Applied Evidence

Neonatal hyperbilirubinemia: An evidence-based approach

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References

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.

About 88% of infants requiring phototherapy have normal laboratory study results.

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.

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