Prevention of HSV Morbidity in Pregnancy and in Newborns

Zane Brown, MD

This research program is concerned with the natural history of genital herpes infections that complicate pregnancy and the associated neonatal morbidity. The program is a collaborative effort among the University of Washington, the University of British Columbia and Madigan Army Hospital as each of these study sites is a regional referral center and will provide access to large numbers of study subjects.

The increasing rate of acquisition of HSV-2 infection in young adults as well as the shift in age at first infection with HSV-1 from childhood to early adulthood is expected to result in a continuing increase in neonatal HSV infection. Neonatal herpes infection remains a life-threatening infection despite current antiviral therapy. This research program has shown that most cases of neonatal herpes are seen in infants of mothers who had a primary genital HSV infection at or near the time of delivery. In contrast, neither seroconversion to HSV in pregnant women that is complete by the date of delivery nor exposure of infants to HSV-2 in an HSV-2 seropositive mother are associated with perinatal morbidity. This finding that HSV morbidity is restricted to the late parts of pregnancy has allowed the investigators to develop strategies to reduce HSV acquisition among susceptible women and to reduce the number of excess cesarean sections in women who are HSV-2 seropositive.

The aims of this research program are to:

1. Define both the virologic and obstetric factors associated with the perinatal transmission of HSV. The investigators are working to determine the effect, on the risk of neonatal HSV transmission, of viral load in the genital tract at the time of labor/delivery. An important question is if the viral load is dependent on whether the mother has a symptomatic or asymptomatic infection, whether the mother is experiencing a primary first episode, non-primary first episode or recurrent HSV infection. This research program is also investigating the role of HSV type in maternal genital tract in relation to the risk of neonatal HSV infection and examining the effect of transplacental antibody on the risk of neonatal HSV transmission.
2. Initiate studies among HSV serologically discordant couples (male partner HSV seropositive) to determine if treatment of the male partner with suppressive acyclovir therapy will reduce the rate of maternal acquisition of HSV close to the time of labor.
3. Define strategies for women with symptomatic recurrent genital HSV infection that may reduce the frequency of cesarean section. These strategies include determining the safety and efficacy of suppressive acyclovir therapy for women with recurrent HSV and defining criteria for cesarean delivery of mothers with active recurrent genital HSV.

This research program has defined some of the risk factors associated with neonatal HSV transmission. The risk of neonatal transmission is substantially greater with first episode disease than with reactivated infections. The risk of HSV acquisition during pregnancy is high in the small percentage of the population that remains susceptible at pregnancy and the greatest risk is seen in women who are HSV seronegative and whose partners are HSV-2 seropositive.

Report courtesy of Anna Marie Beckmann

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Recent Publications

Boggess KA, Watts DH, Hobson AC, Ashley RL, Brown ZA, and Corey L. Herpes simplex virus type 2 detection by culture and polymerase chain reaction and relationship to genital symptoms and cervical antibody status during the third trimester of pregnancy. Am J Obstet Gynecol 1997; 176:443-51.

Brown ZA, Selke S, Zeh J, Kopelan J, Maslow A, Ashley RL, Watts DH, Berry S, Herd M, Corey L. The acquisition of herpes simplex virus during pregnancy. N Eng J Med 1997; 337:509.