Preterm Birth among Pregnant Persons with Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Newton Suzanne M. , Reeves Emily L. , Olsen Emily O'Malley , Woodworth Kate , Farr Sherry L. , Galang Romeo R. , Reynolds Megan R. , Harvey Elizabeth , Shi Jing , Nestoridi Eirini , Barton Jerusha , Ngo Van P. , Lush Mamie , Longcore Nicole D. , Dzimira Paula , Im Lucille K. , Sokale Ayomide , Siebman Samantha , Lopez Camille Delgado , Chen Tiffany , Nyquist-Smith Natasha , Mobley Evan L. , Khuwaja Salma , Romitti Paul A. , Fredette Carolyn , Ellis Esther M. , Silcox Kristin , Hall Aron J. , Azziz-Baumgartner Eduardo , Gilboa Suzanne M. , Shapiro-Mendoza Carrie K. , Tong Van T. 
Published: March 2022

Abstract
Background: Pregnant persons with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are at increased risk of preterm birth, and evidence suggests this risk may be higher among pregnant persons with severe coronavirus disease 2019 (COVID-19) or among those infected later in pregnancy. However, the relationship between trimester of SARS-CoV-2 infection, severity of COVID-19, and preterm birth is not fully understood.Objective: This study examined the relationship between trimester of SARS-CoV-2 infection, illness severity, and risk for preterm birth after adjusting for maternal age, selected underlying conditions, and pregnancy complications.Study Design: Using a cohort of 6,396 pregnant persons with SARS-CoV-2 infection in 2020 identified through the Surveillance for Emerging Threats to Mothers and Babies Network, we analyzed data for those with infection at <37 weeks gestation who delivered a singleton liveborn infant. Illness severity groups (asymptomatic infection, mild, moderate-to-severe, and critical) were adapted from National Institutes of Health and World Health Organization criteria. Risk ratios for preterm birth (<37 weeks) were calculated for illness severity categories (referent=mild), trimester of SARS-CoV-2 infection (referent=first trimester), and illness severity stratified by trimester of infection adjusted for age, selected underlying medical conditions, and pregnancy complications.Results: Pregnant persons with critical COVID-19, compared to mild COVID-19, in the second (aRR 3.9; 95% CI: 1.7-9.0) or third (aRR 4.6; 95% CI: 3.2-6.6) trimester were at increased risk of preterm birth. Among persons infected in the second or third trimester, those with critical COVID-19 delivered sooner after infection compared with persons with mild COVID-19 (p<0.001 for second trimester and p=0.02 for third trimester). Nearly half of those with moderate-to-severe or critical COVID-19 delivered by cesarean, with most critical COVID-19 cesarean deliveries as emergent (76.6% weighted [65/96 unweighted]).Conclusion: When infection occurred in the second or third trimester, critical COVID-19 was associated with increased risk of preterm birth, and those with critical COVID-19 delivered sooner after infection compared to those with mild COVID-19. These findings can be used to guide prevention strategies, including vaccination, and inform clinical practices for pregnant persons, particularly those presenting with critical COVID-19 later in pregnancy.