Neonates are particularly vulnerable to infections caused by HSV. In most cases, the infection is the result of vertical transmission during the peripartum period; more rarely, in utero or postpartum transmission occurs. Neonatal HSV infection occurs in 1 in 2500 to 5000 deliveries. Neonates have the highest risk of developing HSV visceral infection and encephalitis. Without prompt initiation of treatment, more than 70% of infants who have HSV infection will progress to disseminated or CNS disease. Most neonatal infections are due to HSV-2, although 30% of cases are caused by HSV-1. A frustrating aspect of this entity is that 70% to 80% of infected infants are born to mothers who do not suspect that they have genital HSV infection because primary infection frequently is asymptomatic. Thus, preventive strategies targeted at women known to harbor HSV infection have had limited impact on the incidence of neonatal HSV infection.

Eighty-five percent of neonatal HSV infections are transmitted during the peripartum period through disrupted membranes or through direct contact with the infected cervix or vaginal secretions. Perinatal HSV infection causes three syndromes: skin, eye, mouth (SEM) disease, CNS disease, and disseminated disease. SEM disease is limited to the skin, eyes, and mucous membranes and accounts for 45% of peripartum infections. CNS disease is defined as encephalitis without additional visceral involvement and accounts for 35% of peripartum infections. Disseminated disease is characterized by visceral involvement, such as hepatitis, pneumonitis, or disseminated intravascular coagulation, and accounts for 20% of peripartum infections.

Typically, SEM disease presents in the first or second weeks of life, although it can present later. This is the most readily recognizable form of neonatal HSV infection. Vesicular skin lesions can be found on any part of the body but may be clustered on the presenting part or traumatized areas such as scalp monitor sites. Herpetic skin lesions classically have an erythematous base with clear or cloudy fluid or may appear pustular. If the infection does not progress to involve the CNS or viscera, SEM disease is associated with low mortality. However, recurrences occur in 90% of patients and may cause significant morbidity. Even in the absence of documented CNS involvement, 20% of infants who experience more than three recurrences in the first 6 months of life have delayed development. The risk of subsequent neurologic sequelae also appears to be higher with HSV-2 infections than HSV-1 infections.

Neonatal CNS HSV disease often presents in the second to third week of life, although earlier presentations can occur. These infants may have skin lesions suggestive of HSV infection at the time of presentation, and initial findings often are nonspecific. In fact, only 60% will develop skin lesions at any time during the illness. Untreated, HSV CNS disease has a 50% mortality, but with prompt institution of therapy, mortality is 18%. Therefore, the diagnosis must be entertained in any infant who has signs and symptoms consistent with encephalitis, including focal, multifocal, or generalized seizures; apnea; bradycardia; and cranial nerve abnormalities. Typical CSF findings are nonspecific and include pleocytosis and increased protein. As in all cases of neonatal HSV infection, prompt initiation of therapy is critical and should be instituted in infants in whom the diagnosis is suspected while confirmatory diagnostic procedures are pursued. Even with therapy, at least two thirds of survivors will exhibit neurologic impairment.

When HSV causes disseminated disease, any organ is susceptible to infection, including the lungs, liver, adrenal glands, and brain. Disseminated HSV disease classically presents in the first week of life. CNS symptoms such as seizures and lethargy may occur on the first day of life, whereas the bilateral patchy infiltrates that herald HSV pneumonitis often appear in the third through tenth days of life. As in cases of CNS disease, skin lesions may not be present initially. This syndrome typically cannot be discerned on clinical grounds alone from disseminated infections caused by other viruses such as enterovirus or bacteria such as group B Streptococcus or Listeria monocytogenes. The diagnosis of disseminated HSV disease should be considered in any infant who has a clinical picture suggestive of sepsis syndrome and does not respond promptly to antibiotic therapy or who has both pneumonitis and hepatitis Without treatment, disseminated HSV infection is associated with a mortality of greater than 80%. With antiviral therapy, the mortality is 50% to 60%. HSV pneumonitis is associated with poor outcome; there is 80% mortality even with treatment.

