Risk of Sensorineural Hearing Loss and Bilirubin Exchange Transfusion Thresholds.
OBJECTIVE
High bilirubin levels are associated with sensorineural hearing loss (SNHL). However, few large studies of relative and excess risk exist. We sought to quantify the risk of SNHL in newborns who had bilirubin levels at or above American Academy of Pediatrics exchange transfusion thresholds (ETT).


METHODS
Infants born at ≥35 weeks gestation in 15 Kaiser Permanente Northern California hospitals from 1995-2011 were eligible (N = 525 409). We used a nested double cohort design. The exposed cohort included subjects with ≥1 bilirubin level at or above ETT. The unexposed cohort was a 3.6% random sample of subjects with all bilirubin levels below ETT (10 unexposed per exposed). An audiologist, blinded to bilirubin levels, reviewed the charts of children in whom SNHL had been diagnosed before age 8 years to confirm the diagnosis. We calculated Cox proportional hazard ratios for time to diagnosis of SNHL.


RESULTS
SNHL was confirmed in 11 (0.60%) of the 1834 exposed subjects and in 43 (0.23%) of the 19 004 unexposed. Only bilirubin levels ≥10 mg/dL above ETT were associated with a statistically significant increased risk of SNHL (hazard ratio: 36 [95% confidence interval (CI): 13 to 101]). Likewise, only bilirubin levels ≥35 mg/dL were associated with a statistically significant increased risk of SNHL (hazard ratio: 91 [95% CI: 32 to 255]). For subjects with total serum bilirubin levels 0 to 4.9 mg/dL above ETT, the upper limit of the 95% CI for excess risk was 0.5%.


CONCLUSIONS
Only bilirubin levels well above ETT were associated with SNHL. At lower bilirubin levels, the excess risk of SNHL was low.
Department of Pediatrics, Kaiser Permanente Northern California, Santa Clara, California; Departments of Epidemiology & Biostatistics, andrea.wickremasinghe@kp.org.
Andrea C
AC
Wickremasinghe
Hearing Health Center, Oak Brook, Illinois; and.
Robert J
RJ
Risley
Division of Research, Kaiser Permanente Northern California, Oakland, California Pediatrics, and.
Michael W
MW
Kuzniewicz
Pediatrics, and Neurology, University of California, San Francisco, California;
Yvonne W
YW
Wu
Division of Research, Kaiser Permanente Northern California, Oakland, California.
Eileen M
EM
Walsh
Division of Research, Kaiser Permanente Northern California, Oakland, California.
Soora
S
Wi
Departments of Epidemiology & Biostatistics.
Charles E
CE
McCulloch
Departments of Epidemiology & Biostatistics, Division of Research, Kaiser Permanente Northern California, Oakland, California Pediatrics, and.
Thomas B
TB
Newman
D001663:Bilirubin / Q000097:blood; D016022:Case-Control Studies; D005078:Exchange Transfusion, Whole Blood; D006319:Hearing Loss, Sensorineural / Q000209:etiology*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000097:blood / Q000150:complications* / Q000628:therapy; D007231:Infant, Newborn; D007234:Infant, Premature; D012307:Risk Factors
D001663:Bilirubin