Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
JAMA. 2010 Aug 25;304(8):859-66. doi: 10.1001/jama.2010.1206.
Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented.
To investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and risk of major birth defects.
DESIGN, SETTING, AND PARTICIPANTS: Population-based historical cohort study of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses (categorized according to a standardized classification scheme), and potential confounders.
Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by exposure to antiviral drugs.
Among 1804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir in the first trimester, 40 infants (2.2%) were diagnosed with a major birth defect compared with 19,920 (2.4%) among the unexposed (adjusted POR, 0.89; 95% confidence interval [CI], 0.65-1.22). For individual antivirals, a major birth defect was diagnosed in 32 of 1561 infants (2.0%) with first-trimester exposure to acyclovir (adjusted POR, 0.82; 95% CI, 0.57-1.17) and in 7 of 229 infants (3.1%) with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56-2.62). Famciclovir exposure was uncommon (n = 26), with 1 infant (3.8%) diagnosed with a birth defect. Exploratory analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small.
In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects.
单纯疱疹和带状疱疹感染很常见，通常用抗病毒药物治疗，包括阿昔洛韦、伐昔洛韦和泛昔洛韦。这些抗病毒药物在妊娠早期使用的安全性记录不足。
研究妊娠早期使用阿昔洛韦、伐昔洛韦和泛昔洛韦与主要出生缺陷风险之间的关系。
设计、地点和参与者：这是一项基于人群的历史队列研究，纳入了 1996 年 1 月 1 日至 2008 年 9 月 30 日期间在丹麦出生的 837795 名活产婴儿。参与者没有染色体异常、遗传综合征、已知病因的出生缺陷综合征或先天性病毒感染的诊断。利用全国性登记处获取有关抗病毒药物用药、出生缺陷诊断（按标准化分类方案分类）和潜在混杂因素的个体水平信息。
通过暴露于抗病毒药物，在生命的头一年诊断出任何主要出生缺陷的患病率比值比（POR）。
在 1804 例妊娠早期暴露于阿昔洛韦、伐昔洛韦或泛昔洛韦的妊娠中，有 40 例（2.2%）婴儿被诊断为主要出生缺陷，而 19920 例（2.4%）未暴露于抗病毒药物的婴儿中（调整后的 POR，0.89；95%置信区间 [CI]，0.65-1.22）。对于个别抗病毒药物，在 1561 例妊娠早期暴露于阿昔洛韦的婴儿中，有 32 例（2.0%）被诊断为主要出生缺陷（调整后的 POR，0.82；95% CI，0.57-1.17），在 229 例妊娠早期暴露于伐昔洛韦的婴儿中，有 7 例（3.1%）被诊断为主要出生缺陷（调整后的 POR，1.21；95% CI，0.56-2.62）。泛昔洛韦暴露的情况很少见（n=26），其中 1 例（3.8%）婴儿被诊断为出生缺陷。探索性分析显示，抗病毒药物暴露与 13 种不同的出生缺陷亚组之间没有关联，但每个亚组的暴露病例数都很少。
在这项大型全国性队列研究中，妊娠早期暴露于阿昔洛韦或伐昔洛韦与主要出生缺陷风险增加无关。