At least four factors influence the development of neonatal disease (Table ).  Table : Factors Associated with Increased Risk of Neonatal HSV Disease

First, women who have primary infection are 10 to 20 times more likely to transmit the virus to their infants than are women who have recurrent HSV infection; they also are more likely to transmit HSV than are women who have nonprimary, first episode HSV infection. Maternal HSV antibody status also influences the risk of transmission and the severity of neonatal disease. Therefore, primary and first episode maternal infections acquired late in gestation are associated with a greater risk of neonatal disease than those acquired earlier in gestation. Infants who are born more than 4 hours after rupture of membranes are at greater risk of neonatal HSV infection than those born less than 4 hours after rupture of membranes. Procedures that interrupt skin integrity, such as fetal scalp monitoring, also increase the risk of HSV transmission to the infant. Finally, there is evidence that prematurity increases the risk of neonatal HSV infection.

Based on the previously mentioned risk factors, recommendations have been made about the management of pregnant women who have recognized genital HSV infection to decrease the risk of neonatal disease. The most reliable means of predicting which women are at risk of transmitting HSV is a thorough physical examination at the onset of labor to determine if active genital lesions are present. If such lesions are found during labor, prompt cesarean section, preferably before membranes have ruptured, is recommended. Instrumentation during labor and delivery, such as fetal scalp monitoring and forceps manipulation, should be avoided. Maternal virus cultures obtained at the time of delivery may be useful in the subsequent management of the infant. Women who have a first episode genital HSV infection during the last trimester may continue to shed virus after their lesions have resolved. In this circumstance, the obstetrician may consider weekly cultures to document the cessation of HSV shedding and plan a vaginal delivery if this occurs. Alternatively, if symptoms of first episode genital HSV infection begin within 4 to 6 weeks of delivery, the obstetrician may choose to deliver the infant by cesarean section. Treating women who are at risk of transmitting HSV to their infants with acyclovir has not been studied.

The optimal management of infants exposed to HSV at delivery also is not clear. Recognizing that the majority will not be infected, most experts recommend managing such infants expectantly. During the time when HSV-exposed infants are in the hospital, they should be placed in contact isolation and observed closely for any signs or symptoms of disease. Circumcision should be deferred. Additional management options include obtaining virus cultures of the infant's conjunctivae, pharynx, skin folds, CSF, and rectum at 24 to 48 hours of life to determine if HSV has been transmitted. Cultures obtained before this time may reflect transient HSV colonization and are unnecessary unless signs and symptoms of infection occur. After obtaining surveillance cultures at 24 to 48 hours, the clinician may choose to continue to follow the infant while awaiting the results or to treat with acyclovir. Because neither of these strategies has been studied systematically, the best option cannot be recommended definitively. Infants who are culture-positive for HSV from any site after 24 hours of life should receive antiviral therapy. Regardless of management chosen, careful instruction regarding the signs and symptoms of HSV infection and the need for prompt intervention should they occur must be given to the parents of HSV-exposed infants at the time of discharge.

Six percent of neonatal HSV infections are the result of in utero spread. The outcome of these infections depends on the timing of transmission. HSV infection has been associated with fetal demise and preterm labor. Infants may have a number of stigmata of congenital infection, including microcephaly, hydrocephalus, hydranencephaly, microophthalmia, chorioretinitis, and cicatricial, vesicular, or hypopigmented skin lesions. Surviving infants have latent infection and are at risk for subsequent recurrences. Fewer than 10% of neonatal HSV infections are the result of postpartum transmission from a caregiver or other contact with an oral lesion or herpetic whitlow. Depending on the age of the infant at the time of infection and the maternal antibody status, postpartum HSV infection may be indistinguishable from peripartum infection and may carry the same ominous prognosis.