No Association Between Hyperbilirubinemia and Attention-Deficit Disorder

Abstract

To the Editor.—Jangaard et al1 recently reported outcomes of healthy newborns with total serum bilirubin (TSB) levels of ≥19 mg/dL in Nova Scotia. Although they found no cases of kernicterus and no increased risk of cerebral palsy, developmental delay, deafness, visual abnormalities, or autism in infants with TSB levels of ≥19 mg/dL, they reported an increased risk of attention-deficit disorder (ADD) (adjusted relative risk: 1.9 [95% confidence interval (CI): 1.1–3.3]).To investigate a possible association between TSB levels in infancy and subsequent risk of ADD, we linked laboratory, demographic, and outpatient visit databases of infants from 1995 to 2004 in the Northern California Kaiser Permanente Medical Care Program as previously described.2–4 We included infants born at ≥34 weeks and ≥2000 g who had at least 1 outpatient visit at ≥3 years of age (N = 161 141). TSB levels were measured at the discretion of the clinicians. We investigated the association between maximum reported TSB levels in the first 30 days after birth and ever having an outpatient visit that included a diagnosis of ADD (International Classification of Diseases, 9th Revision codes 314–314.9).We found no association between TSB levels and ADD diagnoses (Table 1). Dichotomizing at 19 mg/dL, the relative risk was 1.08 (95% CI: 0.91–1.28). A Cox proportional hazards model of time to first ADD diagnosis, controlling for race, gender, birth weight, gestational age, facility of birth, and maternal age, yielded similar results (adjusted hazard ratio for TSB ≥ 19 mg/dL: 1.07 [95% CI: 0.90–1.27]).The association between ADD and hyperbilirubinemia seems not to have been hypothesized a priori. This finding could easily be a result of chance, as commonly occurs when investigators look for associations not initially hypothesized (ie, with low previous probability).5 We conclude that hyperbilirubinemia is unlikely to be clinically significantly associated with ADD.This work was supported by National Institute of Child Health and Human Development grant RO1 HD047557.