Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization

IF 2.5 3区医学 Q3 IMMUNOLOGY American Journal of Reproductive Immunology Pub Date : 2024-09-13 DOI:10.1111/aji.13922

Yixiao Wang, Fengyuan Zhang, Li Xu, Xiaohong Ji, Shanshan Wang, Xiao Shen, Haiyan Chen, Shengyuan Jiang, Chengqian Wu, Min Chen, Hong Yu

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Abstract

Objective

Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes.

Methods

The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. “TwoSampleMR” and “MR-PRESSO” packages were used for data analysis in this study.

Results

Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p = 0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p = 0.041), preeclampsia (p = 0.008), premature rupture of membranes (p = 0.030), and preterm (p = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p = 0.012), gestational hypertension (p < 0.001), preeclampsia (p = 0.002), and preterm (p = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (p = 0.010), the number of spontaneous miscarriages (p = 0.024), and placental abruption (p = 0.027). In addition, we found a causal association between nRA and birth weight (p = 0.007), but not between RA and pRA and birth weight.

Conclusion

The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.

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类风湿性关节炎与不良妊娠结局的因果关系：孟德尔随机化的遗传证据

目的虽然类风湿性关节炎（RA）与多种不良妊娠结局之间的关系已被充分研究，但 RA 患者血清抗体水平与多种不良妊娠结局之间的关系尚未得到确证。在此，我们全面评估了 RA、血清抗体阳性 RA（pRA）和血清抗体阴性 RA（nRA）对 14 种不良妊娠结局风险的因果影响。方法采用双样本孟德尔随机法（MR）全面评估了 RA、pRA 和 nRA 对 14 种不良妊娠结局的因果影响。根据这些双样本 MR 分析的结果绘制了证据图。该分析采用了英国生物库和芬兰基因数据库的数据。反方差加权（IVW）检验被用作估计因果关系的主要方法。本研究使用 "TwoSampleMR "和 "MR-PRESSO "软件包进行数据分析。结果通过双样本 MR 分析，我们发现 RA 与剖宫产风险增加（p = 0.003）、妊娠高血压（p < 0.001）、自然流产次数（p = 0.041）、子痫前期（p = 0.pRA 与剖宫产风险增加（p = 0.012）、妊娠高血压（p < 0.001）、子痫前期（p = 0.002）和早产（p = 0.007）有显著的正因果关系。nRA 与妊娠高血压（p = 0.010）、自然流产次数（p = 0.024）和胎盘早剥（p = 0.027）之间也存在明显的正向因果关系。此外，我们还发现 nRA 与出生体重之间存在因果关系（p = 0.007），但 RA 和 pRA 与出生体重之间没有因果关系。结论本研究结果对 RA 患者，尤其是血清抗体水平呈阳性的 RA 患者的个体化治疗具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.