Fetal and neonatal outcomes of posterior fossa anomalies: a retrospective cohort study.

The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.

Perinatal Results and Long-Term Follow-Up of Fetal Cardiac Tumors: A 30-Year Historical Cohort Study. / Resultados Perinatais e Seguimento em Longo Prazo de Tumores Cardíacos Fetais: Estudo de Coorte Histórica de 30 Anos.

BACKGROUND: This was a 30-year retrospective cohort study that approximates closely to the natural history of cardiac tumors diagnosed in the fetus, since there was no case of pregnancy interruption. OBJECTIVE: To assess morbidity and mortality in the perinatal period and at long term in fetuses diagnosed with cardiac tumor. Our secondary objective was to assess the evaluating factors of perinatal and postnatal results. METHODS: This was a retrospective cohort study with 74 pregnant women with an echocardiographic diagnosis of fetal cardiac tumor at two referral centers between May 1991 and November 2021. A descriptive analysis was performed, and data were expressed as absolute (n) and relative (%) frequencies, median and interquartile range. Fisher's exact test was used to evaluate the association of echocardiographic characteristics and clinical manifestations with perinatal and postnatal results. Global survival was calculated using the Kaplan-Meier method and the curves were compared by the log-rank test. The time of follow-up, calculated in months, corresponded to the time elapsed from hospital discharge to current status (survived/ censoring or death). The level of significance was set at 5% (p<0.05). RESULTS: Rhabdomyoma is the most common type of cardiac tumor (85%), with a high morbidity (79.3%) and overall mortality of 17.4%. The presence of fetal hydrops was a predictor of death. CONCLUSION: The presence of fetal hydrops had an impact on mortality, and hence is an important factor in counselling and determining the prognosis. Most deaths occurred before hospital discharge.

FUNDAMENTO: Seguimento de coorte retrospectiva de 30 anos que se aproxima da história natural dos tumores cardíacos diagnosticados no feto uma vez que nenhum caso foi submetido à interrupção da gestação. OBJETIVO: Avaliar a morbidade e mortalidade perinatal e em longo prazo em fetos com diagnóstico de tumor cardíaco. Como objetivo secundário avaliar os fatores que influenciaram os resultados perinatais e pós-natais. MÉTODO: Estudo de coorte retrospectiva envolvendo 74 gestantes com diagnóstico ecocardiográfico fetal de tumor cardíaco acompanhadas em dois serviços de referência no período de maio de 1991 a novembro de 2021. Foi realizada análise descritiva dos dados por meio de frequências absolutas (n) e relativas (%), mediana e intervalos interquartis. Para avaliar a associação entre as características ecocardiográficas e as manifestações clínicas com os resultados perinatais e pós-natais, foi aplicado o teste exato de Fisher. O cálculo da sobrevida global foi realizado pelo método de Kaplan-Meier e a comparação de curvas pelo teste de log-rank. O tempo de seguimento, calculado em meses, foi definido a partir da data de alta do hospital à data do status atual (vivo/censura ou óbito). O nível de significância considerado foi de 5% (p<0,05). RESULTADOS: o rabdomioma é o tipo mais frequente (85%) de tumor cardíaco; apresenta alta morbidade (79,3%) e mortalidade geral de 17,4%; a presença de hidropisia fetal preditiva de óbito. CONCLUSÃO: A presença de hidropisia fetal teve impacto na mortalidade, sendo fator importante para aconselhamento e estabelecimento de prognóstico. A maioria dos óbitos ocorrem antes da alta hospitalar.

Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Congenital brain tumour in a neonate: a therapeutic challenge.

A term neonate with history of ventriculomegaly in the fetal period was diagnosed with a central nervous system tumour after radiological investigations. It was confirmed as an immature teratoma after histopathological examination. He underwent left frontal craniotomy with tumour excision. Intraoperatively, massive haemorrhage (venous bleed) occurred due to the high vascularity of the tumour and led to haemodynamic instability. A massive transfusion protocol was initiated. Despite multiple transfusions and shock management, he succumbed at 2 weeks of life. This case report highlights the importance of antenatal diagnosis and fetal MRI in prognostication and also the possible role of neoadjuvant chemotherapy in reducing tumour vascularity and, hence, bleeding.

Congenital bronchogenic cyst: From prenatal diagnosis to postnatal management.

