Evidence Based Strategies for Common Clinical Questions

Don't Be Silly -- Know Your Bili!

Author: Ali Fowler, MD | Pediatric Resident

Column Editor: Kathleen Berg, MD | Co-Director, Department of Evidence Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 

Jaundice affects over 80% of newborns, and though the risk for permanent neurotoxicity – or kernicterus – is small, it cannot be overlooked.^1,2 To help us protect our littlest patients, the American Academy of Pediatrics (AAP) provides a comprehensive clinical practice guideline (CPG) for the diagnosis and management of neonatal hyperbilirubinemia. In August 2022, the AAP revised its 2004 CPG and subsequent update in 2009.^3-5 This article answers two questions: first, why did we need new guidelines, and second, what do they mean for the general pediatrician? 

Since publication of the previous guidelines, new research has expanded our understanding of the risks associated with hyperbilirubinemia. The widespread implementation of universal screening, as recommended in the 2009 version of the CPG, decreased the incidence of hazardous hyperbilirubinemia (defined as serum bilirubin > 30 mg/dL).³ Phototherapy, while generally benign, is not without its downsides, including prolonged hospitalization, increased resource utilization, interruption of breastfeeding, stress on families and a very small increased risk for childhood seizures.^6,7 Taking into account the risks and benefits of treatment, the new guidelines provide slightly higher thresholds for treating hyperbilirubinemia. By raising these thresholds, we can ease medical, emotional and financial burdens. 

The revised CPG now includes four different nomograms to guide treatment. There are two for phototherapy thresholds, one for infants with one or more risk factors for neurotoxicity and another for infants without such risks. Similarly, there are two for exchange transfusion thresholds based on risk. They each provide treatment thresholds based on gestational age and age in hours [KAS 10, 23].³ These treatment thresholds are a change from the 2004 CPG, which grouped gestational age and neurotoxicity risk together to create fewer individual thresholds. The popular websites peditools.org and bilitool.org, which generate individualized recommendations based on provider-entered data, are updated to reflect these changes.  

In addition to updated nomograms, the new CPG provides more specific recommendations for repeating bilirubin levels after initiation of phototherapy, discontinuing therapy, and timing repeat measurements after discontinuation [KAS 12, 15, 16]. It also details a subset of low-risk infants for whom home phototherapy may be considered [KAS 11, 13]. For infants who did not require phototherapy or other treatment, the new CPG provides recommendations for discharge planning based on the difference between measured bilirubin and age-specific treatment threshold [KAS 24].³ These guidelines are likely in line with existing practice patterns of many pediatricians, but now are corroborated by the guideline expert committee.  

The 2004 CPG contained an additional nomogram demonstrating “risk zones,” which were a tool to predict risk of progression to clinically significant hyperbilirubinemia.⁴ The new CPG replaces these “risk zones” with more specific recommendations for escalation of care and discharge planning. At serum bilirubin levels 2 mg/dL below the exchange transfusion threshold or higher, the clinician should obtain STAT labs, start IV fluid hydration, give IVIG if isoimmune hemolysis is identified, and initiate transfer to a high-level NICU with exchange transfusion capabilities [KAS 17-21].³  

Another timely update in the new CPG is removal of race or ethnicity as a variable for risk stratification. The AAP is committed to eliminating race-based guidelines, recognizing that race, a social construct, cannot be used as a proxy for genetic ancestry.⁸ In this way, the 2004 guidelines were problematic, including Black race as a protective factor for severe hyperbilirubinemia.⁴ Further research into health disparities found that Black babies are disproportionately affected by kernicterus, largely related to glucose-6-phosphate dehydrogenase (G6PD) deficiency, a cause of kernicterus prevalent among certain ancestry groups (Mediterranean, Middle Eastern, Sub-Saharan African, Arabian, and Southeast Asian).^3,9 The new CPG advises, therefore, that the clinician elicit information about ancestry, rather than race, to consider risk for G6PD.   

In summary, the new CPG uses updated evidence to provide clearer, more specific decision-making tools. The new guidelines may lead to fewer neonates requiring phototherapy or exchange transfusion and should help to mitigate some of the adverse effects of race-based medicine. All clinicians who care for neonates in newborn nurseries, neonatal intensive care units, primary care clinics and general inpatient settings should be familiar with these new guidelines. 

References: 

1. Bhutani VK, Stark AR, Lazzeroni LC, et al. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr. 2013;162(3):477-482.e1. doi:10.1016/j.jpeds.2012.08.022 
2. Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M. Rates of extreme neonatal hyperbilirubinemia and kernicterus in children and adherence to national guidelines for screening, diagnosis, and treatment in Sweden. JAMA Netw Open. 2019;2(3):e190858. doi:10.1001/jamanetworkopen.2019.0858 
3. Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022;150(3):e2022058859. doi:10.1542/peds.2022-058859 
4. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation [published correction appears in Pediatrics. 2004 Oct;114(4):1138]. Pediatrics. 2004;114(1):297-316. doi:10.1542/peds.114.1.297 
5. Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the newborn infant > or =35 weeks’ gestation: an update with clarifications. Pediatrics. 2009;124(4):1193-1198. doi:10.1542/peds.2009-0329 
6. Slaughter JL, Kemper AR, Newman TB. Technical report: diagnosis and management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022;150(3):e2022058865. doi:10.1542/peds.2022-058865 
7. Newman TB, Wu YW, Kuzniewicz MW, Grimes BA, McCulloch CE. Childhood seizures after phototherapy. Pediatrics. 2018;142(4):e20180648. doi:10.1542/peds.2018-0648 
8. Wright JL, Davis WS, Joseph MM, et al. Eliminating race-based medicine. Pediatrics. 2022;150(1):e2022057998. doi:10.1542/peds.2022-057998 
9. Wright JL, Trent ME. Applying an equity lens to clinical practice guidelines: getting out of the gate. Pediatrics. 2022;150(3):e2022058918. doi:10.1542/peds.2022-058918