Risk of Pregnancy Loss Prior to 20 weeks Gestation with COVID-19

JACOBY, Vanessa L.; MURTHA, Amy; AFSHAR, Yalda; GAW, Stephanie; ASIODU, Ifeyinwa; TOLOSA, Jorge; NORTON, Mary E.; BOSCARDIN, John; FLAHERMAN, Valerie

Objective Many studies have evaluated birth outcomes with COVID-19, but there has been less attention paid to the risk of early pregnancy loss, despite the known association of miscarriage with viral infection.1 The current literature is limited by small numbers of cases, a focus on inpatients, and lack of longitudinal follow-up.2-5 These studies have primarily been conducted in Europe and Asia which limits generalizability to a diverse US population with unique patient characteristics. To address this evidence gap, we present data on a cohort of U.S. women with SARS-CoV-2 infection in early pregnancy to help inform clinical practice. Study Design PRIORITY is an ongoing nationwide prospective cohort study of COVID-19 during pregnancy in the U.S. Participants are ≥ 13 years, under investigation for or had confirmed COVID-19 defined as positive PCR for SARS-CoV-2, enrolled from March-October 2020. For this analysis, we selected participants who enrolled at <14 weeks gestation and had SARS-CoV-2 testing; 7 were excluded that did not have longitudinal follow-up. The study was approved by the UCSF Institutional Review Board (IRB #20-30410). Participants completed questionnaires at enrollment, weekly for 4 weeks, and then multiple times throughout pregnancy. Medical record review was used to adjudicate adverse outcomes in a subsample of the population. We calculated the incidence and 95% confidence intervals for early pregnancy loss (EPL) defined as pregnancy loss <20 weeks gestation. Results Among the 1,338 PRIORITY participants, 109 comprise the analysis set who enrolled at <14 weeks gestation; 94 were COVID-19 positive, 15 were COVID-19 negative. All 109 were outpatients and all were symptomatic. Average age of the population was 31 years; 30% of participants were Latinx (Table). The mean gestational age at enrollment was approximately 9 weeks; 83% of participants had at least 1 month of longitudinal follow-up prior to ending pregnancy. In the COVID-19 positive group, 6/94 (6.4%, 95% CI 2.4%-13.4%) had EPL compared with 1/15 in the COVID-19 negative group (6.7%, 95% CI 0.1%-31.9%). In the COVID-19 positive group, 5 EPLs occurred at 7-12 weeks and one at 15 weeks. In a subgroup analysis of 34 COVID-19 positive participants enrolled at <8 weeks gestation, 2/34 had EPL (5.9%). In the COVID-19 positive group, 82/90 (91.1%, 95% CI 83.2%-96.1%) had live births; 84.4% (95% CI 75.3%-91.2%) at term and 15.6% (95% CI 8.8%-24.7%) at <37 weeks; 6/94 pregnancies are ongoing but all are >24 weeks. Conclusion In this nationwide study of pregnant people in the U.S., the risk of pregnancy loss at <20 weeks gestation was about 6%, both for participants with COVID-19 (N=94) and COVID-19 negative controls (N=15). This data compares favorably to the 10% rate of miscarriage among clinically recognized first trimester pregnancies prior to the pandemic.6 To our knowledge, this is the largest analyses of COVID-19 in the first trimester in a U.S. longitudinal cohort. With this sample size, the upper bound of the confidence interval for pregnancy loss of 13.4% is reassuring because it is not significantly higher than the expected miscarriage rate without viral infection. These results can guide counseling for people infected with SARS-CoV-2 early in pregnancy.