Low Apgar score, cord pH linked to ADHD risk

A low Apgar score combined with a low umbilical cord pH level at birth may be an indicator of attention-deficit/hyperactivity disorder (ADHD) risk, according to a recent study published in JAMA Network Open.¹

Perinatal hypoxia has been linked to mortality and long-term disability, including neurodevelopmental impairment.² Experts have hypothesized this condition may also be linked to ADHD incidence, which has risen in recent years. Clinical and biochemical measures of hypoxia exposure include Apgar score and umbilical cord pH level.¹

“The association between perinatal hypoxia assessed by combining clinical and biochemical features and ADHD remains poorly examined,” wrote investigators.

Assessing ADHD incidence

The study was conducted to determine the link between hypoxia exposure and ADHD based on combined Apgar score and umbilical cord blood pH. Data was obtained from nationwide registries in Denmark, with participants including live-born, singleton newborns from 35-weeks’ gestation onward between January 1, 2004, and December 31, 2018.

Exclusion criteria included missing gestational age and birth weight data, chromosomal abnormalities, and major malformations of the heart system, respiratory system, nervous system, or gastrointestinal tract. Follow-up lasted until December 31, 2022.

The Danish Medical Birth Registry was assessed for 5-minute Apgar scores and umbilical cord blood pH levels. Categories of Apgar score at 5 minutes included 0 to 3, 4 to 6, and 7 to 10. The lowest registered pH value was used in the analysis. References included newborns with an Apgar score of 7 to 10 and a pH of at least 7.20.

Diagnosing ADHD and patient characteristics

ADHD was determined by diagnoses recorded in the Danish National Patient Registry and the Danish Psychiatric Central Registry, alongside prescriptions in the Danish National Prescription Registry. Diagnosis codes were based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Prescriptions related to ADHD included dexamphetamine, methylphenidate, atomoxetine, and lisdexamphetamine. Patients with at least 2 diagnosis codes, 2 prescriptions, or 1 diagnosis and prescription code were considered to have ADHD.

There were 819,658 newborns included in the final analysis, 51.2% of whom were male and 52.5% born between 39- and 40-weeks’ gestation. Of this population, 0.3% had a low Apgar score of 0 to 3 and a pH below 7.10. Apgar score data was missing in 0.6% and umbilical cord pH values in 22.1%.

ADHD was reported in 3.4% of the overall cohort, 4.8% with a pH below 7.10 and an Apgar score of 0 to 3, and 3.1% of references. Additionally, those with a low pH and Apgar score were diagnosed at a median age of 7.5 years, vs 9.3 years for references.

Association between combined hypoxia measures and ADHD risk

A significant increase in ADHD risk was reported in patients with a combined pH less than 7.20 and Apgar score less than 7 vs references. Those with the lowest Apgar score and pH reported the greatest adjusted odds ratio (OR) of 1.86.

A negative correlation between the OR and Apgar score was reported in patients with reduced pH, but this trend was not observed in those with a pH greater than 7.20. Overall, no association between Apgar score in ADHD was observed in patients with a pH greater than 7.20. There was also no link between pH and ADHD in patients with an Apgar score between 7 and 10.

These results indicated an increased risk of ADHD in children with perinatal hypoxia determined by a combination of low Apgar score and low umbilical cord blood pH. However, no risks were observed from Apgar score or pH alone.

“These findings are important as they may reduce anxiety in the parents of these large groups of children,” wrote investigators.

References

1. Pedersen MV, Lindhard MS, Moster D, Lie RT, Henriksen TB. Umbilical cord blood pH level, apgar score, and attention-deficit/hyperactivity disorder. JAMA Netw Open. 2026;9(1):e2554672. doi:10.1001/jamanetworkopen.2025.54672
2. Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ, Robertson NJ. New horizons for newborn brain protection: enhancing endogenous neuroprotection.Arch Dis Child Fetal Neonatal Ed. 2015;100(6):F541-F552. doi:10.1136/archdischild-2014-306284