Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

OBJECTIVE: Exome or genome sequencing (ES or GS) can identify genetic causes of otherwise unexplained congenital anomaly and perinatal death (PND) but is not routine practice. The evidence base for \"genomic autopsy\" after termination of pregnancy for fetal anomaly (TOPFA) and PND has been synthesized to determine the value of this investigation.
METHODS: We conducted a systematic review and meta-analysis of studies meeting prespecified inclusion criteria and containing ≥10 cases of TOPFA or PND (with or without major congenital abnormality), in which ES or GS was conducted. We determined test performance, including diagnostic yield, accuracy, and reliability. We also reported outcomes associated with clinical utility and harms, where described.
RESULTS: From 2245 potentially eligible studies, 32 publications were eligible and had data extracted, representing 2120 cases that could be meta-analyzed. No diagnostic accuracy or comparative studies were identified, although some analysis of concordance between different ES/GS methodologies could be performed. Studies reporting parent-related outcomes or long-term follow-up did not do so in a systematic or quantifiable manner.
CONCLUSIONS: Evidence suggests that approximately one-fourth to one-third of fetal losses associated with TOPFA or unexplained PND are associated with a genetic cause identifiable on ES or GS-albeit this estimate varies depending on phenotypic and background risk factors. Despite the large body of evidence on ES and GS, little research has attempted to validate the accuracy of testing, nor measure the clinical or societal outcomes in families that follow the diagnostic investigation in this context.

BACKGROUND: Fraser syndrome, named after George Fraser, is an autosomal recessive disorder showing a highly variable interfamilial phenotypic variation, with malformations ranging from minor symptoms to lethal anomalies like renal agenesis, incompatible with survival. Limb reduction defects have not been reported to be associated with it.
METHODS: A 21-year-old primigravida presented to the antenatal outpatient department with a level two targeted anomaly scan report suggestive of severe oligohydramnios with suspected renal agenesis. The cranial vault bones were compressed, and orbital globes and lenses could not be visualized. Renal agenesis was confirmed due to sleeping adrenals sign, non-visualization of the urinary bladder, and Doppler of renal arteries. A detailed examination of the fetal head in the sagittal section showed the absence of an eye globe and lens, arousing suspicion of Fraser syndrome. After pregnancy termination, a complete fetal autopsy was done to look for any additional findings.
CONCLUSIONS: Patients who have a syndromic mix of acrofacial and urogenital abnormalities with or without cryptophthalmos should be evaluated for Fraser syndrome, which can be diagnosed by clinical examination and perinatal autopsy.

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways).

In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein into the ductus venosus (DV), then enters the inferior vena cava, and subsequently reaches the right atrium of the heart. The DV serves as a shunt, allowing this oxygen-rich blood to bypass the liver. The absence of the DV (ADV), also known as agenesis of the DV, is a rare congenital anomaly. Without a DV, blood from the umbilical vein must follow alternative routes to the heart. In ADV cases, blood from the umbilical vein must follow 1 of 2 primary drainage patterns: either an extrahepatic shunt or an intrahepatic shunt. This report details the antenatal ultrasound and postmortem findings of 2 fetuses diagnosed with ADV by prenatal imaging studies. The first case involved a fetus with a persistent right umbilical vein connected directly to the suprahepatic IVC, accompanied by early obliteration of the left umbilical vein and true agenesis of the DV. This fetus also had additional congenital anomalies. In contrast, the second case involved a fetus with a normal left umbilical vein that entered the liver. However, despite an ultrasound diagnosis of \"absence\" of the DV, a DV was present, though markedly hypoplastic and probably minimally functional or non-functional. In this case, blood from the umbilical vein likely followed an alternate intrahepatic route through the portal and hepatic veins, before reaching the heart (intrahepatic shunt). These contrasting cases emphasize the heterogeneity of vascular anomalies and embryologic origins captured by the term \"ADV.\" Additionally, the terminology of \"absence\" or \"agenesis\" may be misleading in some purported ADV cases. Specifically, in the second case, the DV was not absent; it was markedly hypoplastic instead. This also appears to be the first reported case of a hypoplastic DV in a fetus. Both cases underscore the importance of effective collaboration and clear communication between maternal-fetal medicine specialists and pathologists.

