Proteinuria and venous thromboembolism in pregnancy: a population-based cohort study

Background — Pregnancy associated venous thromboembolism (VTE) is associated with high morbidity and mortality. Identification of risk factors of VTE may lead to improved maternal and fetal outcomes Proteinuria confers a pro-thrombotic state; however, its association with VTE) in pregnancy remains unknown. We set out to assess the association of proteinuria and VTE during pregnancy.

Methods — Population-based, retrospective cohort study of all pregnant women (≥ 16 years old) with a proteinuria measure within 20 weeks of conception date (n = 306,244, mean age 29.8) from Ontario, Canada. Proteinuria was defined by any of the following: urine albumin to creatinine ratio ≥3 mg/mmol, urine protein to creatinine ratio ≥ 5 mg/mmol or urine dipstick proteinuria ≥ 1. The main outcome measure was a diagnosis of VTE up to 24 weeks post-partum.

Results — A positive proteinuria measurement occurred in 8,508 (2.78%) women and was more common with a history of kidney disease, gestational or non-gestational diabetes mellitus, and hypertension. VTE events occurred in 625 (0.20%) individuals with a higher risk among women with a positive proteinuria (32 events, 0.38%) compared to women without proteinuria (593 events, 0.20%) [inverse probability weighted risk ratio 1.79, 95% CI 1.25 to 2.57]. The association was consistent using a more specific VTE definition, in the post-partum period, in high risk subgroups (hypertension or diabetes) and when the sample was restricted to women with preserved kidney function.

Conclusions and Relevance — The presence of proteinuria in the first 20 weeks of pregnancy is associated with a significantly higher risk of VTE.