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Objective: To determine the diagnostic accuracy of virtual autopsy using whole‐body postmortem ultra‐high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2‐weighted imaging (T2‐WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second‐trimester fetuses. Methods: Thirty consecutive fetuses at 13–19 weeks' gestation (weight, 17–364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two‐dimensional turbo high‐resolution T2‐WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational‐age intervals (13–14, 15–16 and 17–19 weeks). Results: Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42–96.29%) and a specificity of 97.87% (95% CI, 94.64–99.42%), with a positive predictive value of 96.30% (95% CI, 90.78–98.56%) and a negative predictive value of 95.34% (95% CI, 91.61–97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73–97.68%) for detecting structural abnormalities in second‐trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. Conclusion: Virtual fetal autopsy using 7‐T MRI and a turbo high‐resolution T2‐WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Fetal and neonatal mortality serves as the most sensitive index of maternal and neonatal care. Congenital malformations remain a common cause of perinatal deaths and account for 10-15% in developing countries. Antenatal anomaly scan has become a standard element of obstetric care and their time for a fetal malformation is about 18 weeks. Fetal autopsy serves as a methodology to confirm the sonogram findings with regard to fetal anomalies. Aims and Objectives: The aim of our present study is to review and evaluate fetal autopsy of stillbirth/fetal losses and to confirm the malformations that were diagnosed by ultrasound. Materials and Methods: A cross-sectional study of a total of 10 cases received during the period of September 2023-October 2023 at the Institute of Obstetrics and Gynaecology. All the cases were spontaneous fetal losses. A standard protocol of autopsy procedure was followed which included external, internal, and histopathological examination. In fetuses with prenatally diagnosed malformations, ultrasound findings were compared with autopsy findings. Results: We analyzed a total of 10 fetuses, which included one chromosomal abnormality, four cardiac anomalies, one multiple anomaly, three central nervous system (CNS) anomalies, and one lethal skeletal dysplasia. The fetal autopsy confirmed the prenatal ultrasound findings in eight cases. Fetuses with CNS abnormality were not appreciated grossly due to early autolysis of the brain in the post-mortem. Conclusion: Prenatal imaging and screening are considered milestone development which detects fetal anomalies. However, the time-tested clinical autopsy which used to be conducted for all hospital deaths to find the cause of death was the norm of yesteryears which threw light on many unidentified causes and many syndromic associations not detected antemortem. Likewise, this case highlights the importance of autopsy correlation with prenatal imaging to highlight the same findings and to detect findings not picked up during imaging. [ABSTRACT FROM AUTHOR]

Background: Fetal and neonatal mortality serves as the most sensitive index of maternal and neonatal care. Congenital malformations remain a common cause of perinatal deaths and account for 10–15% in developing countries. Antenatal anomaly scan has become a standard element of obstetric care and their time for a fetal malformation is about 18 weeks. Fetal autopsy serves as a methodology to confirm the sonogram findings with regard to fetal anomalies. Aims and Objectives: The aim of our present study is to review and evaluate fetal autopsy of stillbirth/fetal losses and to confirm the malformations that were diagnosed by ultrasound. Materials and Methods: A cross-sectional study of a total of 10 cases received during the period of September 2023–October 2023 at the Institute of Obstetrics and Gynaecology. All the cases were spontaneous fetal losses. A standard protocol of autopsy procedure was followed which included external, internal, and histopathological examination. In fetuses with prenatally diagnosed malformations, ultrasound findings were compared with autopsy findings. Results: We analyzed a total of 10 fetuses, which included one chromosomal abnormality, four cardiac anomalies, one multiple anomaly, three central nervous system (CNS) anomalies, and one lethal skeletal dysplasia. The fetal autopsy confirmed the prenatal ultrasound findings in eight cases. Fetuses with CNS abnormality were not appreciated grossly due to early autolysis of the brain in the post-mortem. Conclusion: Prenatal imaging and screening are considered milestone development which detects fetal anomalies. However, the time-tested clinical autopsy which used to be conducted for all hospital deaths to find the cause of death was the norm of yesteryears which threw light on many unidentified causes and many syndromic associations not detected antemortem. Likewise, this case highlights the importance of autopsy correlation with prenatal imaging to highlight the same findings and to detect findings not picked up during imaging.