OBJECTIVE: Bronchogenic cysts are rare congenital abnormalities, and usually asymptomatic until adulthood. We present a fetus prenatally diagnosed with a bronchogenic cyst, experiencing compression symptoms immediately after birth and underwent thoracoscopic surgery at 14 days old. CASE REPORT: A 33-year-old primigravida had a suspicion of fetal tracheal cyst. Prenatal ultrasound scan revealed a cyst near the trachea at 23 weeks' gestation. Fetal MRI defined a cystic lesion in the upper mediastinum, displacing surrounding vessels. A 3,940 g girl was delivered vaginally at 38 weeks' gestation. Shortly after birth, she developed respiratory distress, and imaging revealed a mediastinal cyst compressing the trachea and esophagus. The cyst was successfully removed through video-assisted thoracoscopic surgery at 14 days old, and pathology confirmed it as a bronchogenic cyst. Follow-up images demonstrated well-aerated lungs. At present, this 1-year-old girl develops normally without respiratory symptoms. CONCLUSION: Early detection in utero, accurate diagnosis, and timely management are crucial for bronchogenic cysts in neonates.

Genotype-phenotype correlations in a fetus with Kleefstra syndrome.

OBJECTIVE: Kleefstra syndrome (KS), formerly known as 9q subtelomeric deletion syndrome, is characterized by multiple structural abnormalities. However, most fetuses do not have obvious abnormal phenotypes. In this study, the fetus with KS presented with multiple system structural anomalies, and we aimed to explore the genotype-phenotype correlations of KS fetuses. CASE REPORT: Multiple systematic structural anomalies, including severe intrauterine growth restriction (IUGR) and cardiac defects, were detected by ultrasound in the fetus at 33 + 5 weeks' gestation. These abnormalities may be caused by the pathogenic deleted fragment at 9q34.3, including the euchromatic histone methyltransferase 1 (EHMT1) and collagen type V alpha 1 chain (COL5A1) genes, detected by copy number variation sequencing (CNV-seq). CONCLUSIONS: It is essential for clinicians to perform CNV-seq combined with multidisciplinary consultation for suspected KS fetuses, especially those with multiple systematic structural anomalies.

The Auditory Pathway in Congenitally Cytomegalovirus-Infected Human Fetuses.

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss.

Magnetic Resonance Imaging of Dural Sinus Malformation in a Fetus: A Case Report.

BACKGROUND: Dural sinus malformation (DSM) is a rather rare congenital condition that can be encountered in the fetus and infants. The cause and etiology of DSM remain unclear. Obstetric ultrasound plays a key role in screening fetal brain malformations, and MRI is frequently used as a complementary method to confirm the diagnosis and provide more details. OBJECTIVE: Here, we present a fetus with DSM by multiple imaging methods to help better understand the imaging characteristics of this malformation. CASE PRESENTATION: A 22-year-old primipara was referred to our hospital at 25 weeks of gestation following the detection of a fetal intracranial mass without any symptoms. A prenatal ultrasound performed in our hospital at 25 + 2 gestational weeks showed a large anechoic mass with liquid dark space, while no blood flow was detected. After the initial evaluation, this primipara received a prenatal MRI in our hospital. This examination at 25 + 5 gestational weeks delineated a fan-shaped mass in the torcular herophili, which was iso-to hyperintense on T1WI and hypointense on T2WI. At the lower part of this lesion, a quasi-circular hyperintense on T1WI and a signal slightly hyperintense on T2WI could be seen. Meanwhile, the adjacent brain parenchyma was compressed by the mass. CONCLUSION: We reviewed the current literature to obtain a better understanding of the mechanisms, imaging characteristics, and survival status of DSM. Although the primipara of the present study regretfully opted for elective termination of pregnancy, the reevaluation of DSM survival deserves more attention because of the better survival data from recent studies.

Expanding the phenotypic spectrum of LIG4 pathogenic variations: neuro-histopathological description of 4 fetuses with stenosis of the aqueduct.

Severe ventriculomegaly is a rare congenital brain defect, usually detected in utero, of poor neurodevelopmental prognosis. This ventricular enlargement can be the consequence of different mechanisms: either by a disruption of the cerebrospinal fluid circulation or abnormalities of its production/absorption. The aqueduct stenosis is one of the most frequent causes of obstructive ventriculomegaly, however, fewer than 10 genes have been linked to this condition and molecular bases remain often unknown. We report here 4 fetuses from 2 unrelated families presenting with ventriculomegaly at prenatal ultra-sonography as well as an aqueduct stenosis and skeletal abnormalities as revealed by fetal autopsy. Genome sequencing identified biallelic pathogenic variations in LIG4, a DNA-repair gene responsible for the LIG4 syndrome which associates a wide range of clinical manifestations including developmental delay, microcephaly, short stature, radiation hypersensitivity and immunodeficiency. Thus, not only this report expands the phenotype spectrum of LIG4-related disorders, adding ventriculomegaly due to aqueduct stenosis, but we also provide the first neuropathological description of fetuses carrying LIG4 pathogenic biallelic variations.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.

