Preterm delivery increases the risk of stroke in long-term, Circulation study.

Sweden. Stroke is the third leading cause of death worldwide and has a higher burden of disease in women. The risk factor profile differs between females and males with pregnancy related complications playing a significant, yet not much explored, role in the pathogenesis of stroke in the former. Crump et al in the online issue of Circulation journal have now shown in a national cohort study of >2 million women that preterm delivery is associated with higher future risks of both hemorrhagic and ischemic stroke up to 40 years later.

Nearly 11% of all births worldwide occur preterm, affecting 15 million deliveries each year. Women who deliver preterm have been reported to have modestly higher future risks of hypertension, diabetes, and hyperlipidemia, which are established risk factors for stroke. However, it is unclear whether such associations might be attributable to confounding by shared familial (genetic or environmental) determinants of both preterm delivery and stroke.

Other major knowledge gaps also remain, including risks of specific types of stroke (hemorrhagic or ischemic) associated with preterm delivery, how such risks change across the life course, and risks by specific types of preterm delivery (spontaneous or medically indicated).

A national cohort study was conducted of all 2188043 women with a singleton delivery in Sweden in 1973 through 2015 who were followed up for stroke identified from nationwide diagnoses through 2015. Cox regression was used to compute adjusted hazard ratios (aHRs) for stroke associated with pregnancy duration, and cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors.

In 48.0 million person-years of follow-up, 36,372 (1.7%) women were diagnosed with stroke. In the 10 years after delivery, the aHR for stroke associated with preterm delivery (gestational age <37 weeks) was 1.61, which was further stratified to 2.81 for extremely preterm (22–27 weeks), 2.07 for very preterm (28–33 weeks), 1.38 for late preterm (34–36 weeks), and 1.15 (95% CI, 1.06–1.24) for early term (37–38 weeks), compared with full-term (39–41 weeks) delivery.

These risks remained similarly elevated at 10 to 19 years after delivery and then declined but remained significantly elevated at 20 to 29 years and 30 to 43 years.

Preterm delivery was associated with both hemorrhagic and ischemic stroke across the entire follow-up period (up to 43 years). These findings were not explained by shared determinants of preterm delivery and stroke within families.

Stroke risks were higher after either spontaneous or medically indicated preterm delivery, and recurrent preterm delivery was associated with further increases in risk.

This is the largest study to date of preterm delivery in relation to stroke risks and the first to assess for potential confounding by shared familial factors using a cosibling design. The findings suggest that women who delivered preterm have substantially higher risks of stroke that persist at least 40 years, especially those who delivered extremely or very preterm.

The present findings are consistent with associations between preterm delivery and future risks of IHD and all-cause and cardiovascular mortality.

The findings can have an impact on day-to-day clinical practice. Cardiovascular risk assessment in women should routinely include reproductive history that covers preterm delivery and other adverse pregnancy outcomes.

Women with a history of preterm delivery warrant early preventive actions and long-term clinical follow-up to reduce other modifiable risk factors for stroke, including obesity, hypertension, diabetes, hyperlipidemia, smoking, and physical inactivity.

Source: Crump C, Sundquist J, Sundquist K. Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study. Circulation. 2021 May 10. doi: 10.1161/CIRCULATIONAHA.120.052268.