Why screen for hyperbilirubinemia?

A: Elevated concentrations of unconjugated bilirubin in blood (typically >30 mg/dL) can induce a type of permanent brain damage called kernicterus. Conditions in newborns that cause excessive bilirubin production, such as maternal antibodies to red blood cell antigens and inherited red blood cell disorders—that cause decreased clearance of bilirubin in the blood—including low albumin and decreased activity of conjugating enzymes—are associated with an increased risk for hyperbilirubinemia and subsequent neurotoxicity. Fortunately, hyperbilirubinemia is treatable, and with prompt recognition and intervention, many cases of kernicterus can be prevented.

What guidance is available for managing this condition?

Last year, the American Academy of Pediatrics (AAP) updated its guidelines for managing hyperbilirubinemia in newborns 35 weeks of gestation or older (Pediatrics 2022;150: e2022058859). Like the previous version published in 2004, the 2022 guidelines focus on prevention, risk assessment, monitoring, and therapy for hyperbilirubinemia. In 2009, the AAP added further commentary to endorse universal pre-discharge bilirubin screening by total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) measurement (Pediatrics 2009;124:1193–8). Since then, the incidence of devastating neurologic impairments associated with unconjugated hyperbilirubinemia has decreased in major U.S. health systems.

What’s new in 2022?

Recognizing the impact of previous recommendations, the 2022 guidelines reaffirm universal screening by TSB or TcB, update treatment thresholds, and clarify which risk factors dictate follow-up practices. The 2009 updates first suggested universal TSB or TcB measurement, but the 2022 guidelines go further by promoting TSB as the definitive test needed for the escalation of care. Before that, the 2004 guidelines promoted visual assessment for jaundice (skin blanching via digital pressure) every 8 hours in newborns, and immediate TSB or TcB measurement was advised if jaundice was observed before 24 hours of life (HOL) or seemed excessive for the infant’s age; beyond 24 HOL, visual assessment and TcB were the main screening methods promoted.

The 2022 guidelines specify that bilirubin measurement should be made between 24–48 HOL or prior to discharge (whichever is earlier) for infants not visibly jaundiced in the first 24 HOL. While TcB is still approved as a screening technique because it is non-invasive and reasonably accurate near decision limits, the new guidance decreases reliance on visual assessment and clarifies situations when TSB should be assessed. For example, the expert group now encourages measuring for TSB when TcB is within 3 mg/dL of age-specific phototherapy threshold or >15 mg/dL.

Another important change is related to monitoring the rate of increase between two sequential TSB or TcB measurements (when available). In the 2022 guidelines, a rise of ≥0.3 mg/dL in the first 24 HOL or ≥0.2 mg/dL after 24 HOL is considered to raise the risk for developing significant hyperbilirubinemia and should prompt additional workup to evaluate for an underlying hemolytic condition.

How will the guidelines affect pediatric labs?

Depending on local practices and the population served, the new guidelines may modestly affect TSB volumes. Newborns with a positive result on the direct antiglobulin test (DAT) will be tested more frequently, in accordance with 2022 guidelines. Thus, institutions that do not use TcB likely will see an increase in TSB requests for DAT-positive newborns. However, the overall number of TSBs will likely decrease at institutions that use TcB because the thresholds for phototherapy and exchange transfusion are slightly higher than previous nomograms. Accordingly, outpatient newborns who present for well-child visits to community pediatricians may present with more jaundice than in previous years, leading to additional referrals for TSB measurement.

Stephen Roper, PhD, DABCC, is an associate professor of pathology & immunology and pediatrics at Washington University School of Medicine and the associate director of pediatric laboratory services at St. Louis Children’s Hospital in St. Louis. +Email: [email protected]