Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation

Pediatrics. 2022 Sep 1;150(3):e2022058865. doi: 10.1542/peds.2022-058865.


Context: Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk.

Objective: To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation.

Data source: PubMed.

Study selection: English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants.

Data extraction: Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion).

Results: New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis.

Limitations: The search was limited to 1 database and English language studies.

Conclusions: Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

MeSH terms

  • Child
  • Digestive System Diseases*
  • Exchange Transfusion, Whole Blood
  • Female
  • Gestational Age
  • Humans
  • Hyperbilirubinemia, Neonatal* / diagnosis
  • Hyperbilirubinemia, Neonatal* / therapy
  • Immunoglobulins, Intravenous
  • Infant, Newborn
  • Kernicterus* / diagnosis
  • Kernicterus* / etiology
  • Kernicterus* / prevention & control
  • Phototherapy
  • Pregnancy


  • Immunoglobulins, Intravenous