Fetal Deaths in Ireland Due to SARS-CoV-2 Placentitis Caused by SARS-CoV-2 Alpha

Abstract

Context.- A severe third wave of COVID-19 disease affected Ireland in the first 3 months of 2021. In this wave, 1 second trimester miscarriage and 6 stillbirths were observed in the Irish population due to placental insufficiency as a result of SARS-CoV-2 placentitis. This observation was at odds with the country's previous experience with COVID-19 disease in pregnant mothers. Objective.- To describe the clinical and pathological features of these pregnancy losses. Design.- Retrospective review of clinical and pathological data of cases of second trimester miscarriage, stillbirth or neonatal death identified by perinatal pathologists as being due to SARS-CoV-2 placentitis during the third wave of COVID-19 in Ireland. Results.- Clinical and pathological data was available for review in 6 pregnancies. Sequencing or genotyping of the virus identified SARS-CoV-2 Alpha (B.1.1.7) in all cases. Three of the 6 cases had maternal thrombocytopenia, while fetal growth restriction was not prominent suggesting a rapidly progressive placental disease. Conclusions.- The identification of SARS-CoV-2 Alpha in all these cases suggests that the emergence of the variant was associated with an increased risk of fetal death due to SARSCoV-2 placentitis when compared to the original virus. Maternal thrombocytopenia, may have potential as a clinical marker of placentitis but other inflammatory markers need investigation. Three of the 6 women had been assessed for reduced fetal movements in hospital some days before the fetal deaths actually occurred; this could suggest that there may be a window for intervention in some cases.

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

“…Extensive intervillous fibrin deposition, involving up to 70% or more of the placental tissues in one case, was present in the placentas from all 5 fetuses. Following this report, additional case reports of the placental pathology from stillborn fetuses delivered to mothers with COVID-19 were reported that showed all the placentas to be markedly abnormal and extensively involved with similar destructive features–increased or massive intervillous fibrin deposition, villous trophoblast necrosis, and chronic histiocytic intervillositis [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. In their report of a stillbirth from a mother having COVID-19 at 30 weeks 4 days gestation in Bratislava, Biringer et al [ 80 ] believed the cause of death to be acute placental insufficiency based upon their findings of placental destruction due to SARS-CoV-2 placentitis and an autopsy revealing fetal organs to have no morphological abnormalities.…”

“…In addition to individual case reports, there have been reports of cohorts of stillborn fetuses delivered to unvaccinated mothers with COVID-19 that have also demonstrated SARS-CoV-2 placental infection with microscopic findings of SARS-CoV-2 placentitis and fetal death that most probably resulted from placental insufficiency. Analysis of the placentas from the cluster of six perinatal deaths associated with the Alpha (B.1.1.7) variant of SARS-CoV-2 in County Cork (Ireland) [ 78 ] all demonstrated the same severe findings of increased or massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis—a triad of lesions termed SARS-CoV-2 placentitis by Watkins et al [ 49 ]. Autopsy examination was performed in five cases that showed that all stillborns were anatomically normal with no microscopic evidence that SARS-CoV-2 had affected any fetal organ, and the authors ascribed the fetal deaths as due to placental insufficiency resulting from SARS-CoV-2 placentitis.…”

“…Maternal viremia with SARS-CoV-2 has been described to occur in cases of SARS-CoV-2 placentitis and intrauterine fetal demise [ 97 ], and it is highly probable that reported cases of SARS-CoV-2 placentitis and stillbirth were the result of an episode of the virus circulating in the mothers’ bloodstream at some time during the pregnancy. In the 68 cases of stillbirth and early neonatal death from placental insufficiency arising from SARS-CoV-2 placentitis described by Schwartz et al [ 93 ], as well as the six perinatal deaths from Ireland described by Fitzgerald et al [ 78 ], the five stillborns from France reported by Debucs et al [ 92 ], five stillborns from Sweden reported by Zaigham et al [ 91 ], and others [ 98 ], the mothers were all unvaccinated for coronavirus.…”

Answering Ireland’s call: pathology during the COVID-19 pandemic

“…3 Among the first cases of fatal fetal death due to placentitis were reports from Irish pathologists, and publicity surrounding this issue, helped ensure high uptake of vaccination among pregnant women. 4 With critical care colleagues, the role of pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19 leading to death was described. 5 The significance of symptoms after acute COVID-19 among healthcare staff and their implications were highlighted by occupational health and pathology departments.…”

Understanding COVID-19 susceptibility and presentation based on its underlying physiology

“…This notion is supported by a large United States-based cohort of women in which pregnant women infected with SARS-CoV-2 were found to have an increased risk of hospitalization, ICU admission, and mechanical ventilation compared with infected nonpregnant women. Placental insufficiency, miscarriage, and stillbirths resulting from SARS-CoV-2 placentitis have recently been reported in a study on pregnant mothers suffering from COVID-19 ( 9 ). Therefore, special conditions such as pregnancy need to be further evaluated for the effects of COVID-19.…”