Guideline sources The following summarized guidelines for the evaluation and management of neonatal hyperbilirubinemia are prepared by our editorial team based on guidelines from the American Academy of Pediatrics (AAP 2022) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN/NASPGHAN 2017). 1 2 Guidelines 1. Diagnostic investigations History and physical examination: As per AAP 2022 guidelines, assess all infants visually for jaundice at least every 12 hours following delivery until discharge. B As per NASPGHAN 2017 guidelines: Perform a thorough physical examination for the proper evaluation of infant patients with jaundice. Pay special attention to hepatomegaly, splenomegaly, and ill appearance. A https://web.pathway.md/diseases/recn4Sonx1q0br2sg 1/5 6/30/23, 1:15 AM Neonatal hyperbilirubinemia Pathway Perform direct visualization of stool pigment for the complete evaluation of infant patients with jaundice. A Bilirubin measurement: As per AAP 2022 guidelines, measure total serum bilirubin or transcutaneous bilirubin as soon as possible in infants noted to be jaundiced < 24 hours after birth. B Show 6 more As per NASPGHAN 2017 guidelines, measure total and conjugated serum bilirubin for the evaluation of cholestasis in any formula-fed infant noted to be jaundiced after 2 weeks of age. A Consider observing otherwise well-appearing breastfed infants clinically until 3 weeks of age. Measure total and conjugated serum bilirubin if they appear icteric at that time. Show 2 more Direct antiglobulin test: obtain a direct antiglobulin test and determine blood type in infants as soon as possible using either cord or peripheral blood if the maternal antibody screen is positive or unknown because the mother did not have prenatal antibody screening. B Show 2 more Hepatobiliary imaging: obtain abdominal ultrasound for excluding choledochal cyst or gallstone disease causing extrahepatic bile duct obstruction, as well as to demonstrate an absent or abnormal gallbladder, or other features suggestive, but not diagnostic, of biliary atresia. A Show 2 more G6PD testing: measure G6PD activity in any infant with jaundice of unknown cause if total serum bilirubin increases despite intensive phototherapy, increases suddenly or increases after an initial decline, or if escalation of care is required. B 2. Diagnostic procedures Liver biopsy: Perform an appropriately timed liver biopsy and histological examination by an experienced pediatric pathologist to elicit histopathological findings of bile duct proliferation, bile plugs, and fibrosis in the evaluation of infants with protracted conjugated hyperbilirubinemia. B Consider performing a liver biopsy and histological examination for identifying diseases causing cholestasis other than biliary atresia. Obtain intraoperative cholangiography and histological examination of the duct remnant as the gold standard for the diagnosis of biliary atresia. A 3. Medical management Intravenous immunoglobulin: consider administering IVIG (0.5-1 g/kg) over 2 hours in infants with isoimmune hemolytic disease (positive direct antiglobulin test) if total serum bilirubin reaches or exceeds the escalation-of-care threshold. Consider repeating the dose in 12 hours. C https://web.pathway.md/diseases/recn4Sonx1q0br2sg 2/5 6/30/23, 1:15 AM Neonatal hyperbilirubinemia Pathway 4. Therapeutic procedures Phototherapy (indications for initiation): Initiate intensive phototherapy at the total serum bilirubin thresholds on the basis of gestational age, hyperbilirubinemia neurotoxicity risk factors, and age of the infant in hours. B Consider offering treatment with a home LED-based phototherapy device rather than readmission to the hospital as an option in infants already discharged and then developed hyperbilirubinemia (above the phototherapy threshold) and meeting the following criteria: gestational age 38 weeks 48 hours old clinically well with adequate feeding no known hyperbilirubinemia neurotoxicity risk factors no previous phototherapy total serum bilirubin concentration 1 mg/dL above the phototherapy treatment threshold an LED-based phototherapy device will be available in the home without delay total serum bilirubin can be measured daily. C Phototherapy (monitoring of treatment): Measure total serum bilirubin within 12 hours after starting phototherapy in hospitalized infants. Guide the timing of the initial total serum bilirubin measure after starting phototherapy and the frequency of total serum bilirubin monitoring during phototherapy by the following factors: age of the infant presence of hyperbilirubinemia neurotoxicity risk factors total serum bilirubin concentration total serum bilirubin trajectory. B Show 3 more Phototherapy (escalation of treatment): escalate care when total serum bilirubin reaches or exceeds the escalation-of-care threshold, defined as 2 mg/dL below the exchange transfusion threshold. B Show 3 more Phototherapy (indications for discontinuation): consider discontinuing phototherapy when the total serum bilirubin has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy. Consider continuing phototherapy for a longer period if there are risk factors for rebound hyperbilirubinemia (such as gestational age < 38 weeks, age < 48 hours at the start of phototherapy, hemolytic disease). C Exchange transfusion: Perform an urgent exchange transfusion in infants with signs of intermediate or advanced stages of acute bilirubin encephalopathy (such as hypertonia, arching, retrocollis, opisthotonos, high-pitched cry, or recurrent apnea). B Perform an urgent exchange transfusion in infants with a total serum bilirubin level at or above the exchange transfusion threshold. Consider deferring the exchange transfusion while https://web.pathway.md/diseases/recn4Sonx1q0br2sg 3/5 6/30/23, 1:15 AM Neonatal hyperbilirubinemia Pathway continuing intensive phototherapy if, while preparing for but before starting the exchange transfusion, a total serum bilirubin concentration is below the exchange transfusion threshold and the infant does not show signs of intermediate or advanced stages of acute bilirubin encephalopathy, and following the total serum bilirubin every 2 hours until the total serum bilirubin is below the escalation-of-care threshold. B 5. Patient education Counseling before discharge: provide written and verbal education about neonatal jaundice to all families before discharge. Provide 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 transcutaneous bilirubin or total serum bilirubin. Transmit birth hospitalization information, including the last transcutaneous bilirubin or total serum bilirubin and the age at which it was measured, and direct antiglobulin test results (if any) to the primary care provider who will see the infant at follow-up. Provide this information to families if there is uncertainty about who will provide the follow-up care. B 6. Preventative measures Primary prevention: do not offer oral supplementation of water or dextrose water to prevent hyperbilirubinemia or decrease bilirubin concentrations. D 7. Follow-up and surveillance Follow-up after discharge: calculate and use the difference between the bilirubin concentration measured closest to discharge and the phototherapy threshold at the time of the bilirubin measurement, beginning at least 12 hours after birth, to guide follow-up if patient discharge is being considered. B Clinical findings Past medical history Ocular exam Abo incompatibility Scleral icterus Asphyxia Integument exam Biliary atresia Choledochal cyst Dehydration Crigler-najjar syndrome Jaundice Dubin-johnson syndrome Hematological findings G6PD deficiency Gilbert's syndrome DIC Hemolytic disease https://web.pathway.md/diseases/recn4Sonx1q0br2sg 4/5 6/30/23, 1:15 AM Neonatal hyperbilirubinemia Pathway Rotor syndrome Spherocytosis Sepsis direct Coombs test Abdominal exam Hepatomegaly Splenomegaly Lab findings serum TBIL References 1. Alex R Kemper, Thomas B Newman, Jonathan L Slaughter et al. Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2022 Sep 1;150 3):e2022058859. Open 2. Rima Fawaz, Ulrich Baumann, Udeme Ekong et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2017 Jan;64 1 154 168. Open 3. Riskin A, Abend-Weinger M, Bader D. How accurate are neonatologists in identifying clinical jaundice in newborns?. Clin Pediatr Phila). 2003 Mar;42 2 153 8. Open https://web.pathway.md/diseases/recn4Sonx1q0br2sg 5/5