Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women
Liang, Chen; Chung, Hsin-Fang; Dobson, Annette J; Hayashi, Kunihiko; van der Schouw, Yvonne T; Kuh, Diana; Hardy, Rebecca; Derby, Carol A; El Khoudary, Samar R; Janssen, Imke; Sandin, Sven; Weiderpass, Elisabete; Mishra, Gita D
(2022) BMJ (Clinical research ed.), volume 377
(Article)
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
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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: 618 851 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; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 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.
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Keywords: Abortion, Habitual/epidemiology, Brain Ischemia, Female, Humans, Infertility, Male, Pregnancy, Prospective Studies, Risk Factors, Stillbirth/epidemiology, Stroke/epidemiology, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0959-8138
Publisher: British Medical Association
Note: Funding Information: Funding: This study is funded by the Australian National Health and Medical Research Council Centres of Research Excellence (APP1153420). GDM is supported by an Australian National Health and Medical Research Council Investigator grant (APP2009577). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. Funding Information: The data on which this research is based were drawn from eight observational studies. The research included data from the Australian Longitudinal Study on Women’s Health (ALSWH), the University of Newcastle, Australia, and the University of Queensland, Australia. We are grateful to the Australian Government Department of Health for funding and to the women who provided the survey data. The authors acknowledge the Australian Government Department of Health for providing Aged Care data, and the Australian Institute of Health and Welfare (AIHW) as the integrating authority. The authors acknowledge the assistance of the Data Linkage Unit at the Australian Institute of Health and Welfare (AIHW) for undertaking the data linkage to the National Death Index (NDI). The authors acknowledge the following: Centre for Health Record Linkage (CHeReL), NSW Ministry of Health and ACT Health for the NSW Admitted Patients, and the ACT Admitted Patient Care Data Collections; Department of Health Western Australia, including the Data Linkage Branch, and the WA Hospital Morbidity Data Collection; SA NT Datalink, SA Health, and Northern Territory Department of Health for the SA Public Hospital Separations and NT Public Hospital Inpatient Activity-Data Collections; Department of Health Tasmania, and the Tasmanian Data Linkage Unit for the Public Hospital Admitted Patient Episodes Data Collection; Department of Health Victoria and Centre for Victorian Data Linkage for the Victorian Admitted Episodes Dataset. Funding Information: Women’s Lifestyle and Health Study (WLHS) was funded by a grant from the Swedish Research Council (grant No 521-2011-2955). MRC National Survey of Health Development (NSHD) has core funding from the UK Medical Research Council (MC UU 12019/1). Baseline survey of the Japan Nurses’ Health Study (JNHS) was supported in part by a Grant-in-Aid for Scientific Research (B: 14370133, 18390195) from the Japan Society for the Promotion of Science, and by grants from the Japan Menopause Society. The China Kadoorie Biobank has grant support from the Kadoorie Charitable Foundation in Hong Kong, the Wellcome Trust in the UK (088158/Z/09/Z) and the Chinese Ministry of Science and Technology (2011BAI09B01). The UK Medical Research Council, the British Heart Foundation (BHF) and Cancer Research UK also provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. This research has been conducted using the UK Biobank resource under application 26629. Funding Information: The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Ageing (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. Publisher Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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