Hyperbilirubinemia: What’s New?

In 2022, the AAP released the Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation, an update to the 2004 guideline of the same name. Expanded evidence motivating the update focuses on the monitoring and treatment of hyperbilirubinemia. Below are some of the updates:

Challenges in recognizing G6PD deficiency

G6PD deficiency is one of the most important causes of hyperbilirubinemia leading to kernicterus around the world. But identifying these infants is challenging. Most affected infants do not have a positive family history, although ancestry from certain populations may be helpful in gauging risk (e.g., Sub-Saharan Africa, Middle East, Mediterranean, Arabian Peninsula, and Southeast Asia).

Clinical events that should raise our suspicion of G6PD deficiency include phototherapy before hospital discharge, severe hyperbilirubinemia, or atypical hyperbilirubinemia (e.g., elevated TSB in a formula-fed infant, late-onset jaundice, or sudden-onset TSB elevation).

Importantly, even after what appears to be an acute hemolytic event, there may be little laboratory evidence of hemolysis. Measuring the G6PD activity during or soon after a hemolytic event can lead to a falsely normal result. If G6PD deficiency is strongly suspected but the measurement of G6PD activity is normal or close to normal, the G6PD activity should be measured at least 3 months later.

Risk factors for neurotoxicity

Decisions to initiate phototherapy are guided by the gestational age, the hour-specific TSB, and the presence of risk factors for
bilirubin neurotoxicity. The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated. Neurotoxicity risk factors include

  • Gestational age <38 wk (and this risk increases with the degree of prematurity)
  • Albumin <3.0 g/dL (which leads to greater availability of unbound bilirubin)
  • Isoimmune hemolytic disease (i.e., positive direct antiglobulin test), G6PD deficiency, or other hemolytic conditions
  • Sepsis
  • Significant clinical instability in the previous 24 hours

(Slightly) increased thresholds for phototherapy

Phototherapy decreases bilirubin concentrations through a variety of photochemical reactions that allow the bilirubin to be more easily excreted. The primary goal of phototherapy is to decrease the likelihood of further increases in the TSB concentration that would lead to a need for escalation of care, including exchange transfusion.

The recommended phototherapy thresholds are far below those at which overt acute bilirubin neurotoxicity or kernicterus occurs. The updated guideline notes that new evidence that bilirubin neurotoxicity does not occur until concentrations well above the 2004 exchange transfusion thresholds justified raising the phototherapy treatment thresholds by a narrow range.

Accordingly, follow-up bilirubin testing is based on the difference between bilirubin level and the phototherapy threshold. No more risk zones!

Source: Kemper et al. Pediatrics 2022

Rebound phenomenon

Rebound hyperbilirubinemia is defined as a TSB concentration that reaches the phototherapy threshold for the infant’s age within 72 to 96 hours of discontinuing phototherapy. Infants who receive phototherapy during their birth hospitalization are much more likely to experience rebound hyperbilirubinemia than those whose first treatment with phototherapy occurs on readmission.

The risk factors for rebound hyperbilirubinemia include younger postnatal age (i.e., <48 hours) at the start of phototherapy, hemolytic disease, gestational age <38 weeks, and higher TSB at the time of phototherapy discontinuation in relationship to the phototherapy threshold.

The timing of follow-up bilirubin testing after discontinuing phototherapy should be based on the risk of rebound hyperbilirubinemia. In general, at least 12 hours, and preferably 24 hours, should elapse to allow sufficient time for the bilirubin concentration to demonstrate whether there is rebound hyperbilirubinemia.

Home phototherapy

For newborn infants who have already been discharged and then develop a TSB above the phototherapy threshold, treatment with a home LED-based phototherapy device rather than readmission to the hospital is an option for infants who meet the following criteria:

  • Gestational age ≥38 weeks
  • ≥48 hours old
  • Clinically well with adequate feeding
  • No known hyperbilirubinemia neurotoxicity risk factors (see above)
  • No previous phototherapy
  • TSB concentration no more than 1 mg/dL above the phototherapy treatment threshold
  • An LED-based phototherapy device will be available in the home without delay
  • TSB can be measured daily

Blog post based on Med-Peds Forum talk by Jevin Clark, PGY1, and Maya Tsao-Wu, PGY2

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