澳大利亚昆士兰大学公共卫生学院Gita D Mishra团队研究了不孕症、反复流产和死产与中风风险的相关性。相关论文发表在2022年6月22日出版的《英国医学杂志》上。

为了研究不孕症、反复流产和死产与首次非致命性和致命性中风风险的相关性，并进一步按中风亚型分层，研究组在七个国家（澳大利亚、中国、日本、荷兰、瑞典、英国和美国）进行了一项队列研究，参与2012年6月成立的InterLACE（生殖健康和慢性疾病事件生命历程方法国际合作）联合会，并对8项前瞻性队列研究的个体参与者进行汇总分析。

共招募了618851名基线年龄在32.0-73.0岁之间，有不孕、流产或死产数据的女性，且至少有一个结局事件（非致命性或致命性中风）以及协变量信息；93119名女性被排除在外。在参与者中，275863人有非致命性和致命性中风的数据，54716人只有非致命性中风的数据，288272人只有致命性中风的数据。非致命性中风通过自我报告的问卷、相关医院数据或国家患者登记簿来确定。通过死亡登记数据确定致命性中风。

非致命性中风和致命性中风的平均随访时间分别为13.0年和9.4年。9265名（2.8%）女性经历了首次非致命性中风，4003名（0.7%）女性经历了致命性中风。非致命性或致命性中风的危险比按高血压分层，并根据种族或族裔、体重指数、吸烟状况、教育水平和研究进行校正。

不孕与非致命性中风风险增加相关（危险比为1.14）。反复流产（至少三次）与非致命性和致命性中风的高风险相关（危险比分别为1.35和1.82）。死产女性患非致命性中风的风险高31%（1.31），反复死产女性患致命性中风的风险高26%（1.26）。与不孕症或反复死产相关的中风（非致命性或致命性）风险增加主要由单一中风亚型（非致命性缺血性中风和致命性出血性中风）驱动，而与反复流产相关的中风（非致命性或致命性）风险增加则由两种亚型驱动。

研究结果表明，有反复流产史和出生前或出生期间死亡或丢失婴儿可被视为女性特有的中风风险因素，不同中风亚型的风险不同。这些发现有助于改善对有此类病史女性的监测和中风预防。

附：英文原文

Title: Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618851 women

Author: Chen Liang, Hsin-Fang Chung, Annette J Dobson, Kunihiko Hayashi, Yvonne T van der Schouw, Diana Kuh, Rebecca Hardy, Carol A Derby, Samar R El Khoudary, Imke Janssen, Sven Sandin, Elisabete Weiderpass, Gita D Mishra

Issue&Volume: 2022/06/22

Abstract:

Objective To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes.

Design Individual participant pooled analysis of eight prospective cohort studies.

Setting Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012.

Participants 618851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93119 women were excluded. Of the participants, 275863 had data on non-fatal and fatal stroke, 54716 only had data on non-fatal stroke, and 288272 only had data on fatal stroke.

Main outcome and measures Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data.

Results The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes.

Conclusion A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

DOI: 10.1136/bmj-2022-070603

Source: https://www.bmj.com/content/377/bmj-2022-070603