Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet and Department of Internal Medicine, Danderyd Hospital, Stockholm, Sweden.
Centre for Pharmacoepidemiology, Department of Medicine Solna and Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Pharmacoepidemiol Drug Saf. 2020 Mar;29(3):316-327. doi: 10.1002/pds.4930. Epub 2020 Feb 4.
To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy.
Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics.
Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases.
Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.
研究抗肿瘤坏死因子（anti-TNF）治疗在妊娠期间对早产、剖宫产和胎儿小于胎龄（small for gestational age，SGA）的风险。
本研究为基于人群的研究，纳入了来自丹麦、芬兰和瑞典国家健康登记处的 2006 年至 2013 年间患有炎症性肠病、类风湿关节炎、强直性脊柱炎、银屑病关节炎和银屑病的女性及其婴儿。与接受非生物性系统性治疗的女性相比，接受 anti-TNF 治疗的女性。阿达木单抗、依那西普和英夫利昔单抗进行两两比较。早期妊娠时继续治疗与停药进行比较。在逻辑回归模型中，使用国家和产妇特征进行调整，计算比值比（odds ratio，OR）及其 95%置信区间（confidence interval，CI）。
在 1 633 909 例分娩中，有 1027 例婴儿的母亲接受了 anti-TNF 治疗，9399 例婴儿的母亲接受了非生物性系统性治疗。与非生物性系统性治疗相比，接受 anti-TNF 治疗的女性早产的风险更高，OR 为 1.61（1.29-2.02），剖宫产的风险更高，OR 为 1.57（1.35-1.82）。SGA 的 OR 为 1.36（0.96-1.92）。在两两比较中，英夫利昔单抗与炎症性关节和皮肤疾病的严重 SGA 风险增加相关，但与炎症性肠病无关。对于炎症性肠病和炎症性关节和皮肤疾病，抗 TNF 药物的停用对早产有相反的影响。
anti-TNF 药物与早产、剖宫产和 SGA 的风险增加相关。然而，不同疾病组之间的不同发现可能表明与潜在疾病活动相关的关联，而不是与药物特异性相关的影响。
