Newer-Generation Antiepileptic Drugs and the Risk of Major Birth Defects
Newer-Generation Antiepileptic Drugs and the Risk of Major Birth Defects
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DOI：
10.1001/jama.2011.624
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发表时间：
2011-05-18
影响因子：
120.7
通讯作者：
Hviid, Anders
中科院分区：
文献类型：
--
作者：
Molgaard-Nielsen, Ditte;Hviid, Anders
妊娠期癫痫是一个治疗上的挑战。自20世纪90年代以来，获得许可的抗癫痫药物的数量大幅增加，但关于妊娠早期使用新一代抗癫痫药物与出生缺陷的安全性数据有限。目的研究妊娠早期胎儿暴露于新一代抗癫痫药物与重大出生缺陷风险之间的关系。研究对象：1996年1月1日至2008年9月30日，丹麦837795名活产婴儿的基于人群的队列研究。个体水平的信息分发抗癫痫药物的母亲，出生缺陷的诊断，和潜在的混杂因素，从全国范围内的健康registrations.Main结果测量患病率比值比（PORs）的任何重大出生缺陷诊断的第一年内，胎儿暴露于抗癫痫药物。或左乙拉西坦治疗的836263名孕妇中，有49人被诊断为严重的出生缺陷，而没有服用抗癫痫药物的836263名孕妇中有19911人被诊断为严重的出生缺陷。（分别为3.2%和2.4%;调整后的POR [APOR]，0.99; 95%置信区间[CI]，0.72-1.36）。1019名婴儿中有38名被诊断为重大出生缺陷（3.7%）在妊娠早期暴露于拉莫三嗪（APOR，1.18; 95% CI，0.83-1.68），393例婴儿中有11例（2.8%）暴露于奥卡西平组（APOR，0.86; 95% CI，0.46-1.59），5/108例（4.6%）暴露于托吡酯组（APOR，1.44; 95% CI，0.58-3.58）。加巴喷丁（n=59）和左乙拉西坦（n=58）暴露在前三个月是不常见的，只有1（1.7%）和0婴儿诊断为出生缺陷，分别。结论在活产婴儿在丹麦，前三个月暴露于拉莫三嗪，奥卡西平，托吡酯，加巴喷丁，或左乙拉西坦相比，没有暴露与重大出生缺陷的风险增加。JAMA. 2011; 305（19）：1996-2002年
Context Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on first-trimester use of newer-generation antiepileptic drugs and birth defects are limited.Objective To study the association between fetal exposure to newer-generation antiepileptic drugs during the first trimester of pregnancy and the risk of major birth defects.Design, Setting, and Participants Population-based cohort study of 837 795 live-born infants in Denmark from January 1, 1996, through September 30, 2008. Individual-level information on dispensed antiepileptic drugs to mothers, birth defect diagnoses, and potential confounders were ascertained from nationwide health registries.Main Outcome Measures Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by fetal exposure to antiepileptic drugs.Results Of the 1532 infants exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam during the first trimester, 49 were diagnosed with a major birth defect compared with 19 911 of the 836 263 who were not exposed to an antiepileptic drug (3.2% vs 2.4%, respectively; adjusted POR [APOR], 0.99; 95% confidence interval [CI], 0.72-1.36). A major birth defect was diagnosed in 38 of 1019 infants (3.7%) exposed to lamotrigine during the first trimester (APOR, 1.18; 95% CI, 0.83-1.68), in 11 of 393 infants (2.8%) exposed to oxcarbazepine (APOR, 0.86; 95% CI, 0.46-1.59), and in 5 of 108 infants (4.6%) exposed to topiramate (APOR, 1.44; 95% CI, 0.58-3.58). Gabapentin (n=59) and levetiracetam (n=58) exposure during the first trimester was uncommon, with only 1 (1.7%) and 0 infants diagnosed with birth defects, respectively.Conclusion Among live-born infants in Denmark, first-trimester exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam compared with no exposure was not associated with an increased risk of major birth defects. JAMA. 2011; 305(19): 1996-2002