Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions.

PURPOSE: The purpose of this study was to evaluate the clinical performance of carrier screening for cystic fibrosis, hemoglobinopathies, and spinal muscular atrophy with reflex single-gene noninvasive prenatal screening (sgNIPS), which does not require paternal carrier screening. METHODS: An unselected sample of 9151 pregnant individuals from the general US pregnant population was screened for carrier status, of which 1669 (18.2%) were identified as heterozygous for one or more pathogenic variants and reflexed to sgNIPS. sgNIPS results were compared with newborn outcomes obtained from parent survey responses or provider reports for a cohort of 201 pregnancies. RESULTS: Overall, 98.7% of pregnant individuals received an informative result (no-call rate = 1.3%), either a negative carrier report or, if identified as heterozygous for a pathogenic variant, a reflex sgNIPS report. In the outcomes cohort, the negative predictive value of sgNIPS was 99.4% (95% CI = 96.0%-99.9%) and average positive predictive value (PPV) of sgNIPS was 48.3% (95% CI = 36.1%-60.1%). Importantly, personalized PPVs accurately reflected the percentage of affected pregnancies in each PPV range, and all pregnancies with a sgNIPS fetal risk of >9 in 10 (90% PPV) were affected. CONCLUSION: Although traditional carrier screening is most effective when used to assess reproductive risk before pregnancy, more than 95% of the time it is pursued during a pregnancy and is complicated by incomplete uptake of paternal carrier screening (<50%) and misattributed paternity (∼10%). Even in an idealized setting, when both partners have carrier screening, the maximum risk for having an affected pregnancy is 1 in 4 (equivalent of a 25% PPV). Carrier screening with sgNIPS during pregnancy is an alternative that does not require a paternal sample and provides accurate fetal risk in a timely manner that can be used for prenatal counseling and pregnancy management.

Corioamnionitis Histológica Asociada a Muerte Fetal / Histological Chorioamnionitis Associated with Fetal Death

INTRODUCCIÓN. Anualmente ocurren más de 2 millones de muertes fetales a nivel mundial, siendo fundamental el estudio anatomopatológico placentario para disminuir el número de muertes inexplicadas. OBJETIVO. Revisar la literatura existente acerca de corioamnionitis histológica, los criterios para establecer su diagnóstico, su presencia y posible asociación en estudios de causas de muerte fetal. METODOLOGÍA. Se realizaron búsquedas en bases de datos electrónicas para recopilar estudios de causas de muerte fetal que incluyeron corioamnionitis histológica. RESULTADOS. Se encontraron 13 estudios que evaluaron mortalidad fetal y que entre sus causas incluyeron corioamnionitis histológica. DESARROLLO. El estudio microscópico placentario en muertes fetales es esencial al investigar una muerte fetal. Las anomalías placentarias son la causa más común de muerte fetal, la corioamnionitis aguda es la lesión inflamatoria más frecuente. Se detallaron los criterios más relevantes para definir corioamnionitis aguda histológica pero aún no se establece un consenso. Estudios de causas de muerte fetal en años recientes han reportado corioamnionitis histológica entre 6,3% y 41,3% de casos. Las alteraciones inflamatorias del líquido amniótico son una causa importante de muerte fetal, siendo la corioamnionitis la más frecuente en este grupo. CONCLUSIÓN. En estudios para determinar las causas de muerte fetal se evidenció corioamnionitis aguda histológica en hasta el 41,3% de casos, por lo que podría estar asociada a dicho evento. Sin embargo, es necesario establecer un sistema de estadiaje de corioamnionitis histológica mediante un panel de expertos a nivel mundial.

