim was to evaluate the lactate con- centration and acid-base balance (pH, pCO 2 , pO 2 , HCO 3 c and BEb) in umbilical cord blood to predict high risk of neuroapoptosis and analyze the relationship between the levels of these biomarkers and umbilical cord blood S100B protein concentration at birth. Methods: Apparently healthy newborns were included. S100B protein and blood gas test (lactate and acid-base balance) were determined in umbilical cord blood at birth. Newborns were classified into two groups: with and without high risk of neuroapoptosis. Newborns with high umbilical cord blood S100B protein con- centration were considered newborns at high risk of neuroapoptosis. Results: Sixty-one newborns were included, 12 had high risk of neuroapoptosis and 49 did not. S100B protein concentration correlate directly with pCO 2 levels (Rho: 0.286, p = .0321) and lactate concentration (Rho: 0.278, p = .0315); and indirectly with pH (Rho: −0.332, p = .01). The analysis of the ROC curves yielded significant curves for pH and pCO 2 to predict high risk of neuroapoptosis, pH optimal cutoff value was 7.19 (sensitivity: 50%, specificity: 83.7%, AUC: 0.708); and pCO 2 optimal cutoff value was 60 mmHg (sensitivity: 30%, specificity: 85.4%, AUC: 0.705). Conclusions: Respiratory acidosis is associated to high concentrations of S100B protein in umbilical cord blood at birth. Umbilical cord blood pH and pCO 2 may be useful in differentiating newborns at high risk of neuroapoptosis. Umbilical cord blood gas test may be valuable as risk indicator for neuroapoptosis at birth. 1. Introduction Neuronal cell death can occur through neuronal cell apoptosis, or neuroapoptosis, which is the programmed death of neuronal cells. An increase in neuroapoptotic activity can cause brain damage. S100B protein is one of the most accurate biomarkers for diagnosis of neu- roapoptosis and brain damage. In a healthy patient, serum S100B protein concentration is low and acts as a neurotrophic factor, however, levels in brain damaged patients increase and act as a neuroapoptotic factor [1–3]. High levels of serum S100B protein are associated with brain damage in adult patients with various diseases such as head trauma [4], cerebral ischemia [5] or cerebral hemorrhage [6]. New- borns with high levels of umbilical cord blood S100B protein have been associated with hypoxic-ischemic encephalopathy [7] or with indirect signs of asphyxia during birth [8]. Fetal hypoxia is related to neonatal morbidity and mortality. Reduced pH and increased lactate concentrations in umbilical cord blood are considered biomarkers of fetal hypoxia and predictors of neonatal morbidity and mortality [9]. The aim of this study was to evaluate the lactate concentration and acid-base balance [pH, partial pressure of carbon dioxide (pCO 2 ), par- tial pressure of oxygen (pO 2 ), bicarbonate concentrations (HCO 3 c), base excess/deficit (BEb)] in umbilical cord blood to predict high risk of neuroapoptosis and analyze the relationship between the levels of these biomarkers and umbilical cord blood S100B protein at birth. 2. Materials and methods 2.1. Study design This is a cross-sectional descriptive study carried out in Puerto Real University Hospital, Cádiz, Spain. The study was approved by the https://doi.org/10.1016/j.clinbiochem.2019.08.013 Received 30 April 2019; Received in revised form 11 August 2019; Accepted 28 August 2019 ⁎ Corresponding author at: Department of Clinical Laboratory, Puerto Real University Hospital, Carretera Nacional IV – Km. 665, 11510 Puerto Real (Cadiz), Spain. E-mail address: jdsantotoribioc@gmail.com (J.D. Santotoribio). Clinical Biochemistry xxx (xxxx) xxx–xxx 0009-9120/ © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Please cite this article as: José D. Santotoribio, et al., Clinical Biochemistry, https://doi.org/10.1016/j.clinbiochem.2019.08.013