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

TL;DR

Low Apgar scores and low umbilical cord blood pH at birth are linked to a higher risk of ADHD in children, but only when both factors are abnormal.

Contribution

This study identifies a combined clinical and biochemical marker for perinatal hypoxia associated with ADHD risk.

Findings

A low Apgar score and low umbilical cord pH were linked to increased ADHD risk.

ADHD risk was highest when Apgar was 0-3 and pH was below 7.10.

No ADHD risk was found if either Apgar or pH was normal.

Abstract

Is perinatal hypoxia assessed by clinical and biochemical measures associated with attention-deficit/hyperactivity disorder (ADHD)?

In this nationwide cohort study of 819 658 singleton newborns, with a gestational age of 35 weeks or more, the combination of an Apgar score of less than 7 and an umbilical cord blood pH level of less than 7.20 were associated with ADHD. When the Apgar score was normal, there was no association between pH level and ADHD; when the pH level was normal, there was no association between Apgar score and ADHD.

These findings suggest that perinatal hypoxia was associated with an increased risk of ADHD only when both clinical and biochemical features were affected.

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).

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.

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.

Combinations of a 5-minute Apgar score category (0-3, 4-6, and 7-10) and an umbilical cord blood pH category (<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.

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.

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.

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.

This cohort study evaluates whether perinatal hypoxia, defined as low Apgar score and low umbilical cord blood pH level), is associated with subsequent attention-deficit/hyperactivity disorder (ADHD) diagnosis among Danish near-term and full-term infants.

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