Abstract：
Placental 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.
This 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.
Among 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.
At 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.
This 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.
Among 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.
At 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.
摘要：
目的：胎盘感染SARS-CoV2可导致胎盘功能不全和胎儿宫内死亡。目前尚不清楚SARS-CoV2的胎儿胎盘感染是胎儿死亡的原因。我们的目的是确认和量化SARS-CoV2作为胎儿死亡原因的可归性。
方法：我们在1月1日（法国）巴黎地区31家妇产医院的三个胎儿病理单元进行了尸检，2020年1月1日,2022年。所有胎儿死亡和终止妊娠的病例都受益于这些单位的详细胎盘病理检查。在数据库中搜索了宫内胎儿死亡和终止妊娠的病例。排除胎儿畸形或细胞遗传学异常的病例，以避免偏倚。我们包括1）胎盘或“不确定”原因的宫内胎儿死亡2）在子宫内胎儿生长严重受限的情况下终止妊娠。每个胎盘被送到一个病毒学单元，由对最初的验尸报告不知情的同一实验室技术人员进行RT-PCR测试。我们的主要终点是这些纳入病例中胎盘SARS-CoV2-PCRs阳性的比例。
结果：超过2年，在147,722次交付中，记录了788次子宫内胎儿死亡和在子宫内胎儿生长严重受限的情况下终止妊娠的尸检，其中462次（58.6％）。共有13/462（2.8％）胎盘检测出SARS-CoV2阳性。鉴定了野生型及其α和δ变体。所有阳性病例均有胎盘功能障碍的组织学病变。SARS-CoV2胎盘炎与胎盘上的慢性夹耳炎和/或大量纤维蛋白沉积之间存在很强的相关性。当两个病变都存在时，诊断胎盘SARS-CoV2感染的特异性和阴性预测值分别为0.99(CI95[0.98-1.00])和0.96(CI95[0.94-0.98]).
结论：在SARS-CoV2大流行的高峰期，巴黎地区超过一半的胎儿死亡原因被标记为胎盘或基于尸检结果的不明来源，但是我们的研究表明，在这些原因中，2.8％是由于胎盘SARS-CoV2感染，具有特定的组织学参与模式。这项研究强调了在死产评估中进行SARS-CoV2筛查的必要性。疫苗接种覆盖率的影响尚待确定。本文受版权保护。保留所有权利。
方法：我们在1月1日（法国）巴黎地区31家妇产医院的三个胎儿病理单元进行了尸检，2020年1月1日,2022年。所有胎儿死亡和终止妊娠的病例都受益于这些单位的详细胎盘病理检查。在数据库中搜索了宫内胎儿死亡和终止妊娠的病例。排除胎儿畸形或细胞遗传学异常的病例，以避免偏倚。我们包括1）胎盘或“不确定”原因的宫内胎儿死亡2）在子宫内胎儿生长严重受限的情况下终止妊娠。每个胎盘被送到一个病毒学单元，由对最初的验尸报告不知情的同一实验室技术人员进行RT-PCR测试。我们的主要终点是这些纳入病例中胎盘SARS-CoV2-PCRs阳性的比例。
结果：超过2年，在147,722次交付中，记录了788次子宫内胎儿死亡和在子宫内胎儿生长严重受限的情况下终止妊娠的尸检，其中462次（58.6％）。共有13/462（2.8％）胎盘检测出SARS-CoV2阳性。鉴定了野生型及其α和δ变体。所有阳性病例均有胎盘功能障碍的组织学病变。SARS-CoV2胎盘炎与胎盘上的慢性夹耳炎和/或大量纤维蛋白沉积之间存在很强的相关性。当两个病变都存在时，诊断胎盘SARS-CoV2感染的特异性和阴性预测值分别为0.99(CI95[0.98-1.00])和0.96(CI95[0.94-0.98]).
结论：在SARS-CoV2大流行的高峰期，巴黎地区超过一半的胎儿死亡原因被标记为胎盘或基于尸检结果的不明来源，但是我们的研究表明，在这些原因中，2.8％是由于胎盘SARS-CoV2感染，具有特定的组织学参与模式。这项研究强调了在死产评估中进行SARS-CoV2筛查的必要性。疫苗接种覆盖率的影响尚待确定。本文受版权保护。保留所有权利。
