妊娠丢失与多发性硬化和自身免疫性神经障碍风险：一项全国性队列研究。
Pregnancy loss and risk of multiple sclerosis and autoimmune neurological disorder: A nationwide cohort study.
机构信息
Department of Gynaecology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
出版信息
PLoS One. 2022 Mar 31;17(3):e0266203. doi: 10.1371/journal.pone.0266203. eCollection 2022.
BACKGROUND
The loss of one or more pregnancies before viability (i.e. pregnancy loss or miscarriage), has been linked to an increased risk of diseases later in life such as myocardial infarction and stroke. Recurrent pregnancy loss (i.e. three consecutive pregnancy losses) and multiple sclerosis have both been linked to immunological traits, which could predispose to both occurrences. The objective of the current study was to investigate if pregnancy loss is associated with later autoimmune neurological disease.
METHODS
This register-based cohort study, included the Danish female population age 12 or older between 1977-2017. Women were grouped hierarchically: 0, 1, 2, ≥3 pregnancy losses, primary recurrent pregnancy loss (i.e. not preceded by a delivery), and secondary recurrent pregnancy loss (i.e. preceded by a delivery). The main outcome was multiple sclerosis and additional outcomes were amyotrophic lateral sclerosis, Guillain-Barré syndrome, and myasthenia gravis. Bayesian Poisson regression estimated incidence rate ratios [IRR] and 95% credible intervals [CI] adjusted for year, age, live births, family history of an outcome, and education.
RESULTS
After 40,380,194 years of follow-up, multiple sclerosis was diagnosed among 7,667 out of 1,513,544 included women (0.5%), median age at diagnosis 34.2 years (IQR 27.4-41.4 years), and median age at symptom onset 31.2 years (IQR 24.8-38.2). The adjusted IRR of multiple sclerosis after 1 pregnancy loss was: 1.03 (95% CI 0.95-1.11), 2 losses: 1.02 (95% CI 0.86-1.20), ≥3 non-consecutive losses: 0.81 (95% CI 0.51-1.24), primary recurrent pregnancy loss: 1.18 (95% CI 0.84-1.60), secondary recurrent pregnancy loss: 1.16 (95% CI 0.81-1.63), as compared to women with no pregnancy losses. Seven sensitivity analyses and analyses for additional outcomes did not show significantly elevated adjusted risk estimates.
CONCLUSIONS
In this nationwide study, pregnancy loss was not significantly associated with autoimmune neurological disorder.
背景
在存活能力之前（即妊娠丢失或流产）发生一次或多次妊娠丢失与心肌梗死和中风等生命后期疾病的风险增加有关。复发性妊娠丢失（即连续 3 次妊娠丢失）和多发性硬化症都与免疫特征有关，这些特征可能导致两者同时发生。本研究的目的是调查妊娠丢失是否与随后发生的自身免疫性神经疾病有关。
方法
本登记队列研究纳入了 1977 年至 2017 年间年龄在 12 岁及以上的丹麦女性人群。女性按以下层次分组：0、1、2、≥3 次妊娠丢失、原发性复发性妊娠丢失（即无分娩史）和继发性复发性妊娠丢失（即有分娩史）。主要结局为多发性硬化症，次要结局为肌萎缩侧索硬化症、吉兰-巴雷综合征和重症肌无力。贝叶斯泊松回归估计了调整年份、年龄、活产、结局家族史和教育后发病率比[IRR]和 95%可信区间[CI]。
结果
在 40380194 年的随访后，在纳入的 1513544 名女性中有 7667 人（0.5%）被诊断为多发性硬化症，中位诊断年龄为 34.2 岁（IQR 27.4-41.4 岁），中位症状发作年龄为 31.2 岁（IQR 24.8-38.2 岁）。1 次妊娠丢失后多发性硬化症的调整 IRR 为：1.03（95%CI 0.95-1.11），2 次丢失：1.02（95%CI 0.86-1.20），≥3 次非连续丢失：0.81（95%CI 0.51-1.24），原发性复发性妊娠丢失：1.18（95%CI 0.84-1.60），继发性复发性妊娠丢失：1.16（95%CI 0.81-1.63），与无妊娠丢失的女性相比。7 项敏感性分析和其他结局分析均未显示出显著升高的调整风险估计值。
结论
在这项全国性研究中，妊娠丢失与自身免疫性神经疾病无显著相关性。
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