Centre for Pharmacoepidemiology, Unit of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Centre for Pharmacoepidemiology, Unit of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Clin Gastroenterol Hepatol. 2016 Feb;14(2):234-41.e1-5. doi: 10.1016/j.cgh.2015.08.039. Epub 2015 Sep 12.
BACKGROUND & AIMS: Safety data on anti-tumor necrosis factor (anti-TNF) treatment during pregnancy are limited. We studied the risk of birth defects after anti-TNF treatment in early pregnancy.
We collected data on 1,272,424 live-born infants identified from the Danish (2004-2012) and Swedish (2006-2012) population-based health registers. We determined the prevalence of birth defects among infants born to women with chronic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis), with (n = 683) and without (n = 21,549) anti-TNF treatment during early pregnancy, and in the general population. We compared the risk of any major birth defect and birth defect by organ system for infants born to women with chronic inflammatory disease, with and without anti-TNF treatment. Risks were presented as odds ratios (ORs) with 95% confidence intervals (CIs). We adjusted for maternal age, parity, smoking, body mass index, multiple gestation, country, and chronic inflammatory diagnosis.
Birth defects were more prevalent among infants born to women with chronic inflammatory disease, regardless of anti-TNF treatment status, than in the general population (4.8% vs 4.2%). Birth defects occurred in 43 of the infants born to the 683 women who received anti-TNF treatment (6.3%), and 1019 of the infants born to women with chronic inflammatory disease (4.7%). The OR for any defect in women receiving anti-TNF therapy was 1.32 (95% CI, 0.93-1.82); the OR for a cardiovascular defect was 1.60 (95% CI, 0.93-2.58), and the OR for a urinary defect was 2.22 (95% CI, 0.86-4.71).
Based on an analysis of data from the health registries in Denmark and Sweden, women who received anti-TNF agents during pregnancy had a slightly (but not significantly) higher risk of having children with birth defects. Although larger studies are needed, the heterogeneity of the observed birth defects did not indicate a common etiology.
关于抗肿瘤坏死因子（anti-TNF）治疗期间妊娠安全性的数据有限。我们研究了早期妊娠时抗 TNF 治疗后出生缺陷的风险。
我们从丹麦（2004-2012 年）和瑞典（2006-2012 年）的基于人群的健康登记处收集了 1272424 名活产婴儿的数据。我们确定了患有慢性炎症性疾病（炎症性肠病、类风湿关节炎、强直性脊柱炎、银屑病关节炎或银屑病）的女性所生婴儿（n=683）和未接受抗 TNF 治疗的女性（n=21549）中出生缺陷的发生率，以及在普通人群中。我们比较了慢性炎症性疾病女性所生婴儿在接受和未接受抗 TNF 治疗时，任何主要出生缺陷和器官系统出生缺陷的风险。风险以比值比（OR）及其 95%置信区间（CI）表示。我们调整了母亲年龄、产次、吸烟、体重指数、多胎妊娠、国家和慢性炎症性疾病诊断等因素。
无论是否接受抗 TNF 治疗，患有慢性炎症性疾病的女性所生婴儿的出生缺陷发生率均高于普通人群（4.8% vs 4.2%）。在接受抗 TNF 治疗的 683 名女性所生的 43 名婴儿（6.3%）和患有慢性炎症性疾病的女性所生的 1019 名婴儿（4.7%）中出现了出生缺陷。接受抗 TNF 治疗的女性任何缺陷的 OR 为 1.32（95%CI，0.93-1.82）；心血管缺陷的 OR 为 1.60（95%CI，0.93-2.58），泌尿系统缺陷的 OR 为 2.22（95%CI，0.86-4.71）。
基于丹麦和瑞典健康登记处的数据分析，怀孕期间接受抗 TNF 药物治疗的女性所生孩子出生缺陷的风险略高（但无统计学意义）。尽管需要更大规模的研究，但观察到的出生缺陷的异质性并未表明存在共同病因。
