Pregnancy and Infant Outcomes by Trimester of SARS-CoV-2 Infection in Pregnancy – SET-NET, 22 Jurisdictions, January 25, 2020 - December 31, 2020
Authors: Neelam Varsha , Reeves Emily L , Woodworth Kate R , Olsen Emily O'Malley , Reynolds Megan R , Rende Joy , Wingate Heather , Manning Susan E , Romitti Paul , Ojo Kristen D , Silcox Kristin , Barton Jerusha , Mobley Evan , Longcore Nicole D , Sokale Ayomide , Lush Mamie , Delgado-Lopez Camille , Diedhiou Abdoulaye , Mbotha Deborah , Simon Wanda , Reynolds Bethany , Hamdan Tahani S , Beauregard Suzann , Ellis Esther M , Seo Jennifer Y , Bennett Amanda , Ellington Sascha , Hall Aron J , Azziz-Baumgartner Eduardo , Tong Van T , Gilboa Suzanne M 
Published: May 2022

Abstract
Background: People with SARS-CoV-2 infection during pregnancy are at increased risk for adverse pregnancy outcomes, such as preterm birth and stillbirth. Few studies have assessed whether the risk of adverse pregnancy and infant outcomes varies by trimester of infection.Objectives: We describe clinical characteristics (i.e., treatment among pregnant people with moderate to critical illness) and pregnancy and infant outcomes in pregnant people with laboratory-confirmed SARS-CoV-2 infection by trimester of infection.Study Design: The Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) collects longitudinal data on people with confirmed SARS-CoV-2 infection during pregnancy and their infants. This analysis included people reported to SET-NET with infection in 2020, with known timing of infection and pregnancy outcome. Outcomes are described by trimester of infection. Pregnancy outcomes examined were live birth and pregnancy loss (<20 weeks gestation and ≥20 weeks gestation). Infant outcomes included preterm birth (<37 weeks gestation), small for gestational age (SGA), birth defects, and neonatal intensive care unit (NICU) admission. Adjusted prevalence ratios (aPR) were calculated for pregnancy and selected infant outcomes by trimester of infection, controlling for age, race/ethnicity and health insurance. Among those with moderate-to-critical COVID-19 illness, demographic and clinical characteristics of pregnant people by COVID-19 specific treatment status were described.Results: Among 44,914 people with SARS-CoV-2 infection in pregnancy, 35,200 (78.3%) people with known timing of infection and pregnancy outcome were included. There were 35,574 liveborn infants and 193 pregnancy losses (<20 weeks (n=52) and ≥20 weeks (n=141)) reported. Half (50.8%) of pregnant people had infection in the third trimester, 30.8% in the second, and 18.3% in the first. Third trimester infection was associated with a higher frequency of preterm birth compared to first or second trimester infection combined (17.8% vs. 11.8%; aPR 1.44 95% CI: 1.35-1.54). For term infants, those born to people with third trimester infection were more likely to be admitted to the NICU compared to those born to people with first or second trimester infections (6.7% vs. 4.5%, aPR 1.29, 95% CI: 1.16-1.36). Approximately five percent of infants were born SGA, with a higher frequency among infants born to people with third trimester infection (aPR 1.16, 95% CI: 1.06-1.27). Prevalence of birth defects was 553.4/10,000 live births, with no difference by trimester of infection. Of 1,732 pregnant people with moderate-to-critical illness, 24.4% (422 cases) were reported to have received any treatment, with 15.3% (265) receiving COVID-19 specific treatment. The most common COVID-19 treatments were remdesivir (57.0%), dexamethasone (45.8%), and azithromycin with hydroxychloroquine (15.4%).Conclusions: There were no signals for increased birth defects or SGA among infants in this population relative to national baseline estimates, regardless of timing of infection. However, the prevalence of preterm birth in people with SARS-CoV-2 infection in pregnancy in our analysis was higher relative to national baseline data (10.0-10.2%), particularly among people with third trimester infection. Consequences of COVID-19 during pregnancy, including preterm birth, support recommended COVID-19 prevention strategies, including vaccination for people who are pregnant or may become pregnant. The findings in this report further highlight gaps in COVID-19 treatment for pregnant people.