A 4-week-old full-term female is seen for routine follow-up with her pediatrician. Her mother reports that she has been taking breast milk well with good weight gain. She has no specific concerns; however does report she noticed lighter colored stools recently. On physical exam, jaundice and scleral icterus are noted, along with dark urine in her diaper. The pediatrician orders labs drawn urgently and calls the pediatric gastroenterologist for immediate assistance. The work-up is expedited and she is found to have biliary atresia (Figures 61-1 and 61-2). The Kasai portoenterostomy procedure is performed to treat the cholestatic jaundice. This surgery involves exposing the porta hepatis and attaching part of the small intestine to the exposed liver surface to allow bile to drain out of the liver into the intestines.

• Neonatal jaundice can be a common finding in the first 2 weeks of life.

• Majority of cases are caused by physiologic jaundice and breast milk jaundice, characterized by unconjugated hyperbilirubinemia, which can spontaneously resolve.

• However, neonatal jaundice persisting after the 2nd week of life is concerning and requires urgent investigation to differentiate unconjugated hyperbilirubinemia from the less frequent, but pathological and more serious condition of cholestatic jaundice.

• Cholestatic jaundice is characterized by the elevation of conjugated bilirubin, indicating impaired hepatobiliary function.

• Conjugated hyperbilirubinemia has been defined as (1) direct bilirubin >1 mg/dL if total bilirubin is <5 mg/dL or (2) direct bilirubin >20 percent of the total bilirubin if the total bilirubin >5 mg/dL.¹

• Neonatal cholestatic jaundice can be serious and requires early detection by the primary care physician with prompt referral to a pediatric gastroenterologist to ensure timely diagnosis and appropriate treatment for a favorable prognosis.

• Early intervention for underlying infectious or metabolic causes for cholestasis can be crucial, and in particular, timely surgical management of extra-hepatic biliary obstruction is of paramount importance.

Neonatal cholestasis, neonatal conjugated hyperbilirubinemia.

• Neonatal cholestasis is estimated to affect about 1 in every 2,500 infants.²

• There are many causes for neonatal cholestasis, with the most common cause being biliary atresia.

• The incidence of biliary atresia is estimated to be between 1 in 8,000 to 1 in 21,000 live births.³

• Neonatal cholestasis is caused by:

  • Biliary atresia in about 1/3 of cases.

  • Idiopathic neonatal hepatitis is estimated to comprise about 10 to 15 percent.

  • Alpha-1-antitrypsin deficiency about 10 percent.

  • Inborn errors of metabolism about 20 percent.

  • Various inherited forms of cholestasis 10 to 20 percent.

  • Congenital infections about 5 percent of cases.^3,4

• Cholestasis is a result of either reduced bile formation by hepatocytes or obstruction of bile flow through the intra- or extrahepatic biliary tree. This can lead to accumulation of biliary substances in the liver, extrahepatic tissue, and blood.

Clinical Features

• Cholestasis may be recognized by findings of jaundice, scleral icterus (Figure 61-3), pale (or acholic) stools, and/or dark urine. Hepatomegaly can also be found on exam.

• Infants may sometimes initially present with gastrointestinal blood loss, intracranial hemorrhage, bleeding from umbilical stump, or bruising as a result of a coagulopathy from poor hepatic synthetic function and vitamin K deficiency.

• Ascites (Figure 61-4) and edema can also be seen in the setting of impaired hepatic function with advanced disease such as cirrhosis. Splenomegaly may be found in the setting of advanced disease, but can also be found in the presence of infection.

• The clinical presentation of neonatal cholestasis may vary depending on the underlying etiology.

• Infants with biliary atresia may present with jaundice, acholic stools, and/or dark urine, and they can often be healthy appearing and asymptomatic until later in their disease progression

• Poor feeding, irritability, lethargy, and vomiting may be seen in metabolic disorders such as galactosemia and tyrosinemia, but also may be a sign of generalized infections causing cholestasis.

• Infants with cholestasis secondary to congenital infections may present with low birth weight, microcephaly, chorioretinitis, and purpura.

• Dysmorphic facial features (Figure 61-5), heart murmur, and anomalies of vertebrae, eyes, and kidneys may be found in Alagille syndrome.⁵