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 foetal 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: We conducted a population-based, retrospective cohort study of all pregnant women (≥16 years of age) with a proteinuria measure within 20 weeks of conception (n = 306 244; mean age 29.8 years) from Ontario, Canada. Proteinuria was defined by any of the following: urine albumin:creatinine ratio ≥3 mg/mmol, urine protein: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 8508 (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 positive proteinuria [32 events (0.38%)] compared with women without proteinuria [593 events (0.20%); inverse probability-weighted risk ratio 1.79 (95% confidence interval 1.25-2.57)]. 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: The presence of proteinuria in the first 20 weeks of pregnancy is associated with a significantly higher risk of VTE.