Hyperbilirubinemia management in newborn infants: AAP updates recommendations
USA: The American Academy of Pediatrics (AAP) has revised a clinical practice guideline and updated recommendations for the management of hyperbilirubinemia in newborn infants ≥35 weeks of gestation. The updated guidelines have been published online on Aug. 5 in Pediatrics.
Some degree of jaundice is said to be present in more than 80% of newborn infants. Careful monitoring of all newborn infants and applying appropriate treatments is essential as high bilirubin concentrations can cause acute bilirubin encephalopathy and kernicterus.
For developing the guidelines, the AAP convened a clinical practice guideline committee with a membership that included hospitalists, neonatologists, a nurse, primary care pediatricians, and breastfeeding experts. Some members had special expertise in neonatal hyperbilirubinemia. The committee worked from 2014 to 2022 to review new evidence and to identify opportunities to clarify and improve the 2004 guideline. A wide array of clinicians and experts in neonatal hyperbilirubinemia and parents of children with kernicterus extensively peer-reviewed the guidelines.
The recommendations described below are formatted as Key Action Statements (KAS) for easy identification.
Prevention of Hyperbilirubinemia
KAS 1: If the maternal antibody screen is positive or unknown because the mother did not have prenatal antibody screening, the infant should have a direct antiglobulin test (DAT) and the infant's blood type should be determined as soon as possible using either cord or peripheral blood.
KAS 2: Oral supplementation with water or dextrose water should not be provided to prevent hyperbilirubinemia or decrease bilirubin concentrations.
Assessment and Monitoring of Hyperbilirubinemia
KAS 3: Use TSB as the definitive test to guide phototherapy and escalation-of-care decisions, including exchange transfusion.
KAS 4: All infants should be visually assessed for jaundice at least every 12 hours following delivery until discharge. TSB or TcB should be measured as soon as possible for infants noted to be jaundiced <24 hours after birth.
KAS 5: The TcB or TSB should be measured between 24 and 48 hours after birth or before discharge if that occurs earlier.
KAS 6: TSB should be measured if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold or if the TcB is ≥15 mg/dL.
KAS 7: If more than 1 TcB or TSB measure is available, the rate of increase may be used to identify infants at higher risk of subsequent hyperbilirubinemia. A rapid rate of increase (≥0.3 mg/dL per hour in the first 24 hours or ≥0.2 mg/dL per hour thereafter) is exceptional73 and suggests hemolysis. In this case, perform a DAT if not previously done.
KAS 8: If appropriate follow-up cannot be arranged for an infant recommended to have an outpatient follow-up bilirubin measure, discharge may be delayed.
KAS 8: If appropriate follow-up cannot be arranged for an infant recommended to have an outpatient follow-up bilirubin measure, discharge may be delayed.
KAS 9: For breastfed infants who are still jaundiced at 3 to 4 weeks of age, and for formula-fed infants who are still jaundiced at 2 weeks of age, the total and direct-reacting (or conjugated) bilirubin concentrations should be measured to identify possible pathologic cholestasis.
Treatment of Hyperbilirubinemia
KAS 10: Intensive phototherapy is recommended at the total serum bilirubin thresholds on the basis of gestational age, hyperbilirubinemia neurotoxicity risk factors, and age of the infant in hours.
KAS 11: 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.
KAS 12: For hospitalized infants, TSB should be measured within 12 hours after starting phototherapy. The timing of the initial TSB measure after starting phototherapy and the frequency of TSB monitoring during phototherapy should be guided by the age of the child, the presence of hyperbilirubinemia neurotoxicity risk factors, the TSB concentration, and the TSB trajectory.
KAS 13: For infants receiving home phototherapy, the TSB should be measured daily. Infants should be admitted for inpatient phototherapy if the TSB increases and the difference between the TSB and the phototherapy threshold narrows or the TSB is ≥1 mg/dL above the phototherapy threshold.
KAS 14: For infants requiring phototherapy, measure the hemoglobin concentration, hematocrit, or complete blood count to assess for the presence of anemia and to provide a baseline in case subsequent anemia develops. Evaluate the underlying cause or causes of hyperbilirubinemia in infants who require phototherapy by obtaining a DAT in infants whose mother had a positive antibody screen or whose mother is blood group O regardless of Rh(D) status or whose mother is Rh(D)−. G6PD activity should be measured in any infant with jaundice of unknown cause whose TSB increases despite intensive phototherapy, whose TSB increases suddenly or increases after an initial decline, or who requires escalation of care.
