Influence of SARS-CoV-2 variants on stillbirth rate - data from the CRONOS registry

Abstract

Background: During the COVID-19 pandemic, reports of stillbirths associated with SARS-CoV-2 infection increased. This study aims to assess whether and to what extent these stillbirths are associated with placental changes and specific viral variants.

Methods: Data from the multicenter, prospective CRONOS registry (COVID-19-Related Obstetric and Neonatal Outcome Study) including 8032 women infected with SARS-CoV-2 during their pregnancy were analyzed. In case of stillbirth, additional data were obtained by contacting the respective clinic.

Results: Data on pregnancy outcomes were available for 7224 women giving birth after 22 + 0 weeks of gestational age. Cases with chromosomal disorders or severe congenital malformations were excluded from the analysis. 45 women had a stillbirth, the stillbirth rate was 0.6 %. 13 children were born in the wild-type phase, 11 with Alpha and Delta each, and 10 with Omicron. For the corresponding number of women in each phase, the stillbirth rates were 0.6 %, 1.6 %, 0.8 % and 0.3 %, respectively (p = 0.002). Placental pathology, available from 23 of the 45 stillbirths, showed features of SARS-CoV-2 placentitis in 10 of 14 placentas (71 %) in the Alpha and Delta phases. In contrast, no features of SARS-CoV-2 placentitis were described in the wild-type and Omicron phases.

Conclusions: The CRONOS data confirm a virus-type-dependent effect of the Alpha and Delta variants on the placenta with a possible causal effect on stillbirth. In the context of an infection, targeted fetal monitoring appears appropriate. A stillbirth due to COVID-19 is unlikely more than 4 weeks after infection.

Keywords: COVID-19 placentitis; SARS-CoV-2 in pregnancy; Stillbirth; Stillborn.