SARS-CoV-2 infection in pregnant women and incidence of thromboembolic disease: an analysis of the Covid-19-Related Obstetric and Neonatal Outcome Study (CRONOS) in Germany

Abstract

Purpose: The aim of the present study was to quantify the rate of thromboembolic events (TE) in pregnant women with SARS-CoV-2 infection and to characterize risk factors to provide a basis for individualized recommendation on prophylactic measures.

Methods: CRONOS is a multicenter, prospective observational study conducted in Germany and Austria during the COVID-19 pandemic. Pregnant women with confirmed SARS-CoV-2 infection were enrolled. Data on demographics, medical history, COVID-19-related aspects, and pregnancy and birth outcomes were collected. TE was particularly queried and used as the primary outcome. A combination of "TE," "maternal or fetal death," or "severe postpartum hemorrhage" was defined as a secondary endpoint. Risk analyses were performed using univariate and multivariable logistic regression models.

Results: Data from 8033 pregnant patients showed 40 TEs (0.5% incidence). TE rates were 10% in ICU patients, 0.2-0.4% in those with moderate-to-mild COVID-19, and < 0.1% in asymptomatic women. Pulmonary embolism occurred in 21 cases, deep vein thrombosis in 12, and 7 had atypical or arterial TE. Risk factors included advanced gestational age, COVID-19 symptoms, hospitalization or ICU admission, premature birth, cesarean section, delivery within 4 weeks of infection, higher weight gain, anemia, and chronic inflammatory bowel disease. COVID-19 vaccination reduced risk. The logistic risk model yielded an AUC of 0.87 (95% CI 0.81-0.94).

Conclusion: The TE rate in pregnant women is largely determined by the severity of the disease. In asymptomatic or mild cases, other factors outweigh TE risk, while severe COVID-19 requiring ICU admission poses a high TE risk despite prophylaxis.

Keywords: Blood transfusion; Heparin; Invasive ventilation; Maternal death; Stillbirth.

Fig. 1

Flowchart of data cleaning and analysis steps. The initial dataset included 8541 cases, with exclusions due to missing entries, duplicate cases, and missing infection or gestational age data, resulting in a final cohort of 8033 cases. The figure illustrates the process for analyzing the primary endpoint (TE incidence) and the secondary combined endpoint (TE, maternal death, stillbirth, and/or blood transfusion)