AbstractBackground: Autopsy has been a gold standard in cases of antenatal detected anomalies or fetal demise. This helped clinicians in getting insights into the future management. In current times, ultrasound and genomic testing has become extremely powerful in further refining the etiological basis; however, fetal autopsy still has its role even now. Material and Methods: We have discussed the utility of fetal autopsy in current times by diving the cases in seven groups. Results: Case based discussions to discuss the utility of fetal autopsy. Conclusions: We suggest that fetal autopsy should be the standard of care in case of any abnormal fetal outcomes alongwith fetal genomic testing. Fetal autopsy is complementary to the ultrasound assessment and genomic investigations in reaching the final diagnosis and provides invaluable information regarding recurrence risk which may not be available when couple plans next pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: 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. Case presentation: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background & Aims: According to the March of Dimes (MOD) global report on birth defects, 7.9 million births occur annually worldwide with serious birth defects. The prevalence of congenital anomalies in India is 6-7%. Worldwide, NTDs affect 323,904 infants with a prevalence rate of 0.5 to 11 per 1000 births. Although prenatal sonography has been developed in recent years, the definitive diagnosis of fatal fetal malformations is best made by fetal autopsy. An autopsy not only confirms, but also provides additional information and is useful in advising parents about the risks and prevention of similar malformations in future pregnancies. The aim of the study is to study the spectrum of Neural tube defects in foetal autopsies. Materials & Methods:This retrospective study was conducted in the Department of Pathology, Hassan Institute of Medical sciences, Hassan, Karnataka, India. 97 fetal autopsies were performed between July 2010 to June 2020, out of which 39 cases had CNS malformations. 36 cases with NTD were included in this study. All the essential clinical data were retrieved from the autopsy forms and case files. In every case, the location and morphology of the NTD and associated morphologic anomalies were noted. The statistical analysis was performed by using frequency and percentage using SPSS version 24. Results: Out of 36 cases, the majority of the cases were Spina bifida (27.78%) followed by Anencephaly (25%). Conclusion: Congenital disorders are a great public health issue in developing countries. The multidisciplinary approaches to fetal malformations have ever increasing importance in prenatal medicine. Fetal autopsy has a vital role in diagnosis of congenital malformations and detecting the cause of death.

Objective: Pulmonary hypoplasia (PH) is one of the commonest causes of neonatal morbidity and mortality. The suggested diagnostic criteria for PH are the Lung Weight:Body Weight (LW:BW) ratio ≤ 0.012 and/or Radial Alveolar Count (RAC) ≤ 4.1. The present study was done to determine the relative frequency of PH in fetal autopsy study by the LW:BW ratio and RAC along with evaluation of the defects/anomalies associated with PH. Material and Method: A prospective observational study was done on fetal autopsy specimens in the Department of Pathology. Examination and grossing were done as per the standard format of fetal autopsy study. Evaluation of PH was done using the LW:BW ratio and RAC. Diagnostic criteria for PH were taken as LW:BW ratio

Adverse events during the pregnancy deter the mother's health and raise questions regarding the country's existent healthcare. India is among the few nations responsible for two-thirds of all intrauterine fatalities worldwide. Intrauterine deaths risk medical negligence lawsuits by the aggrieved family members against the treating doctors and the hospital authorities. Fetal autopsy forms a valuable audit of clinical care, enables learning about such adverse pregnancy outcomes, and assists in administering justice in medical lawsuits. We discuss a case of a 30-year-old pregnant female at 38 weeks +1 day of gestation. She was reported to a hospital with lower abdominal pain. Per abdomen examination, fetal heart sound was reported to be present, and she was sent home. She presented with complaints of lower abdominal pain, rupture of membrane, and loss of fetal movements the next day and was diagnosed as intrauterine fetal death. The family members alleged it as medical negligence, and the fetus was sent for a medicolegal autopsy. During the autopsy, skin desquamation of about 75% of the total body surface area was present. The umbilical cord stump was dark reddish brown colored. Overriding of the cranial bones was noted. The diaphragm was present at the level of the 4th rib. The lungs were non-crepitant and had liver-like consistency. Hydrostatic and stomach-bowel tests were negative. Cut sections of the lower end of the femur, the upper end of the tibia, and the body of the sternum, calcaneum, and talus showed the appearance of the ossification centers. Medicolegal autopsy helped answer the investigating officer's questions and establish fetal age, time since intrauterine death, and whether the fetus was live or dead born. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary hypoplasia (PH) is one of the commonest causes of neonatal morbidity and mortality. The suggested diagnostic criteria for PH are the Lung Weight:Body Weight (LW:BW) ratio ≤ 0.012 and/or Radial Alveolar Count (RAC) ≤ 4.1. The present study was done to determine the relative frequency of PH in fetal autopsy study by the LW:BW ratio and RAC along with evaluation of the defects/anomalies associated with PH. Material and Methods: A prospective observational study was done on fetal autopsy specimens in the Department of Pathology. Examination and grossing were done as per the standard format of fetal autopsy study. Evaluation of PH was done using the LW:BW ratio and RAC. Diagnostic criteria for PH were taken as LW:BW ratio <0.012 and/or RAC < 4.1. Chi-square test, Student T test and Kruskal Wallis test were used in statistical analysis. Results: A diagnosis of PH was made in 45 cases. Concordance between the LW:BW ratio and RAC was observed in 33 cases amounting to 73.33%. The mean LW:BW ratio was the lowest in oligohydramnios. The mean RAC was the lowest in congenital cystic adenomatoid malformation. Conclusion: A diagnosis of PH was rendered in a greater number of cases when evaluation was done by considering both the LW:BW ratio and RAC. Hence, evaluation by both the LW:BW ratio and RAC provides a reliable index of lung growth and should be an essential part of fetal autopsy study. [ABSTRACT FROM AUTHOR]

