The Importance of Vaccination, Variants and Time Point of SARS-CoV-2 Infection in Pregnancy for Stillbirth and Preterm Birth Risk: An Analysis of the CRONOS Register Study

Abstract

Background: The risk of preterm birth (PTB) and stillbirth increases after a SARS-CoV-2 infection during gestation. We aimed to estimate the risk depending on gestational age at infection (early <28 + 0 and late ≥28 weeks of gestation, WoG), virus variants, severity of infection, and vaccination. Methods: PTB was divided into early PTB (<32 + 0) and late PTB (32 + 0–36 + 6 WoG). The prospective register COVID-19 Related Obstetrics and Neonatal Outcome Study (CRONOS) included 8032 pregnant women with a confirmed SARS-CoV-2 infection from 3 April 2020 to 31 December 2022, in Germany and Austria. Results: Stillbirth and early preterm births rates were higher during the Alpha (1.56% and 3.13%) and Delta (1.56% and 3.44%) waves than during the Omicron wave (0.53% and 1.39%). Early SARS-CoV-2 infection increased the risk for stillbirth (aRR 5.76, 95% CI 3.07–10.83) and early PTB before 32 + 0 (aRR, 6.07, 95% CI 3.65–10.09). Hospital admission increased the risks further, especially in the case of ICU admission. Vaccination against SARS-CoV-2 significantly reduced the risk of stillbirth (aRR 0.32, 95% CI 0.16–0.83). Conclusions: This multicentric prospective study shows an increased risk of stillbirth and preterm birth after infection early in pregnancy and therefore the importance of obstetrical surveillance thereafter. Vaccination offers effective protection.

CCN1-Mediated Signaling in Placental Villous Tissues after SARS-CoV-2 Infection in Term Pregnant Women: Implications for Dysregulated Angiogenesis

“…Furthermore, longitudinal assessments including serial measurements throughout pregnancy and follow-up analyses postpartum were not conducted, which could provide valuable insights into the temporal dynamics of placental changes and their implications for maternal and neonatal outcomes. It is likely that these changes may be more dangerous in the second and early third trimesters and may explain the observed increased risk of preterm birth and intrauterine fetal death, as demonstrated in the prospective german register study COVID-19 Related Obstetrics and Neonatal Outcome Study including 8032 pregnant women [59]. Moreover, while the role of CCN1 and its downstream pathway was emphasized, further exploration using placental cell lines is needed for the intricate interaction of inflammatory cells and cytokines within placental tissues to unravel the whole signaling mechanism.…”