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Reuters Health Information (2010-11-30): Conjugated and direct bilirubin levels not interchangeable in newborns


Conjugated and direct bilirubin levels not interchangeable in newborns

Last Updated: 2010-11-30 10:53:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Conjugated bilirubin (CB) and direct bilirubin (DB) level measurements cannot be interpreted interchangeably, cautions a group of pediatricians from San Francisco in a new report. Their study, they say, also provides clear evidence that even mildly elevated CB levels are abnormal.

In an e-mail to Reuters Health, Dr. Adam Rahn Davis from California Pacific Medical Center said, "Even low elevations in conjugated bilirubin levels may need to be investigated, while low elevations of direct bilirubin levels are found in many infants due to the measuring technique. Conjugated bilirubin is more specific for the presence of disease than direct bilirubin."

"We believe conjugated bilirubin measurements are superior to direct bilirubin measurements and hope that labs continue to move towards measuring conjugated bilirubin," he wrote.

Neonatal jaundice is common, occurring in roughly two-thirds of all newborns, the clinicians point out in the November 15 online issue of the Journal of Pediatrics.

CB and DB levels, although often measured, are inherently different. In a retrospective birth cohort study, the investigators examined the distribution of serum CB and DB levels in a large community health care population and the diagnoses that were associated with elevated levels.

Subjects included 271,186 full-term newborns within the Northern California Kaiser Permanente Medical Care Program from 1995 to 2004. All CB and DB levels were available in a database and were correlated with the patients' inpatient and outpatient ICD-9 diagnoses.

An undetectable amount of CB is the norm, the authors note, and anything above 0.3 mg/dL is two standard deviations higher than the mean. The 99th percentile for CB is 0.5 mg/dL and the 99th percentile for DB is 2.1 mg/dL.

Based on their findings, Dr. Davis and colleagues say CB levels between 0.5 and 1.9 mg/dL "can be associated with infection, but most often remain unexplained."

Liver and biliary tract disease, they report, become increasingly likely as CB levels increase; for CB of 5 mg/dL or above, 47% of newborns have biliary disease and 43% have liver disease.

With a CB level in the first two weeks after birth of 0.5 to 1.9 mg/dL, the likelihood ratio for hepatobiliary disease is 2.77, the authors note; it jumps to 80.6 with a moderately elevated CB level of 2.0 to 4.9 in the first two weeks of life. Only 0.3% of newborns have CB in this range and more than 30% of them have an associated disease.

With a DB level in the first two weeks after birth of 2.0 to 4.9 mg/dL, the likelihood ratio for hepatobiliary disease is 17.6 and jumps to 223 at a level of 5 mg/dL or higher.

Dr. Davis and colleagues suggest that infection be considered in any newborn with CB levels of 0.5 mg/dL or higher and less than 2 mg/dL, "because severe infection occurs in 2% of these patients." They also recommend "observing these patients closely in time and rechecking a CB level to assure it has returned to reference range."

Furthermore, they say their study suggests that CB levels of 2 mg/dL or higher indicate that a "more in-depth assessment of the hepatobiliary system is warranted."

"I think that the most pertinent take-home message from this article is for clinicians to understand the clinical difference between direct and conjugated bilirubin and knowing which one their lab is measuring," Dr. Davis told Reuters Health.

The study is limited, he and colleagues note in their report, in that it was a database review and not a chart review. "ICD-9 codes may be used inconsistently or inaccurately, and this could make our conclusions less accurate," they note.


J Ped 2010.

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