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

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.

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.

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.

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.