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Prenatal biochemical screening and long term risk of maternal cardiovascular disease: population based cohort study

BMJ 2018; 362 doi: (Published 11 July 2018) Cite this as: BMJ 2018;362:k2739
  1. Joel G Ray, professor1 2,
  2. Tianhua Huang, assistant professor3 4,
  3. Wendy S Meschino, assistant professor4 5,
  4. Eyal Cohen, professor4 6,
  5. Alison L Park, epidemiologist2
  1. 1Departments of Medicine, Health Policy Management and Evaluation, and Obstetrics and Gynecology, St Michael’s Hospital, Toronto, ON, Canada, M5B 1W8
  2. 2Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, ON, Canada
  3. 3Genetics Program, North York General Hospital, Toronto, ON, Canada
  4. 4Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
  5. 5Department of Paediatrics, University of Toronto, Toronto, ON, Canada
  6. 6Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada
  1. Correspondence to: J G Ray rayj{at}
  • Accepted 6 June 2018


Objective To examine whether abnormal prenatal biochemical screening results are associated with an increased risk of premature cardiovascular disease after pregnancy.

Design Population based cohort study.

Setting The entire province of Ontario, Canada, where healthcare is universally available.

Participants Women aged 12-55 years, without pre-existing cardiovascular disease, who underwent prenatal screening between 1993 and 2011. One pregnancy per woman was randomly selected.

Exposures Low (≤5th centile multiple of the median) serum total chorionic gonadotropin, unconjugated estriol, and pregnancy associated plasma protein A and high (≥95th centile multiple of the median) alphafetoprotein and dimeric inhibin-A.

Main outcome measures Composite of hospital admission or revascularisation for coronary artery, cerebrovascular, or peripheral arterial disease or hospital admission for heart failure or dysrhythmia at least 365 days after pregnancy.

Results Among 855 536 pregnancies, and after a median of 11.4 (interquartile range 6.8-17.5) years of follow-up, 6209 women developed the main cardiovascular disease outcome. Abnormal results for each of the five prenatal biochemical screening analytes, especially dimeric inhibin-A, were associated with a higher risk of cardiovascular disease. Women with an abnormally high dimeric inhibin-A (≥95th centile) had the highest rate of cardiovascular disease (30 events or 8.3 per 10 000 person years versus 251 events or 3.8 per 10 000 person years for those <95th centile; multivariable adjusted hazard ratio 2.0, 95% confidence interval 1.4 to 3.0). Compared with women without any abnormal biochemical measure, the hazard ratio for the cardiovascular disease composite outcome was 1.2-1.3 times higher with one abnormal analyte and 1.5-2.0 times higher with two or more abnormal analytes.

Conclusions Women with abnormal prenatal biochemical screening results, especially for dimeric inhibin-A, may be at higher risk of cardiovascular disease. If these findings are replicated elsewhere, a massive amount of data exists that could aid in identifying women at higher risk of premature cardiovascular disease and that could be conveyed to them or their healthcare providers.


  • Contributors: JGR and ALP developed the study concept, analysed and interpreted the data, drafted and revised the manuscript, and approved the final version. TH and WM interpreted the data, revised the manuscript, and approved the final version. EC revised the manuscript and approved the final version. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. JGR is the guarantor

  • Funding: This work was supported by a grant from the Canadian Institutes of Health Research (CIHR). This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work other than that described above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The Research Ethics Boards of the Sunnybrook Health Sciences Centre and the North York General Hospital granted ethics approval.

  • Transparency declaration: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.

  • Data sharing: No additional data available. Only ALP is permitted to access the data.

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