SARS‐CoV‐2 infection as cause of in‐utero fetal death: regional multicenter cohort study

Abstract

ABSTRACTObjectivePlacental infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can lead to placental insufficiency and in‐utero fetal death (IUFD). The objective of this study was to confirm and quantify the extent to which fetoplacental infection with SARS‐CoV‐2 is a cause of fetal death.MethodsThis was a multicenter retrospective cohort study of fetal deaths that underwent postmortem examination between January 2020 and January 2022 in three fetal pathology units in Paris, France. All cases of IUFD and termination of pregnancy (TOP) occurring in 31 maternity hospitals in the Paris region undergo detailed placental pathological examination in these units. Databases were searched for cases of IUFD and TOP. Cases with fetal malformation or cytogenetic abnormality were excluded to avoid bias. We included cases of IUFD with a placental or undetermined cause and cases of TOP in the context of severe intrauterine growth restriction (IUGR). Placentas were sent to a single virology unit for reverse‐transcription polymerase chain reaction (RT‐PCR) testing by a single laboratory technician blinded to the initial postmortem examination report. Our primary endpoint was the proportion of positive placental SARS‐CoV‐2 RT‐PCR tests in the cohort.ResultsAmong 147 722 deliveries occurring over 2 years, 788 postmortem examinations for IUFD and TOP for severe IUGR were recorded, of which 462 (58.6%) were included. A total of 13/462 (2.8%) placentas tested positive for SARS‐CoV‐2 by RT‐PCR. Wild‐type virus and alpha and delta variants were identified. All positive cases had histological lesions consistent with placental dysfunction. There was a strong correlation between SARS‐CoV‐2 placentitis and the presence of chronic intervillositis and/or massive fibrin deposits in the placenta. When both lesion types were present, the specificity and negative predictive value for the diagnosis of placental SARS‐CoV‐2 infection were 0.99 (95% CI, 0.98–1.00) and 0.96 (95% CI, 0.94–0.98), respectively.ConclusionsAt the height of the SARS‐CoV‐2 pandemic, the cause of more than half of fetal deaths in the Paris area was determined by postmortem analysis to be of placental or undetermined origin. Of these cases, 2.8% were due to placental SARS‐CoV‐2 infection with a specific pattern of histological involvement. This study highlights the need for SARS‐CoV‐2 screening in stillbirth assessment. The impact of vaccination coverage remains to be established. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.