KAS 15: Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy. A longer period of phototherapy is an option if there are risk factors for rebound hyperbilirubinemia (eg, gestational age <38 weeks, age <48 hours at the start of phototherapy, hemolytic disease).
KAS 16: Repeat bilirubin measurement after phototherapy is based on the risk of rebound hyperbilirubinemia.
KAS 17: Care should be escalated when an infant's TSB reaches or exceeds the escalation-of-care threshold, defined as 2 mg/dL below the exchange transfusion threshold, (infants with no known hyperbilirubinemia neurotoxicity risk factors) or (infants whose TSB is increasing despite phototherapy or infants with at least 1 recognized hyperbilirubinemia neurotoxicity risk factor.
KAS 18: For infants requiring escalation of care, blood should be sent STAT for total and direct-reacting serum bilirubin, a complete blood count, serum albumin, serum chemistries, and type and crossmatch.
KAS 19: Infants requiring escalation of care should receive intravenous hydration and emergent intensive phototherapy. A neonatologist should be consulted about urgent transfer to a NICU that can perform an exchange transfusion.
KAS 20: TSB should be measured at least every 2 hours from the start of the escalation-of-care period until the escalation-of-care period ends. Once the TSB is lower than the escalation-of-care threshold, management should proceed according to the section "C. Monitoring Infants Receiving Phototherapy."
KAS 21: Intravenous immune globulin (IVIG; 0.5 to 1 g/kg) over 2 hours may be provided to infants with isoimmune hemolytic disease (ie, positive DAT) whose TSB reaches or exceeds escalation of care threshold. The dose can be repeated in 12 hours.
KAS 22: An urgent exchange transfusion should be performed for infants with signs of intermediate or advanced stages of acute bilirubin encephalopathy (eg, hypertonia, arching, retrocollis, opisthotonos, high-pitched cry, or recurrent apnea).
KAS 23: An urgent exchange transfusion should be performed for infants if the TSB is at or above the exchange transfusion threshold. If, while preparing for the exchange transfusion but before starting the exchange transfusion, a TSB concentration is below the exchange transfusion threshold and the infant does not show signs of intermediate or advanced stages of acute bilirubin encephalopathy, then the exchange transfusion may be deferred while continuing intensive phototherapy and following the TSB every 2 hours until the TSB is below the escalation of care threshold.
KAS 24: Beginning at least 12 hours after birth, if a discharge is being considered, the difference between the bilirubin concentration measured closest to discharge and the phototherapy threshold at the time of the bilirubin measurement should be calculated and used to guide follow-up.
KAS 25: Before discharge, all families should receive written and verbal education about neonatal jaundice. Parents should be provided written information to facilitate postdischarge care, including the date, time, and place of the follow-up appointment and, when necessary, a prescription and appointment for a follow-up TcB or TSB. Birth hospitalization information, including the last TcB or TSB and the age at which it was measured, and DAT results (if any) should be transmitted to the primary care provider who will see the infant at follow-up. If there is uncertainty about who will provide the follow-up care, this information should also be provided to families.
"The clinical practice guideline emphasizes the opportunities for primary prevention, the need to obtain an accurate history and physical examination to determine the presence of hyperbilirubinemia and hyperbilirubinemia neurotoxicity risk factors, and the importance of predicting the risk of future hyperbilirubinemia including a predischarge measurement of TSB or TcB, and the importance of postdischarge follow-up," the researchers wrote in their study.
"This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued," they concluded. "For all recommendations, the committee recognizes that clinicians should understand the rationale for what is recommended, use their clinical judgment, and, when appropriate, engage in shared decision making."
Reference:
Kemper AR, Newman TB, Slaughter JL, Maisels MJ, Watchko JF, Downs SM, Grout RW, Bundy DG, Stark AR, Bogen DL, Holmes AV, Feldman-Winter LB, Bhutani VK, Brown SR, Panayotti GMM, Okechukwu K, Rappo PD, Russell TL. Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2022 Aug 5:e2022058859. doi: 10.1542/peds.2022-058859. Epub ahead of print. PMID: 35927462.
