Objectives Leflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans. Methods From a cohort of 289 688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions. Also second or third-trimester leflunomide exposures were examined for associations with prematurity and LBW. Logistic regression model-based generalised estimating equations were used. Results 51 pregnancies were exposed to leflunomide during the first trimester, and 21 during the second/third trimesters. Adjusting for potential confounders, use of leflunomide during the first trimester of pregnancy was not associated with the risk of MCM (adjusted OR (aOR) 0.97, 95% CI 0.81 to 1.16; 5 exposed cases). No association was found between second/third-trimester exposure to leflunomide and the risk of prematurity (aOR 4.03, 95% CI 0.91 to 17.85; 7 exposed cases) nor LBW (aOR 1.06, 95%CI 0.90 to 1.25; 8 exposed cases). Pregnancy exposure to leflunomide was also not associated with the risk of spontaneous abortion (aOR 1.09, 95% CI 0.90 to 1.32; 11 exposed cases). Conclusions Maternal exposure to leflunomide during pregnancy was not associated with statistically significant increased risk of MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively few women were exposed to leflunomide during pregnancy in this cohort, caution remains warranted.

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怀孕期间使用来氟米特和不良妊娠结局的风险

目的 已知来氟米特对啮齿动物具有胚胎毒性和致畸作用。然而，在人类中的证据较少。我们量化了人类妊娠期间与来氟米特暴露相关的严重先天性畸形 (MCM)、早产、低出生体重 (LBW) 和自然流产的风险。方法 从 1998 年至 2015 年在加拿大魁北克省蒙特利尔的 289 688 例妊娠队列中，研究了妊娠早期来氟米特暴露和其他抗风湿药物暴露与 MCM 和自然流产的关联。还检查了孕中期或孕晚期来氟米特暴露与早产和 LBW 的关联。使用基于逻辑回归模型的广义估计方程。结果 51 名孕妇在妊娠早期暴露于来氟米特，21 名妊娠在妊娠中期/晚期暴露于来氟米特。调整潜在混杂因素后，在妊娠头三个月使用来氟米特与 MCM 风险无关（调整后 OR (aOR) 0.97，95% CI 0.81 至 1.16；5 例暴露病例）。未发现孕中期/孕晚期暴露于来氟米特与早产风险（aOR 4.03，95% CI 0.91 至 17.85；7 例暴露病例）和 LBW（aOR 1.06，95% CI 0.90 到 1.25；8 例暴露病例）之间没有关联. 妊娠期暴露于来氟米特也与自然流产风险无关（aOR 1.09，95% CI 0.90 至 1.32；11 例暴露病例）。结论 母亲在怀孕期间暴露于来氟米特与 MCM、早产、LBW 或自然流产风险的统计学显着增加无关。然而，鉴于该队列中怀孕期间接触来氟米特的女性相对较少，