The estimated rate of occurrence of neonatal herpes simplex virus (HSV) infection in the United States is approximately 1 per 3,000 to 20,000 deliveries per year. Most neonatal infections are caused by HSV-2, with some 25% to 30% caused by HSV-1. The seroprevalence of HSV-2 antibodies among American women of childbearing age is 20% to 30%. However, only 5% of these seropositive women have a history of genital HSV infection. It is therefore not surprising that 70% of infants who develop HSV infection are born to women who are asymptomatic for genital infection with HSV at the time of delivery and have neither a history of genital herpes nor a sexual partner with genital HSV infection. The frequency of asymptomatic shedding of HSV at the time of delivery varies from 0.01% to 0.39%. Among women with a past history of genital HSV infection, asymptomatic excretion at delivery is approximately 1% to 2%. Among those who had a primary infection during pregnancy, viral shedding at delivery is 36%. If HSV is diagnosed before the pregnancy, and clinical recurrences have been fewer than six per year, the risk of reactivation at delivery is 10%. If six or more episodes of HSV infection have occurred per year, then the risk of reactivation at delivery increases to 25%. Most important, however, one is unable to reliably predict viral shedding at delivery in any of these women.

The acquisition of HSV by the infant can occur in utero, during delivery, or after birth. In utero infection with HSV accounts for approximately 5% of cases. Transmission occurs either transplacentally, during a maternal viremia, or through an ascending route from an infected maternal genital tract. The virus may pass through microscopic tears in the amniotic membranes to produce infection in infants delivered by cesarean section with intact membranes. HSV has been isolated from the blood of a pregnant woman with primary HSV infection, as well as from amniotic fluid, placenta, umbilical cord blood, and fetal tissue obtained at the time of spontaneous abortion. In utero acquisition of HSV, presumably from a transplacental route, also is suggested by reports of congenital malformations in infants born to women with genital herpes infection during pregnancy.

The transmission of HSV to the newborn infant usually occurs at delivery (85% of cases). The risk of neonatal infection is higher with primary maternal HSV infection than with recurrent infection (30% to 50% versus 3%) because of the infant’s prolonged exposure to large quantities of virus in the absence of protective neutralizing and antibody-dependent cellular cytotoxicity antibodies (Table 78.1). Prematurity, duration of rupture of amniotic membranes greater than 4 to 6 hours, and use of a scalp electrode for fetal heart rate monitoring also increase the risk of HSV infection.

The postnatal transmission of HSV (10% of cases) to the newborn infant may occur after contact with a maternal breast lesion during breast-feeding or from direct contact with other
family members or, rarely, with health care workers who have active herpes labialis lesions. The nosocomial transmission of HSV in newborn nurseries has been documented by restriction endonuclease analysis of viral isolates, but it is rare.

The clinical manifestations of intrauterine HSV infection are present at birth or within the first 48 hours of delivery. Skin vesicles with scars are common. Seizures, microcephaly, hydranencephaly, porencephaly, intracranial calcifications, microphthalmia, hepatomegaly with or without splenomegaly, and abnormalities on bone roentgenography may be seen. The adrenal gland frequently is involved, and chorioretinitis either is present at birth or develops in the first week of life.

Neonatal HSV infection acquired at birth is categorized by extent of disease: disseminated disease with or without evidence of central nervous system, skin, eye, and mouth involvement; central nervous system disease (encephalitis) with or without skin, eye, and mouth involvement; and localized infection of the skin, eye, mouth, or a combination of the three without visceral organ or central nervous system involvement. Subclinical infection may occur but is uncommon.

Disseminated disease currently accounts for 25% of neonatal HSV infection. Its frequency has decreased from as high as 50% in the years 1973 to 1981. This decrease is probably a result of the prompt diagnosis and treatment of localized infection before dissemination occurs. The average onset of illness is between 10 to 12 days of age, and the principal organs involved are the liver and adrenal glands. Approximately 60% to 75% of infants manifest central nervous system involvement from hematogenous spread of the virus, and 60% to 80% manifest skin, mouth, or eye lesions. The presenting signs and symptoms are nonspecific and include fever, lethargy, irritability, anorexia, vomiting, respiratory distress, apnea, jaundice, seizures and, in the most severe cases, shock with disseminated intravascular coagulation. Elevated transaminase levels and direct hyperbilirubinemia with or without hepatomegaly are common. Splenomegaly often is present. Pneumonitis, pleural effusion, and roentgenographic lesions in long bones also may occur.

Central nervous system disease from axonal transmission of virus accounts for approximately 30% of neonatal HSV infections. Clinical manifestations typically occur at 16 to 19 days of age and include lethargy, irritability, bulging fontanelle, focal or generalized seizures, opisthotonos, decerebrate posturing, and coma. Almost 40% of infants have no skin vesicles. An examination of the cerebrospinal fluid (CSF) reveals an elevated leukocyte count, with a predominance of lymphocytes and an elevated protein content. Red blood cells are occasionally present, indicating hemorrhagic brain involvement. A normal cell count and protein concentration, however, may be found on the initial lumbar puncture.

Localized diseases of skin, eye, mouth, or all three occur in 45% of infants with HSV infection. The hallmark of neonatal HSV infection is the discrete vesicular lesions that occur in 90% of infants with localized infection (see Color Fig. 129.5 in color section). The vesicles usually appear first on the presenting part of the body that was in direct contact with the virus during delivery. Differential diagnosis includes superficial trauma resulting in vesicles on newborn skin. Other vesicular lesions are discussed in Chapter 68. Approximately 70% of untreated infants who present with skin vesicles develop disseminated infection or have progression of disease to involve the eyes or central nervous system. Ulcerative lesions of the mouth, tongue, or palate occur less commonly (10%). Ocular involvement with HSV is manifested by keratoconjunctivitis, uveitis, chorioretinitis, cataracts, and retinal dysplasia. Sequelae of ocular HSV infection include corneal ulceration, microphthalmia, optic atrophy, and blindness. About 2% to 12% of treated infants with a localized infection of the skin, eyes, or oral cavity have subclinical involvement of the central nervous system, as manifested by the development of severe neurologic impairment. About 50% of infants with skin lesions experience one to twelve cutaneous recurrences during the first 6 to 12 months of age.