Pregnancy and infant outcomes following SARS-CoV-2 infection in pregnancy during delta variant predominance - Surveillance for Emerging Threats to Pregnant People and Infants

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. Previous research suggests an increased risk of severe COVID-19 illness and stillbirth in pregnant people during delta variant predominance in 2021; however, those studies did not assess timing of infection during pregnancy, and few of them 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 6 US jurisdictions reporting to the Surveillance for Emerging Threats to Pregnant People and Infants Network. Data were collected through case reports of polymerase chain reaction-positive pregnant persons and linkages to birth certificates, fetal death records, and immunization records. We described clinical characteristics and compared frequency of spontaneous abortion (<20 weeks of gestation), stillbirth (≥20 weeks), preterm birth (<37 weeks), small for gestational age, and term infant neonatal intensive care unit 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, 2021-December 25, 2021). Adjusted prevalence ratios were estimated for each outcome measure using Poisson regression and were adjusted for continuous maternal age, race and ethnicity, and insurance status at delivery.

Results: Among 57,563 pregnancy outcomes, 57,188 (99.3%) were liveborn infants, 65 (0.1%) were spontaneous abortions, and 310 (0.5%) were stillbirths. Most pregnant persons were unvaccinated at the time of SARS-CoV-2 infection, with a higher proportion in pre-delta (99.4%) than in the delta period (78.4%). 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% vs 0.4%; adjusted prevalence ratio, 1.55; 95% confidence interval, 1.14-2.09) and preterm births (12.8% vs 11.9%; adjusted prevalence ratio, 1.14; 95% confidence interval, 1.07-1.20). The delta period was associated with a lower frequency of neonatal intensive care unit admission (adjusted prevalence ratio, 0.74; 95% confidence interval, 0.67-0.82) than in the pre-delta period. During the delta period, infection during the third trimester was associated with a higher frequency of preterm birth (adjusted prevalence ratio, 1.41; 95% confidence interval, 1.28-1.56) and neonatal intensive care unit admission (adjusted prevalence ratio, 1.21; 95% confidence interval, 1.01-1.45) compared to the first and second trimester combined.

Conclusion: In this US-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 than in the pre-delta period. During the delta period, frequency of preterm birth and neonatal intensive care unit admission was higher among infections occurring in the third trimester vs those earlier in pregnancy. These findings demonstrate population-level increases of adverse fetal and infant outcomes, specifically in the presence of a COVID-19 variant with more severe presentation.

Keywords: COVID-19; SARS-CoV-2; adverse perinatal outcomes; delta variant; fetal death; pregnancy; preterm birth; stillbirth.