Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Hum Reprod. 2019 Jun 4;34(6):1139-1145. doi: 10.1093/humrep/dez035.
STUDY QUESTION: Is the risk of juvenile idiopathic arthritis (JIA) increased in children conceived after fertility treatment, and is an observed association caused by specific types of fertility treatment or by factors associated with the underlying infertility? SUMMARY ANSWER: The risk of JIA in children conceived after fertility treatment (any and specific types of fertility treatment) was not convincingly affected when compared with children born to fertile women. WHAT IS KNOWN ALREADY: It has been suggested that fertility treatment may affect the development of the immune system and thereby increase the risk of developing autoimmune diseases, including JIA. STUDY DESIGN, SIZE, DURATION: This retrospective population-based cohort study included all live-born children in Denmark between 1 January 1996 and 31 December 2012 (n = 1 084 184). The study population was followed from date of birth until first diagnosis of JIA as registered in the Danish National Patient Registry, date of 16th birthday, date of emigration, date of death or end of follow-up (31 December 2014), whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort was linked to the Danish Infertility Cohort in order to identify children born to women with fertility problems (n = 174 702) and fertility treatment (n = 89 931). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During a median follow-up period of 10.3 years, 2237 children were diagnosed with JIA. Children born to women with fertility problems had an increased risk of JIA (HR 1.18, 95% CI 1.05-1.32) compared with children born to fertile women. However, the risk was not increased in children conceived after any fertility treatment (HR 1.11; 95% CI 0.95-1.29), or after specific types of fertility treatment being ART (HR 1.05; 95% CI 0.83-1.33), IVF (HR 1.01; 95% CI 0.73-1.38), ICSI (HR 0.98; 95% CI 0.64-1.50) or any fertility drugs (HR 1.10; 95% CI 0.94-1.28) compared with children born to fertile women. The associations between fertility treatment and JIA were also assessed by using children born to women with fertility problems without fertility treatment in the index pregnancy as a reference group, however, the findings did not change substantially. LIMITATIONS REASONS FOR CAUTION: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of JIA cases. There may be some misclassification of fertility problems, as some women have undiagnosed fertility problems and are therefore not included in the Danish Infertility Cohort; potentially leading to slight attenuation of the association between fertility problems and JIA. WIDER IMPLICATIONS OF THE FINDINGS: The results are based on national data and our findings can therefore be applied to other similar populations. Our results indicate that fertility treatment per se do not increase the risk of JIA but merely that the increased risk of JIA observed among children born to women with fertility problems may be due to underlying factors related to both infertility and JIA. However, as this is the first large study in this field, further studies are needed to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Jascha Foundation, the Aase and Ejner Danielsens Foundation and The Danish Rheumatism Association. All authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
研究问题:生育治疗后受孕的儿童患幼年特发性关节炎(JIA)的风险是否增加,观察到的关联是由特定类型的生育治疗引起的,还是由与潜在不孕相关的因素引起的?
总结答案:与生育能力正常的女性所生的儿童相比,任何类型或特定类型的生育治疗后受孕的儿童患 JIA 的风险并没有明显增加。
已知情况:有人认为生育治疗可能会影响免疫系统的发育,从而增加患包括 JIA 在内的自身免疫性疾病的风险。
研究设计、大小和持续时间:这是一项回顾性基于人群的队列研究,纳入了 1996 年 1 月 1 日至 2012 年 12 月 31 日期间丹麦所有活产儿(n=1084184)。研究人群从出生日期开始随访,直至首次诊断为 JIA 并在丹麦国家患者登记处登记,或随访至 16 岁生日、移民、死亡或随访结束日期(2014 年 12 月 31 日),以先发生者为准。
参与者/材料、设置、方法:该研究队列与丹麦不孕队列相联系,以确定患有生育问题的女性(n=174702)和接受生育治疗的女性(n=89931)所生的儿童。使用 Cox 比例风险回归模型估计危险比(HR)和 95%置信区间(CI),并进行了潜在混杂因素的调整。
主要结果和机遇的作用:在中位随访期为 10.3 年期间,2237 名儿童被诊断为 JIA。与生育能力正常的女性所生的儿童相比,患有生育问题的女性所生的儿童患 JIA 的风险增加(HR 1.18,95%CI 1.05-1.32)。然而,任何生育治疗(HR 1.11;95%CI 0.95-1.29)或特定类型的生育治疗(ART(HR 1.05;95%CI 0.83-1.33)、IVF(HR 1.01;95%CI 0.73-1.38)、ICSI(HR 0.98;95%CI 0.64-1.50)或任何生育药物(HR 1.10;95%CI 0.94-1.28)后受孕的儿童,其患 JIA 的风险并未增加。使用索引妊娠中患有生育问题但未接受生育治疗的女性所生的儿童作为参考组来评估生育治疗与 JIA 之间的关联,然而,发现结果并没有实质性改变。
局限性/谨慎原因:尽管研究人群庞大,但由于 JIA 病例数量较少,某些亚组分析的统计精度可能会受到影响。生育问题的分类可能存在一些偏差,因为有些女性患有未确诊的生育问题,因此未被纳入丹麦不孕队列;这可能会导致生育问题与 JIA 之间的关联略有减弱。
更广泛的影响:研究结果基于国家数据,因此可以应用于其他类似人群。我们的研究结果表明,生育治疗本身并不会增加 JIA 的风险,但仅是在患有生育问题的女性所生的儿童中观察到的 JIA 风险增加,可能是由于与不孕和 JIA 相关的潜在因素所致。然而,由于这是该领域的第一项大型研究,因此需要进一步的研究来证实我们的发现。
研究资金/利益冲突:该研究得到了 Jascha 基金会、Aase 和 Ejner Danielsens 基金会以及丹麦风湿病协会的资助。所有作者均报告无利益冲突。
试验注册:无。
Paediatr Perinat Epidemiol. 2020-3