Maternal and perinatal outcomes of SARS-CoV-2 infection in unvaccinated pregnancies during Delta and Omicron waves

Abstract

Objective: there is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves. Methods: this was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection. Results: during the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001). Conclusions: among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2.