Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study

Abstract

Background and purpose: Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort.

Methods: A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors.

Results: In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12–1.43; P<0.001), and further stratified was 1.42 (1.11–1.81; P=0.005) for early preterm (22–33 weeks) and 1.22 (1.06–1.40; P=0.004) for late preterm (34–36 weeks), compared with full-term (39–41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04–1.94]; any preterm: 1.15 [0.97–1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87–2.03]; any preterm: 1.31 [1.07–1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families.

Conclusions: In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.

Keywords: Sweden; hemorrhagic stroke; ischemic stroke; premature birth; survivors.