Outcomes in a Population of Healthy Term and Near-Term Infants With Serum Bilirubin Levels of ≥325 μmol/L (≥19 mg/dL) Who Were Born in Nova Scotia, Canada, Between 1994 and 2000

OBJECTIVE. The goal was to study the incidence of kernicterus, developmental delay, autism, cerebral palsy, and hearing loss in infants with peak total serum bilirubin levels of ≥325 μmol/L (≥19 mg/dL), compared with infants with less-severe or no hyperbilirubinemia, in a population of healthy term and late preterm infants.

METHODS. Prospectively gathered, standardized, maternal and neonatal data for infants at ≥35 weeks of gestation who were born between January 1, 1994, and December 31, 2000, were extracted from the Nova Scotia Atlee Perinatal Database. Infants with Rh factor isoimmunization, significant congenital or chromosomal abnormalities, or severe peripartum asphyxia were excluded. Comparisons were made on the basis of peak total serum bilirubin levels. Diagnoses were obtained through data linkage with the Medical Services Insurance Database for office visits and the Canadian Institute for Health Information Database for hospital admissions. The registration file provided information allowing calculation of follow-up times, which were determined for each separate outcome. Follow-up periods ranged from 2 to 9 years, with the end point being the first time the diagnostic code was encountered in either database. Cox proportional-hazards regression analyses were used to examine the relationships between outcomes and total serum bilirubin levels.

RESULTS. Of 61238 infants included in the study cohort, 4010 (6.7%) did not have linkage data, which left 56019 infants for analysis. There were no cases of kernicterus and no significant differences in rates of cerebral palsy, deafness, developmental delay, or visual abnormalities between the groups. There were suggestions of associations with attention-deficit disorder in the severe hyperbilirubinemia group and with autism in the combined moderate and severe hyperbilirubinemia group.

CONCLUSIONS. There was no increase in adverse effects reported previously to be associated with bilirubin toxicity. Associations with developmental delay, attention-deficit disorder, and autism were observed.