Clinical outcomes of fetuses with cardiac rhabdomyoma: A case series from a tertiary center.

AIMS: The study aims to evaluate the genetic and clinical outcomes of fetal cardiac rhabdomyoma in our tertiary center. METHODS: Data of cases with cardiac rhabdomyoma detected by fetal echocardiography during antenatal follow-up were analyzed retrospectively. RESULTS: Nine cases were included in the study. The incidence of cardiac rhabdomyoma was 0.003%. The median fetal diagnosis time was 26th weeks, the most common location was the LV. There was no hemodynamic disorder requiring cardiovascular intervention in any of the cases. Of the eight genetically tested cases, four were tuberous sclerosis complex (TSC) gene-negative, one hereditary TSC2, one de novo TSC1, and two de novo TSC2 gene mutants. Postnatal first-year survival rate of the cases was 88.8%. CONCLUSIONS: Cardiac rhabdomyoma is a rare fetal and pediatric pathology that generally is a remarkable finding in the clinical process of TSC. Therefore, cases should be evaluated multisystemically and genetic counseling should be given to the family.

Characteristic findings in the human fetus vestibule: A human temporal bone study.

OBJECTIVE: The "collapse," a highly flexed, dented, or caved membrane between the endo- and peri-lymph of the saccule and utricle in adults, is considered as a morphological aspect of Ménière's syndrome. Likewise, when mesh-like tissues in the perilymphatic space are damaged or lost, the endothelium loses mechanical support and causes nerve irritation. However, these morphologies were not examined in fetuses. METHODS: By using histological sections from 25 human fetuses (crown-rump length[CRL] 82-372 mm; approximately 12-40 weeks), morphologies of the perilymphatic-endolymphatic border membrane and the mesh-like tissue around the endothelium were examined. RESULTS: The highly flexed or caved membrane between the endo- and peri-lymphatic spaces was usually seen in the growing saccule and utricle of fetuses, especially at junctions between the utricle and ampulla at midterm. Likewise, the perilymphatic space around the saccule, utricle and semicircular ducts often lost the mesh-like tissues. The residual mesh-like tissue supported the veins, especially in the semicircular canal. CONCLUSION: Within a cartilaginous or bony room showing a limited growth in size but containing increased perilymph, the growing endothelium appeared to become wavy. Owing to a difference in growth rates between the utricle and semicircular duct, the dentation tended to be more frequently seen at junctions than at free margins of the utricle. The difference in site and gestational age suggested that the deformity was not "pathological" but occurred due to unbalanced growth of the border membrane. Nevertheless, the possibility that the deformed membrane in fetuses was an artifact caused by delayed fixation is not deniable.

Metastatic Lymphomas of the Placenta: A Literature Review With an Illustrative Case.

Lymphoma is the fourth most common tumor to display placental metastasis. This study aimed to report a case of high-grade lymphoma involving the placenta and review the literature on lymphomas metastatic to the placenta. A systematic review was performed following the PRISMA guidelines, using the keywords "lymphoma" AND "placenta." All case reports and case series on lymphoma infiltrating the placenta were collected. Eight cases from 7 studies, including the present case, were synthesized. The mean patient age is 29.5 years. The clinical presentation is non-specific. Hematologic derangements included cytopenias or cytoses, and elevated prothrombin time. The mean gestational age (GA) when a diagnosis of lymphoma was rendered is 27 weeks. Five cases presented with either lymphadenopathy or visceral masses on imaging. Four of these cases eventually led to maternal demise. The mean GA when the fetus was delivered is 31 3/4 weeks. Grossly, most placentas had non-specific findings. Leukemic infiltrates were mostly seen within intervillous spaces. Intravillous infiltrates were associated with high-grade lymphomas, resulting in either maternal demise or stillborn fetuses. This study suggests that the placenta has mechanisms to guard against malignancies; however, these defense mechanisms are not foolproof and may be breached by tumor cells.

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients.

BACKGROUND: Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. OBJECTIVE: This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. STUDY DESIGN: This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. RESULTS: Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. CONCLUSION: Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

Neuroimaging Findings in Fetal Hemimegalencephaly: Case Study and Review.

BACKGROUND: Limited information exists in the prenatal literature regarding the neuroimaging features of fetal hemimegalencephaly. SUMMARY: This report describes ultrasound and magnetic resonance imaging (MRI) findings in a second-trimester fetus with an isolated, severe form of hemimegalencephaly. The most prominent imaging findings included unilateral enlarged cerebral hemisphere and ipsilateral ventriculomegaly causing cerebral asymmetry, midline shift, and macrocephaly. Abnormal cortical development imaging signs were also evident. A literature review encompassing 23 reports describing 36 cases, including ours, is presented. KEY MESSAGES: Characteristic ultrasound findings for the diagnosis of hemimegalencephaly are not always apparent prenatally. Asymmetric ventriculomegaly emerges as the most common but nonspecific presenting feature during routine second- or third-trimester ultrasound scans. Subsequent high-resolution prenatal neurosonography and fetal MRI facilitate definitive prenatal diagnosis, showcasting associated features primarily related to cortical migration, differentiation, and maturation. Postnatally, the prognosis is poor due to intractable seizures, hemiplegia, and progressive neurodevelopmental delay.

