CoChat
Sign Up
Cited by 51Infant Development and Preterm CareBirth, Development, and HealthNeonatal and fetal brain pathology

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

Open access
Crump, Casey, Sundquist, Jan, Sundquist, Kristina·2021·Stroke
DOI 10.1161/strokeaha.120.033797PMC PMC8316309
Open this paper in CoChat — free account

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/strokeaha.120.033797

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 39 · Cited by 51

Research works printed but not linked: 35

  1. [1]Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, Landoulsi S, Jampathong N, Kongwattanakul K, Laopaiboon M, Global, regional, and national estimates of levels of preterm birth in 2014: A systematic review and modelling analysis. Lancet Glob Health. 2019; 7: e37– e46 30389451 PMC6293055
  2. [2]Crump C, Winkleby MA, Sundquist J, Sundquist K. Prevalence of survival without major comorbidities among adults born prematurely. JAMA. 2019; 322: 1580– 1588 31638681 PMC6806441
  3. [3]Crump C, Sundquist J, Winkleby MA, Sundquist K. Gestational age at birth and mortality from infancy into mid-adulthood: A national cohort study. Lancet Child Adolesc Health. 2019; 3: 408– 417 30956154 PMC6691360
  4. [4]Crump C, Sundquist J, Sundquist K. Risk of hypertension into adulthood in persons born prematurely: A national cohort study. Eur Heart J. 2020; 41: 1542– 1550 31872206 PMC8453271
  5. [5]Crump C, Winkleby MA, Sundquist K, Sundquist J. Risk of hypertension among young adults who were born preterm: A swedish national study of 636,000 births. Am J Epidemiol. 2011; 173: 797– 803 21320866 PMC3105282
  6. [6]de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort MB. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension. 2012; 59: 226– 234 22158643 PMC3266458
  7. [7]Crump C, Sundquist J, Sundquist K. Preterm birth and risk of type 1 and type 2 diabetes: A national cohort study. Diabetologia. 2020; 63: 508– 518 31802143 PMC6997251
  8. [9]Crump C, Sundquist J, Sundquist K. Association of preterm birth with lipid disorders in early adulthood: A swedish cohort study. PLoS Med. 2019; 16: e1002947 31626652 PMC6799885
  9. [10]Parkinson JR, Hyde MJ, Gale C, Santhakumaran S, Modi N. Preterm birth and the metabolic syndrome in adult life: A systematic review and meta-analysis. Pediatrics. 2013; 131: e1240– 1263 23509172
  10. [11]Crump C, Howell EA, Stroustrup A, McLaughlin MA, Sundquist J, Sundquist K. Association of preterm birth with risk of ischemic heart disease in adulthood. JAMA Pediatr. 2019; 173: 736– 743 31157896 PMC6547251
  11. [12]Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Heart disease and stroke statistics-2020 update: A report from the american heart association. Circulation. 2020; 141: e139– e596 31992061
  12. [13]Ueda P, Cnattingius S, Stephansson O, Ingelsson E, Ludvigsson JF, Bonamy AK. Cerebrovascular and ischemic heart disease in young adults born preterm: A population-based swedish cohort study. Eur J Epidemiol. 2014; 29: 253– 260 24687624
  13. [14]Lawlor DA, Ronalds G, Clark H, Smith GD, Leon DA. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: Findings from the aberdeen children of the 1950s prospective cohort study. Circulation. 2005; 112: 1414– 1418 16129799
  14. [15]Koupil I, Leon DA, Lithell HO. Length of gestation is associated with mortality from cerebrovascular disease. J Epidemiol Community Health. 2005; 59: 473– 474 15911642 PMC1757061
  15. [16]Osmond C, Kajantie E, Forsen TJ, Eriksson JG, Barker DJ. Infant growth and stroke in adult life: The helsinki birth cohort study. Stroke. 2007; 38: 264– 270 17218608
  16. [17]Kajantie E, Osmond C, Eriksson JG. Coronary heart disease and stroke in adults born preterm - the helsinki birth cohort study. Paediatr Perinat Epidemiol. 2015; 29: 515– 519 26250056
  17. [18]Global Burden of Disease 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990–2016: A systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019; 18: 439– 458 30871944 PMC6494974
