Cited by 416Pregnancy and preeclampsia studiesBirth, Development, and HealthCardiovascular Health and Risk Factors

The DOI matches its Crossref record; 161 of the 161 references it cites were found in a registry or an index; 2 of the 155 sources its claims cite were checked for support.

Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review

Open access

Abstract

Objective: To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease. Design: Umbrella review. Data sources: Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019. Review methods: Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke. Results: 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment. Conclusions: From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines. Systematic review registration: PROSPERO CRD42019120076.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This umbrella review consolidates systematic reviews and meta-analyses on reproductive factors in women of reproductive age and later cardiovascular disease. It reports that multiple fertility-related factors and adverse pregnancy outcomes are associated with increased cardiovascular risk, while longer breastfeeding is associated with reduced risk.

Key findings

  • Among 32 included reviews, composite cardiovascular disease associations were twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. Longer breastfeeding was associated with reduced cardiovascular disease risk.
  • For ischaemic heart disease, associations were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current combined oral contraceptive use, recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms.
  • For stroke, associations were twofold or more for current use of any oral contraceptive, pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current combined oral contraceptive use, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. Pre-eclampsia was associated with a fourfold risk of heart failure.
  • No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment.

Methods

  • Umbrella review of systematic reviews and meta-analyses; population was women of reproductive age; exposures were fertility-related factors and adverse pregnancy outcomes; outcomes included ischaemic heart disease, heart failure, peripheral arterial disease, stroke, and composite cardiovascular disease.
  • Medline, Embase, and Cochrane databases were searched from inception until 31 August 2019; PRISMA guidelines were followed and the protocol was registered in PROSPERO (CRD42019120076).
  • Two reviewers independently screened, extracted data, and appraised quality with AMSTAR 2; overlapping reviews were assessed with corrected covered area, outdated reviews were excluded, and findings were synthesised narratively with forest plots and tables.

Limitations

  • The paper states that missing metadata, including participant and event numbers, hindered reporting; systematic reviews on endometriosis, pelvic inflammatory disease, first trimester bleeding without miscarriage, and anaemia in pregnancy could not be identified; some reviews were rated low quality and none high quality; and included evidence was observational, with possible residual confounding, imprecise results from few events, cross-sectional designs, heterogeneity, incomplete publication bias assessment, and self-reported data.
  • The paper also states that presenting absolute numbers on the scale of the problem was not feasible, that causality is unclear, and that the exact magnitude of preventable cardiovascular disease attributable to reproductive risk factors is uncertain.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.m3502

Cites

161 of 161 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Fig 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram
Fig 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagramCC BY-NC · PubMed Central
Fig 2 Forest plot showing studies investigating the association between miscarriage and risk of stroke. Note, weights are from random effects analysis
Fig 2 Forest plot showing studies investigating the association between miscarriage and risk of stroke. Note, weights are from random effects analysisCC BY-NC · PubMed Central
Fig 3 Forest plot showing studies investigating the association between gestational diabetes and risk of stroke. Note, weights are from random effects analysis
Fig 3 Forest plot showing studies investigating the association between gestational diabetes and risk of stroke. Note, weights are from random effects analysisCC BY-NC · PubMed Central
Fig 4 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of composite cardiovascular disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes
Fig 4 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of composite cardiovascular disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomesCC BY-NC · PubMed Central
Fig 5 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of ischaemic heart disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes
Fig 5 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of ischaemic heart disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomesCC BY-NC · PubMed Central
Fig 6 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of stroke. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes. *Ischaemic stroke. †Haemorrhagic stroke
Fig 6 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of stroke. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes. *Ischaemic stroke. †Haemorrhagic strokeCC BY-NC · PubMed Central
Fig 7 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of heart failure. Circles indicate non-fatal outcomes
Fig 7 Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of heart failure. Circles indicate non-fatal outcomesCC BY-NC · PubMed Central

Verification

Claims the paper makes

127 Not checked yet · 91 Own result · 21 Own method · 12 No basis given · 4 Own interpretation · 2 Partly supported · accuracy not yet measured

Verify all 153 references — free account
  • It may state two separate claims as one. 30
  • Probably not a substantial claim. 49
74 of 74
  • The paper relies on this without support.

    The associations between reproductive factors and cardiovascular disease observed in the included observational studies are not entirely due to residual confounding.

    “the reviews included were necessarily based on observational evidence; consequently, as noted by Grandi et al,60 the possibility of confounding remains because of unknown confounders or lack of adjustment for known confounders”
  • The paper relies on this without support.

    The included systematic reviews and meta-analyses provide valid estimates of the associations between reproductive factors and cardiovascular disease.

    “This detailed umbrella review synthesised existing systematic reviews and meta-analyses into one user friendly document”
2 of 2

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.

Each contradiction between two passages listed here was confirmed by an independent check.

4 of 4

Citations

Cites

Show all 161 references

Research works printed but not linked: 1

  1. 2019, Heart and circulatory disease statistics 2019, Stat Compend, 2019, 94

Cited by

Sorted by citations

See all 416

Metadata

Authors
Okoth, K., Chandan, J. S., Marshall, T., Thangaratinam, S., Thomas, G. N., Nirantharakumar, K., & Adderley, N. J.
Affiliations
  • University of Birmingham (GB)
  • Queen Mary University of London (GB)
Corresponding author
Nirantharakumar, Krishnarajah
Venue
BMJ
Publisher
BMJ
Published
2020-10-07
Volume
371
Pages
m3502
ISSN
1756-1833 (ISSN-L)
OpenAlex
W3091804242
Cited by
416
References
161
Citations by year
2026: 38 · 2025: 76 · 2024: 81 · 2023: 90 · 2022: 74 · 2021: 55 · 2020: 2
FWCI
6.51
Type
journal article
Language
en
Open access
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc)
Funders
National Institute for Health and Care Research (ACF-2018-08-001)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
Keywords
polycystic ovary syndrome, preeclampsia, preterm birth, gestational diabetes mellitus, premature ovarian insufficiency, early menopause, breastfeeding, combined oral contraceptives, progestin-only contraception, heart failure, ischemic heart disease, stroke, peripheral arterial disease, adverse pregnancy outcomes, cardiovascular risk, women's reproductive health
MeSH terms
Systematic Reviews as Topic, Correlation of Data, Cardiovascular Diseases, Female, Fertility, Humans, Pregnancy, Pregnancy Complications, Risk Factors, Meta-Analysis as Topic, Risk Assessment, Reproductive Health

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.

A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

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