Introduction: 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. Materials and Methods: 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." Results: 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. Discussion: 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." [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Background: Noncompaction of ventricular myocardium is a cardiomyopathy that typically involves the left ventricle or both ventricles; it has often been associated with mutations in genes encoding sarcomere proteins. Little is known about isolated right ventricular noncompaction, as only a few cases have been reported. Case Report: A 30 year old G2P1 woman experienced a spontaneous fetal loss at 19 weeks and 4 days. An ultrasound examination at 19 weeks showed right ventricular and tricuspid valve abnormalities, ascites, and early hydrops. At autopsy, the right ventricular chamber was dilated with numerous prominent trabeculations and deep intrabecular recesses as well as a dysplastic tricuspid valve. Histologic examination confirmed isolated right ventricular noncompaction. Whole exome sequencing showed a likely pathogenic variant in the MYH7 gene. Conclusions: This appears to be the first report of isolated right ventricular noncompaction associated with a gene mutation as well as the first diagnosis in a fetus. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to compare the prenatal ultrasonography (US) and the autopsy findings of the fetuses of 12–24th gestational weeks. Methods: This retrospective study comprises 84 fetuses autopsied. The correlation between US and autopsy findings was classified into four categories: (A) Compatible, (B) Minor findings added, (C) Major findings added, and (D) Incompatible. Results: Malformations were the most common medical termination indication. The most frequent findings at autopsy were multiple system findings followed by central nervous system. Prenatal US and autopsy findings were completely compatible in 48 fetuses (57.1%), while additional minor and major autopsy findings were found in 26 (31.0%) and 4 (4.8%), respectively. Autopsy and US findings were incompatible in 6 fetuses (7.1%). Conclusion: Prenatal ultrasound and fetal autopsy are complementary tools to obtain detailed and complete diagnosis of fetal anomalies and fetal autopsy is still a valuable tool to obtain further diagnostic information. [ABSTRACT FROM AUTHOR]

Acardiac twin is a rare complication of monozygotic twin pregnancies. It accounts for 1% of monochorionic twin gestations with an incidence of 1 in 35,000 births. We report a rare case of acardiac twin with sacrococcygeal teratoma in a monochorionic twin gestation in view of rare incidence and diagnostic challenge. [ABSTRACT FROM AUTHOR]

Background: 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. Objectives: 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. Research Design, Subjects, Measures: This is a small case series of 2 fetuses with a history of SVT that resulted in fetal hydrops. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective  Historically, fetal autopsy was common after terminations for anomalies. Previous studies report that fetal autopsy confirms ultrasound findings in the majority of cases. This study aims to examine correlation between prenatal and autopsy diagnoses at University of California, San Francisco (UCSF) and evaluate whether autopsy adds diagnostic information, specifically information that changes risk of recurrence for future pregnancies. Study Design  We conducted a retrospective chart review of all fetal autopsies performed at UCSF between 1994 and 2009. Prenatal diagnosis was compared with autopsy diagnosis; for cases where there was a change in diagnosis, an MFM (maternal-fetal medicine specialist) reviewed the case to assign risk of recurrence before and after autopsy. Results  Overall, there was concordance between prenatal diagnosis and autopsy diagnosis in greater than 91.7% of cases. Autopsy added information that resulted in a change in recurrence risk in 2.3% of cases ( n  = 9). Conclusion  For the vast majority of cases, there is agreement between prenatal and autopsy diagnosis after pregnancy loss or termination for fetal anomalies. Only a small percentage of autopsies change recurrence risk. This may be useful when counseling women about method of termination and when counseling couples about whether to have an autopsy.

