Long-term outcomes after neonatal acidemia

Abstract

Background: Sustained intrauterine hypoxia causes some 1 million perinatal deaths annually worldwide. The condition is predicated by neonatal acidemia, as determined by pH in the umbilical cord blood at birth. We aimed to evaluate the association between umbilical cord arterial pH and long-term outcomes up to 20 years of follow-up.

Study design: Using a retrospective cohort design, the umbilical cord arterial pH values from singleton births at Skåne University Hospital Malmö, Sweden, from 1997 to 2012 were cross-linked to data from the Swedish Medical Birth Register, Swedish Patient Register, and Cause of Death Register. The hazard ratio for developing disease later in life, as defined organ-wise with the International Classification of Diseases version 10 with codes 00 to 99, was calculated relative to umbilical cord arterial pH <7.05 and ≥7.05, respectively. In addition, umbilical cord arterial pH thresholds at 6.95, 7.00, 7.05, 7.10, 7.15, and 7.20 were evaluated for mental and behavioral disorders.

Results: Of the 35,931 births that met the inclusion criteria of complete and validated data, 912 (2.5%) had acidemia (umbilical cord arterial pH <7.05) at birth, while 35,019 (97.5%) had nonacidemic values (pH ≥7.05). Acidemia was associated with higher mortality (P=.043). Among groups of organ system diseases, a pH <7.05 was not associated with increased risk of disease. At the group level, the risk was not significantly increased for mental and behavioral disorders (crude hazard ratio 1.05, 95% confidence interval 0.75-1.46); however, subanalysis showed an increased risk of cerebral palsy (crude hazard ratio 4.30, 95% confidence interval 2.16-8.58) and epilepsy (crude hazard ratio 1.70, 95% confidence interval 1.02-2.86). After adjustment for maternal age, parity, smoking, body mass index, and gestational age, the associations strengthened (cerebral palsy adjusted hazard ratio 4.35, 95% confidence interval 2.17-8.73), (epilepsy adjusted hazard ratio 1.71, 95% confidence interval 1.02-2.88). The threshold of umbilical cord arterial pH <6.95 was significantly associated with increased risk of cerebral palsy (hazard ratio 18.38, 95% confidence interval 7.34-46.08), epilepsy (hazard ratio 8.16, 95% confidence interval 4.18-15.92), and intellectual disability (hazard ratio 4.19, 95% confidence interval 1.73-10.17), whereas thresholds 7.00, 7.05, 7.10, and 7.15 were not.

Conclusion: Neonatal acidemia, defined as cord arterial pH <7.05, was associated with an increased risk of death, cerebral palsy, and epilepsy, but not of other types of mental and behavioral disorders or other organ system diseases. An umbilical cord arterial pH <6.95 was significantly associated with cerebral palsy, epilepsy, and intellectual disability whereas pH <7.00 and other thresholds between 7.05 and 7.20 were not.

Keywords: acidemia; asphyxia; birth; cerebral palsy; epilepsy; intellectual disability; long-term outcome; morbidity; mortality; umbilical cord pH.