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妊娠期锂剂使用和心脏畸形风险
Lithium Use in Pregnancy and the Risk of Cardiac Malformations


Elisabetta Patorno ... 心脑血管疾病 妇产科和儿科 • 2017.06.08

妊娠早期应用锂盐或增加婴儿先天性心脏病风险

 

盛伟,黄国英*

复旦大学附属儿科医院,上海市出生缺陷防治重点实验室

*通讯作者

 

在精神疾病中,锂盐被认为是治疗双相障碍的长期有效方案。双相障碍患者的发病年龄平均是30岁左右,这个年龄段存在不少育龄女性,但在安全性数据有限的前提下,对于严重的双相障碍妊娠期患者仍然推荐用锂盐治疗1。因此,观察妊娠早期应用锂盐对胚胎发育的影响具有重要意义。

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摘要


背景

人们一直担心妊娠早期的锂暴露可能与婴儿的Ebstein畸形(一种右心室流出道梗阻性缺陷)和总体先天性心脏缺陷的风险明显升高有关联,但有关数据互相矛盾且有限。

 

方法

我们开展了一项纳入1,325,563例妊娠的队列研究,涉及的女性均加入了美国医疗补助保险计划(Medicaid),并且在2000~2010年分娩产下了一名活产儿。我们对比研究了在妊娠期前3个月内母亲有锂暴露的婴儿和没有锂暴露的婴儿心脏畸形风险,在次要分析中我们对比研究了锂暴露婴儿和拉莫三嗪暴露婴儿的心脏畸形风险(拉莫三嗪是另一种常用的心境稳定剂)。我们对精神疾病和身体疾病、用药以及其他潜在混杂因素的效应进行控制,估算了风险比和95%置信区间。

 

结果

锂暴露组婴儿、无暴露组婴儿和拉莫三嗪暴露组婴儿中心脏畸形的患病率分别为2.41%(16/663)、1.15%(15,251/1,322,955)和1.39%(27/1945)。与无暴露组婴儿相比,锂暴露组婴儿患心脏畸形的校正风险比为1.65(95%置信区间 [CI],1.02~2.68)。日剂量为600 mg或以下的风险比为1.11(95% CI,0.46~2.64),601~900 mg的风险比为1.60(95% CI,0.67~3.80),900 mg以上的风险比为3.22(95% CI,1.47~7.02)。锂暴露组婴儿和无暴露组婴儿右心室流出道梗阻性缺陷的患病率分别为0.60%和0.18%(校正风险比,2.66;95% CI,1.00~7.06)。将拉莫三嗪暴露组婴儿作为参照组得到的结果类似。

 

结论

母亲在妊娠期前3个月内使用锂剂与Ebstein畸形等心脏畸形风险升高有关联;但这种效应的量级小于此前研究所宣称的结果(由美国国立心理健康研究所[National Institute of Mental Health]资助)。





作者信息

Elisabetta Patorno, M.D., Dr.P.H., Krista F. Huybrechts, Ph.D., Brian T. Bateman, M.D., Jacqueline M. Cohen, Ph.D., Rishi J. Desai, Ph.D., Helen Mogun, M.S., Lee S. Cohen, M.D., and Sonia Hernandez-Diaz, M.D., Dr.P.H.
From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine (E.P., K.F.H., B.T.B., R.J.D., H.M.), and the Department of Anesthesiology, Perioperative and Pain Medicine (B.T.B.), Brigham and Women’s Hospital and Harvard Medical School, the Department of Epidemiology, Harvard T.H. Chan School of Public Health (J.M.C., S.H.-D.), and the Center for Women’s Mental Health, Department of Psychiatry, Massachusetts General Hospital (L.S.C.) — all in Boston. Address reprint requests to Dr. Patorno at the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont St., Suite 3030, Boston, MA 02120, or at epatorno@bwh.harvard.edu.

 

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