Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy.

David A Schwartz

doi:10.3390/v14030458

Abstract

Stillbirth is a recently recognized complication of COVID-19 in pregnant women. Other congenitally transmitted infections from viruses, bacteria and parasites can cause stillbirth by infecting fetal organs following transplacental transmission of the agent from the maternal bloodstream. However, recent research on pregnant women with COVID-19 having stillbirths indicates that there is another mechanism of stillbirth that can occur in placentas infected with SARS-CoV-2. In these cases, viral infection of the placenta results in SARS-CoV-2 placentitis, a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, in some cases together with placental hemorrhage, thrombohematomas and villitis, result in severe and diffuse placental parenchymal destruction. This pathology can involve greater than one-half of the placental volume, averaging 77% in the largest study of 68 cases, effectively rendering the placenta incapable of performing its function of oxygenating the fetus. This destructive placental process can lead to stillbirth and neonatal death via malperfusion and placental insufficiency which is independent of fetal infection. Fetal autopsies show no evidence that direct infection of fetal organs is contributory. Because all mothers examined have been unvaccinated, maternal vaccination may prevent viremia and consequent placental infection.

Highlights

Introduction2019 (COVID-19) pandemic were the cause of adverse obstetrical outcomes [1–3]. Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in pregnant women, causing maternal and perinatal morbidity and mortality [1–7]
Human outbreaks from two coronavirus species prior to the coronavirus disease2019 (COVID-19) pandemic were the cause of adverse obstetrical outcomes [1–3]
Additional reports found that placentas testing positively for SARS-CoV-2 were typically characterized by a spectrum of destructive findings that included villous trophoblast necrosis, chronic histiocytic intervillositis and increased fibrin up to the level of massive perivillous fibrin deposition [20,21,24,43–47] (Figures 2–5)

Summary

Introduction

2019 (COVID-19) pandemic were the cause of adverse obstetrical outcomes [1–3]. Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in pregnant women, causing maternal and perinatal morbidity and mortality [1–7]. Microbial agents that are contracted before or during pregnancy which can be transmitted to the fetus are termed TORCH agents (an acronym for Toxoplasma, Other, Rubella, Cytomegalovirus, Herpes) These infectious agents can cause stillbirth by passing from the maternal circulation into the placenta, where they cross the maternal-fetal interface to infect the fetus, typically resulting in organ damage and, in some cases, death. Until recently it had not been determined how SARS-CoV-2 was causing stillbirth and early neonatal death in pregnant women with COVID-19.

SARS-CoV-2 Placentitis

Placental Insufficiency and Stillbirth

Findings

COVID-19 Infection and Stillbirth