Umbilical Cord Blood pH Level, Apgar Score, and Attention-Deficit/Hyperactivity Disorder

Importance Perinatal hypoxia is an important cause of neurodevelopmental impairment and may thus be associated with attention-deficit/hyperactivity disorder (ADHD). In population-based studies, hypoxia is often assessed by Apgar score alone; however, criteria for relevant perinatal hypoxia require both clinical and biochemical abnormalities (eg, a low Apgar score and a low umbilical cord blood pH level). Objectives To identify full-term and near-term newborns exposed to hypoxia by combining the Apgar score and the umbilical cord blood pH level and to investigate their association with ADHD. Design, Setting, and Participants This cohort study, with follow-up from birth until December 31, 2022, identified all singleton newborns with a gestational age of 35 weeks or more, without major malformations, born between January 1, 2004, and December 31, 2018, using a Danish nationwide registry. Data were analyzed from October 2024 to November 2025. Exposure Combinations of a 5-minute Apgar score category (0-3, 4-6, and 7-10) and an umbilical cord blood pH category (lt;7.10, 7.10-7.19, and ≥7.20). Newborns with an Apgar score of 7 to 10 combined with a pH level of 7.20 or higher were considered the reference group. Main Outcomes and Measures The primary outcome was ADHD identified by hospital contacts with ADHD diagnosis and/or prescriptions of ADHD medication. Outcome measures were odds ratios adjusted for relevant confounders. Multiple imputation was used to handle missing data. Results Of 819 658 newborns, 419 581 (51.2%) were male, and 429 492 (52.5%) were born 39 to 40 weeks of gestational age. Both a low Apgar score of 0 to 3 and a pH less than 7.10 were observed for 249 newborns (0.3%). Increased odds of ADHD was observed for most combinations of a pH of less than 7.20 combined with an Apgar score of less than 7 compared with the reference group and was most pronounced when the Apgar score was 0 to 3 and the pH was less than 7.10 (adjusted odds ratio, 1.86 95% CI, 1.04-3.33). If the pH was higher than 7.20, there was no association between Apgar score and ADHD. Similarly, if the Apgar score was 7 or higher, there was no association between pH and ADHD. Conclusions and Relevance In this cohort study, an increased odds of ADHD was observed when clinical and biochemical measures of hypoxia were combined as expressed by a low Apgar score and a low umbilical cord pH level at birth. However, when either the Apgar score or the umbilical cord blood pH level was normal, perinatal hypoxia seemed less likely, and no increased odds of ADHD was observed.