Non-immune fetal hydrops (NIFH) is an etiologically heterogeneous condition. Cardiac anomalies are one of the common causes of NIFH. Cardiac anomalies can be isolated, multifactorial malformations or have a genetic basis. PLD1 variants have been associated with developmental defects involving the right heart. We present a NIFH with a PLD1 associated right heart malformation. We describe a spontaneously aborted 14 weeks old NIFH fetus with a rudimentary right ventricle, pulmonary valve atresia and pulmonary artery stenosis found at fetopsy. After a normal microarray, whole exome sequencing revealed a homozygous missense variant c.2023 C > T (p. Arg675Trp) in the PLD1 gene. Conclusion: Detailed fetopsy and genetic evaluation in this NIFH allowed an etiological explanation, further corroborated the association of PLD1 gene variants and developmental right heart defects, and that this defect can be associated with NIHF. [ABSTRACT FROM AUTHOR]

Objective: To describe the spectrum of congenital renal anomalies and emphasize the critical role of comprehensive autopsy examination in identifying CAKUT, especially of lower urinary tract malformations correlating with prenatal imaging methods. Methods: Retrospective analyses of CAKUT diagnosed at fetal autopsy were analyzed over a 7-y period and correlated with prenatal imaging findings. Result: Among the 255 fetal autopsies, 45 cases were detected with CAKUT. Isolated (27%), syndromic CAKUT (51%), and CAKUT associated with other system anomalies (22%) were found. Hydronephrosis, followed by cystic renal diseases and agenesis were the common renal malformations. The gastrointestinal tract (GIT) was the commonest system associated with CAKUT. Among the syndromic CAKUT, the urorectal septum malformation (URSM) was the most frequent one, followed by VACTER-L, acrorenal syndrome, and OEIS complex. When correlating prenatal USG and autopsy findings, a significant change in final diagnosis was observed in 60% of cases. Conclusion: Extrarenal malformations and syndromic associations of CAKUT predominated over isolated ones. Detection of lower urinary tract anomalies in CAKUT is difficult through antenatal imaging methods if associated with oligohydramnios. In these circumstances, the perinatal autopsy has a significant role in arriving at the final diagnosis which guides the clinician in predicting the recurrence risk and the need for genetic workup. [ABSTRACT FROM AUTHOR]

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. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

Infection is considered a leading cause of fetal death, responsible for approximately 20% of cases. Such estimates are derived from the frequency of acute histological chorioamnionitis and funisitis in cases of fetal death rather than direct detection of microorganisms in the fetal compartment. We report a case of clinically unexplained fetal death at 38 weeks of gestation in an uncomplicated pregnancy resulting in delivery of an appropriate-for-gestational-age fetus. The mother did not have any clinical signs of infection. Overwhelming bacterial invasion in multiple fetal organs, including the heart, liver, spleen, and kidneys, was observed despite the lack of evidence of maternal clinical infection. The bacteria were visualized by using standard histologic techniques (e.g. H&E/ tissue Gram stain) highlighting the value of autopsy in determining the cause of death. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between prenatal ultrasonography (USG) and fetal autopsy findings. Among 453 pregnancy terminations performed because of fetal anomalies on prenatal USG, 54 with skeletal dysplasia on fetal autopsy were included in this retrospective study. The most common diagnoses among the 54 fetal autopsies were osteogenesis imperfecta (n=12), dysostosis (n=10), achondroplasia (n=9), arthrogryposis (n=6), and thanatophoric dysplasia (n=6). The prenatal USG and fetal autopsy findings showed complete agreement in 35 cases (64.8%), partial agreement in nine cases (16.6%), and disagreement in 10 cases (18.5%). Fetal autopsy via perinatal pathology is essential for precise identification of the type of skeletal dysplasia; it should be routinely performed to confirm the diagnosis of prenatally detected fetal anomalies. Autopsy is vital for accurate prenatal diagnosis and the 'gold standard' technique for the identification of clinically important abnormalities. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to determine whether recommended assessments were conducted on stillbirths delivered in our predominantly rural state.Methods: This was a descriptive study of stillbirths delivered in a rural state and included in one site of the Birth Defects Study to Evaluate Pregnancy Exposures stillbirth study. Hospital and fetal death records were examined to determine whether the following areas were evaluated: genetic testing (noninvasive perinatal testing, quad screen, amniocentesis/chorionic villus sampling with karyotype, microarrays, fetal tissue specimen), placenta/membrane/cord sent for pathologic examination, examination of the stillbirth after delivery by the healthcare provider, and fetal autopsy was performed.Results: From July 1, 2015 to June 30, 2020, there were 1108 stillbirths delivered in Arkansas. The most frequent assessments undertaken were placental pathology (72%), genetic testing (67%), fetal inspection (31%), and autopsy (13%). All four assessments were done in 2% of stillbirth cases, three assessments in 27%, two assessments in 47%, one assessment in 14%, and no assessment in 15%. There was no association between stillbirth assessment evaluation by gestational age (<28 weeks and > 28 weeks; P = 0.221); however, there was an overall association between hospital delivery volume with number of components completed (P < 0.0001). Hospitals with >2000 deliveries had a higher proportion of three or four completions compared with those hospitals with <1000 deliveries or 1000 to 2000 deliveries (P = 0.021 and P < 0.0001).Conclusions: Fetal stillbirth assessment is suboptimal in our rural state, with 15% of stillbirths having no assessment and only 2% having all four assessments. There is no association between stillbirth assessment and gestational age (<28 weeks vs >28 weeks), but there is a correlation between delivery volume and stillbirth assessment. [ABSTRACT FROM AUTHOR]

