Stroke Risks with Infertility, Miscarriage, and Stillbirth
This is a large-scale international collaboration that examined evidence associating infertility, miscarriage, and stillbirth with stroke risks.
Study Background
WHAT
What are the associations of infertility, recurrent miscarriage, and stillbirth with risks of stroke?
WHY
Previous research into this topic yielded scant and/or inconclusive evidence
Common cause of morbidity and mortality in women worldwide
WHERE
Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States (pooled databases through InterLACE consortium)
WHEN
Studies started 1989-2010
WHO
Included women with data on infertility, miscarriage, OR stillbirth AND data on race/ethnicity, body mass index (BMI), smoking history, educational history, and hypertension status
Excluded women who had non-fatal stroke before age 40
HOW
Procured reproductive history through baseline and/or follow-up questionnaires
Reproductive questions were based on standardized definitions
infertility: twelve months or more of unsuccessfully trying to conceive, doctor diagnosis, or received infertility treatment
recurrent miscarriages: three more more miscarriages
recurrent stillbirths: two or more stillbirths (subsequent or interspersed with live birth)
Stroke data derived from hospital data and/or self-reported questionnaires
Linked hospital data came from Australia, Netherlands, UK BioBank, and Sweden
Fatal stroke data came through death registries in Australia, China, Netherlands, Japan, and UK Biobank
Sub-typed strokes as hemorrhagic or ischemic; all non-fatal strokes that were unclassified were called “unspecified stroke”
Collected baseline covariates
Asian women had different BMI scale: underweight (<18.5), normal (18.5-22.9), overweight (23-27.4), and obese (≥27.5)
race/ethnicity defined as white, Asian or “others”
Statistics
Included Kaplan-Meier survival curves, Cox proportional hazards tested with Schoenfeld residuals, Fine-Gray sub-distribution hazards using SAS
Survival time models adjusted for history of use of oral contraceptive pill (OCP) or hormone replacement therapy (HRT)
this data not available from China or Japan
led to significant exclusions in both fatal and non-fatal assessments of association
See page 3 of study for additional details
Results
618, 851 women included
data on non-fatal + fatal stroke = 275,863
data on non-fatal stroke only = 54,716
data on fatal stroke only = 288,272
Compared to women without infertility, miscarriages, or stillbirth,
Women with infertility had higher risks of non-fatal stroke
Women with miscarriages had:
higher risks of fatal and non-fatal stroke
risks increased with increasing # of miscarriages
Women with stillbirths had:
higher risks of fatal and non-fatal stroke
risks increased with increasing # stillbirths
Insufficient outcomes
association of infertility with fatal stroke
unspecified fatal stroke with miscarriage or with stillbirth
Authors’ Conclusions
Recurrent miscarriages or stillbirths are a risk factor for strokes in women.
Resources
Hure AJ, Chojenta CL, Powers JR, Byles JE, Loxton D. Validity and reliability of stillbirth data using linked self-reported and administrative datasets. J Epidemiol. 2015;25(1):30-37. doi:10.2188/jea.JE20140032
International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. https://public-health.uq.edu.au/interlace InterLACE website
Liang C, Chung HF, Dobson AJ, et al. Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women. BMJ. 2022;377:e070603. Published 2022 Jun 22. doi:10.1136/bmj-2022-070603
Mishra GD, Anderson D, Schoenaker DA, et al. InterLACE: A New International Collaboration for a Life Course Approach to Women's Reproductive Health and Chronic Disease Events. Maturitas. 2013;74(3):235-240. doi:10.1016/j.maturitas.2012.12.011
OHSU Brain Institute. Understanding Stroke. Accessed June 28th, 2022. https://www.ohsu.edu/brain-institute/understanding-stroke
