Number of Live Births as a Protective Factor Against Clinical and Covert Brain Infarcts: The Framingham Heart Study

Female-specific reproductive factors have been associated with stroke risk, although evidence for some factors (eg, live births) remains conflicting. We determined the association between number of live births and other female-specific reproductive factors and subsequent risk of stroke and magnetic resonance imaging markers of vascular brain injury in a community-based cohort.

This was a prospective cohort study of 1882 (mean age, 61.3±9.6 years) women from the FHS (Framingham Heart Study) Offspring cohort who were stroke free at the baseline examination (1998-2001). Reproductive factors included number of live births, age at menopause, postmenopausal hormone replacement therapy use and serum estradiol and estrone levels. The primary outcome was incident all-cause stroke, with covert brain infarcts and white matter hyperintensity volume on brain magnetic resonance imaging as cross-sectional secondary outcomes.

During a median 18-year follow-up, 126 women had a stroke. On multivariable Cox proportional hazards models controlling for vascular risk factors, ≥3 live births (versus 0, reference) was associated with a reduced risk of stroke (hazard ratio, 0.51 [95% CI, 0.31-0.85]; P<0.01). More live births (≥3 versus 0) was cross-sectionally associated with decreased risk of covert brain infarct (odds ratio, 0.52 [95% CI, 0.30-0.92]; P=0.03). No significant association was detected between other reproductive factors and incident stroke or magnetic resonance imaging markers of vascular brain injury.

A greater number of live births was associated with a decreased risk of stroke and covert brain infarct in women and may be an important factor to include in female-specific clinical prediction rules for stroke.