Itis necessary to distinguish between congenital infection and neonatal infection with HSV. In fact, HSV infection of the newborn can be acquired during pregnancy, intrapartum and postnatally. The mother is the most common source of infection for the first two routes of viral transmission. Congenital infection is very rare due to the acquisition of the virus in utero; it comes to the neonatal HSV infection when the appearances of the lesions are more than 48 hours after birth [24
Intrauterine HSV infection accounts for 5% of HSV infections in neonates. The highest risk of intrauterine infection has been observed in pregnant (about 50%) who develop disseminated HSV infections and 90% of those are related to HSV-2. Both primary and recurrent maternal infection can result in congenital disease, even if the risk after recurrent infection is small.
Intrauterine viral transmission is highest during the first 20
weeks of gestation leading to abortion, stillbirth, and congenital anomalies. The perinatal mortality is 50% [24
In 85–90% of neonatal HSV infections, HSV is acquired at the time of delivery and 5–10% are caused by early postnatal viral acquisition. A percentage of 70–85% of neonatal HSV infections are caused by HSV-2, whereas the remaining cases are due to HSV-1. The HSV-2 infection carries a graver prognosis than that caused by HSV-1 [26
The disease transmission to the newborn is dependent on the type of maternal genital infection at the time of delivery.
In fact, neonatal herpes is much more frequent (50%) in babies from mothers with a primary HSV infection with respect to babies from mothers with recurrent HSV infection (<3%). However, most neonatal HSV infections (about 70%) result from exposure to asymptomatic genital HSV infection in the mother near delivery [27
The prolonged rupture of membranes is a risk factor for acquisition of neonatal infection [28
]. Congenital intrauterine infection is characterized by skin vesicles or scarring, eye lesions (chorioretinitis, microphthalmia, and cataract), neurologic damage (intracranial calcifications, microcephaly, seizures, and encephalomalacia), growth retardation, and psychomotor development. Infants infected intrapartum or postnatally by HSV can be divided into three major categories:
- HSV disease localized to the skin, eye, and/or mouth (SEM); this syndrome is associated with a low mortality but it has a significant morbidity, and it may progress to encephalitis or disseminated disease if left untreated;
- HSV encephalitis with or without skin, eye, and/or mouth involvement which causes neurologic morbidity among the majority of survivors;
- disseminated HSV which manifests as severe multiorgan dysfunction (including central nervous system, liver, lung, brain, adrenals, skin, eye, and/or mouth) and has a mortality risk that exceeds 80% in absence of therapy [27, 28].
At diagnosis, symptoms are found with the following frequency: skin vesicles 68%, fever 39%, lethargy 38%, seizures 27%, conjunctivitis 19%, pneumonia 13%, and disseminated intravascular coagulation 11%. Symptoms may occasionally be present at birth, but occur in 60% later than 5
days after birth and sometimes are present after 4–6
weeks of life [21
Localized infections have been found in 50% of the affected neonates, involvement of the central nervous system (CNS) in 33%, and disseminated infections in 17% of the cases [19
]. Several studies have demonstrated that disseminated HSV infections are characterized mainly by liver and adrenals failure associated with shock symptoms and disseminated intravascular coagulopathy [29
]. Other symptoms of HSV disseminated infection include irritability, seizures, respiratory distress, jaundice, and frequently the characteristic vesicular exanthem that is often considered pathognomonic for infection. However, over 20% of infants with disseminated infection do not develop skin vesicles during the course of their illness. Encephalitis appears to be a common component of this infection form, occurring in about 60–75% of infants with disseminated HSV infection.
Mortality in the absence of therapy exceeds 80% [29
]. The prognosis of infants with disseminated HSV disease or neurological manifestations is poor. The mortality in cases with neurological involvement by about 5% with 50% of children with neurological sequelae, while in cases with multiorgan involvement mortality, is 30% and the percentage of sequelae of 20% [28