Valacyclovir

Pregnancy

Human pregnancy evidence includes both acyclovir and valacyclovir, but the amount of direct valacyclovir evidence is smaller. The historical Valtrex pregnancy registry recorded 111 exposed infants and fetuses: 28 first-trimester, 31 second-trimester, and 52 third-trimester exposures. It reported major birth defects in 4.5% of first-trimester exposures (95% CI 0.24% to 24.9%) and 3.9% across all trimesters (95% CI 1.3% to 10.7%); the label says the sample is too small for firm conclusions. Pasternak and Hviid's 2010 Danish cohort covered 837,795 live-born infants. Among 229 with first-trimester valacyclovir exposure, 7 had a major birth defect; the adjusted POR was 1.21 (95% CI 0.56 to 2.62). The cohort found no association between first-trimester acyclovir or valacyclovir and major birth defects overall, but the VCV estimate is imprecise and the live-birth design cannot answer miscarriage risk. Ahrens et al.'s 2013 NBDPS case-control study found that 10 of 941 gastroschisis cases and 27 of 8,339 controls reported early antiherpetic use. The adjusted odds ratio was 4.7 among women with self-reported genital herpes and 4.7 among women without it, compared with women without medication use or herpes; herpes without medication was also associated with gastroschisis (OR 3.0). The study raises a possible rare-defect signal but cannot separate the medication from the underlying infection, and it combined acyclovir, valacyclovir, and famciclovir. A 2026 umbrella review included 43 systematic reviews and 27 pregnancy cohorts, including acyclovir/valacyclovir for HSV and VZV; it reported no consistent teratogenicity signal across antiviral therapies but noted that most evidence was observational with moderate-to-low certainty. Sheffield et al.'s 2006 randomized trial assigned 350 pregnant women with a genital-herpes history to valacyclovir or placebo from 36 weeks; 338 were evaluated and no infant was diagnosed with neonatal HSV. Pinninti et al.'s 2012 case series described 8 infants with neonatal HSV after maternal suppressive acyclovir; 7 had perinatal transmission, including 5 whose mothers received suppression until delivery. The case series has no comparison group or denominator, so it cannot estimate how often disease occurs or whether suppression changes that chance. MotherToBaby reports no increased miscarriage chance and no overall increase in birth defects, while the Valtrex label says miscarriage and other maternal or fetal outcome data are insufficient. A 2026 Italian observational cohort studied primary maternal CMV infection, not routine HSV treatment: 832 women and 842 fetuses were included, with 588 fetuses treated with VCV. Miscarriages were 4/555 in the treated group and 4/250 in the untreated group (adjusted OR 0.45, 95% CI 0.11 to 1.80; p=0.24), which was not statistically significant and does not establish a causal benefit. A 2023 CMV meta-analysis included 8 studies and 620 women and rated evidence for reduced congenital CMV infection and adverse perinatal outcomes very low. Animal data are separate from human findings: the label reports no adverse embryo-fetal effects at exposures up to about 4 times human exposure in rats and 7 times in rabbits, but early embryo death, reduced fetal growth, and skeletal variations in rats at about 6 times human exposure with maternal adverse effects.

Breastfeeding

Valacyclovir is rapidly converted to acyclovir, which is measured in milk. LactMed calculates that maternal dosing of 500 mg twice daily provides about 0.6 mg/kg/day of acyclovir to a breastfed child, less than 1% of a typical infant dose. Sheffield et al. (2002) gave 500 mg twice daily for 7 days to 5 breastfeeding mothers; the amount in milk was about 2% of therapeutic newborn dosing. Drake et al. (2012) randomized 148 Kenyan pregnant women with HIV-1 and HSV-2 to valacyclovir or placebo; 146 mother-infant pairs were followed postpartum. Mothers and infants also received antiretroviral prophylaxis, and the trial found no increase in infant or maternal adverse events, but this population and co-treatment limit generalization. Kallia et al.'s 2025 systematic review included 12 studies: 3 randomized trials, 5 observational studies, and 4 case reports. The authors noted that most studies focused on HIV co-infection. The Valtrex label says direct effects on breastfed children and milk production have not been studied. LactMed says no special precautions are required; NHS SPS recommends precautionary monitoring for drowsiness, irritability, rash, vomiting, and diarrhea in full-term, healthy infants. These are different precaution approaches, not evidence of established infant harm.

What was tested

Pregnancy evidence includes a historical registry of 111 valacyclovir exposures, a Danish cohort of 837,795 live births with 229 first-trimester VCV exposures, a case-control study of early antiherpetic use and gastroschisis with 941 cases and 8,339 controls, and a 2026 umbrella review of 43 systematic reviews and 27 pregnancy cohorts. Late-pregnancy suppression evidence includes a randomized valacyclovir trial with 338 evaluated participants and a separate eight-infant case series following maternal acyclovir suppression; neither can establish prevention of the rare newborn outcome. Newer CMV studies evaluate maternal primary CMV infection, often with higher doses, rather than routine HSV treatment. Breastfeeding evidence includes a milk-level study in 5 mothers, a randomized trial with 146 mother-infant pairs in an HIV/HSV-2 and antiretroviral-prophylaxis setting, and a 2025 review of 12 studies, many involving HIV co-infection. The evidence is limited for trimester-specific VCV outcomes and for infant outcomes outside those study populations.