Evaluation Of The Neonate

Evaluation of a newborn in whom EV infection is a possible cause of illness should include a thorough history with specific attention to maternal symptoms suggestive of EV infection (e.g., fever and abdominal pain) as well as viral-like symptoms in other close contacts. Examination should include global assessment of well-being, with special attention to organ systems targeted by EVs, including the cardiovascular system (blood pressure, heart rate, perfusion, cyanosis, heart tones, edema); respiratory system (respiratory distress, apnea); central nervous system (lethargy, irritability, bulging fontanelle, focal abnormalities, hypotonia or hypertonia); liver (jaundice, hepatomegaly, liver tenderness, splenomegaly, abdominal distension); and coagulation system (petechiae; ecchymoses; or bleeding from the umbilicus, mucosa, or phlebotomy sites). Presence of a macular or maculopapular rash may be a clue to an EV infection.

Minimum laboratory evaluation should include a complete blood cell count and lumbar puncture, as well as bacterial cultures of blood, urine, and cerebrospinal fluid to rule out bacterial infection. Cerebrospinal fluid analysis, in both nonpoliovirus EV and poliovirus infections, may show a pleocytosis suggestive of viral meningitis (usually <500 white blood cells/mm3). Occasionally, the cerebrospinal fluid profile may mimic that of bacterial meningitis, with up to several thousand white blood cells/cubic millimeter. A neutrophil predominance is frequently present, and in a minority, increased protein or decreased glucose levels may occur. Conversely, cerebrospinal fluid may be positive by culture or PCR despite a normal cytologic and chemical profile (33,36,37). Central nervous system imaging should be considered if an infant is very lethargic or has focal neurological findings or if there is a neurological deterioration in the presence of significant thrombocytopenia or coagulopathy.

If a newborn appears ill or if there are findings suggestive of hepatic involvement (e.g., hepatomegaly or jaundice) or bleeding, liver function tests should be obtained. Transaminase elevation or increased bilirubin suggests the presence of hepatitis. Ammonia levels may need to be monitored in the presence of severe hepatic involvement, especially if profound lethargy is present. In an infant with hepatitis or evidence of bleeding or in any newborn who appears clinically ill, the platelet count and coagulation profile should be monitored. A chest radiograph is indicated in the presence of respiratory or cardiac symptoms. Infiltrates may indicate pneumonia or heart failure, and cardiac enlargement suggests myocarditis or pericarditis.

Microbiologic evaluation should be targeted at EVs and other pathogens that can cause similar disease manifestations. The latter include herpes simplex virus, adenovirus, bacteria such as group B streptococcus and Escherichia coli, and depending on the clinical situation, congenital infections by cytomegalovirus, rubella virus, syphilis, and Toxoplasma gondii (33,37). Viral culture specimens with the highest yield for diagnosis of neonatal EV infections are rectum or stool (91-93% positive), cerebrospinal fluid (62-83% positive), and nasopharyx or throat (52-67% positive). Yields of serum and urine culture are lower (24-47%); however, cultures of serum specimens may grow more rapidly than those of other body fluids/sites (33,37,91). Positive serum cultures are more likely with echoviruses, low serum-neutralizing antibody titer, and onset of illness within the first 5 days of life (85,91).

PCR of serum and urine specimens is more sensitive in neonates than culture of these specimens, with a yield approaching 90%. High sensitivity is maintained for the first several days of illness and provides more rapid diagnosis than achieved with culture (33,37,92). Sensitivity also appears high with PCR assay of cerebrospinal fluid (93). PCR has been used to detect EV infection in neonatal tissue (94), and PCR of serum, cerebrospinal fluid, and stool have been used to identify EV spread in neonatal units and guide infection control efforts (95-97). Serology is generally not useful for acute diagnosis unless the likely infecting serotype is known from epidemiologic circumstances and an IgM assay for that serotype is available.

Viral culture or PCR of maternal rectal or cervical specimens will often yield the same virus as that causing neonatal illness. Maternal serum may also have a significant titer of neutralizing antibody to the causative viral serotype (37,40,85). However, in most cases, diagnosis of a neonatal infection can be made directly from neonatal specimens.

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