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Risk of pregnancy loss before 20 weeks’ gestation in study participants with COVID-19

      Objective

      Many studies have evaluated birth outcomes in patients with COVID-19, but less attention has been paid to the risk of early pregnancy loss (EPL) despite the known association of miscarriage with viral infection.
      • Rasti S.
      • Ghasemi F.S.
      • Abdoli A.
      • Piroozmand A.
      • Mousavi S.G.
      • Fakhrie-Kashan Z.
      ToRCH “coinfections” are associated with increased risk of abortion in pregnant women.
      The current literature is limited by a small number of cases, a focus on inpatient visits, and lack of longitudinal follow-up.
      • Cosma S.
      • Carosso A.R.
      • Cusato J.
      • et al.
      Coronavirus disease 2019 and first-trimester spontaneous abortion: a case-control study of 225 pregnant patients.
      • Juan J.
      • Gil M.M.
      • Rong Z.
      • Zhang Y.
      • Yang H.
      • Poon L.C.
      Effects of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review.
      • la Cour Freiesleben N.
      • Egerup P.
      • Hviid K.V.R.
      • et al.
      SARS-CoV-2 in first trimester pregnancy: a cohort study.
      • Yan J.
      • Guo J.
      • Fan C.
      • et al.
      Coronavirus disease 2019 in pregnant women: a report based on 116 cases.
      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 US women with SARS-CoV-2 infection in early pregnancy to help inform clinical practice.

      Study Design

      The Pregnancy Coronavirus Outcomes Registry (PRIORITY) study is an ongoing, nationwide, prospective cohort study of pregnant people COVID-19 during pregnancy in the United States. Participants were ≥13 years, under investigation for or had confirmed COVID-19 (defined as a positive polymerase chain reaction test for SARS-CoV-2), and were enrolled from March 2020 to October 2020. For this analysis, we selected participants who were enrolled at <14 weeks gestation and who underwent SARS-CoV-2 testing; 7 were excluded owing to a lack of longitudinal follow-up. The study was approved by the University of California, San Francisco Institutional Review Board (IRB #20-30410).
      Participants completed questionnaires at enrollment, weekly thereafter 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 (CIs) for EPL, defined as pregnancy loss at <20 weeks’ gestation.

      Results

      Among the 1338 PRIORITY participants, 109 were enrolled at <14 weeks gestation and comprised the analysis set; 94 had a positive test result for COVID-19 and 15 had a negative test result for COVID-19. All of the 109 patients were outpatients, and all were symptomatic. The average age of the population was 31 years; 33% of the participants were Hispanic (Table). The mean gestational age at enrollment was approximately 9 weeks; 83% of participants had at least 1 month of longitudinal follow-up before the end of pregnancy.
      TableDemographic and clinical characteristics of the study population according to COVID-19 status
      CharacteristicsCOVID-19 positive, n=94COVID-19 negative, n=15
      Age (y), mean±SD31.2±4.7730.5±5.37
      Race and ethnicity, n (%)
       Asian4 (4.0)1 (5.9)
       American Indian or Alaska Native1 (1.0)0 (0.0)
       Black or African American2 (2.1)2 (13.3)
       Hispanic or Latina33 (35.1)3 (20.0)
       Native Hawaiian or Pacific Islander1 (1.1)0 (0.0)
       White62 (66.0)10 (66.7)
      Region, n (%)
       Midwest14 (14.9)4 (26.7)
       Northeast31 (33.0)1 (6.7)
       South17 (18.1)4 (26.7)
       West29 (30.9)6 (40.0)
      Gravida, mean±SD2.68±1.791.87±0.99
      Parity, mean±SD1.02±1.360.467±0.64
      Body mass index (kg/m2), mean±SD26.8±6.4524±4.22
      Gestational age at enrollment (wk), mean±SD9.76±2.849.83±3.24
      Health history, n (%)
       Asthma10 (10.6)1 (6.7)
       Hypertension2 (2.1)0 (0.0)
       Thyroid disease4 (4.3)3 (20.0)
       Depression15 (16.0)3 (20.0)
       Anxiety17 (18.1)6 (40.0)
       Current smoker1 (1.1)0 (0.0)
      SD, standard deviation.
      Jacoby. Risk of pregnancy loss at <20 weeks’ gestation with COVID-19. Am J Obstet Gynecol 2021.
      In the COVID-19–positive group, 6 of 94 patients (6.4%; 95% CI, 2.4%–13.4%) had EPL compared with 1 of 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 to 12 weeks’ gestation and 1 occurred at 15 weeks’ gestation. In a subgroup analysis of 34 COVID-19–positive participants enrolled at <8 weeks’ gestation, 2 of 34 patients had EPL (5.9%). In the COVID-19–positive group, 82 of 90 patients (91.1%; 95% CI, 83.2%–96.1%) had live births, of which 82.9% (95% CI, 73%–90.3%) were at term and 17.1% (95% CI 9.7%–27%) were at <37 weeks’ gestation; 4 of 94 pregnancies are ongoing but all are at >24 weeks’ gestation.

      Conclusion

      In this nationwide study of pregnant people in the United States, the risk for pregnancy loss at <20 weeks’ gestation was about 6% for both the participants with COVID-19 (n=94) and the controls without COVID-19 (n=15). These data compare favorably with the 10% rate of miscarriage among clinically recognized first-trimester pregnancies before the pandemic.
      • Magnus M.C.
      • Wilcox A.J.
      • Morken N.H.
      • Weinberg C.R.
      • Håberg S.E.
      Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study.
      This study conducted analyses of COVID-19 in 109 pregnant people in the first trimester in a longitudinal US cohort. With this sample size, the upper bound of the CI 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.

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