Skeletal Growth Arrest Lines in Fetal Remains: Histopathology and Correlative Placental Pathology.

INTRODUCTION: Skeletal growth arrest lines (GAL) are transverse lines of metaphyseal radiodensity accompanying episodic severe physiological stress. They are poorly described in fetal remains. MATERIALS AND METHODS: We searched our autopsy practice for instances of fetal GAL in post mortem radiology, and correlated them with long bone histology and placental pathology. We describe the appearance, distribution, and pathology of GAL in a cohort of fetal autopsies, and compare the placental pathology accompanying GAL to the placental pathology of asymmetrical growth restriction (AGR) in the same time period. RESULTS: In 2108 consecutive fetal post mortems, we found 20 cases with GAL. About 16 were in singletons with AGR. In these 16, the distribution of placental pathologies was similar to a contemporaneous cohort of 113 cases with AGR. Of the remaining 4, two twins out of 9 sets of monochorionic twins with AGR demonstrated GAL. One case of GAL had symmetrical growth restriction with cytomegalovirus infection, and one case had no AGR and an old, unexplained retroplacental hemorrhage. On histology, GAL are characterized by a region of mineralized chondroid, which is variably incorporated into irregular trabecular bone. DISCUSSION: GALs accompany a variety of placental pathologies and twin-twin transfusion, suggesting episodic disease progression.

Congenital malformations caused by Akabane virus in porcine fetuses in southern Japan.

Akabane virus (AKAV) is known as a major teratogenic agent of ruminant fetuses. In this study, we investigated the relationship between porcine abnormal deliveries and AKAV by serology, pathology, and virology investigations using specimens from 16 stillborn fetuses delivered in southern Japan between 2013 and 2015. The major clinical manifestations in stillborn fetuses were hydranencephaly, arthrogryposis, spinal curvature, and both skeletal muscle and subcutaneous edema. Histologic examination of the specimens identified atrophy of skeletal muscle fibers accompanied by adipose replacement. Nonsuppurative encephalomyelitis and decreased neuronal density in the ventral horn of the spinal cord were shown in two separate fetuses, respectively. Neutralizing antibody titers to AKAV were detected in most of the tested fetuses (13/16). The AKAV sequences detected in the affected fetuses in 2013 and 2015 were highly identical and closely related to Japanese AKAV isolates which were isolated in 2013 and sorted into genogroup I of AKAV. Immunohistochemistry visualized AKAV antigens in the neuronal cells of the central nervous system of the fetuses. These findings indicate that AKAV was involved in the birth of abnormal piglets at the affected farm. The clinical manifestations and histopathological features in the stillborn fetuses were very similar to those in ruminant neonates affected by AKAV. To avoid misdiagnosis and to evaluate the precise impact of AKAV on pig reproduction, AKAV should be considered in differential diagnoses of reproductive failures in pigs.

Establishment and Validation of a Model for Fetal Neural Ischemia Using Necrotic Core-Free Human Spinal Cord Organoids.

Fetal spinal cord ischemia is a serious medical condition that can result in significant neurological damage and adverse outcomes for the fetus. However, the lack of an appropriate experimental model has hindered the understanding of the pathology and the development of effective treatments. In our study, we established a system for screening drugs that affect fetal spinal cord ischemia using spinal cord organoids. Importantly, we produced necrotic core-free human spinal cord organoids (nf-hSCOs) by reducing the organoid size to avoid potential complications of spontaneous necrosis in large organoids. Exposing nf-hSCOs to CoCl2 as a hypoxia mimetic and hypoglycemic conditions resulted in significant neuronal damage, as assessed by multiple assay batteries. By utilizing this model, we tested chemicals that have been reported to exhibit beneficial effects in brain organoid-based ischemia models. Surprisingly, these chemicals did not provide sufficient benefit, and we discovered that rapamycin is a mild neuroprotective reagent for both axon degeneration and neuronal survival. We propose that nf-hSCO is suitable for large-scale screening of fetal neural ischemia due to its scalability, ease of ischemic induction, implementation of quantifiable assay batteries, and the absence of spontaneous necrosis.

Fetal cystic and solid tumor of the atrioventricular node: Autopsy diagnosis at 12 weeks of gestational age.

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.