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Preterm Delivery and Long-Term Risk of Stroke in Women : A National Cohort and Cosibling Study

Crump, Casey LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2021) In Circulation 143(21). p.2032-2044
Abstract

Background: Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women. Methods: A national cohort study was conducted of all 2 188 043 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... (More)

Background: Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women. Methods: A national cohort study was conducted of all 2 188 043 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. Results: 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 (95% CI, 1.45-1.79) and further stratified was 2.81 (95% CI, 2.02-3.91) for extremely preterm (22-27 weeks), 2.07 (95% CI, 1.74-2.46) for very preterm (28-33 weeks), 1.38 (95% CI, 1.21-1.57) 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 (preterm versus full-term: aHR, 1.61 [95% CI, 1.50-1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28-1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27-1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25-1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47-1.61]) 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. Conclusions: In this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cerebrovascular disorders, hemorrhagic stroke, ischemic stroke, premature birth, preterm birth, stroke, women
in
Circulation
volume
143
issue
21
pages
13 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:33966449
  • scopus:85106928154
ISSN
0009-7322
DOI
10.1161/CIRCULATIONAHA.120.052268
language
English
LU publication?
yes
id
0db78c7f-e89e-4033-8b32-8997812372d3
date added to LUP
2021-06-15 15:57:46
date last changed
2024-06-15 12:34:57
@article{0db78c7f-e89e-4033-8b32-8997812372d3,
  abstract     = {{<p>Background: Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women. Methods: A national cohort study was conducted of all 2 188 043 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. Results: 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 &lt;37 weeks) was 1.61 (95% CI, 1.45-1.79) and further stratified was 2.81 (95% CI, 2.02-3.91) for extremely preterm (22-27 weeks), 2.07 (95% CI, 1.74-2.46) for very preterm (28-33 weeks), 1.38 (95% CI, 1.21-1.57) 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 (preterm versus full-term: aHR, 1.61 [95% CI, 1.50-1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28-1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27-1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25-1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47-1.61]) 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. Conclusions: In this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.</p>}},
  author       = {{Crump, Casey and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{0009-7322}},
  keywords     = {{cerebrovascular disorders; hemorrhagic stroke; ischemic stroke; premature birth; preterm birth; stroke; women}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{21}},
  pages        = {{2032--2044}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Circulation}},
  title        = {{Preterm Delivery and Long-Term Risk of Stroke in Women : A National Cohort and Cosibling Study}},
  url          = {{http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052268}},
  doi          = {{10.1161/CIRCULATIONAHA.120.052268}},
  volume       = {{143}},
  year         = {{2021}},
}