胎儿发育与母体类风湿关节炎和幼年特发性关节炎有关。

Eugenia Y Chock, Zeyan Liew, Lars Henning Pedersen, Mette Oestergaard Thunbo
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引用次数: 0

摘要

背景:先前的研究表明,患有类风湿性关节炎(RA)和幼年特发性关节炎(JIA)的妇女发生不良妊娠结局的风险比正常人高一倍,其中包括早产和出生体重不足的婴儿。目前,我们对 RA 和 JIA 如何影响孕期胎儿生长的认识还存在很大差距。研究目的我们旨在通过比较RA/JIA患者与非RA/JIA患者的后代的胎儿生长指标,评估RA/JIA患者的胎儿生长情况。我们假设,与未患有 RA/JIA 的个体相比,RA/JIA 患者的胎儿发育会减慢。研究设计:我们于 2008-2018 年在丹麦开展了一项基于人群的队列研究,共纳入 503,491 名单胎妊娠者。其中,2206 人为 RA 和 JIA 患者。为了达到研究目的,我们将丹麦多个全国性数据库和临床登记处联系起来。通过丹麦胎儿医学数据库(Danish Fetal Medicine Database,DFMD),我们获得了从第二孕期胎儿超声扫描中收集到的胎儿生物测量数据。我们使用国际疾病分类(ICD)-10代码从丹麦全国患者登记册中识别出患有RA/JIA的孕妇,并将他们与DFMD连接起来,其他相关变量则从丹麦不同的临床登记册中获得。接下来,我们利用每个胎儿生长指标的 Z 评分距离的平均差,计算了第二孕期到出生时的胎儿生长梯度。我们还估算了胎龄过小(SGA)的风险,所有结果都在患有和未患有RA/JIA的孕妇之间进行了比较,并对混杂因素进行了调整。结果显示母体RA和JIA与孕中期估计胎儿体重(EFW)的降低无关[调整后的平均EFW Z-score差异为0.05(95% CI为0.01,0.10;p=0.022)],但观察到后代出生体重较低[调整后的平均Z-score差异为-0.08(95% CI为-0.13,-0.04;p<0.001)]。我们观察到,在怀孕期间使用皮质类固醇[-0.26 (95% CI -0.11, -0.41;p<0.001)]和柳氮磺胺吡啶[-0.61 (95% CI -0.45, -0.77;p<0.001)]的RA/JIA患者,其后代从怀孕后三个月到出生时体重梯度的平均Z-score差异减小。母体 RA/JIA 也与 SGA 相关[aOR 为 1.47 (95% CI 1.16, 1.83; p<0.001)]。同样,皮质类固醇[aOR 3.44 (95% CI 2.14, 5.25; p<0.001)]和柳氮磺胺吡啶[(aOR 2.28 (95% CI 1.22, 3.88; p=0.005)]使用者的风险估计值更高。结论在患有 RA/JIA 的孕妇中,胎儿生长受限可能在胎龄 18-22 周后最为明显。应考虑在这一时期对该人群进行更密切的产前监测。
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Fetal Growth Associated with Maternal Rheumatoid Arthritis and Juvenile Idiopathic Arthritis.
Background: Prior studies indicated that women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are at twice higher risk of developing adverse pregnancy outcomes, this include preterm births and infants with low birth weight. A wide knowledge gap exists in our current understanding of how RA and JIA affect fetal growth during pregnancy. Objective: We aimed to evaluate fetal growth among patients with RA/JIA by comparing fetal growth indicators of offspring born to this population, compared to individuals without RA/JIA. We hypothesized that fetal growth among patients with RA/JIA is reduced, compared to individuals without RA/JIA. Study Design: We conducted a population-based cohort study in Denmark from 2008-2018 which included 503,491 individuals with singleton pregnancies. Among them, 2,206 were patients with RA and JIA. We linked several nationwide databases and clinical registries in Denmark to achieve our aim. Through the Danish Fetal Medicine Database (DFMD), we obtained fetal biometric measurements gathered from second trimester fetal ultrasound scans. We used International Classification of Diseases (ICD)-10 codes to identify pregnant patients with RA/JIA from the Danish National Patient Registry and linked them to the DFMD, other variables of interest were obtained from different Danish clinical registries. Next, we computed fetal growth gradient between second trimester and birth, using the mean difference in Z-score distances for each fetal growth indicator. We also estimated the risk of small for gestational age (SGA), all outcomes were compared between pregnant individuals with and without RA/JIA and adjusted for confounders. Results: Maternal RA and JIA was not associated with a reduction of estimated fetal weight (EFW) at mid-pregnancy [adjusted mean EFW Z-score difference of 0.05 (95% CI 0.01, 0.10; p=0.022)], but lower birth weights were observed among offspring [adjusted mean Z-score difference of -0.08 (95% CI -0.13, -0.04; p<0.001)]. We observed reduced mean Z-score differences in weight gradient from second trimester to birth among offspring of patients with RA/JIA who also used corticosteroids [-0.26 (95% CI -0.11, -0.41; p<0.001)], and sulfasalazine [-0.61 (95% CI -0.45, -0.77; p<0.001)] during pregnancy. Maternal RA/JIA was also associated with SGA [aOR of 1.47 (95% CI 1.16, 1.83; p<0.001)]. Similarly, the risk estimates were higher among corticosteroid [aOR 3.44 (95% CI 2.14, 5.25; p<0.001)] and sulfasalazine [(aOR 2.28 (95% CI 1.22, 3.88; p=0.005) users. Conclusion: Among pregnant patients with RA/JIA, fetal growth restriction may be most apparent after 18 to 22 weeks of gestational age. Closer antenatal monitoring around this period should be considered for this population.
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