Fluconazole use and birth defects in the National Birth Defects Prevention Study
Fluconazole use and birth defects in the National Birth Defects Prevention Study
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DOI：
10.1016/j.ajog.2015.11.022
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发表时间：
2016-05-01
影响因子：
9.8
通讯作者：
Druschel, Charlotte M.
中科院分区：
文献类型：
--
作者：
Howley, Meredith M.;Carter, Tonia C.;Druschel, Charlotte M.
背景：低剂量氟康唑通常用于治疗外阴阴道念珠菌病，这是一种在怀孕期间经常发生的疾病。孕妇使用低剂量氟康唑与重大出生缺陷风险之间的关联存在证据信息。研究设计：我们使用了国家出生缺陷预防研究的数据来检查这种关联。国家出生缺陷预防研究是一项多地点，以人群为基础的病例对照研究，包括1997年至2011年估计分娩日期的孕妇。通过自我报告收集了31，645名出生缺陷病例的母亲和11，612名未受影响的对照母亲在妊娠早期使用氟康唑的信息。校正后的比值比和95%的置信区间估计为出生缺陷与5个或更多的暴露cases;粗比值比和确切的95%的置信区间估计为出生缺陷与3-4暴露cases.RESULTS：43,257母亲分析，44例母亲和6例对照母亲报告使用氟康唑。6名暴露婴儿患有唇裂伴腭裂，4名患有房间隔缺损，以下缺陷各有3例暴露病例：尿道下裂、法洛四联症、大动脉d型转位和肺动脉瓣狭窄。氟康唑的使用与唇腭裂相关（优势比= 5.53;置信区间= 1.68-18.24）和D型大动脉转位（比值比= 7.56;置信区间= 1.22-35.45）。氟康唑与唇裂合并腭裂及先天性唇腭裂的相关性研究大动脉转位与早期发表的病例报告一致，但与最近的流行病学研究不一致。尽管全国出生缺陷预防研究的样本量较大，但氟康唑的使用很少。需要在大型研究中进行进一步的调查，特别强调口裂和圆锥干心脏缺陷。
BACKGROUND: Low-dose fluconazole is used commonly to treat vulvovaginal candidiasis, a condition occurring frequently during pregnancy. Conflicting information exists on the association between low-dose fluconazole use among pregnant women and the risk of major birth defects.OBJECTIVE: We used data from the National Birth Defects Prevention Study to examine this association.STUDY DESIGN: The National Birth Defects Prevention Study is a multisite, population-based, case-control study that includes pregnancies with estimated delivery dates from 1997 to 2011. Information on fluconazole use in early pregnancy was collected by self-report from 31,645 mothers of birth defect cases and 11,612 mothers of unaffected controls. Adjusted odds ratios and 95% confidence intervals were estimated for birth defects with 5 or more exposed cases; crude odds ratios and exact 95% confidence intervals were estimated for birth defects with 3-4 exposed cases.RESULTS: Of the 43,257 mothers analyzed, 44 case mothers and 6 control mothers reported using fluconazole. Six exposed infants had cleft lip with cleft palate, 4 had an atrial septal defect, and each of the following defects had 3 exposed cases: hypospadias, tetralogy of Fallot, d-transposition of the great arteries, and pulmonary valve stenosis. Fluconazole use was associated with cleft lip with cleft palate (odds ratio = 5.53; confidence interval = 1.68-18.24) and d-transposition of the great arteries (odds ratio = 7.56; confidence interval = 1.22-35.45).CONCLUSIONS: The associations between fluconazole and both cleft lip with cleft palate and d-transposition of the great arteries are consistent with earlier published case reports but not recent epidemiologic studies. Despite the larger sample size of the National Birth Defects Prevention Study, fluconazole use was rare. Further investigation is needed in large studies, with particular emphasis on oral clefts and conotruncal heart defects.