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) is a rare congenital anomaly characterized by uterus didelphys, unilateral obstructed hemivagina, and ipsilateral renal anomaly. Autopsy performed on a third trimester stillborn fetus unexpectedly revealed uterine didelphys, an obstructed left hemivagina, and a left pelvic, atrophic, duplex kidney, with both left ureters entering the obstructed left hemivagina. Furthermore, the fetus had an imperforate anus, a single right umbilical artery, and spina bifida occulta. Although rare, OHVIRA is a well-documented congenital anomaly. However, prior to this case, there had been no description of OHVIRA in an autopsy or in a fetus. Furthermore, the association of OHVIRA, anorectal malformation, and spinal bifida has never been reported. By sharing this case, we hope to increase the awareness of this entity among perinatal healthcare providers and to help further elucidate genitourinary embryology, which is still not fully understood. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the agreement and disagreement between prenatal ultrasound and fetal autopsy findings in pregnancy terminations due to urogenital anomalies. Methods: Of 453 pregnancy terminations performed due to fetal anomalies, 82 cases with urogenital anomalies on either prenatal ultrasound or fetal autopsy were included in this retrospective study. The discrepancy between prenatal ultrasound and fetal autopsy findings on urogenital anomaly findings was evaluated. Results: Complete agreement between prenatal ultrasound and fetal autopsy findings was noted in 33 (40.2%) cases (particularly for megacystis, bilateral renal agenesis, and infantile polycystic kidney), whereas partial agreement (anal atresia and horseshoe kidney as additional minor findings) and altered diagnosis were noted in 12 (14.6%) and 8 (9.8%) cases, respectively. Disagreement was noted in 29 (35.4%) cases including anomaly only on autopsy in 20 (24.3%) cases (renal agenesis, horseshoe kidney and multicystic dysplastic kidney in particular) and anomaly only on ultrasound in 9 (10.9%) cases. Conclusions: Accordingly, our findings indicate fetal autopsy to be a method of vital importance in complementing prenatal diagnosis; it may add valuable information that may improve future pregnancy management and counseling of parents, and hence prenatal ultrasound and fetal autopsy should be regarded as complementary techniques. Fetal autopsy is crucial in complementing prenatal diagnosis; it can add valuable information that may improve future pregnancy management and counseling of parents. [ABSTRACT FROM AUTHOR]

Holoprosencephaly (HPE) is a clinically and genetically heterogeneous disease, which can be associated with various prenatal comorbidities not always detectable on prenatal ultrasound. We report on the case of a foetus carrying a semi-lobar HPE diagnosed at ultrasound, for which a fetal autopsy and a whole exome sequencing were performed following a medical termination of pregnancy. Neuropathological examination confirmed the semi-lobar HPE and general autopsy disclosed a total pancreas agenesis. Whole exome sequencing found the CNOT1 missense c.1603C>T, p.(Arg535Cys), occurring de novo in the foetus. The same variant was previously reported in 5 unrelated children. All individuals had HPE, and 4 out of 5 presented endo- and exocrine pancreatic insufficiency or total pancreas agenesis. CNOT1 encodes a subunit of the CCRN4-NOT complex, expressed at the early stage of embryonic development. This report is the first fetal description of the phenotype associating HPE and pancreatic agenesis linked to the recurrent CNOT1 missense c.1603C>T, p.(Arg535Cys). This finding strengthens the hypothesis of a specific recurrent variant associated with a particular phenotype of HPE and pancreas agenesis. The fetal autopsy that revealed the pancreas agenesis was crucial in guiding the genetic diagnosis and enabling accurate genetic counselling. [ABSTRACT FROM AUTHOR]

