Ask The Neonatologist: May 2022

MAY 2022 Question: A two-day-old term neonate has a total serum bilirubin concentration of 7.6 mg/dL (130 µmol/L) and conjugated serum bilirubin of 2.3 mg/dL (39.3 µmol/L). He is breast and bottle feeding and has had a two percent weight loss since birth. Physical examination findings are remarkable for a head circumference of 32 cm. Ultrasonography of the abdomen shows a contracted gallbladder with no evidence of biliary atresia.

Of the following, the MOST likely cause of this neonate’s findings is: A. breast milk jaundice B. cytomegalovirus infection C.group B Streptococcus infection D.methylmalonic acidemia ANSWER: B The neonate in the vignette has conjugated hyperbilirubinemia and microcephaly. The most likely cause of these findings is congenital cytomegalovirus (CMV) infection.

Conjugated hyperbilirubinemia is defined by a conjugated serum bilirubin greater than 20 percent of the total serum bilirubin level. The differential diagnosis of conjugated hyperbilirubinemia is broad and, in addition to CMV infection, includes hypothyroidism, hepatitis, Escherichia coli infection, Alagille syndrome, biliary atresia, galactosemia, choledochal cyst, tyrosinemia, and α1-antitrypsin deficiency. Because biliary atresia should be treated with the Kasai procedure within the first eight weeks after birth, the initial evaluation of conjugated hyperbilirubinemia must involve abdominal ultrasonography to confirm the presence of bile ducts.

Breast milk jaundice is not associated with an elevated conjugated bilirubin level. Infection with group B Streptococcus does not typically present with elevated conjugated bilirubin level.

Although inherited diseases of metabolism are associated with an elevated conjugated bilirubin level methylmalonic acidemia is not among those.

See next page.

Symptomatic infection with CMV affects 0.4 percent of neonates in the United States annually.

Neonates with symptomatic congenital CMV exhibit the clinical findings listed in table below.

Finding

%

Clinical • Petechiae

76

• Jaundice

67

• Hepatosplenomegaly

60

• Chorioretinitis/optic atrophy

20

• Prematurity (<38 weeks’ gestational age)

34

• Purpura

13

• Neurologic findings (one or more of the following):

68

- Microcephaly

53

- Lethargy/hypotonia

27

- Poor suck

19

- Seizures

7

Laboratory • Elevated aspartate aminotransferase (80 U/L)

83

• Conjugated hyperbilirubinemia (conjugated bilirubin>4mg/dL [68.4 µmol/L])

81

• Thrombocytopenia (<100x10 / µL [100x10 /L])

77

3

9

Cytomegalovirus is the leading cause of sensorineural hearing loss (SNHL) among children in the United States. Of note, half of children with hearing loss related to congenital CMV infection pass their neonatal hearing screening and exhibit hearing loss in infancy or early childhood.

Fifty percent of women of childbearing age in the United States have a history of past infection with CMV. Among seronegative women, two percent will develop primary CMV infection during their pregnancy. The risk of perinatal transmission is 305 to 405 among those with primary infection compared with one to two percent for those with previous CMV infection. Maternal CMV infection during the first and second trimester is associated with a higher risk for neonatal complications.

Overall, 85 to 95 percent of neonates born to mothers positive for CMV will be asymptomatic.

Asymptomatic CMV infection without SNHL is not associated with long-term sequelae. Children with symptomatic CMV infection should be treated with oral valganciclovir for a total of six months to decrease the risk of SNHL. Infants who are critically ill or do not tolerate the oral formulation may require intravenous ganciclovir. Because of the risk for neutropenia, absolute neutrophil counts should be monitored weekly for the first six weeks, at eight weeks and then monthly until the completion of treatment.