Perinatal hypoxia is a major cause of long-term neurodevelopment impairment and neonatal mortality. This condition results from impaired gas exchange during birth, which disrupts cellular metabolism and leads to neuronal injury. Attention-deficit /hyperactivity disorder (ADHD) is characterized by impulsivity, inattention, and hyperactivity, affects up to 8% of children globally, and may be influenced by perinatal hypoxia. Hypoxia is commonly assessed using umbilical cord pH and Apgar scores. However, each measure alone is non-specific and may not accurately reflect true hypoxic exposure. A recent study published in JAMA Network Open aimed to detect the near-term and full-term newborns exposed to clinically relevant hypoxia through a combination of biochemical and clinical indicators and to evaluate the associations with ADHD.
This population-based cohort study included a total of 819,658 live-born singleton infants (male = 51.2%) with a gestational age of ≥35 weeks born in Denmark from January 1, 2004, to December 31, 2018. Newborns with low birth weight, congenital anomalies, early ADHD diagnosis, and missing key data were excluded from this study. All participants were followed until 2022. Exposure was defined by umbilical cord blood pH (<7.10, 7.10-7.19, ≥7.20) and 5-minute Apgar scores (0-3, 4-6, and 7-10) from the Danish medical birth registry. Newborns with a pH level of ≥7.20 and an Apgar score of 7-10 were considered the reference group. ADHD diagnoses were detected through the Danish national prescription registry, the Danish national patient registry, and the Danish psychiatric central registry. Associations were analyzed by a multivariable logistic regression model adjusted for socioeconomic, perinatal, and maternal factors with sibling clustering and multiple imputations for missing data. All statistical analyses were carried out using Stata statistical software, version 18.
Among the 819,658 newborns, 52.5% (n = 429,492) were born at 39-40 weeks of gestation. A low Apgar score (0-3) with pH <7.10 occurred in 249 newborns (0.03%). Umbilical cord pH was missing in 22.1% (180.907) and Apgar scores in 0.6% (5,020). Overall, 3.4% of children (27,907) developed ADHD. ADHD occurred in 12/249 newborns (4.8%) with pH <7.10 and Apgar 0-3, compared with 15,170/496,395 (3.1%) in the reference group.
Both the Apgar score and the umbilical cord pH alone were associated with ADHD.  When combined, lower Apgar scores with pH <7.20 were associated with higher odds of ADHD compared with the reference group. The highest risk was observed among newborns with Apgar scores 0-3 and pH <7.10 with an adjusted odds ratio (OR) of 1.86 (95% confidence interval [CI]: 1.04-3.33). Within reduced pH categories, odds increased with decreasing Apgar score. No such trend was observed when the pH was ≥7.20. Similarly, no association was found between ADHD and Apgar score at pH ≥7.20 or between ADHD and pH when Apgar scores were 7-10. The study findings were consistent across birth periods (2004-2011 vs 2012-2018) and in sensitivity and sibling analyses.
This study’s limitations include incomplete umbilical cord pH data early in 2004-2005 and the inability to differentiate arterial and venous samples, potentially underestimating risk. Missing pH data were assumed to be at random. Early ADHD diagnoses may be more likely in hypoxic newborns. Adjustments accounted for birth year, evolving neonatal care, and therapeutic hypothermia, which may influence outcomes.
In conclusion, this study highlights that children with both low umbilical cord pH and low Apgar scores had a higher ADHD risk. If either measure was normal, the risk was not increased, providing reassurance for most parents.
Reference: 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
