Topiramate in pregnancy
Topiramate in pregnancy
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怀孕期间托吡酯
作者：
S. Hunt;J. Craig;A. Russell;E. Guthrie;L. Parsons;I. Robertson;R. Waddell;B. Irwin;P. Morrison;J. Morrow
目的：托吡酯（Topamax®）被许可用于单一疗法或辅助治疗，用于全身性强直阵挛性癫痫发作或伴有或不伴有继发性全身性癫痫发作的部分性癫痫发作以及预防偏头痛。托吡酯在人类妊娠中的安全性在很大程度上尚不清楚。在这里，我们报告了我们在怀孕期间接触托吡酯的经历。方法：本研究是前瞻性、观察性、登记和随访研究的一部分。合适的病例是在单独服用托吡酯或与其他抗癫痫药物 (AED) 一起服用托吡酯时怀孕的癫痫女性，并且在得知怀孕结果之前被转诊。主要结果指标是主要先天畸形（MCM）发生率。次要结局包括特定 MCM 的风险、轻微畸形率、出生体重和分娩胎龄。结果：可获得 203 次妊娠的完整结果数据。其中，178 例活产； 16 人患有 MCM（9.0%；95% CI 5.6% 至 14.1%）。在 70 例单药治疗暴露病例中观察到 3 种 MCM（4.8%；95% CI 1.7% 至 13.3%），在托吡酯作为多药治疗方案一部分暴露的病例中观察到 13 例（11.2%；95% CI 6.7% 至 18.2%）。其中 4 个 MCM 为唇裂（2.2%；95% CI 0.9% 至 5.6%）。在 78 名已知活产男婴中报告了 4 例尿道下裂（5.1%；95% CI 0.2% 至 10.1%），其中 2 例被归类为严重畸形。结论：暴露于托吡酯的人类妊娠结局数量较低，但托吡酯联合治疗的主要先天畸形率引起了一些担忧。总体而言，观察到的口裂发生率是背景发生率的 11 倍。尽管目前的数据提供了新的信息，但由于样本量和宽置信区间，应谨慎解释它们。
Objectives: Topiramate (Topamax®) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate. Methods: This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant while taking topiramate either singly or along with other antiepileptic drugs (AEDs), and who are referred before outcome of the pregnancy is known. The main outcome measure is the major congenital malformation (MCM) rate. Secondary outcomes include risk of specific MCM, minor malformation rate, birthweight, and gestational age at delivery. Results: Full outcome data are available on 203 pregnancies. Of these, 178 resulted in live birth; 16 had an MCM (9.0%; 95% CI 5.6% to 14.1%). Three MCMs were observed in 70 monotherapy exposures (4.8%; 95% CI 1.7% to 13.3%) and 13 in cases exposed to topiramate as part of a polytherapy regimen (11.2%; 95% CI 6.7% to 18.2%). Four of the MCMs were oral clefts (2.2%; 95% CI 0.9% to 5.6%). Four cases of hypospadias were reported (5.1%; 95% CI 0.2% to 10.1%) among 78 known live male births of which two were classified as major malformations. Conclusions: The number of outcomes of human pregnancies exposed to topiramate is low, but the major congenital malformation rate for topiramate polytherapy raises some concerns. Overall, the rate of oral clefts observed was 11 times the background rate. Although the present data provide new information, they should be interpreted with caution due to the sample size and wide confidence intervals.