孕期使用锂与心脏畸形风险
Lithium Use in Pregnancy and the Risk of Cardiac Malformations.
作者信息
Patorno Elisabetta, Huybrechts Krista F, Bateman Brian T, Cohen Jacqueline M, Desai Rishi J, Mogun Helen, Cohen Lee S, Hernandez-Diaz Sonia
机构信息
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.
出版信息
N Engl J Med. 2017 Jun 8;376(23):2245-2254. doi: 10.1056/NEJMoa1612222.
BACKGROUND
There has been concern that exposure to lithium early in pregnancy may be associated with a marked increase in the risk of Ebstein's anomaly (a right ventricular outflow tract obstruction defect) in infants and overall congenital cardiac defects, but data are conflicting and limited.
METHODS
We conducted a cohort study involving 1,325,563 pregnancies in women who were enrolled in Medicaid and who delivered a live-born infant between 2000 and 2010. We examined the risk of cardiac malformations among infants exposed to lithium during the first trimester as compared with unexposed infants and, in secondary analyses, with infants exposed to another commonly used mood stabilizer, lamotrigine. Risk ratios and 95% confidence intervals were estimated with control for psychiatric and medical conditions, medications, and other potential confounders.
RESULTS
Cardiac malformations were present in 16 of the 663 infants exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%), and 27 of the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk ratio for cardiac malformations among infants exposed to lithium as compared with unexposed infants was 1.65 (95% confidence interval [CI], 1.02 to 2.68). The risk ratio was 1.11 (95% CI, 0.46 to 2.64) for a daily dose of 600 mg or less, 1.60 (95% CI, 0.67 to 3.80) for 601 to 900 mg, and 3.22 (95% CI, 1.47 to 7.02) for more than 900 mg. The prevalence of right ventricular outflow tract obstruction defects was 0.60% among lithium-exposed infants versus 0.18% among unexposed infants (adjusted risk ratio, 2.66; 95% CI, 1.00 to 7.06). Results were similar when lamotrigine-exposed infants were used as the reference group.
CONCLUSIONS
Maternal use of lithium during the first trimester was associated with an increased risk of cardiac malformations, including Ebstein's anomaly; the magnitude of this effect was smaller than had been previously postulated. (Funded by the National Institute of Mental Health.).
背景
人们一直担心孕期早期接触锂可能会使婴儿患埃布斯坦畸形（一种右心室流出道梗阻性缺陷）及总体先天性心脏缺陷的风险显著增加，但数据相互矛盾且有限。
方法
我们进行了一项队列研究，涉及1325563名参加医疗补助计划且在2000年至2010年间分娩活产婴儿的女性。我们比较了孕早期接触锂的婴儿与未接触锂的婴儿患心脏畸形的风险，在二次分析中，还比较了与接触另一种常用情绪稳定剂拉莫三嗪的婴儿患心脏畸形的风险。在控制精神和医疗状况、药物及其他潜在混杂因素的情况下估计风险比和95%置信区间。
结果
663名接触锂的婴儿中有16名（2.41%）存在心脏畸形，1322955名未接触锂的婴儿中有15251名（1.15%）存在心脏畸形，1945名接触拉莫三嗪的婴儿中有27名（1.39%）存在心脏畸形。与未接触锂的婴儿相比，接触锂的婴儿患心脏畸形的校正风险比为1.65（95%置信区间[CI]，1.02至2.68）。每日剂量600毫克或以下时风险比为1.11（95%CI，0.46至2.64），601至900毫克时为1.60（95%CI，0.67至3.80），超过900毫克时为3.22（95%CI，1.47至7.02）。接触锂的婴儿中右心室流出道梗阻性缺陷的患病率为0.60%，未接触锂的婴儿中为0.18%（校正风险比，2.66；95%CI，1.00至7.06）。以接触拉莫三嗪的婴儿作为参照组时结果相似。
结论
孕早期母亲使用锂与心脏畸形风险增加相关，包括埃布斯坦畸形；这种影响的程度小于先前推测的程度。（由美国国立精神卫生研究所资助。）
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