Umbilical cord acidemia linked to long-term neurodevelopmental risks

Umbilical cord acidemia linked to long-term neurodevelopmental risks | Image Credit: © natali_mis - © natali_mis - stock.adobe.com.

Neonatal acidemia, indicated by umbilical cord arterial pH (UApH) under 7.05 at birth, is associated with a higher risk of death, cerebral palsy (CP), and epilepsy in long-term follow-up, according to a recent Swedish cohort study published in the American Journal of Obstetrics & Gynecology.¹

Umbilical cord blood pH has long been used as a marker of neonatal acid-base status and a diagnostic tool for neonatal acidemia.² However, large-scale evidence linking specific pH thresholds to long-term neurodevelopmental outcomes has been limited.¹

“Cord arterial pH <7.05 is linked to a higher likelihood of death, cerebral palsy (CP) and epilepsy, but no other mental or organ system diseases. A marked increase in risk for CP, epilepsy, and intellectual disability was noted at cord arterial pH <6.95,” wrote investigators.

Mortality and overall morbidity

Researchers conducted a retrospective cohort study using birth data from January 1, 1997, to May 8, 2012, at Skåne University Hospital in Malmö, Sweden. After applying validation criteria for arterial pH and excluding incomplete records, 35,931 singleton infants were included. Of these, 912 were classified as acidemic based on UApH under 7.05, while 35,019 were nonacidemic based on UApH of 7.05 or greater.

Umbilical cord blood samples were drawn immediately after birth, and pH values were analyzed within 15 minutes. Researchers linked maternal and neonatal data to national health care registers, allowing follow-up for up to 20 years. Outcomes included mortality, organ system diseases, and neurodevelopmental disorders, coded according to the International Classification of Diseases.

Mortality up to age 20 years was higher in the acidemic group at 4.1 per 1000 vs nonacidemic infants at 1.4 per 1000. No differences were found in causes of death between groups. Analyses across all organ systems revealed no significant differences in disease incidence between acidemic and nonacidemic infants.

Neurodevelopmental outcomes

Subanalyses revealed a higher risk of CP (1.0% vs 0.2%; adjusted hazard ratio [HR], 4.35; 95% CI, 2.17–8.73) and epilepsy (1.6% vs 0.9%; adjusted HR, 1.71; 95% CI, 1.02–2.88) among acidemic infants. Intellectual disability incidence was higher in acidemic infants (1.4% vs 0.9%), but did not reach statistical significance (adjusted HR, 1.74; 95% CI, 0.99–3.04).

Dose-response analysis showed risk of CP increased with declining UApH, becoming statistically significant at under 6.95. At this threshold, cumulative risk at 20 years was nearly 5% for CP, 12% for epilepsy, and 6% for intellectual disability, compared with less than 1% for nonacidemic infants.

Clinical implications

The findings suggest that adverse neurodevelopmental outcomes may occur at higher UApH values than previously assumed. Additionally, they may inform clinical guidelines on monitoring and intervention for neonates with acidemia. They underscore the need for careful assessment of infants with UApH under 7.05 and particularly under 6.95, for timely detection and management of potential neurodevelopmental disorders.

Investigators recommended further studies to refine risk thresholds and explore combined use of cord pH with other clinical markers to improve prediction of long-term outcomes. The importance of extended follow-up was also highlighted.

“At an age of 20 years the incidence of CP was doubled compared with at 5 years of age. Similarly, the incidence of both epilepsy and intellectual disability quadrupled at 20 years as compared to 5 years when UApH was <6.95," wrote investigators.

References

1. Zaigham M, Källén K, Sundberg T-M, et al. Long-term outcomes after neonatal acidemias. Am J Obstet Gynecol. 2025;233:195.e1-11. doi:10.1016/j.ajog.2025.02.028
2. Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis. BMJ. 2010;340:c1471. doi:10.1136/bmj.c1471