Tumor necrosis factor (TNF) inhibitors are increasingly applied during pregnancy without clear knowledge of the impact on placenta and fetus. We assessed placental transfer and exposure to infliximab (n  = 3) and etanercept (n  = 3) in women with autoimmune diseases. Furthermore, we perfused healthy term placentas for 6 hours with 100 µg/mL infliximab (n  = 4) or etanercept (n  = 5). In pregnant women, infliximab transferred into cord blood but also entered the placenta (cord‐to‐maternal ratio of 1.6 ± 0.4, placenta‐to‐maternal ratio of 0.3 ± 0.1, n  = 3). For etanercept, a cord‐to‐maternal ratio of 0.04 and placenta‐to‐maternal ratio of 0.03 was observed in one patient only. In ex vivo placenta perfusions, the extent of placental transfer did not differ between the drugs. Final concentrations in the fetal compartment for infliximab and etanercept were 0.3 ± 0.3 and 0.2 ± 0.2 µg/mL, respectively. However, in placental tissue, infliximab levels exceeded those of etanercept (19 ± 6 vs. 1 ± 3 µg/g, P  < 0.001). In conclusion, tissue exposure to infliximab is higher than that of etanercept both in vivo as well as in ex vivo perfused placentas. However, initial placental transfer, as observed ex vivo , does not differ between infliximab and etanercept when administered in equal amounts. The difference in placental tissue exposure to infliximab and etanercept may be of clinical relevance and warrants further investigation. More specifically, we suggest that future studies should look into the occurrence of placental TNF inhibition and possible consequences thereof.

中文翻译：

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在患有自身免疫性疾病的女性和离体灌注胎盘中评估英夫利昔单抗和依那西普的胎盘处置。

肿瘤坏死因子（TNF）抑制剂在怀孕期间越来越多地使用，而对于其对胎盘和胎儿的影响尚无明确的了解。我们评估了 患有自身免疫性疾病的妇女的胎盘转移和英夫利昔单抗（n  = 3）和依那西普（n = 3）的暴露。此外，我们用100 µg / mL英夫利昔单抗（n  = 4）或依那西普（n  = 5）灌注了健康足月胎盘6小时。在孕妇中，英夫利昔单抗转移到脐带血中，但也进入胎盘（帘线与母体的比例为1.6±0.4，胎盘与母体的比例为0.3±0.1，n  = 3）。对于依那西普，仅一名患者观察到脐带与母亲的比率为0.04，胎盘与母亲的比率为0.03。在体外胎盘灌注，胎盘转移的程度在两种药物之间没有差异。英夫利昔单抗和依那西普在胎儿区室中的最终浓度分别为0.3±0.3和0.2±0.2 µg / mL。但是，在胎盘组织中，英夫利昔单抗水平超过了依那西普的水平（19±6 vs. 1±3 µg / g，P  <0.001）。总之，英夫利昔单抗在体内以及离体灌注胎盘中的组织暴露均高于依那西普。但是，离体观察到的初始胎盘转移相同剂量的英夫利昔单抗和依那西普之间没有差异。英夫利昔单抗和依那西普的胎盘组织暴露差异可能与临床有关，需要进一步研究。更具体地说，我们建议未来的研究应探讨胎盘TNF抑制的发生及其可能的后果。