Introduction: Congenital cytomegalovirus (cCMV) is a common congenital viral infection. Testing for cCMV usually begins with assessing maternal CMV serology, specifically IgM and IgG antibodies. A negative maternal CMV IgM suggests a low risk of recent maternal CMV infection, thereby suggesting a low risk of cCMV in the fetus. Consequently, cCMV is often ruled out when maternal CMV IgM is negative., Methods: In our perinatal autopsy and placental pathology database, we identified 5 cases of cCMV despite negative maternal CMV IgM results in the second trimester., Results: In all 5 cases, fetal abnormalities were first detected by ultrasound in the second trimester, prompting maternal CMV testing. Since second trimester maternal CMV IgM was negative in all cases, cCMV was considered unlikely, thus precluding further prenatal CMV testing in 4 of these cases. The diagnosis of cCMV was subsequently made through placental and/or autopsy examinations. Following this diagnosis, retrospective CMV serology and IgG avidity testing was performed on stored frozen first-trimester maternal blood samples in 3 cases. Among these, the first-trimester samples in 2 cases were IgG+, IgM+, and exhibited low IgG avidity, suggesting a primary maternal CMV infection around the time of conception. In the third case, both first and second-trimester maternal blood samples were IgG+, IgM-, and showed high IgG avidity, suggesting a non-primary maternal CMV infection (i.e., reactivation or reinfection of CMV)., Conclusion: A negative maternal CMV IgM in the second trimester cannot exclude cCMV infection. While CMV IgG avidity testing and analysis of stored frozen first-trimester maternal blood samples provide valuable insights, they have limitations. CMV PCR performed on amniotic fluid is a useful prenatal diagnostic tool. For cases of unexplained fetal abnormalities or death, autopsy and placental examination are recommended., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Tricuspid valve abnormalities detected in fetal life include Ebstein anomaly and tricuspid valve dysplasia. The differentiation between these 2 entities can sometimes be challenging in the 2nd trimester fetus. We report a case of tricuspid valve dysplasia diagnosed on fetal autopsy. Case Report: A primigravida was diagnosed at 22 weeks' gestation to have Ebstein anomaly with severe tricuspid regurgitation. There was intra-uterine fetal demise. On fetal autopsy, the tricuspid valve leaflets were not apically displaced and the leaflets were nodular with rolled up edges. This supported a diagnosis of tricuspid valve dysplasia. Conclusion: The difficulties in differentiating Ebstein anomaly from tricuspid valve dysplasia due to inherent limitations in fetal imaging can be resolved by fetal autopsy. Valvular dysplasia will not have apical displacement of the valve leaflets. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Few studies exist that research the association between umbilical cord characteristics with cardiac malformations. In this study, we describe a population of newborns with congenital heart defects (CHD) and the frequency of presentation of umbilical cord (UC) alterations, based upon the hypothesis that the continuity of the cardio-placental circuit can be affected by similar noxas during early development. METHODS: We carried out a descriptive study at a hospital in Bogota based on clinical records from newborns with congenital heart disease with placental and UC pathology results. Group analyses were done according to the major categories of the ICD-10. RESULTS: We analyzed 122 cases and found that the most frequent alterations where hypercoiling (27.9%) and abnormal UC insertion (16.4%). Additionally, in almost every group of CHD, more than 65%of patients had some type of cord alteration. CONCLUSION: We discovered a high frequency of UC alterations in patients with CHD. This outcome suggests that a possible association exists between the two phenomena, further research is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Worldwide approximately 2.6 million are stillborn, mostly occurring in developing countries. In the great part these deaths are inexplicable. The evenness and standardisation of the diagnostic criteria are prerequisites to understand their pathogenesis. The core goal of this article is to propose new evidence based investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as “unexplained”. The proposed protocol is mainly focused on the anatomopathological examination of the autonomic nervous system and in particular of the brainstem where the main centers that control vital functions are located. Methods Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines. Results Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in over 100 cases of unexplained fetal death sent to the “Lino Rossi Research Center” of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases. Conclusions We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians. Trial registration not applicable for this study.

Introduction and aim Malformations of the central nervous system (CNS) are one of the most devastating, yet most common congenital anomalies. Congenital CNS anomalies are structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental period and have a high intrauterine mortality. This study aimed to determine the frequency and distribution of neural tube defects (NTDs) in a tertiary care center for a period of 4.5 years. The neural tube defect was analyzed along with the other associated anomalies in the fetus. Its association with maternal risk factors was also analyzed. Materials and methods This retrospective study includes a total of 48 cases of neural tube defects, over a period of 4.5 years from January 2019 to June 2023, retrieved from the archives of the Department of Pathology at Saveetha Medical College. The study population included all fetuses diagnosed with NTDs during the fetal autopsies conducted at Saveetha Medical College during the period of study. The variables studied include maternal age, maternal risk factors, sex of the fetus, other associated anomalies in the fetus, and placental anomalies associated with the NTDs. Results A total of 48 cases of NTDs were included in this study. NTDs were more common among the female fetuses when compared with the male fetuses. The most common NTD observed in our study was anencephaly. The associated anomalies seen with NTDs include dysplastic kidney, unilateral renal agenesis, agenesis of urinary bladder, sacral agenesis, diaphragmatic hernia, bilateral talipes equinovarus deformity in both lower limbs. In the present study, among the placental defects seen in fetuses with NTDs, single umbilical artery was seen in four fetuses with NTDs. Twelve out of the 48 females included in the study did not take folic acid supplements during the antenatal period, and two females had a history of neural tube defects in their previous pregnancies. Conclusion  This study emphasizes that intensive screening and documentation of coexistent abnormalities of NTDs is needed. Either ultrasonography/MRI or fetal autopsy should be conducted in order to exhibit certain diagnoses and to conduct proper prenatal genetic counseling for parents with fetuses having NTDs or having a history of fetuses with NTDs regarding ongoing and future pregnancies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Scientific Review Board of Saveetha University issued approval #126/03/2024/PG/SRB/SMCH. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, K et al.)

