Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation

Publication Date: August 1, 2022

Prevention of Hyperbilirubinemia

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. (B, R)

Oral supplementation with water or dextrose water should not be provided to prevent hyperbilirubinemia or decrease bilirubin concentrations. (B, S)

Assessment and Monitoring for Hyperbilirubinemia

Use TSB as the definitive test to guide phototherapy and escalation-of-care decisions, including exchange transfusion. (X, R)

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. (X, S)

The TcB or TSB should be measured between 24 and 48 hours after birth or before discharge if that occurs earlier. (C, R)

The TcB or TSB should be measured between 24 and 48 hours after birth or before discharge if that occurs earlier. (C, R)

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.70–72 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 exceptional 73 and suggests hemolysis. In this case, perform a DAT if not previously done. (D, O)

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. (X, R)

Treatment of Hyperbilirubinemia

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. (X, R)

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 (Table 2)
  • No previous phototherapy
  • TSB concentration no more than 1 mg/dL above the phototherapy treatment threshold (Fig 2; Supplemental Table 1 and Supplemental Fig 1)
  • An LED-based phototherapy device will be available in the home without delay
  • TSB can be measured daily
(D, O)

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. (X, R)

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. (X, R)

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. (X, R)

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). (C, O)

Repeat bilirubin measurement after phototherapy is based on the risk of rebound hyperbilirubinemia.
  • Infants who exceeded the phototherapy threshold during the birth hospitalization and (1) received phototherapy before 48 hours of age; (2) had a positive DAT; or (3) had known or suspected hemolytic disease, should have TSB measured 6 to 12 hours after phototherapy discontinuation and a repeat bilirubin measured on the day after phototherapy discontinuation.
  • All other infants who exceeded the phototherapy threshold during the birth hospitalization should have bilirubin measured the day after phototherapy discontinuation.
  • Infants who received phototherapy during the birth hospitalization and who were later readmitted for exceeding the phototherapy threshold should have bilirubin measured the day after phototherapy discontinuation.
  • Infants readmitted because they exceeded the phototherapy threshold following discharge but who did not receive phototherapy during the birth hospitalization and infants treated with home phototherapy who exceeded the phototherapy threshold should have bilirubin measured 1 to 2 days after phototherapy discontinuation or clinical follow-up 1 to 2 days after phototherapy to determine whether to obtain a bilirubin measurement. Risk factors for rebound hyperbilirubinemia to consider in this determination include the TSB at the time of phototherapy discontinuation in relationship to the phototherapy threshold, gestational age <38 weeks, the adequacy of feeding and weight gain, and the other hyperbilirubinemia and hyperbilirubinemia neurotoxicity risk factors.
It is an option to measure TcB instead of TSB if it has been at least 24 hours since phototherapy was stopped. (X, R)

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. (X, R)

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. (X, R)

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. (C, R)

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 “Monitoring Infants Receiving Phototherapy.” (X, R)

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. (C, O)

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). (C, R)

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. (C, R)

 Postdischarge Follow-Up

Beginning at least 12 hours after birth, if 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. (C, R)

Hospital Policies and Procedures

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. (X, S)

Tables and Figures

TABLE 1. Risk Factors for Developing Significant Hyperbilirubinemia

  • Lower gestational age (ie, risk increases with each additional week less than 40 wk)
  • Jaundice in the first 24 h after birth
  • Predischarge transcutaneous bilirubin (TcB) or total serum bilirubin (TSB) concentration close to the phototherapy threshold
  • Hemolysis from any cause, if known or suspected based on a rapid rate of increase in the TSB or TcB of >0.3 mg/dL per hour in the first 24 h or >0.2 mg/dL per hour thereafter.
  • Phototherapy before discharge
  • Parent or sibling requiring phototherapy or exchange transfusion
  • Family history or genetic ancestry suggestive of inherited red blood cell disorders, including glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Exclusive breastfeeding with suboptimal intake
  • Scalp hematoma or significant bruising
  • Down syndrome
  • Macrosomic infant of a diabetic mother

TABLE 2. Hyperbilirubinemia Neurotoxicity Risk Factors

  • Gestational age <38 wk and this risk increases with the degree of prematuritya
  • Albumin <3.0 g/dL
  • Isoimmune hemolytic disease (ie, positive direct antiglobulin test), G6PD deficiency, or other hemolytic conditions
  • Sepsis
  • Significant clinical instability in the previous 24 h
aGestational age is required to identify the phototherapy thresholds (Figs 2 and 3; Supplemental Tables 1 and 2, and Supplemental Figs 1 and 2) and the exchange transfusion thresholds (Figs 5 and 6; Supplemental Tables 3 and 4, and Supplemental Figs 3 and 4).

Recommendation Grading




Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation

Authoring Organization

Publication Month/Year

August 1, 2022

Document Type


Country of Publication


Document Objectives

More than 80% of newborn infants will have some degree of jaundice. Careful monitoring of all newborn infants and the application of appropriate treatments are essential, because high bilirubin concentrations can cause acute bilirubin encephalopathy and kernicterus. Kernicterus is a permanent disabling neurologic condition characterized by some or all of the following: choreoathetoid cerebral palsy, upward gaze paresis, enamel dysplasia of deciduous teeth, sensorineural hearing loss or auditory neuropathy or dyssynchrony spectrum disorder, and characteristic findings on brain MRI. A description of kernicterus nomenclature is provided in Appendix A. Central to this guideline is having systems in place including policies in hospitals and other types of birthing locations to provide the care necessary to minimize the risk of kernicterus. This article updates and replaces the 2004 American Academy of Pediatrics (AAP) clinical practice guideline for the management and prevention of hyperbilirubinemia in the newborn infant ≥35 weeks gestation. This clinical practice guideline, like the previous one, addresses issues of prevention, risk assessment, monitoring, and treatment.

Inclusion Criteria

Male, Female, Infant

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Diagnosis, Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D051556 - Hyperbilirubinemia, Neonatal, D006932 - Hyperbilirubinemia


phototherapy, jaundice, infant jaundice, Hyperbilirubinemia, neonatal jaundice, newborn

Source Citation

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.

Supplemental Methodology Resources

Technical Review, Data Supplement