OBJECTIVE Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations. CONCLUSIONS The risk associated with lithium exposure at any time during pregnancy is low, and the risk is higher for first-trimester or higher-dosage exposure. Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient.

中文翻译：

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孕期和产后锂暴露：安全性和有效性结果的系统评价和荟萃分析。

目的 不确定性围绕着双相情感障碍女性在怀孕期间使用锂的风险。作者试图对围产期锂治疗的有效性和安全性相关证据进行批判性评估，重点关注患有双相情感障碍的女性及其后代。方怀孕和产后。纽卡斯尔-渥太华量表和 Cochrane 偏倚风险工具用于评估截至 2018 年 10 月可用的 PubMed 和 Scopus 记录的质量。结果 29 项研究被纳入分析（20 项研究质量良好，6 项质量差；一项研究的偏倚风险不明确，两项研究的偏倚风险高）。29 项研究中有 13 项可纳入定量分析。怀孕期间服用锂与任何先天性异常的发生率较高相关（N=23,300，k=11；患病率=4.1%，k=11；优势比=1.81，95% CI=1.35-2.41；需要伤害的人数（NNH )=33, 95% CI=22-77) 和心脏异常 (N=1,348,475, k=12; 患病率=1.2%, k=9; 优势比=1.86, 95% CI=1.16-2.96; NNH=71 , 95% CI = 48-167)。孕早期锂暴露与较高的自然流产几率相关（N=1,289，k=3，患病率=8.1%；优势比=3.77，95% CI=1.15-12.39；NNH=15，95% CI=8 -111)。比较锂暴露与未暴露的妊娠，任何畸形（在任何妊娠期或妊娠早期暴露）和心脏畸形（在妊娠早期暴露）的重要性仍然存在，但对于自然流产（在妊娠早期暴露）和心脏畸形（在任何妊娠期暴露）不显着。在预防产后复发方面，锂比不含锂更有效（N=48，k=2；优势比=0.16，95% CI=0.03-0.89；需要治疗的人数=3，95% CI=1-12）。定性综合表明，血清锂水平<0.64 mEq/L 和剂量<600 mg/天的母亲有更多反应性新生儿，而心脏畸形风险没有增加。结论 怀孕期间任何时候接触锂的风险都较低，而孕早期或更高剂量接触锂的风险较高。理想情况下，