Ostensen M, Ramsey-Goldman R
Department of Rheumatology, University Hospital of Trondheim, Norway.
Drug Saf. 1998 Nov;19(5):389-410. doi: 10.2165/00002018-199819050-00006.
The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean fever. Azathioprine can be used when the maternal condition requires a cytotoxic drug during the first trimester. Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.
妊娠与风湿性疾病的相互作用各不相同，从某些自身免疫性疾病中危及生命的情况，如血栓栓塞事件和进行性肾病，到炎性风湿性疾病中外周关节炎的轻微发作。因此，治疗策略将根据预期的母体或胎儿损害情况而有所不同。所有非甾体类抗炎药（NSAIDs），包括高剂量阿司匹林（乙酰水杨酸），在孕期都会因抑制前列腺素合成而产生不良反应。妊娠和分娩延长、动脉导管收缩、持续性胎儿循环、肾功能损害和出血是孕妇在妊娠晚期接触所有环氧化酶抑制剂的风险。这些不良反应大多可通过在分娩前8周停用NSAIDs来预防。低剂量阿司匹林与胎儿或新生儿毒性无关。一些皮质类固醇，如泼尼松和泼尼松龙不易穿过胎盘，可在孕期作为免疫抑制药物安全使用。与皮质类固醇相关的母体并发症可能会发生，因此必须密切监测。关于改善病情的抗风湿药物（包括金制剂、抗疟药、青霉胺（D-青霉胺）、柳氮磺胺吡啶和环孢素）的安全性信息有限。在这些药物中，柳氮磺胺吡啶的耐受性记录最佳，可用于孕妇。一旦确认怀孕，应停用金化合物和青霉胺。羟氯喹与先天性畸形无关，在需要使用抗疟药治疗的患者中似乎比氯喹更可取。对于患有严重风湿性疾病的孕妇，使用环孢素可能是其他治疗方法的一种替代选择。除家族性地中海热外，孕期使用秋水仙碱的指征很少。如果母体情况需要在孕早期使用细胞毒性药物，可使用硫唑嘌呤。环磷酰胺、苯丁酸氮芥和甲氨蝶呤在孕期因其致畸潜力而禁用。如果母亲患有危及生命的疾病，可在妊娠晚期考虑使用。
