pediatrics
Neonatal Hyperbilirubinemia
Treatment of Neonatal Hyperbilirubinemia
Treatment of hyperbilirubinemia is directed at the underlying disorder. In addition, treatment for hyperbilirubinemia itself may be necessary. Physiologic jaundiceusually is not clinically significant and resolves within 1 week. Frequent formula feedings can reduce the incidence and severity of hyperbilirubinemia by increasing gastrointestinal motility and frequency of stools, thereby minimizing the enterohepatic circulation of bilirubin. The type of formula does not seem important in increasing bilirubin excretion. Breastfeeding jaundicemay be prevented or reduced by increasing the frequency of feedings. If the bilirubin level continues to increase>18 mg/dL (>308 micromol/L) in a term infant with early breastfeeding jaundice, a temporary change from breast milk to formula may be appropriate; phototherapy also may be indicated at higher levels. Stopping breastfeeding is necessary for only 1 or 2 days, and the mother should be encouraged to continue expressing breast milk regularly so she can resume nursing as soon as the infant’s bilirubin level starts to decline. She also should be assured that the hyperbilirubinemia has not caused any harm and that she may safely resume breastfeeding. It is not advisable to supplement with water ordextrosebecause that may disrupt the mother’s production of milk. Definitive treatmentof hyperbilirubinemia involves Phototherapy Exchange transfusion This treatment remains the standard of care, most commonly using fluorescent white light. (Blue light, wavelength 425 to 475 nm, is most effective for intensive phototherapy.) Phototherapy is the use of light to photoisomerize unconjugated bilirubin into forms that are more water-soluble and can be excreted rapidly by the liver and kidney without glucuronidation. It provides definitive treatment of neonatal hyperbilirubinemia and prevention of kernicterus. (See also the American Academy of Pediatrics'technical reporton using phototherapy to prevent severe neonatal hyperbilirubinemia in neonates who are ≥ 35 weeks gestation.) 72 hours ( see Figure: Risk of hyperbilirubinemia in neonates ). Phototherapy is not indicated for conjugated hyperbilirubinemia. For neonates born at < 35 weeks gestation, threshold bilirubin levels for treatment are lower because premature infants are at a greater risk of neurotoxicity. The more preterm the infant, the lower the threshold ( see Table: Suggested Thresholds* for Starting Phototherapy or Exchange Transfusion in Infants ). Gestational Age (weeks) Phototherapy (total serum bilirubin, mg/dL [micromol/L]) Exchange Transfusion (total serum bilirubin, mg/dL [micromol/L]) < 28 5–6 [86–103] 11–14 [188–239] 28 to < 30 6–8 [103–137] 12–14 [205–239] 30 to < 32 8–10 [137–171] 13–16 [222–274] 32 to < 34 10–12 [171–205] 15–18 [257–308] 34 to < 35 12–14 [205–239] 17–19 [291–325] * Consensus-based recommendations adapted from Maisels MJ, Watchko JF, Bhutani VK, Stevenson DK: An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation.J Perinatol32:660–664, 2012. doi: 10.1038/jp.2012.71 Because visible jaundice may disappear during phototherapy even though serum bilirubin remains elevated, skin color cannot be used to evaluate jaundice severity. Blood taken for bilirubin determinations should be shielded from bright light, because bilirubin in the collection tubes may rapidly photo-oxidize. This treatment can rapidly remove bilirubin from circulation and is indicated for severe hyperbilirubinemia, which most often occurs with immune-mediated hemolysis. Small amounts of blood are withdrawn and replaced through an umbilical vein catheter, or other access as available, to remove partially hemolyzed and antibody-coated red blood cells (RBCs) as well as circulating immunoglobulins. The blood is replaced with uncoated donor RBCs that do not have the RBC membrane antigen that binds the circulating antibodies. That is, type O blood is used if the neonate is sensitized to AB antigens and Rh-negative blood is used if the neonate is sensitized to Rh antigen. Because adult donor RBCs have more ABO antigen sites than fetal cells, type-specific transfusion will intensify the hemolysis. Only unconjugated hyperbilirubinemia can cause kernicterus, so if conjugated bilirubin is elevated, the level of unconjugated rather than total bilirubin is used to determine the need for exchange transfusion. For term infants, specific indications are serum bilirubin≥20 mg/dL (≥342 micromol/L) at 24 to 48 hours or≥25 mg/dL (≥428 micromol/L) at>48 hours and failure of phototherapy to result in a 1- to 2-mg/dL (17- to 34-micromol/L) decrease within 4 to 6 hours of initiation or at the first clinical signs of kernicterus regardless of bilirubin levels. If the serum bilirubin level is>25 mg/dL (≥428 micromol/L) when the neonate is initially examined, preparation for an exchange transfusion should be made in case intensive phototherapy fails to lower the bilirubin level. Thresholds have been suggested for neonates born at < 35 weeks gestation (see table Suggested Thresholds* for Starting Phototherapy or Exchange Transfusion in Infants ). Previously, some clinicians used criteria based solely on patient weight, but these criteria have been replaced by the more specific guidelines described above. Most often, 160 mL/kg (twice the infant’s total blood volume) of packed RBCs is exchanged over 2 to 4 hours; an alternative is to give 2 successive exchanges of 80 mL/kg each over 1 to 2 hours. To do an exchange, a volume of blood is withdrawn and then immediately replaced by transfused blood. The volume of each can vary depending on the infant's size, but volumes are typically near 20 mL for the average term infant. This procedure is repeated until the total desired volume is exchanged. For critically ill or premature infants, aliquots of 5 to 10 mL are used to avoid sudden major changes in blood volume. The goal is to reduce bilirubin by nearly 50%, with the knowledge that hyperbilirubinemia may rebound to about 60% of pretransfusion level within 1 to 2 hours. It is also customary to lower the target level by 1 to 2 mg/dL (17 to 34 micromol/L) in conditions that increase the risk of kernicterus (eg, fasting, sepsis, acidosis). Exchange transfusions may need to be repeated if bilirubin levels remain high. Finally, there are risks and complications with the procedure, and the success of phototherapy has reduced the frequency of exchange transfusion. 