Purpose: 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., Conclusion: 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., Competing Interests: Conflict of Interest Camille Schubert’s salary was partially funded by the Genomic Autopsy Study (Australian government MRFF grant funded research). All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. Stillbirth investigations incur healthcare costs, but these investigations are necessary to provide information that will help reduce the risk of a recurrent stillbirth, as well as advice regarding family planning and future pregnancies. The aims of this study were to determine the healthcare costs of investigations for stillbirths, identify drivers and assess cost differences between explained and unexplained stillbirths. Methods. Data from 697 stillbirths were extracted from the Stillbirth Causes Study covering the period 2013-18. The dataset comprised all investigations related to stillbirth on the mother, baby and placenta. Unit costs applied were sourced from the Australian Medicare Benefits Schedule, local hospital estimates and published literature. Multivariable regression analyses were used to assess key factors in cost estimates. Results. In all, 200 (28.7%) stillbirths were unexplained and 76.8% of these had between five and eight core investigations. Unexplained stillbirths were twice as likely to have eight core investigations as explained stillbirths (16.5% vs 7.7%). The estimated aggregated cost of stillbirth investigations for 697 stillbirths was A$2.13 million (mean A$3060, median A$4246). The main cost drivers were autopsies or cytogenetic screening. Mean costs were similar when stillbirths had known or unknown causes and by reason for stillbirth among cases with definable causes. Conclusion. Investigations for stillbirth in Australia cost approximately A$4200 per stillbirth on average and are critical for managing future pregnancies and preventing more stillbirths. These findings improve our understanding of the costs that may be averted if stillbirths can be prevented through primary prevention initiatives. [ABSTRACT FROM AUTHOR]

Objective: Stillbirth is one of the most devastating adverse pregnancy outcome, but it is often associated with a missing post-mortem histological examination. We aimed at evaluating whether the staining of amniotic fluid reflects the fetal conditions surrounding the death and if it correlates with any histologic sign of fetal distress.Study Design: Terminal gasping (represented by the massive presence of intra-alveolar squamous cells), thymic and adrenal cortex modifications were evaluated as histologic signs of fetal distress in stillbirths, and stratified according to the degree of staining of the amniotic fluid.Results: The presence of meconium-stained amniotic fluid did not correlate with the presence of gasping and/or thymic and/or adrenal cortex changes. Clear amniotic fluid was not associated with the absence of histologic signs of distress.Conclusions: The evaluation of the staining of the amniotic fluid fails to identify distressed fetuses. A histologic evaluation of fetal organs provides detailed information, irrespective of the presence/absence of meconium-stained amniotic fluid. [ABSTRACT FROM AUTHOR]

Background: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. Purpose: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. Methods: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. Results: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia. Fisher's exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P <.05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. Conclusion: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this study is to analyze the second-trimester fetal autopsies and to reemphasize the role of autopsy by comparing autopsy findings with prenatal ultrasound observations. MATERIALS AND METHODS: Retrospective analysis of second-trimester fetal autopsies over a period of 7.5 years (January 2009–June 2016). A standard protocol of autopsy procedure was followed, which included external examination with photography, X-ray, internal examination, and histopathological examination. In fetuses with congenital malformations (CMs), the findings of prenatal ultrasonogram and autopsy examination were compared. RESULTS: We analyzed a total of 66 fetuses, which includes 17 intrauterine fetal death, 49 terminations for CM, and increased risk for chromosomal abnormality. In fetuses with CM, multiple anomalies were more common than a single anomaly. The most common anomalies were seen involving central nervous system (neural tube defect) followed by the genitourinary system. Autopsy confirmed prenatal ultrasound findings in all cases except three. Complete agreement between USG findings and autopsy were seen in 17 cases (39.7%). Additional findings on autopsy were noted in 25 cases (62.2%). Among these, 15 cases had a significant change of recurrence risk due to altered initial ultrasound diagnosis. CONCLUSION: Fetal autopsy plays an important role in arriving at the final diagnosis and detecting the cause of death. This information is very essential for the clinicians, in genetic counseling of the parents, and management of future pregnancies.