  18. [19]Crump C, Sundquist K, Winkleby MA, Sundquist J. Early-term birth (37–38 weeks) and mortality in young adulthood. Epidemiology. 2013; 24: 270– 276 23337240
  19. [20]Koster M, Asplund K, Johansson A, Stegmayr B. Refinement of swedish administrative registers to monitor stroke events on the national level. Neuroepidemiology. 2013; 40: 240– 246 23364278
  20. [21]Merlo J, Lindblad U, Pessah-Rasmussen H, Hedblad B, Rastam J, Isacsson SO, Janzon L, Råstam L. Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two swedish prospective cohort studies using local and national routine registers. Eur J Epidemiol. 2000; 16: 235– 243 10870938
  21. [23]Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.
  22. [24]Grambsch PM. Goodness-of-fit and diagnostics for proportional hazards regression models. Cancer Treat Res. 1995; 75: 95– 112 7640169
  23. [25]Crump C, Sundquist K, Sundquist J, Winkleby MA. Gestational age at birth and mortality in young adulthood. JAMA. 2011; 306: 1233– 1240 21934056
  24. [26]Bonamy AK, Andolf E, Martin H, Norman M. Preterm birth and carotid diameter and stiffness in childhood. Acta Paediatr. 2008; 97: 434– 437 18363953
  25. [27]Bonamy AK, Martin H, Jorneskog G, Norman M. Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm. J Intern Med. 2007; 262: 635– 642 17986202
  26. [28]Lewandowski AJ, Davis EF, Yu G, Digby JE, Boardman H, Whitworth P, Singhal A, Lucas A, McCormick K, Shore AC, Elevated blood pressure in preterm-born offspring associates with a distinct antiangiogenic state and microvascular abnormalities in adult life. Hypertension. 2015; 65: 607– 614 25534704
  27. [29]Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Excess placental soluble fms-like tyrosine kinase 1 (sflt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003; 111: 649– 658 12618519 PMC151901
  28. [30]Ahmad S, Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res. 2004; 95: 884– 891 15472115
  29. [31]Shore AC, Tooke JE. Microvascular function in human essential hypertension. J Hypertens. 1994; 12: 717– 728 7963499
  30. [32]Antonios TF, Rattray FM, Singer DR, Markandu ND, Mortimer PS, MacGregor GA. Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension. Heart. 2003; 89: 175– 178 12527671 PMC1767555
  31. [33]Clausson B, Lichtenstein P, Cnattingius S. Genetic influence on birthweight and gestational length determined by studies in offspring of twins. BJOG. 2000; 107: 375– 381 10740335
  32. [34]Wilcox AJ, Skjaerven R, Lie RT. Familial patterns of preterm delivery: Maternal and fetal contributions. Am J Epidemiol. 2008; 167: 474– 479 18048376
  33. [36]Wang T, Tang Z, Yu X, Gao Y, Guan F, Li C, Huang S, Zheng J, Zeng P. Birth weight and stroke in adult life: Genetic correlation and causal inference with genome-wide association data sets. Front Neurosci. 2020; 14: 479 32595438 PMC7301963
  34. [37]Crump C Medical history taking in adults should include questions about preterm birth. BMJ. 2014; 349: g4860 25085466
  35. [38]Hogberg U, Larsson N. Early dating by ultrasound and perinatal outcome. A cohort study. Acta Obstet Gynecol Scand. 1997; 76: 907– 912 9435727

Authors
Crump, C., Sundquist, J., & Sundquist, K.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Lund University (SE)
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-08
Volume
52
Issue
8
Pages
2609-2617
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/strokeaha.120.033797
PMC
PMC8316309
OpenAlex
W3168394575
Cited by
51
References
39
Citations by year
2026: 7 · 2025: 9 · 2024: 19 · 2023: 8 · 2022: 4 · 2021: 2 · 2015: 1 · 2012: 1
FWCI
8.16
Type
journal article
Language
en
Open access
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL139536)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
Keywords
preterm birth, stroke risk, gestational age, hemorrhagic stroke, ischemic stroke, familial confounding, hypertension, survivorship bias, sex differences in stroke risk, perinatal risk factors
MeSH terms
Adolescent, Adult, Female, Follow-Up Studies, Humans, Infant, Newborn, Male, Pregnancy, Risk Factors, Sweden, Cohort Studies, Survivors, Stroke, Siblings, Premature Birth, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review