Premature birth associated with elevated stroke risk later in life
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Younger adults born early preterm experienced up to a 42% greater risk for stroke compared with those born full term, an association not entirely explained by genetic or environmental factors, according to data published in Stroke.
“To our knowledge, this is the largest study to date of preterm birth in relation to stroke risks, and the first with sufficient power to assess stroke types or potential familial confounding in co-sibling analyses,” Casey Crump, MD, PhD, vice chair for research in the department of family medicine and community health, and professor of epidemiology in the department of population health science and policy at Mount Sinai, and colleagues wrote. “The present study extends prior evidence by determining stroke risks in a large national cohort with more than fivefold as many strokes as in previous studies, affording the statistical power needed to assess hemorrhagic and ischemic stroke risks, sex-specific differences and familial confounding.”
For this national cohort study of Swedish citizens, researchers assessed more than 2.1 million individuals born from 1973 to 1994 who survived to age 18 years and were followed up for first-time stroke through 2015. To evaluate the association between preterm birth (< 37 weeks) and risk for stroke, researchers adjusted for other perinatal and parental factors and performed a co-sibling analysis to identify potential shared familial confounders, genetic or environmental.
Preterm and very preterm birth
During 28 million person-years of follow-up, approximately 0.2% of the cohort was diagnosed with stroke.
Researchers reported that, from age 18 to 43 years, individuals born preterm experienced a 26% greater risk for stroke (adjusted HR = 1.26; 95% CI, 1.12-1.43; P < .001) compared with those born full term (39 to 41 weeks).
Risk for stroke was greatest among individuals born early preterm (22 to 33 weeks; aHR = 1.42; 95% CI, 1.11-1.81; P = .005) but was also elevated among those born late preterm (34 to 36 weeks; aHR = 1.22; 95% CI, 1.06-1.4; P = .004) compared with those born full term.
Moreover, researchers found positive associations between any preterm birth and both hemorrhagic stroke (aHR = 1.15; 95% CI, 0.97-1.35) and ischemic stroke (aHR = 1.31; 95% CI, 1.07-1.6), with the greatest risk observed among individuals born early preterm (aHR for hemorrhagic stroke = 1.42; 95% CI, 1.04-1.94; aHR for ischemic stroke = 1.33; 95% CI, 0.87-2.03).
According to the study, results were similar among both men and women and were only partially explained by shared familial confounders.
Early preventive evaluation needed
“Multiple underlying mechanisms may potentially link preterm birth with increased stroke risks,” the researchers wrote. “Preterm birth interrupts fetal angiogenesis during a critical developmental period, leading to reduced capillary density and increased arterial stiffness. Preterm birth also has been associated with persistently elevated levels of anti-angiogenic factors (eg, soluble endoglin and soluble fms-like tyrosine kinase-1), which are correlated with blood pressure.
“Our findings suggest that preterm birth survivors need early preventive evaluation and long-term clinical follow-up into adulthood to reduce their lifetime risk of stroke,” the researchers wrote. “More aggressive reduction of other modifiable risk factors may be needed, including obesity, hypertension, diabetes, hyperlipidemia, smoking and physical inactivity. In patients of all ages, medical records and history-taking should routinely include gestational age at birth to facilitate preventive actions (including healthy lifestyle counseling) across the life course in those born preterm.”
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