1例类风湿关节炎患者暴露甲氨蝶呤与来氟米特意外妊娠的胎儿风险评估

Fetal Risk Assessment of an Unintended Pregnancy Exposed to Methotrexate and Leflunomide in a Patient with Rheumatoid Arthritis

目的 通过分享1例类风湿关节炎患者妊娠16周内意外暴露甲氨蝶呤与来氟米特联合治疗的胎儿风险评估,为妊娠期用药风险咨询与沟通提供参考。方法 药师充分查阅国内外文献资料,借助妊娠期用药风险评估工具,从甲氨蝶呤、来氟米特药物代谢特点、动物生殖毒性及人类妊娠期用药安全证据等方面分析药物可能对胎儿造成的影响,与患者充分沟通,并实施暴露登记及持续追踪随访。结果 药物致胎儿畸形及发育异常多来源于动物研究及个案报道,部分较大型队列研究结果较乐观。基于现有证据尚不能作出甲氨蝶呤、来氟米特妊娠期用药风险定论。药物风险不能排除,但患者服药剂量低于文献报道常见致畸剂量,需综合考虑,谨慎权衡利弊。患者要求继续妊娠,最终足月顺利分娩一小于胎龄儿女婴,外观、骨骼、内脏无明显畸形。结论 该个案中低剂量甲氨蝶呤联合来氟米特治疗未增加出生缺陷风险。胎儿宫内生长受限可能与孕妇自身疾病及用药相关,婴儿远期结局需进一步随访。

OBJECTIVE To provide reference for the risk assessment and consultation of medication use during pregnancy by sharing practice of fetal risk assessment of a patient with rheumatoid arthritis who was exposed to leflunomide and methotrexate within 16 weeks of unintended pregnancy.METHODS Pharmacists fully reviewed the relevant literatures at home and abroad,and analyzed the possible impacts of methotrexate and leflunomide on fetus from the aspects of drug metabolism characteristics,animal reproductive toxicity and human pregnancy evidence with the aid of pregnancy drug risk assessment tools.The patient was fully informed,then pregancy registry and follow-up were performed.RESULTS Information about drug-induced fetal malformation and developmental abnormalities mostly came from animal studies and case reports,but some large cohort studies had optimistic data.On the evidence so far,no conclusion could be drawn on the risk of leflunomide and methotrexate use during pregnancy.The risk of drug exposure couldn't be excluded,but the dose taken by the patient was lower than the teratogenic dose reported in the literature,which need to be taken into consideration and the risks and benefits should be weighed carefully.The patient continued pregnancy,and successfully gave birth to a small-for-gestational-age baby at term without obvious deformities in appearance,skeleton,and internal organs.CONCLUSION The low-dose leflunomide and methotrexate exposure did not increase the risk of birth defects in this case.The fetal growth restriction may be related to both maternal conditions and medication exposure,and further follow-up for long-term outcome of the baby is required.