Abstract
IMPORTANCE: Perinatal hypoxia is an important cause of cerebral palsy (CP). Although criteria for relevant perinatal hypoxia require both clinical and biochemical abnormalities, such as low Apgar score and low umbilical cord blood pH, most observational studies have considered only 1 of these measures. OBJECTIVE: To investigate the association of perinatal hypoxia assessed by Apgar score combined with umbilical cord blood pH with CP. DESIGN, SETTING, AND PARTICIPANTS: This registry-based cohort study was conducted nationwide in Denmark with follow-up until December 31, 2022. Analyses were performed from October 2024 to May 2025. All singleton newborns with a gestational age of 35 weeks or older without major malformations between January 1, 2004, and December 31, 2018, with at least 1 year of follow-up were included. EXPOSURE: Combinations of 5-minute Apgar score category (0-3, 4-6, and 7-10) and umbilical cord blood pH category (<7.00, 7.00-7.09, 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 greater were considered as a reference group. MAIN OUTCOMES AND MEASURES: Any diagnosis of CP. Associations between Apgar score combined with pH level and CP were estimated with multivariable log-binomial regression. Severe CP was defined as Gross Motor Function Classification System level IV to V. RESULTS: The cohort included 825 159 newborns (422 409 male [51.2%]; 432 398 born at 39-40 weeks of gestation among 822 913 with gestational age data [52.5%]). Among 145 children with the lowest Apgar score (0-3) combined with the lowest pH level (<7.00), 22 individuals (15.2%) were diagnosed with CP, corresponding to an adjusted relative risk (aRR) of 159.0 (95% CI, 104.0-243.0). In 2463 children with a normal Apgar score (7-10) but the lowest pH level (<7.00), 14 individuals (0.6%) were diagnosed with CP (aRR, 6.1; 95% CI, 3.7-10.0). Among 388 children with the lowest Apgar score (0-3) combined with a normal pH level (≥7.20), 8 individuals (2.1%) were diagnosed with CP (aRR, 22.0; 95% CI, 11.0-44.0). Severe CP was observed in 31 of 63 children (49.2%) with CP and an Apgar score of 0 to 6 combined with a pH level less than 7.20 compared with 39 of 385 children (10.1%) with CP and a normal Apgar score and pH level (P < .001). CONCLUSION AND RELEVANCE: In this study, perinatal hypoxia assessed by clinical and biochemical measures was associated with CP risk, with a higher risk when both measures were abnormal. These findings may guide future identification for follow-up of children with perinatal hypoxia.