Abstract
Objective This study aimed to determine whether neonatal hyperbilirubinemia is associated with
a risk of autism spectrum disorder (ASD) using a large population-based cohort.
Study Design This retrospective cohort study used data from the children's database (2000–2012)
of the National Health Insurance Research Database (1996–2012) in Taiwan. We included
neonates who were born between 2000 and 2004 and aged <1 month diagnosed with and
without hyperbilirubinemia. The primary outcome was physician-diagnosed ASD. At the
end of 2012, multivariate Cox's regression analysis was used to estimate hazard ratios
(HRs).
Results A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were
associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval
[CI]: 1.05–1.57) compared with those without hyperbilirubinemia. In subanalysis to
determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia
were associated with ASD showed no association between treatment and ASD, suggesting
the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys
had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI: 4.41–7.86).
Additionally, neonates born with preterm birth and low birth weight were associated
with a risk of ASD (HR = 1.46, 95% CI: 1.00–2.13).
Conclusion We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal
hyperbilirubinemia may be an independent risk factor for ASD if there is a residual
confounding by other perinatal complications. Therefore, this study does not support
a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.
Keywords
autism spectrum disorder - neonatal hyperbilirubinemia - risk factor - boy - preterm
birth and low birth weight
