Pregnancy and Infant Outcomes Following SARS-CoV-2 Infection in Pregnancy during Delta Variant Predominance – Surveillance for Emerging Threats to Pregnant People and Infants
Authors: Reeves Emily L. , Neelam Varsha , Olsen Emily O. , Carlson Jeffrey M. , Fox Charise J. , Woodworth Kate R. , Nestoridi Eirini , Mobley Evan , Castro Shaila Montero , Dzimira Paula , Sokale Ayomide , Sizemore Lindsey , Hall Aron J. , Ellington Sascha , Cohn Amanda , Gilboa Suzanne , Tong Van T. 
Published: September 2023

Abstract
Background: SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse birth outcomes, such as preterm birth, stillbirth, and maternal and infant complications. Prior research suggests an increased risk of severe COVID-19 illness and stillbirth in pregnant people during the Delta variant predominance in 2021; however, those studies did not assess timing of infection during pregnancy, and few described COVID-19 vaccination status.
Objective: Using a large population-based cohort, this study compared pregnancy and infant outcomes and described demographic and clinical characteristics of pregnant people with SARS-CoV-2 infection prior to and during the Delta variant period.
Study Design: This retrospective cohort analysis included persons with confirmed SARS-CoV-2 infection in pregnancy from six U.S. jurisdictions reporting to the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET). Data were collected through case reports of polymerase chain reaction (PCR) positive pregnant persons and linkages to birth certificates, fetal death records, and immunization records to obtain outcomes and COVID-19 vaccination status. We described clinical characteristics and compared frequency of spontaneous abortion (<20 weeksgestation), stillbirth (≥20 weeks), preterm birth (<37 weeks), small for gestational age, and term infant NICU admission between the time periods of pre-Delta and Delta variant predominance. Study time periods were determined by when variants constituted more than 50% of sequences isolated according to regional SARS-CoV-2 genomic surveillance data, with time periods defined for pre-Delta (March 3, 2020-June 25, 2021) and Delta (June 26-December 25, 2021). Adjusted prevalence ratios (aPR) were estimated for each outcome measure using Poisson regression and were adjusted for continuous maternal age, race/ethnicity, and insurance status at delivery.
Results: Among 57,529 pregnancy outcomes, 57,171 (99.4%) were liveborn infants, 56 (0.1%) were spontaneous abortions, and 302 (0.5%) were stillbirths. Most pregnant persons were unvaccinated at the time of SARS-CoV-2 infection, with the highest proportion in pre-Delta (99.4%) compared to Delta (78.5%). Of those with infections during Delta and who were previously vaccinated, the timing from last vaccination to infection was a median of 183 days. Compared to pre-Delta, infections during Delta were associated with a higher frequency of stillbirths (0.7% versus 0.4%, aPR 1.57, 95% CI: 1.15, 2.14) and preterm births (12.8%versus 11.9%, aPR 1.14, CI: 1.07, 1.21). The Delta period was associated with a lower frequency of NICU admission (aPR 0.72 95%, CI: 0.64, 0.79) compared to pre-Delta. During the Delta period, infection during the third trimester was associated with a higher frequency of preterm birth compared to the first andsecond trimester combined (aPR 1.42, 95% CI: 1.29,1.57).
Conclusion: In this U.S.-based cohort of persons with SARS-CoV-2 infection in pregnancy, the majority were unvaccinated, and frequencies of stillbirth and preterm birth were higher during the Delta variant predominance period compared to pre-Delta. In the Delta period, frequency of preterm birth was higher among infections occurring in the third trimester versus those earlier in pregnancy. These findings confirm the risks of COVID-19 in pregnancy on adverse fetal and infant outcomes, specifically in the presence of a variant with more severe presentation.