a Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology , St. Olavs Hospital - Trondheim University Hospital , Norway.
Expert Rev Clin Pharmacol. 2017 Jun;10(6):661-669. doi: 10.1080/17512433.2017.1305268. Epub 2017 Mar 22.
An increasing number of female patients with autoimmune diseases are treated with biologic drugs. Concerns in regard to safety of biologics during pregnancy arise in patients who have not completed their families. Areas covered: A review of the literature dealing with child outcomes of pregnancies exposed to biologics shows that TNF inhibitors (TNFi) are the best studied in regard to human pregnancy. In studies comparing exposed pregnancies to disease-matched controls no increased risk of spontaneous abortion, low birth weight, prematurity or congenital malformations has been observed. For rituximab, tocilizumab, anakinra, belimumab and ustekinumab no prospective, controlled studies are available, and firm conclusions about their safety during pregnancy cannot be drawn. Expert commentary: TNFi appear fairly safe when given in early pregnancy. For biologics other than TNFi prospective, controlled studies on outcomes after early and late pregnancy exposure are urgently needed. Possible effects of TNFi and all other biologics on children's immune function, infection rate and vaccination responses are either limited or absent and need to be extended. Development of laboratory tests to measure concentrations of biologics routinely in children exposed in utero would facilitate decisions in regard to the time point of vaccination with live vaccines.
越来越多患有自身免疫性疾病的女性患者接受生物制剂治疗。对于尚未完成生育的患者，在怀孕期间使用生物制剂的安全性问题引起了关注。
对暴露于生物制剂的妊娠所生孩子结局的文献进行综述表明，TNF 抑制剂（TNFi）在人类妊娠方面研究最多。在比较暴露于妊娠的疾病匹配对照的研究中，没有观察到自然流产、低出生体重、早产或先天性畸形的风险增加。对于利妥昔单抗、托珠单抗、阿那白滞素、贝利木单抗和乌司奴单抗，没有前瞻性对照研究，因此无法得出关于其在怀孕期间安全性的明确结论。
在妊娠早期使用 TNFi 似乎相当安全。对于除 TNFi 以外的生物制剂，迫切需要进行早期和晚期妊娠暴露后结局的前瞻性、对照研究。TNFi 和所有其他生物制剂对儿童免疫功能、感染率和疫苗接种反应的可能影响有限或不存在，需要进一步研究。开发常规测量胎儿暴露于生物制剂的浓度的实验室检测方法将有助于决定接种活疫苗的时间点。
