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BMJ. 2018 Jul 11;362:k2739. doi: 10.1136/bmj.k2739.

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

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Departments of Medicine, Health Policy Management and Evaluation, and Obstetrics and Gynecology, St Michael's Hospital, Toronto, ON, Canada, M5B 1W8.
Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, ON, Canada.
Genetics Program, North York General Hospital, Toronto, ON, Canada.
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.



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


Population based cohort study.


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


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.


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.


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.


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.


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.

Conflict of interest statement

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.

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