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Umbilical Cord Blood pH Level, Apgar Score, and Attention-Deficit/Hyperactivity Disorder
Mette Vestergård Pedersen1,2, Morten Søndergaard Lindhard2,3, Dag Moster4,5
1Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Insights
Perinatal hypoxia, indicated by low Apgar scores and umbilical cord pH, is linked to increased attention-deficit/hyperactivity disorder (ADHD) odds. Normalizing either measure negated this association, suggesting combined indicators are crucial for risk assessment.
Area of Science:
- Neuroscience
- Pediatrics
- Public Health
Background:
- Perinatal hypoxia is a known risk factor for neurodevelopmental impairments, including attention-deficit/hyperactivity disorder (ADHD).
- Accurate assessment of perinatal hypoxia requires evaluating both clinical (Apgar score) and biochemical (umbilical cord blood pH) markers.
- Previous studies often relied solely on Apgar scores, potentially underestimating hypoxia-related risks.
Purpose of the Study:
- To identify newborns exposed to perinatal hypoxia using combined Apgar score and umbilical cord blood pH criteria.
- To investigate the association between this combined hypoxia assessment and the subsequent development of ADHD.
Main Methods:
- A nationwide Danish cohort study included singleton newborns (gestational age ≥35 weeks) from 2004-2018.
- Hypoxia was categorized by combinations of 5-minute Apgar scores (0-3, 4-6, 7-10) and umbilical cord blood pH (<7.10, 7.10-7.19, ≥7.20).
- ADHD outcomes were determined by hospital diagnoses and medication prescriptions, with data analyzed using adjusted odds ratios and multiple imputation.
Main Results:
- The study analyzed 819,658 newborns; 0.3% had both a low Apgar score (0-3) and low pH (<7.10).
- Increased ADHD odds were observed for combinations with pH <7.20 and Apgar <7, most significantly with Apgar 0-3 and pH <7.10 (aOR=1.86).
- No association between Apgar score and ADHD was found if pH was ≥7.20, nor between pH and ADHD if Apgar score was ≥7.
Conclusions:
- Combined clinical and biochemical indicators of perinatal hypoxia (low Apgar score and low umbilical cord pH) are associated with increased odds of ADHD.
- The absence of increased ADHD risk when either Apgar score or pH is normal suggests these combined measures are critical for identifying at-risk neonates.
- This finding underscores the importance of comprehensive perinatal assessment for predicting neurodevelopmental outcomes like ADHD.
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 (<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.
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