A Danish study reports that pregnant mothers who take antiviral drugs frequently used to treat herpes simplex and herpes zoster infections during the first trimester of pregnancy do not appear to have an increased risk of major birth defects. The study is published in JAMA (Journal of the American Medical Association), August 25th issue.
The authors inform that over 1% of susceptible females acquire herpes simplex during their first trimester of pregnancy - antiviral treatments are indicated for a considerable number of such patients during pregnancy.
The authors write:
Although the safety of acyclovir, valacyclovir, and famciclovir in general has been well established, data on the use of these antivirals in early pregnancy are limited.
Bjorn Pasternak, M.D., Ph.D., and Anders Hviid, M.Sc., Dr.Med.Sci., of Statens Serum Institut, Copenhagen, Denmark, carried out a registry-based study involving 837,795 live-born infants in Denmark from Januray 1996 to September 2008, to determine whether there was any link between acyclovir, valacyclovir, and famciclovir use in the first trimester of pregnancy and major birth defects.
The infants did not have any diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections, the researchers found.
The researchers used nationwide registries to determine individual-level data on dispensed antiviral medications, birth defect diagnoses and factors which might influence outcomes (potential confounders).
Among the 1,804 pregnancies in which acyclovir, valacyclovir, or famciclovir was administered at any time in the first trimester:
2.2% (40) of the infants had a diagnosis of a major birth defect
2.4% (19,920) of the 835,991 infants among the unexposed pregnancies had a diagnosis of a major birth defect
After adjusting for several variables, the researchers found that acyclovir, valacyclovir, or famciclovir exposure at any time in the first trimester was not linked to a higher risk of major birth defects.
2% of the pregnancies exposed to acyclovir, the most commonly prescribed antiviral, had major birth defects, compared to 2.4% of the unexposed pregnancies. 3.1% of pregnancies exposed to valacyclovir and 3.8% OF famciclovir exposures resulted in major birth defects (famciclovir use was very uncommon).
Further analyses found no link between exposure to antiviral drugs during the first trimester of pregnancy and 13 different subgroups of birth defects - however, the number of exposed cases was small in each subgroup.
The authors concluded:
Our study, to our knowledge the largest of its kind, found no significant association between first-trimester exposure to antiherpetic antiviral drugs and major birth defects. Consequently, it has immediate clinical implications and may support informed decisions on safety when prescribing antivirals for herpes infections in early pregnancy. Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient. Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding.
In an accompanying editorial, James L. Mills, M.D., M.S., and Tonia C. Carter, Ph.D., of the National Institutes of Health, Bethesda, Md., commented:
The study by Pasternak and Hviid is helpful in demonstrating the safety of acyclovir in pregnancy, but additional strategies must be developed to resolve the remaining issues. At a time when the health care system in the United States is facing enormous financial challenges, it is important not to ignore any sources of data that could answer critical medical questions.
"Use of Acyclovir, Valacyclovir, and Famciclovir in the First Trimester of Pregnancy and the Risk of Birth Defects"
BjГ¶rn Pasternak, MD, PhD; Anders Hviid, MSc, DrMedSci