First Department of Pathology, Perinatal Pathology Unit, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Laboratory of Pathology, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Ultrasound Obstet Gynecol. 2022 Jun;59(6):813-822. doi: 10.1002/uog.24906.
To describe the placental pathology, fetal autopsy findings and clinical characteristics of pregnancies that resulted in stillbirth owing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, and to identify potential risk factors.
This was a prospective multicenter study of non-vaccinated pregnant women affected by coronavirus disease 2019 (COVID-19) in Greece from April 2020 to August 2021. A total of 165 placentas were examined histologically and six cases of stillbirth associated with SARS-CoV-2 placentitis were retrieved. Complete fetal autopsy was performed in three of these cases. Gross, histopathological, immunohistochemical, molecular and electron microscopy examinations were carried out in the stillbirth placentas and fetal organs. The histological findings of cases with SARS-CoV-2 placentitis were compared with those in 159 cases with maternal COVID-19 which resulted in a live birth. Regression analysis was used to identify predisposing risk factors for SARS-CoV-2 placentitis.
The placentas of all six stillborn cases showed severe and extensive histological changes typical of SARS-CoV-2 placentitis, characterized by a combination of marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage, associated with intensely positive immunostaining for SARS-CoV-2 spike protein, the presence of virions on electron microscopy and positive reverse-transcription polymerase chain reaction test of placental tissues. The histological lesions obliterated over 75% of the maternal intervillous space, accounting for intrauterine fetal death. Similar histological lesions affecting less than 25% of the placenta were observed in seven liveborn neonates, while the remaining 152 placentas of COVID-19-affected pregnancies with a live birth did not show these findings. Complete fetal autopsy showed evidence of an asphyctic mode of death without evidence of viral transmission to the fetus. The mothers had mild clinical symptoms or were asymptomatic, and the interval between maternal COVID-19 diagnosis and fetal death ranged from 3 to 15 days. Statistically significant predisposing factors for SARS-CoV-2 placentitis included thrombophilia and prenatally diagnosed fetal growth restriction (FGR). Multiple sclerosis was seen in one case.
SARS-CoV-2 placentitis occurred uncommonly in COVID-19-affected pregnancies of non-vaccinated mothers and, when extensive, caused fetal demise, with no evidence of transplacental fetal infection. Thrombophilia and prenatally detected FGR emerged as independent predisposing factors for the potentially lethal SARS-CoV-2 placentitis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
描述因严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）胎盘炎导致的死胎的胎盘病理学、胎儿尸检结果和临床特征，并确定潜在的危险因素。
这是一项在希腊进行的前瞻性多中心研究，纳入了 2020 年 4 月至 2021 年 8 月期间受 2019 年冠状病毒病（COVID-19）影响的未接种疫苗的孕妇。对 165 例胎盘进行了组织学检查，共检出 6 例与 SARS-CoV-2 胎盘炎相关的死胎。对其中 3 例死胎进行了完整的胎儿尸检。对死胎胎盘和胎儿器官进行了大体检查、组织病理学、免疫组织化学、分子和电子显微镜检查。将 SARS-CoV-2 胎盘炎病例的组织学发现与 159 例因 COVID-19 导致活产的病例进行比较。采用回归分析识别 SARS-CoV-2 胎盘炎的易患危险因素。
所有 6 例死胎的胎盘均显示出严重且广泛的组织学改变，这些改变是 SARS-CoV-2 胎盘炎的典型特征，表现为明显的绒毛膜炎伴混合炎症浸润和大量绒毛膜下纤维蛋白样沉积，伴有 SARS-CoV-2 刺突蛋白强烈免疫染色阳性、电镜下可见病毒颗粒和胎盘组织逆转录聚合酶链反应检测阳性。组织学病变累及母体绒毛间隙的 75%以上，导致宫内胎儿死亡。在 7 例活产新生儿中观察到累及胎盘不到 25%的类似组织学病变，而其余 152 例 COVID-19 相关活产妊娠的胎盘则未显示这些发现。完整的胎儿尸检显示窒息死亡模式的证据，没有病毒向胎儿传播的证据。母亲的临床症状轻微或无症状，母亲 COVID-19 诊断与胎儿死亡之间的间隔时间为 3 至 15 天。SARS-CoV-2 胎盘炎的统计学显著易患因素包括血栓形成倾向和产前诊断的胎儿生长受限（FGR）。1 例患者有多发性硬化症。
在未接种疫苗的 COVID-19 孕妇中，SARS-CoV-2 胎盘炎罕见发生，且当广泛发生时可导致胎儿死亡，但没有证据表明存在胎盘内胎儿感染。血栓形成倾向和产前发现的 FGR 是潜在致命 SARS-CoV-2 胎盘炎的独立易患因素。© 2022 年国际妇产科超声学会。
