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What’s Up (And Down) With the New Bilirubin Guidelines

August 5, 2022

Dr. Alex Kemper from Nationwide Children’s Hospital and Deputy Editor of Pediatrics and colleagues have led the development of a newly revised Clinical Practice Guideline (CPG) (10.1542/peds.2022-058859) and associated AAP Technical Report (10.1542/peds.2022-058865) being early released this week in the journal on the “Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 Weeks or More of Gestation”. These 2 important and timely documents are both “must reads” for primary care pediatricians and those caring for newborns. The rationale for revision and updating of the original 2004 guideline and the 2009 update with clarifications was two-fold. First, new evidence emerged that bilirubin neurotoxicity does not occur until levels well above the 2004 exchange transfusions thresholds, justifying a slightly higher treatment threshold for phototherapy with the goal of avoiding overtreatment. Second, there were increasing reports that phototherapy could have rare but serious late (childhood) adverse effects. New treatment thresholds specifically aim to balance the very small risks of phototherapy with the profound benefits of preventing hyperbilirubinemia that mandates exchange transfusion or is at a level at which kernicterus occurs.

An accompanying commentary (10.1542/peds.2022-058918) by Drs. Joseph Wright and Maria Trent celebrates the guidelines’ equity lens with publication of this first CPG following release of the AAP’s new “Eliminating Race-Based Medicine” policy statement (10.1542/peds.2022-057998). The old 2004 hyperbilirubinemia guideline listed “East Asian race” as a major risk factor for severe hyperbilirubinemia and asserted that African American infants “have much lower TSB (total serum bilirubin) levels than White or Asian infants” despite elevated risk of severe hyperbilirubinemia and kernicterus associated with G6PD (glucose-6-phosphate-dehydrogenase) deficiency. The new CPG directly address this important clinical risk using the equity lens of genetic ancestry (Sub-Saharan Africa, Middle East, Mediterranean, Arabian Peninsula, Southeast Asia) rather than race per se, acknowledging the importance and challenge of identifying infants with G6PD deficiency who usually do not present with a clear family history of the disorder.  This is an important moment for the AAP as it moves past race-based medicine to an equity-focused approach that respects biological differences between peoples without confusing these with social constructs.

The AAP Technical Report explains how the committee went about its work. To address the key issues above, Dr. Jonathan Slaughter, an epidemiologist and author, formulated PICO (patient, intervention, comparison, outcome) questions to guide the literature search; the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for each of the resulting systematic reviews that addressed those questions. The reviews focused on the emerging topic of phototherapy-related harms, both medical (e.g., childhood cancer, seizures, asthma) and parent-related (family bonding, breastfeeding). Another review focused on the effectiveness of IVIG (intravenous immunoglobulin) to prevent exchange transfusion – not a new topic but one with new information.

The CPG focuses on the opportunities for prevention of hyperbilirubinemia, for example by treatment to prevent isoimmune hemolytic disease and lactation support, and on parent education, referencing an AAP handout that explains jaundice. The big changes are the new phototherapy and exchange transfusion treatment thresholds, now anchored on gestational age and neurotoxicity risk factors, and the move away from race as a medical risk factor. Additionally, there are valuable sections on the perennially challenging and controversial topics of safely managing “rebound” following phototherapy and the role of home phototherapy in managing hyperbilirubinemia. The authors acknowledge that expert consensus has driven much of this CPG when evidence-based literature was not available. I found both reports easy reading despite their length, the documents are well-written, and this topic is crucial to my everyday clinical care. Thanks to the authors for the incredible amount of work that went into these reports, which will improve our care of newborns with hyperbilirubinemia. Please also read Drs. Wright and Trent’s excellent commentary as you tackle this new CPG and AAP Technical Report. Let us know what you think!

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