Neonatal hyperbilirubinemia: An evidence-based approach
This review provides the latest advice on the screening and management of hyperbilirubinemia in term infants.
PRACTICE RECOMMENDATIONS
› Diagnose hyperbilirubinemia in infants with bilirubin measured at >95th percentile for age in hours. Do not use visual assessment of jaundice for diagnosis as it may lead to errors. C
› Determine the threshold for initiation of phototherapy by applying serum bilirubin and age in hours to the American Academy of Pediatrics phototherapy nomogram along a risk curve assigned based on gestational age and neurotoxicity risk factors (not major and minor risk factors for severe hyperbilirubinemia). C
› Make arrangements to ensure that all infants are seen by a health care provider within 2 days of discharge (within 1 day if significant risk factors for development of severe hyperbilirubinemia are present). C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Available evidence does not provide a clear answer regarding whether formula supplementation should be initiated in breastfed infants with hyperbilirubinemia. Cow’s milk formula supplementation decreases intestinal reabsorption of bilirubin, lowering serum bilirubin levels, but may interfere with successful breastfeeding.39 The Academy of Breastfeeding Medicine recommends an individual discussion about formula supplementation in place of, or prior to, phototherapy if an infant’s bilirubin is approaching (within 2-3 mg/dL) or above the threshold for phototherapy.39 Routine supplementation with intravenous fluids or other non–milk-based supplementation is not recommended for infants receiving phototherapy.9
Adjuvant therapies and exchange transfusion
Clofibrate, metalloporphyrins, and ursodiol have been studied in the management of unconjugated hyperbilirubinemia as augmentation to phototherapy. Honar et al40 found that ursodiol added at the time of phototherapy initiation demonstrated a significant reduction in peak bilirubin levels and duration of phototherapy in term infants with unconjugated hyperbilirubinemia without any adverse effects. Cochrane reviews of clofibrat5 and metalloporphyrins41 found that when added to phototherapy, these medications significantly decreased serum bilirubin levels and duration of phototherapy. However, there was insufficient evidence to recommend their use due to inadequate data on safety and long-term outcomes.
Exchange transfusion. Infants with bilirubin levels >25 mg/dL, those who are not responding to phototherapy, and those with evidence of acute bilirubin encephalopathy should be treated with exchange transfusion, with initiation based on an infant’s age in hours and neurotoxicity risk factors.9 Exchange transfusion involves taking small aliquots of blood from the infant and replacing them with donor red cells until the infant’s blood volume has been replaced twice to remove bilirubin and antibodies that may be causing hemolysis. It should be carried out in a neonatal intensive care unit due to significant risks.
Approximately 12% of infants have a complication from exchange transfusion including infection, electrolyte imbalances, thrombosis, thrombocytopenia, and necrotizing enterocolitis.8 The mortality rate in neonates without hemolysis who undergo exchange transfusion is 3 to 4 per 1000 treated.42
Post-discharge follow-up
Infants discharged before 72 hours of life should be seen within 2 days of discharge. Those infants with significant risk factors for development of severe hyperbilirubinemia should be seen within 1 day. Arrangements for follow-up should be made prior to discharge. Some infants discharged before 48 hours of life may require 2 follow-up visits. If follow-up cannot be ensured for an infant with risk factors for the development of severe hyperbilirubinemia, delay of discharge may be appropriate.9
CORRESPONDENCE
Katharine C. DeGeorge, MD, MS, Department of Family Medicine, University of Virginia, PO Box 800729, Charlottesville, VA, 22908-0729; kd6fp@virginia.edu.
