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孕期使用肿瘤坏死因子抑制剂与类风湿关节炎患者后代出生体重增加有关。

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients' offspring.

作者信息

Smeele Hieronymus T W, Röder Esther, Mulders Annemarie G M G J, Steegers Eric A P, Dolhain Radboud J E M

机构信息

Rheumatology, Erasmus MC, Rotterdam, The Netherlands

Rheumatology, Erasmus MC, Rotterdam, The Netherlands.

出版信息

Ann Rheum Dis. 2022 Sep 12;81(10):1367-1373. doi: 10.1136/ard-2022-222679.

Abstract

OBJECTIVES

To study pregnancy outcomes in a closely monitored, well-defined cohort of women with rheumatoid arthritis (RA). In particular, pregnancy outcomes of women that used a TNFi during pregnancy.

METHODS

Patients were derived from a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Multivariate linear regression analysis was used to describe which variables influenced birth weight.

RESULTS

188 patients were included, 92 (48.9%) patients with RA used a TNFi during pregnancy. Disease Activity Score in 28 joints C reactive protein (DAS28CRP) was low at all time points during pregnancy (DAS28CRP in the third trimester: 2.17 (SD 0.73). TNFi use was not associated with an increase of adverse pregnancy outcomes such as low birth weight (<2500 g), (emergency) caesarian section, hypertensive disorders or congenital malformations. TNFi use resulted in less children born small-for-gestational age (p=0.05), however, did not increase the risk of large-for-gestational age (p=0.73). Mean birth weight was 173 g higher in women that used a TNFi during pregnancy (3.344 kg vs 3.171 kg, p=0.03). In the multivariate analysis, maternal age (β -0.023, 95% CI -0.040 to -0.0065, p=0.007), TNFi use (β 0.20, 95% CI 0.066, 0.34, p=0.004), diabetes mellitus (β 0.37, 95% CI 0.12, 0.63, p=0.004) and gestational age (β 0.18, 95% CI 0.15, 0.2, p<0.001) were statistically significant associated with birth weight.

CONCLUSIONS

This is the first study to show that TNFi use during pregnancy is associated with increased birth weight of offspring of women with well-controlled RA. The underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring should be explored in future research.

摘要

目的

研究在密切监测、定义明确的类风湿关节炎(RA)女性队列中的妊娠结局。特别是在孕期使用肿瘤坏死因子抑制剂(TNFi)的女性的妊娠结局。

方法

患者来自一项关于妊娠与RA的前瞻性研究(活动期RA的孕前咨询研究),并根据旨在实现最小疾病活动度的治疗方案进行治疗。采用多变量线性回归分析来描述哪些变量会影响出生体重。

结果

纳入了188例患者,其中92例(48.9%)患有RA的患者在孕期使用了TNFi。孕期所有时间点的28个关节C反应蛋白疾病活动评分(DAS28CRP)均较低(孕晚期DAS28CRP:2.17(标准差0.73))。使用TNFi与不良妊娠结局如低出生体重(<2500g)、(急诊)剖宫产、高血压疾病或先天性畸形的增加无关。使用TNFi导致小于胎龄儿出生减少(p=0.05),然而,并未增加大于胎龄儿的风险(p=0.73)。孕期使用TNFi的女性的平均出生体重高173g(3.344kg对3.171kg,p=0.03)。在多变量分析中,母亲年龄(β -0.023,95%可信区间 -0.040至 -0.0065,p=0.007)、TNFi使用(β 0.20,95%可信区间0.066,0.34,p=0.004)、糖尿病(β 0.37,95%可信区间0.12,0.63,p=0.004)和孕周(β 0.18,95%可信区间0.15,0.2,p<0.001)与出生体重在统计学上显著相关。

结论

这是第一项表明孕期使用TNFi与病情控制良好的RA女性后代出生体重增加相关的研究。未来研究应探索TNF抑制对出生体重的潜在机制以及对后代的长期影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f63a/9484384/4339c20394cf/ard-2022-222679f01.jpg

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