Hyperbilirubinemia Among Infants Born Preterm: Peak Levels and Association with Neurodevelopmental Outcomes

Objective: To describe the distribution of peak bilirubin levels among infants born before 29 weeks of gestation in the first 14 days of life and to study the association between quartiles of peak bilirubin levels at different gestational ages and neurodevelopmental outcomes.

Study design: Multicenter, retrospective, nationwide cohort study of neonatal intensive care units in the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network, including neonates born preterm at 22^0/7 to 28^6/7 weeks of gestation born between 2010 and 2018. Peak bilirubin levels were recorded during the first 14 days of age. Main outcome was significant neurodevelopmental impairment, defined as cerebral palsy with Gross Motor Function Classification System ≥3, or Bayley III-IV scores of <70 in any domain, or visual impairment, or bilateral hearing loss requiring hearing aids.

Results: Among 12 554 included newborns, median gestational age was 26 weeks (IQR 25-28) and birth weight was 920 g (IQR 750-1105 g). The median peak bilirubin values increased as gestational age increased (112 mmol/L [6.5 mg/dL] at 22 weeks and 156 mmol/L [9.1 mg/dL] at 28 weeks). Significant neurodevelopmental impairment was identified in 1116 of 6638 (16.8%) of children. Multivariable analyses identified an association between peak bilirubin in the highest quartile and neurodevelopmental impairment (aOR 1.27, 95% CI 1.01-1.60) and receipt of hearing aid/cochlear implant (aOR 3.97, 95%CI: 2.01-7.82) compared with the lowest quartile.

Conclusion: In this multicenter cohort study, peak bilirubin levels in neonates of <29 weeks of gestation increased with gestational age. Peak bilirubin values in the highest gestational age-specific quartile were associated with significant neurodevelopmental and hearing impairments.