In 1990, we initiated a study to evaluate the frequency and morbidity of acquiring genital herpes simplex virus infections in pregnancy. Utilizing the obstetrical populations of the University of Washington and Madigan Army Hospital, we have obtained sera for HSV serologies by Western blot at the first prenatal visit and at the onset of labor. In addition, HSV cultures have been obtained from labia and cervix on admission in labor. HSV cultures have been obtained from nasopharynx and conjunctivae of the newborn infants. Our preliminary data indicates that overall, seroconversion occurs in 2.3% of the entire population and in 3.7% of women who were HSV negative in early pregnancy. It appears that more than half of these seroconversions are subclinical and that HSV seroconversion is associated with increased rates of late fetal loss, preterm delivery and HSV shedding at the onset of labor. Utilizing PCR, we have demonstrated HSV DNA in the genital secretions of 20% of HSV-2 seropositive pregnant women at or near term, suggesting that in the infant of the HSV-2 seropositive women, the risk of HSV infection following exposure is very low. Moreover, we have shown high titers of HSV DNA in specimens that were negative by standard HSV isolation but were associated with an infected infant, i.e. false negative viral isolation. The current proposal builds upon these findings to further define the seroepidemeologic risk factors for seroconversion, the frequency of obstetrical morbidity and pregnancy loss among those with clinical and subclinical seroconversion, the timing of subclinical seroconversion during pregnancy and the effect of heterologous antibody on pregnancy outcome, HSV shedding at the onset of labor and neonatal HSV. The proposed studies will recruit the sexual partners of pregnant women to evaluate the effects of heterologous antibody in either the patient or her partner on the rates of seroconversion, viral load during seroconversion and obstetrical consequences of seroconversion. Using PCR technology, we propose to define more clearly the frequency of asymptomatic reactivation in the third trimester of pregnancy among women with symptomatic and subclinical genital herpes. Our goal is to develop an intervention strategy to interrupt what appears to be a high complication rate of first episode genital herpes in pregnancy.