Metoclopramide in Pregnancy and Risk of Major Congenital Malformations and Fetal Death
Metoclopramide in Pregnancy and Risk of Major Congenital Malformations and Fetal Death
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DOI：
10.1001/jama.2013.278343
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发表时间：
2013-10-16
影响因子：
120.7
通讯作者：
Hviid, Anders
中科院分区：
文献类型：
--
作者：
Pasternak, Bjorn;Svanstrom, Henrik;Hviid, Anders
重要性甲氧氯普胺，药物经常用于恶心和呕吐在怀孕期间，被认为是安全的，但具体畸形和胎儿死亡的风险信息是lacked.OBJECTIVE调查的安全性甲氧氯普胺使用在pregnancy.DESIGN，SETTING，AND PARTICIPANTS注册为基础的队列研究在丹麦，1997-2011。从一个队列的1 222 503怀孕，甲氧氯普胺暴露和未暴露的妇女进行了匹配（1：4的比例）的基础上的年龄，日历年，和倾向scores.Main结局和措施的主要结果是主要的先天性畸形的整体，20个单独的畸形类别（根据权力标准选择），自然流产，死产。结果28486例孕早期服用甲氧氯普胺的孕妇中，721例有1个婴儿患有严重先天性畸形，100例有1个婴儿患有严重先天性畸形，100例有1个婴儿患有严重先天性畸形，100例有1个婴儿患有严重先天性畸形，100例有1个婴儿患有严重先天性畸形（每1 000例分娩中有25.3例[95% CI，23.5-27.1]病例），而113 698名未暴露妇女中有3024例（每1 000例分娩中有26.6例[95% CI，25.7-27.5]病例）。总体而言，甲氧氯普胺的使用与畸形之间无显著相关性（患病率比值比，0.93 [95% CI，0.86-1.02]）或20种单独畸形类别中的任何一种，例如神经管缺损、大血管转位、室间隔缺损、房间隔缺损、法洛四联症、主动脉缩窄、唇裂、腭裂、肛门直肠闭锁/狭窄，和肢体复位（20个类别中有17个类别的95% CI上限低于2.0）。胃复安与自然流产风险增加无关（37 946名甲氧氯普胺暴露妇女中757例[20.0 {95%CI，18.5-21.4}/1000]，151 661名未暴露妇女中9414例[62.1 {95%CI，60.9-63.3}/1000]; HR，0.35 [95% CI，0.33-0.38]）和死产（在40306名接触甲氧氯普胺的妇女中有142例[3.5/1000]，在161098名未接触甲氧氯普胺的妇女中有634例[3.9/1000];结论和相关性妊娠期使用甲氧氯普胺总体上与主要先天性畸形的风险增加无关，评估了20种单独畸形类别中的任何一种，自然流产或死产。这些安全性数据可能有助于在妊娠期间考虑使用甲氧氯普胺治疗时做出决策。
IMPORTANCE Metoclopramide, a drug frequently used for nausea and vomiting in pregnancy, is thought to be safe, but information on the risk of specific malformations and fetal death is lacking.OBJECTIVE To investigate the safety of metoclopramide use in pregnancy.DESIGN, SETTING, AND PARTICIPANTS Register-based cohort study in Denmark, 1997-2011. From a cohort of 1 222 503 pregnancies, metoclopramide-exposed and unexposed women were matched (1: 4 ratio) on the basis of age, calendar year, and propensity scores.MAIN OUTCOMES AND MEASURES Primary outcomes were major congenital malformations overall, 20 individual malformation categories (selected according to power criteria), spontaneous abortion, and stillbirth. In matched analyses, logistic regression was used to estimate prevalence odds ratios of malformations and Cox regression to estimate hazard ratios (HRs) of spontaneous abortion.RESULTS Among 28 486 women exposed to metoclopramide in the first trimester, 721 had an infant with a major congenital malformation (25.3 [95% CI, 23.5-27.1] cases per 1000 births), compared with 3024 among 113 698 unexposed women (26.6 [95% CI, 25.7-27.5] per 1000 births). There were no significant associations between metoclopramide use and malformations overall (prevalence odds ratio, 0.93 [95% CI, 0.86-1.02]) or any of the 20 individual malformation categories, eg, neural tube defects, transposition of great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip, cleft palate, anorectal atresia/stenosis, and limb reduction (upper limit of 95% CI below 2.0 for 17 of 20 categories). Metoclopramide was not associated with increased risk of spontaneous abortion (757 cases [20.0 {95% CI, 18.5-21.4} per 1000] among 37 946 metoclopramide-exposed women and 9414 cases [62.1 {95% CI, 60.9-63.3} per 1000] among 151 661 unexposed women; HR, 0.35 [95% CI, 0.33-0.38]) and stillbirth (142 cases [3.5 {95% CI, 2.9-4.1} per 1000] among 40 306 metoclopramide-exposed women and 634 cases [3.9 {95% CI, 3.6-4.2} per 1000] among 161 098 unexposed women; HR, 0.90 [95% CI, 0.74-1.08]).CONCLUSIONS AND RELEVANCE Metoclopramide use in pregnancy was not associated with increased risk of major congenital malformations overall, any of the 20 individual malformation categories assessed, spontaneous abortion, or stillbirth. These safety data may help inform decision making when treatment with metoclopramide is considered in pregnancy.