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

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.