Abstract
Pregnant and puerperal women are at increased risk of venous thromboembolism (VTE) owing to hemostatic changes in preparation for childbirth. The objective of this study was to investigate if COVID-19 infection was associated with VTE in pregnancy or 12 weeks postpartum when considering (prophylactic or therapeutic) anticoagulant use. This population-based register study included all women in Sweden and Norway giving birth after 22 gestational weeks, with conception dates from March 2020 to 2022. A PCR-verified COVID-19 test was used as the exposure, and a VTE diagnosis during pregnancy or 12 weeks postpartum was the outcome. Non-infected women consisted of those testing negative and untested individuals. Cox regression analyses, with COVID-19 infection as a time-varying exposure, and adjusted for maternal characteristics and anticoagulant use, provided overall hazard ratios. To evaluate whether there was a particular increased risk of VTE shortly after testing positive for COVID-19, we estimated time-specific risk of VTE in the first 2, 4, 8, 12, and 16 weeks following COVID-19 infection. Data from each country were first analyzed separately and then meta-analyzed. Among 323,868 participants, 46,048 (14.2%) had COVID-19 during pregnancy, and 80 (0.2%) were diagnosed with VTE. Pregnant women with COVID-19 had a higher VTE incidence rate compared to non-infected (4.9 vs. 2.9 per 1000 person-years; adjusted overall hazard ratio [aHR] 1.26, 95% Confidence Interval [CI] 0.80-2.00). The highest risk was within two weeks of infection (aHR 4.63, 95% CI 2.71-7.90) but remained elevated up to 12 weeks post-infection (aHR 1.86, 95% CI 1.17-2.94). In the postpartum period, 8,515 (2.6%) had COVID-19, and 6 (0.07%) were diagnosed with VTE (aHR 5.17, 95% CI 2.50-10.69). Although VTE post-COVID-19 infection was rare, the infection was associated with increased VTE risk during pregnancy and postpartum, even after adjusting for anticoagulant use. These findings should contribute to the individual risk assessment when evaluating the need for prophylactic anticoagulants in pregnancy and postpartum.