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Maternal reproductive history and premenopausal risk of hypertension and cardiovascular disease: a Danish cohort study
  1. Shannon X Chen1,
  2. Kathleen M Rasmussen1,
  3. Julia Finkelstein1,
  4. H Støvring2,
  5. Ellen Aa Nøhr3,
  6. Helene Kirkegaard3
  1. 1 Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
  2. 2 Department of Public Health, Section for Biostatistics, Aarhus University, Aarhus, Denmark
  3. 3 Department of Clinical Research, the Research Unit of Gynecology and Obstetrics, University of Southern Denmark, Odense, Denmark
  1. Correspondence to Dr Helene Kirkegaard; hkirkegaard{at}


Objectives The metabolic changes of pregnancy resemble a cardiovascular risk profile and may persist postpartum, with body mass index (BMI) as a potential modifier. We examined the association between the number of live-birth pregnancies and maternal premenopausal risks of hypertension and cardiovascular disease (CVD), accounting for pre-pregnancy BMI as well as abortions and stillbirths.

Design A prospective cohort study.

Setting Mothers from the Danish National Birth Cohort (1996 to 2002). For each of these women, registry data on all pregnancies from 1973 to 2011 were obtained, as were self-reported pre-pregnancy weight and height.

Participants A total of 44 552 first-time mothers in the Danish National Birth Cohort.

Outcome measures Risks of hypertension and CVD during and between live-birth pregnancies separately and combined as live-birth cycles.

Results After adjustment for abortions, stillbirths, pre-pregnancy BMI and other covariates, a higher risk of hypertension was observed in the first (HR 1.53, 95% CI: 1.37 to 1.72) and fourth and subsequent live-birth cycles (HR 1.72, 95% CI: 1.15 to 2.58), compared with the second. However, as number of live-birth pregnancies increased, risk of hypertension decreased during live-birth pregnancies and increased between live-birth pregnancies (tests for trend, p<0.01). For CVD, we found an overall J-shaped but non-significant association with number of live-birth pregnancies. No interaction with pre-pregnancy BMI (<25 versus ≥25 kg/m2) was observed.

Conclusions Premenopausal women had the highest risk of hypertension and CVD during their first live-birth pregnancy and after their fourth live-birth pregnancy. All risks were independent of BMI before the first live-birth pregnancy and of number of abortions and stillbirths.

  • Hypertension
  • Maternal medicine
  • Cardiac Epidemiology

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  • Contributors HK, EAN, KMR and SXC designed research; SXC, HS and HK analysed data; SXC drafted the manuscript; HK, KMR, EAN, JLF and HS interpreted results and revised the manuscript; SXC and HK have primary responsibility for final content. All authors approved the final version for publication.

  • Funding The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. Helene Kirkegaard received a grant from the Danish Heart foundation grant number 14-R97-A5163. The Danish Heart foundation had no involvement in the design and conduct of the study, management, analysis and interpretation of the data or preparation, review or approval of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement The data that provide the findings of this study are available from the Danish National Birth Cohort, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Therefore, data described in the manuscript, code book, and analytic code will not be made available. All requests for data from the Danish National Birth Cohort must include a short protocol with a specific research question and a plan for analysis. More information can be found on

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