With the incidence of genital herpes simplex virus (HSV) infections increasing, the occurrence of neonatal HSV disease is likely to increase in the future. Disease categorization in affected babies includes: 1) disseminated disease; 2) central nervous system (CNS) disease; and 3) disease limited to the skin, eyes, or mouth (SEM disease). Mortality rates in disseminated HSV disease have decreased from 85% in the pre-antiviral era to 29% today. Mortality rates in CNS disease have been even more dramatic, decreasing from 50% in the pre-antiviral era to 4% today. Survivors of disseminated disease and SEM disease have seen improvements in neurological outcomes, while survivors of CNS disease still face a significant likelihood of neurological sequelae. Despite these advances, morbidity and mortality remain unacceptably high, and prevention of disease continues to be of paramount importance. Several small studies have suggested that antiviral suppressive therapy of gravid women in the last weeks of pregnancy decreases the occurrence of clinically apparent genital HSV disease at the time of delivery, thereby decreasing Caesarean section rates for the indication of genital HSV. Subclinical shedding is not fully suppressed in patients studied to date, however, suggesting that neonatal transmission is likely still possible despite antiviral suppression in the mother. Furthermore, aciclovir concentrations in cord blood of babies whose mothers have received valaciclovir approach levels that have appeared to cause significant neutropenia in infants receiving long-term suppressive therapy. While neutropenia has yet to be observed among infants born to women receiving suppressive therapy, ongoing studies continue to investigate this possibility.

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