No link between antiviral use during early pregnancy and birth defects

The authors investigated whether the use of acyclovir, valacyclovir or famciclovir during the first trimester of pregnancy increased the risk of major birth defects among a large cohort. They found no association between the risk of major birth defects and first-trimester exposure to any of these antiviral drugs used to treat herpes simplex and herpes zoster infections. However, they conclude that acyclovir should be the drug of choice in early pregnancy because it is the most extensively documented antiviral. Although risk estimates were similar for acyclovir and valacyclovir, they said that data on valacyclovir and famciclovir are still insufficient.

To conduct the study, the authors used a national birth registry to identify a cohort of 837,795 live births in Denmark between 1996 and 2008. From additional national registries, they obtained data on birth defects among the cohort and on prescriptions filled for oral acyclovir, valacyclovir or famciclovir by mothers in the cohort from four weeks before conception until birth.

They found that among the 1804 pregnancies exposed to acyclovir, valacyclovir or famciclovir during the first trimester, 40 infants (2.2 percent) were diagnosed with a major birth defect compared with 19,920 infants (2.4 percent) among those not exposed. Among infants exposed to acyclovir during the first trimester, a major birth defect was diagnosed in 32 of 1561 (2.0 percent). Major birth defects were also diagnosed among seven of 229 infants (3.1 percent) with first-trimester exposure to valacyclovir. Famciclovir exposure was uncommon, with 1 of 26 infants (3.8 percent) diagnosed with a birth defect. Exploratory analyses revealed no associations between antiviral drug exposure and 13 subgroups of birth defects.

The authors said that since the famciclovir data were based on only 26 exposed pregnancies, the results do not provide evidence of the drug's safety. While analysis of valacyclovir was based on a limited number of exposed cases, they said the results indicate that it is not a major human teratogen.