Adedinsewo Demilade A, Thurman David J, Luo Yao-Hua, Williamson Rebecca S, Odewole Oluwaseun A, Oakley Godfrey P
Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA.
Birth Defects Res A Clin Mol Teratol. 2013 Jun;97(6):403-8. doi: 10.1002/bdra.23147. Epub 2013 Jun 3.
Scientific evidence has consistently shown taking valproate during pregnancy increases risks of congenital malformations and cognitive impairment. As such, elimination of its use would be an important step in birth defects prevention. There are guidelines discouraging its use among women with epilepsy, but none exists for women without epilepsy, nor is the prevalence of valproate for nonepilepsy indications known.
Using de-identified data from the National Hospital and Ambulatory Medical Care Surveys (1996-2007), we examined individual prescriptions for reproductive-age adolescent girls and adult women ages 15 to 44 years in the United States, and estimated the number of antiepileptic drug and valproate prescriptions in the aggregate. We classified our study population using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, as women with epilepsy and women without epilepsy. The prevalence of antiepileptic drug and valproate prescriptions among women without epilepsy was estimated as prescriptions per 1000 patient visits for every 3-year time interval and the overall study period.
We found 83% of valproate prescriptions were issued to women without epilepsy and 74% of these were for psychiatric diagnoses. The prevalence of antiepileptic drug prescriptions among women without epilepsy tripled during the study period (10.3 [1996-1998] vs. 34.9 [2005-2007] per 1000 patient visits), whereas valproate prescriptions remained relatively stable (3.1 [1996-1998] vs. 3.7 [2005-2007] per 1000 patient visits).
Most women of reproductive age who receive a valproate prescription do not have epilepsy. Valproate prescriptions did not decline, despite increasing knowledge of its teratogenicity. Reducing valproate use among women of reproductive age, especially among those who use the drug for psychiatric indications, would prevent birth defects and cognitive deficits.
科学证据一直表明，孕期服用丙戊酸盐会增加先天性畸形和认知障碍的风险。因此，停止使用丙戊酸盐将是预防出生缺陷的重要一步。现有指南不鼓励癫痫女性使用丙戊酸盐，但对于非癫痫女性却没有相关指南，而且用于非癫痫适应症的丙戊酸盐的流行情况也未知。
利用美国国家医院门诊医疗调查（1996 - 2007年）中经过去识别化处理的数据，我们研究了美国15至44岁育龄期少女和成年女性的个体处方，并估算了抗癫痫药物和丙戊酸盐处方的总数。我们使用《国际疾病分类第九版临床修订本》诊断编码将研究人群分为癫痫女性和非癫痫女性。每3年时间间隔以及整个研究期间，非癫痫女性中抗癫痫药物和丙戊酸盐处方的流行率按每1000次患者就诊的处方数来估算。
我们发现83%的丙戊酸盐处方开具给了非癫痫女性，其中74%用于精神疾病诊断。在研究期间，非癫痫女性中抗癫痫药物处方的流行率增加了两倍（每1000次患者就诊中，1996 - 1998年为10.3，2005 - 2007年为34.9），而丙戊酸盐处方相对稳定（每1000次患者就诊中，1996 - 1998年为3.1，2005 - 2007年为3.7）。
大多数接受丙戊酸盐处方的育龄女性没有癫痫。尽管对丙戊酸盐致畸性的认识有所增加，但其处方量并未下降。减少育龄女性尤其是那些将该药物用于精神疾病适应症的女性对丙戊酸盐的使用，将预防出生缺陷和认知缺陷。