UNASSIGNED: Canadian stillbirth data are limited, and a significant proportion of pregnancies resulting in stillbirth have no attributable cause. The objective of this study was to characterize stillbirth case investigations and management at a tertiary care hospital in Ontario, Canada.
UNASSIGNED: This was a retrospective chart review study of all cases of singleton stillbirth at The Ottawa Hospital between 1 January 2012 and 31 December 2017. Terminations and multiples stillbirths were excluded. Chart reviews were conducted to extract maternal sociodemographic, obstetrical, and fetal characteristics, including results from antenatal ultrasounds, autopsy, placenta pathology, and laboratory investigations.
UNASSIGNED: A total of 155 eligible cases of stillbirth were identified, resulting in a 6-year stillbirth rate of 4.2 per 1000 total births. The median maternal age was 31.0 years (IQR: 29.0, 35.0) and the median gestational age at delivery was 28 weeks (IQR: 24, 35). A total of 9 (5.8%) pregnant individuals had a history of previous stillbirth. Of the 155 stillbirths, 35% underwent the full suite of post-loss laboratory, placental, and fetal autopsy investigations. 63.2% of cases had post-loss laboratory investigations completed. 76% and 71% of cases had fetal autopsy and placenta pathology evaluations completed, respectively. Antenatal characteristics associated with stillbirth included fetal anomalies/genetic markers (27.1%), umbilical cord and placental anomalies (24.5%), fetal growth abnormalities (27.7%), cervical/uterine abnormalities (11.6%), and amniotic fluid abnormalities (25.1%). The most common autopsy findings included evidence of infection (22.7%), fetal anomalies (12.6%), and fetal hypoxia (10%). The most common placental pathology findings included features of placental insufficiency (21.8%), retroplacental abnormalities (16.3%), and umbilical cord accident/infarct (15.4%).
UNASSIGNED: Our findings demonstrate that as many as two-thirds of singleton stillbirth cases at our center did not receive the post-perinatal loss investigations recommended by clinical practice guidelines. More thorough collection of post-stillbirth data at all levels (institutional, provincial, national) is warranted to improve our understanding of stillbirth epidemiology, etiology, and management in Canada.

Primary cardiac tumors are uncommon clinical entities with an incidence of 0.0017% to 0.03% of all autopsies. Cystic tumor of the atrioventricular node (CTAVN) comprises of 2.7% of cardiac tumors causing sudden death associated with complete heart block. CTAVN is a congenital benign cystic and solid mass located in the triangle of Koch in atrioventricular nodal region of the heart. It has been described from infancy to adulthood, most often as an incidental finding at autopsy, but has been not yet described in fetuses. We report a case of late spontaneous abortion detected during the first ultrasound follow-up consultation at 12w+1d of gestation in a healthy 23-year-old pregnant woman, gravida 2 para 0 and one previous termination of pregnancy. Pathological study of abortion product was request. No abnormalities were detected on gross examination, but microscopically, characteristics features of cardiac cystic and solid tumor of the atrioventricular node were identified. We present the first case described in literature of a congenital benign CTAVN in a non-macerate, normal, female fetus with an appropriate growth and development for 12w+1d of gestational age. There are many reasons for performing a fetal post-mortem autopsy foremost of which is identifying an accurate cause of death.

