Association Between Asthma Risk & Moderate Bilirubin Most Likely Genetic


The association between moderate hyperbilirubinemia and childhood asthma and lack of association with higher bilirubin levels indicates the association is not causal.

Michael W. Kuzniewicz, MD

Michael W. Kuzniewicz, MD

Though past analyses have shown an link between jaundice/phototherapy and the development of childhood asthma, a recent study found that high bilirubin levels is not associated with asthma.

Whereas nearly all relevant previous studies relied on using administrative codes instead of assessment of actual bilirubin levels to make a jaundice diagnosis, investigators preferred the latter option in order to differentiate jaundice and phototherapy, study author Michael W. Kuzniewicz, MD, director of the Perinatal Research Unit at the Kaiser Permanente Northern California (KPNC) Division of Research, said.

Bilirubin is produced by the standard breakdown of red blood cells, which then pass through the liver, into the intestines, and finally out of the body in fecal matter. Jaundice occurs when bilirubin levels become too high in the blood.

Newborns are particularly susceptible to jaundice because they have higher turnover of red blood cells than adults, and their immature livers may not be able to remove bilirubin from their blood quickly enough. The classic visual sign of jaundice is a yellowing of the skin.

Most cases of jaundice resolve without treatment. If it persists, phototherapy, where the skin is exposed to ultraviolet light, is administered.

As a supplement to a study assessing the late impact of hyperbilirubinemia or phototherapy, researchers performed a retrospective cohort analysis. Subjects were infants born at 35 weeks gestation or more, between January 1, 2010 and December 31, 2014, at KPNC hospitals. Only the 11 facilities that performed universal bilirubin screening with total serum bilirubin (TSB) before discharge were included.

Infants had to remain in the KPNC system during their entire hospitalization (from birth to discharge). Children who did not remain in the health plan for at least 25 months after birth and those with no TSB levels were excluded.

Asthma occurrence was defined as a child having both of the following: 2 asthma diagnoses from any outpatient or inpatient encounter, separated by 30 days, after 2 years of age and at least 2 asthma medication prescriptions in a 12-month period, separated by at least 30 days, after 2 years of age.

Of the 109,212 infants included in the cohort, 16.7% had TSB levels of 15 mg/dL or more, 4.5% had 18 mg/dL or more, and 11.5% were treated with phototherapy. When compared with children who had TSB levels between 3 to 5.9 mg/dL, children with TSB levels of 9 to 11.9 mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL had a higher risk of asthma (HR: 1.22 [95% CI: 1.11 - 1.3]; HR: 1.18 [95% CI: 1.08 - 1.29]; and HR: 1.30 [95% CI: 1.18 - 1.43], respectively).

However, children with TSB levels of 18 mg/dL or more were not at a higher risk of asthma (HR: 1.04; 95% CI: 0.90 - 1.20). Phototherapy was not associated with asthma risk (HR: 1.07; 95% CI: 0.96 - 1.20).

The association between moderate hyperbilirubinemia and childhood asthma and lack of association with higher bilirubin levels indicates the association is not causal, noted Kuzniewicz.

“More likely there is another factor, perhaps an unmeasured cofounder such as mutations in the glutathione S-transferase gene, that is both associated with moderate levels of hyperbilirubinemia and the development of asthma,” he said, adding that further studies should focus on evaluating genetics to shed more light on the association between moderate bilirubin levels and childhood asthma risk.

The study, “Hyperbilirubinemia, Phototherapy, and Childhood Asthma," was published online in Pediatrics.

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