Background: The antiviral agents acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) are commonly used to treat initial and recurrent cases of herpes simplex virus infection, and to lessen the severity of herpes zoster virus infection. More than 1 percent of susceptible women acquire herpes simplex virus infection during the first trimester of pregnancy, and there is a high prevalence of recurrent infection; therefore, antiviral medication is recommended in a significant number of pregnant women. The U.S. Food and Drug Administration considers acyclovir, valacyclovir, and famciclovir category B drugs in pregnancy, but there are few data on early pregnancy exposure. Pasternak and Hviid investigated the risk of major birth defects in the infants of mothers who took antiviral medication in their first trimester.

The Study: This retrospective cohort study compiled data from three national registries in Denmark. A cohort of all live births between January 1996 and September 2008 was selected. The authors extracted data on the cohort mothers for prescriptions of oral acyclovir, valacyclovir, and famciclovir, as well as topical acyclovir and penciclovir (Denavir) that were filled from four weeks before conception through birth. The registry was not able to capture data from inpatient prescribing or for over-the-counter formulations of topical acyclovir and penciclovir.

Birth defects were identified through the National Patient Register, which lists all diagnoses assigned to persons during hospital admissions and emergency department and outpatient visits. Data for the study period were accessed, and major birth defect diagnoses were compiled using a surveillance classification system. Infants with chromosomal or genetic disorders, minor defects, birth defect syndromes with known causes, and congenital viral infections that can cause birth defects were excluded. To avoid confounding, the authors collected maternal information on medical conditions, including diabetes mellitus and immunodeficiency status, smoking status, history of sexually transmitted infections, exposure to corticosteroids and antibiotics in the first trimester, and history of birth defects in older siblings.

Results: A major birth defect in the first year of life was diagnosed in 19,960 of 837,795 live births (2.4 percent). The rate of birth defects did not differ between the women who received antivirals (1,804 pregnancies with 40 birth defects; 2.2 percent) and those who did not (835,991 pregnancies with 19,920 birth defects; 2.4 percent). These results did not change when the analysis was restricted to acyclovir. Risk estimates were similar for acyclovir and valacyclovir; however, the authors caution that there were relatively few exposures reported for valacyclovir and famciclovir.

Conclusion: Use of acyclovir in the first trimester does not increase birth defects, and it should be the antiviral drug of choice in early pregnancy.