Congenital Infection

Clinical Findings

Of the estimated 40,000 children born each year in the United States with congenital CMV infection, about 10-15% exhibit clinical findings suggestive of congenital infection at birth (symptomatic infection) (11,12). It was thought that clinically apparent or symptomatic congenital CMV occurs almost exclusively following a primary CMV

Table 2

Clinical and Laboratory Findings in Infants With Symptomatic Congenital CMV Infection

Finding abnormality

Clinical abnormality

Petechiae 76

Jaundice 67

Hepatosplenomegaly 60

Microcephaly 53

Small for gestational age 50

Chorioretinitis/optic atrophy 20

Purpura 13

Seizures 7 Laboratory abnormality

Elevated transaminases (serum aspartate 83

aminotransferase >80 U/L)

Conjugated hyperbilirubinemia (>2 mg/dL) 81

Thrombocytopenia (<100 x 103/mm3) 77

Elevated CSF protein (<120 mg/dL) 46

Modified from ref. 77.

infection (11,55). However, more recent data from natural history studies of congenital CMV infection from the United States and Europe have documented that symptomatic infection occurs in children born to immune mothers more frequently than has previously been recognized (56,57). The typical findings that have been associated with generalized cytomegalic inclusion disease are characterized by multiorgan disease with prominent involvement of the reticuloendothelial system and CNS; however, around half of symptomatic infants have mild or atypical findings.

The frequency of various clinical and laboratory findings in 106 neonates with symptomatic congenital CMV infection is shown in Table 2. Petechiae, jaundice, and hepatosplenomegaly are the most frequently noted abnormalities and are present in approx 75% of symptomatic neonates (77). In addition, half the infants are micro-cephalic and small for gestational age, and about a third are born prematurely, suggestive of significant prenatal insult. About two-thirds of symptomatic infants have clinical neurological abnormalities such as microcephaly, lethargy/hypotonia, poor suck, or seizures. Of the neonates who had ophthalmologic and audiologic assessments, chorioretinitis or optic atrophy was noted in 20% and an abnormal hearing screen in about half the children (77). Other less-frequent findings include hydrocephalus, pneu-monitis, and hemolytic anemia. About 10% of infants with symptomatic congenital CMV infection die during early infancy because of multiorgan disease with severe hepatic dysfunction, bleeding diathesis, and secondary bacterial infections (77).

Laboratory Findings

The laboratory abnormalities seen in infants with symptomatic congenital CMV infection include (in decreasing order of frequency) elevated serum aspartate aminotransferase (>80 IU/L), conjugated hyperbilirubinemia (direct bilirubin >2 mg/dL), thrombocytopenia (<100,000/mm3), atypical lymphocytosis, hemolytic anemia, and elevated cerebrospinal (CSF) fluid protein (>120 mg/dL). Elevations of serum transaminases and direct bilirubin are present in the immediate newborn period and peak during the second week of life (77). However, hyperbilirubinemia and liver function abnormalities often persist beyond the neonatal period, resolving over a few months (77). Thus, invasive procedures such as liver biopsy are not justified on the basis of persistent liver function abnormalities in infants with symptomatic congenital CMV infection. Thrombocytopenia is noted in the first few days of life in the majority of infants. The platelet count nadir occurs in the second week of life and normalizes in most patients by the third week of life. CSF abnormalities, especially elevated protein (>120 mg/dL) appear to correlate with clinical indicators of CNS damage (78). About 70% of infants with symptomatic congenital CMV infection have an abnormal neonatal cranial computed tomographic scan; intracerebral calcifications are the most frequent finding (78). Other less frequently noted computed tomographic scan findings include ventricular dilation, cortical atrophy, white matter abnormalities, and migration abnormalities.

Diagnosis of Congenital Infection

Congenital CMV infection is proven by isolation of virus from body fluids during the first 3 weeks of life. Urine and saliva (mouth swab) are equally useful for this purpose, although the latter is more easily collected. As newborns shed large amounts of virus, the detection of CMV in saliva and urine of newborns can be readily accomplished. Traditional virus isolation in tissue culture is the standard against which other methods are evaluated. Centrifugation-enhanced, rapid techniques (shell vial or Detection of Early Antigen Fluorescent Foci) are similar in sensitivity and specificity to standard viral isolation procedures; however, the rapid methods use monoclonal antibody to CMV immediate early antigens to detect infected tissue culture cells and provide results in 24 hours compared with several days to 2 weeks for tissue culture (79-81).

The detection of CMV DNA in urine or saliva by PCR and other methods can also be used, but there is less experience with these methods and less certainty about their sensitivity and specificity (82). Viremia is not present in all newborn infants with congenital CMV infection; therefore detection of virus in peripheral blood should not be relied upon to diagnose congenital infection (83). Detection of IgM antibody to CMV is not as reliable as viral isolation and is not recommended for the diagnosis of congenital infection.

The age of the patient at the time of sample collection for detection of CMV is of some importance. Neonates who acquire CMV during birth or from breast milk shed virus after 3 weeks of age. Thus, detection of CMV in urine or saliva after 3 weeks of age is not unequivocal proof of CMV acquisition in utero.

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