Background: Fetal autopsy has been an indispensable tool in evaluating the cause of death. The most common cause for fetal deaths is associated with respiratory disorders accounting for around 60%. This study was undertaken to evaluate the gross and microscopic features of lungs in fetal autopsies and estimate the incidence of deaths attributable to pulmonary causes. Materials and Methods: All fetuses received for autopsy at our institute were included in the study with prior consent. Gross and microscopic findings along with relevant clinical data were recorded. Results: A total of 426 autopsies were conducted from January 2011 to August 2016. Of those, 184 had abnormal pulmonary findings constituting 43.19%. Aspiration pneumonia was the most common finding with 67 cases (36.4%), followed by atelectasis 54 cases (29.3%), congenital cystic adenomatoid malformation in 13 cases (7.1%), lung hypoplasia 12 cases (6.5%), pulmonary hemorrhage 21 (11.4%), 15 cases (8.15%) of hyaline membrane disease, one case (0.5%) of heterotaxy, and one case of extralobar pulmonary sequestration (0.5%). Congenital malformations of lungs were seen in 27 (14.67%) cases and 38 cases (20.65%) had other associated anomalies. Conclusion: Pulmonary pathology is the most common finding in fetal deaths with aspiration pneumonitis being the most common avoidable cause. Accurate fetal autopsy along with clinical data are important in evaluating fetal deaths and can help in reduction of unexplained stillbirths.

Background: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. Purpose: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. Methods: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. Results: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia. Fisher's exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. Conclusion: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management. [ABSTRACT FROM AUTHOR]

Background: Worldwide approximately 2.6 million are stillborn, mostly occurring in developing countries. In the great part these deaths are inexplicable. The evenness and standardisation of the diagnostic criteria are prerequisites to understand their pathogenesis. The core goal of this article is to propose new evidence based investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as "unexplained". The proposed protocol is mainly focused on the anatomopathological examination of the autonomic nervous system and in particular of the brainstem where the main centers that control vital functions are located.Methods: Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines.Results: Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in over 100 cases of unexplained fetal death sent to the "Lino Rossi Research Center" of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases.Conclusions: We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians.Trial Registration: not applicable for this study. [ABSTRACT FROM AUTHOR]

• Fetal cystic tumor of atrioventricular node is for the first time diagnosed and described in the postmortem female fetus. • There are many reasons for performing a complete fetal autopsy even in routine cases, foremost of which is identifying an accurate etiology of death, because small lesions may be missed on gross examination. • Pathologists and administrators who refuse to understand the enormous importance of the postmortem fetal pathological autopsy study fail to address the parent´'s suffering in fetal loss. 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. [ABSTRACT FROM AUTHOR]

An updated neuropathological protocol for the examination of the nervous system in case of unexplained stillbirth has been elaborated and presented in this review. It is focused on the examination of the nervous centers located in the brainstem, which are involved in monitoring the vital functions. Only through a deep analysis of the brainstem it is possible to highlight developmental alterations of these essential centers, and then provide a plausible explanation of the pathogenetic mechanism behind the death. The guidelines, drawn up on the basis of numerous researches performed by the authors, include a histopathological protocol, with an indication of standardized samples, and an immunohistochemical protocol for the study of biological markers, frequently involved in these deaths. The main risk factors that can be related to the neuronal alterations are also reported, together with the indications for the toxicological examination, which should be possibly applied. The authors hope that this protocol will be soon adopted in all the institutions where a fetal death, after a routine autopsy procedure, is diagnosed as “unexplained”, in order to make standardized investigations on stillbirth. Nowadays, preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians are necessary.

Fetal gastroschisis and omphalocele are congenital defects of abdominal wall that are often diagnosed by prenatal ultrasound done for routine screening or for obstetric indications, such as evaluating an elevated maternal serum alpha-fetoprotein. Prenatal ultrasound could potentially identify the overwhelming majority of abdominal wall defects and accurately distinguish omphalocele from gastroschisis. Here, we report a case of gastroschisis diagnosed at routine prenatal ultrasound along with a thorough fetal autopsy which gives the final diagnosis of disease.

Abstract Objective Historically, fetal autopsy was common after terminations for anomalies. Previous studies report that fetal autopsy confirms ultrasound findings in the majority of cases. This study aims to examine correlation between prenatal and autopsy diagnoses at University of California, San Francisco (UCSF) and evaluate whether autopsy adds diagnostic information, specifically information that changes risk of recurrence for future pregnancies. Study Design We conducted a retrospective chart review of all fetal autopsies performed at UCSF between 1994 and 2009. Prenatal diagnosis was compared with autopsy diagnosis; for cases where there was a change in diagnosis, an MFM (maternal-fetal medicine specialist) reviewed the case to assign risk of recurrence before and after autopsy. Results Overall, there was concordance between prenatal diagnosis and autopsy diagnosis in greater than 91.7% of cases. Autopsy added information that resulted in a change in recurrence risk in 2.3% of cases (n = 9). Conclusion For the vast majority of cases, there is agreement between prenatal and autopsy diagnosis after pregnancy loss or termination for fetal anomalies. Only a small percentage of autopsies change recurrence risk. This may be useful when counseling women about method of termination and when counseling couples about whether to have an autopsy.