UNASSIGNED: Gestational diabetes mellitus (GDM) is a common metabolic disorder linked to adverse pregnancy outcomes. Recent research indicates that HbA1c is reliable in detecting maternal glycemia during the first trimester but may underestimate glucose intolerance in the late second to third trimesters. Therefore, it is reasonable to hypothesize that mothers with GDM, despite apparently normal HbA1c levels in the third trimester, may give birth to infants displaying characteristic features often seen in infants of diabetic mothers with suboptimal glycemic control. This study aimed to describe a case series of autopsy cases involving stillborn or deceased neonates delivered in the third trimester to mothers diagnosed with GDM and having normal HbA1c levels at or around the time of delivery. The primary focus was on identifying and documenting the characteristic features commonly associated with \"infants of diabetic mothers\" with suboptimal glycemic control in this series of cases.
UNASSIGNED: We conducted a retrospective review of autopsy reports from our institution spanning 7.5 years. The study included cases that met the following criteria: (1) stillborn or infants who died in the early neonatal period, delivered in the third trimester; (2) mothers diagnosed with GDM; (3) normal maternal HbA1c levels of ≤6.1% at or around the time of delivery; (4) birthweight or femoral length exceeding the 90th percentile for gestational age; and (5) absence of genetic aberrations. We also examined these cases for other characteristic features associated with \"infants of diabetic mothers.\"
UNASSIGNED: Ten autopsy cases met our inclusion criteria, including 9 stillbirths and 1 neonatal death. Gestational age at delivery ranged from 32 to 39 weeks (mean: 35.7 weeks). Femoral length exceeded the 90th percentile in all cases, and 6 cases had birthweights above the 90th percentile. Puffy facies were observed in 6 cases. Among the 9 cases with complete autopsies including internal examination, 6 exhibited excess adipose tissue, 4 had cardiomegaly, and 3 showed pancreatic islet hyperplasia. Hypoxic-ischemic encephalopathy was detected in 7 cases. No structural abnormalities were noted.
UNASSIGNED: Our findings demonstrated that fetuses and neonates born to mothers with apparently normal HbA1c levels in the third trimester could still display characteristic features commonly observed in infants of diabetic mothers with poor glycemic control, also known as \"infants of diabetic mothers.\" This study underscores the potential of third-trimester maternal HbA1c measurements to underestimate maternal glycemia and its consequential impact on fetal development, as well as the subsequent manifestation of features of \"infants of diabetic mothers.\"

Background: In cases of intrauterine fetal death (IUFD), autopsy and placenta pathology can provide additional information to sonographic findings. We assessed the frequency of prenatally missed relevant diagnoses. Materials and methods: A retrospective evaluation of fetal autopsies from 2006 to 2021 was performed and were classified as: i) agreement, ii) cases where autopsy revealed additional findings, or iii) postmortem findings which changed the diagnosis. Results: A total of 199/251 spontaneous IUFD and 52/251 induced abortions were included. In spontaneous IUFD, placenta pathologies were the leading cause of death (89%). Full agreement was found in most cases (91% and 87% in spontaneous IUFD and induced abortion, respectively), while additional findings (7% and 12%) and major discrepancies (each 2%) were detected less frequently. Conclusion: In some cases where major findings were missed, autopsy could establish a diagnosis.

UNASSIGNED: Atrioventricular (AV) reentrant tachycardia is a common type of supraventricular tachycardia (SVT) that occurs in the fetus and neonate. Although many tachycardias resolve within several weeks of birth or respond to medical management, disruptions in the cardiac annulus fibrosus and development of additional accessory pathways may lead to refractory dysrhythmia resulting in fetal hydrops and ultimately, fetal death.
UNASSIGNED: While accessory pathways have been well documented anatomically in adult and childhood tachyarrhythmias, there are no reports of the histology of these pathways in human fetuses with SVT.
UNASSIGNED: This is a small case series of 2 fetuses with a history of SVT that resulted in fetal hydrops.
UNASSIGNED: In both cases, examination of the cardiac conduction system was unremarkable and examination of the atrioventricular junction revealed a focally thinned and/or discontinuous annulus fibrosus with documented direct continuity between the atrial and ventricular myocardium in 1 case.
UNASSIGNED: This case series demonstrates that thinning or absence of the annulus fibrosus is a feature seen in fetal SVT, and the development of subsequent aberrant AV connections due to defective formation of the annulus fibrosus suggests a possible cause for these arrhythmias.