INTRODUCTION. Annually more than 2 million fetal deaths occur worldwide, being fundamental the placental anatomopathological study to reduce the number of unexplained deaths. OBJECTIVE. To review the existing literature on histological chorioamnionitis, the criteria to establish its diagnosis, its presence and possible association in studies of causes of fetal death. METHODOLOGY. Electronic databases were searched to collect studies of causes of fetal death that included histologic chorioamnionitis. RESULTS. Thirteen studies were found that evaluated fetal mortality and that included histologic chorioamnionitis among their causes. DEVELOPMENT: Placental microscopic study in fetal deaths is essential when investigating a fetal death. Placental abnormalities are the most common cause of fetal death, acute chorioamnionitis being the most frequent inflammatory lesion. The most relevant criteria for defining histologic acute chorioamnionitis have been detailed but consensus has not yet been established. Studies of causes of fetal death in recent years have reported histologic chorioamnionitis in between 6,3% and 41,3% of cases. Inflammatory changes in the amniotic fluid are an important cause of fetal death, with chorioamnionitis being the most frequent in this group. CONCLUSIONS. In studies to determine the causes of fetal death, histological acute chorioamnionitis was evidenced in up to 41,3% of cases, so it could be associated with this event. However, it is necessary to establish a histological chorioamnionitis staging system by means of a worldwide panel of experts.

Fetal Organ Anomaly Classification Network for Identifying Organ Anomalies in Fetal MRI.

Rapid development in Magnetic Resonance Imaging (MRI) has played a key role in prenatal diagnosis over the last few years. Deep learning (DL) architectures can facilitate the process of anomaly detection and affected-organ classification, making diagnosis more accurate and observer-independent. We propose a novel DL image classification architecture, Fetal Organ Anomaly Classification Network (FOAC-Net), which uses squeeze-and-excitation (SE) and naïve inception (NI) modules to automatically identify anomalies in fetal organs. This architecture can identify normal fetal anatomy, as well as detect anomalies present in the (1) brain, (2) spinal cord, and (3) heart. In this retrospective study, we included fetal 3-dimensional (3D) SSFP sequences of 36 participants. We classified the images on a slice-by-slice basis. FOAC-Net achieved a classification accuracy of 85.06, 85.27, 89.29, and 82.20% when predicting brain anomalies, no anomalies (normal), spinal cord anomalies, and heart anomalies, respectively. In a comparison study, FOAC-Net outperformed other state-of-the-art classification architectures in terms of class-average F1 and accuracy. This work aims to develop a novel classification architecture identifying the affected organs in fetal MRI.

Pulmonary atresia with a ventricular septal defect and left pulmonary artery discontinuity: a case report.

BACKGROUND: Unilateral pulmonary artery discontinuity is a rare malformation that is associated with other intracardiac abnormalities. Cases accompanied by other cardiac abnormalities are often missed on prenatal echocardiography. The prenatal diagnosis of isolated unilateral pulmonary artery discontinuity can also be delayed. However, undiagnosed this malformation would have an effect on further prognosis. We report our case of a prenatal diagnosis of pulmonary atresia with ventricular septal defect and left pulmonary artery discontinuity. CASE PRESENTATION: A 33-year-old Asian woman visited our institution at 24 weeks of gestation because of suspected fetal congenital heart disease. Fetal echocardiography revealed a small atretic main pulmonary artery giving rise to the right pulmonary artery without bifurcation and the left pulmonary artery arising from the ductus arteriosus originating from the left subclavian artery. The neonate was delivered by cesarean section at 376/7 weeks of gestation. Postnatal echocardiography and multidetector computed tomography showed a right aortic arch, with the small right pulmonary artery originating from the atretic main pulmonary artery and the left pulmonary artery originating from the left subclavian artery. Patency of the ductus arteriosus from the left subclavian artery was maintained with prostaglandin E1. Right ventricular outflow tract reconstruction and pulmonary angioplasty with Gore-Tex graft patch was performed 25th day after birth. Unfortunately, the neonate died because of right heart failure 8 days postoperation. CONCLUSION: There is a possibility that both pulmonary arteries do not arise from the same great artery (main pulmonary artery or common arterial trunk). Therefore, clinicians should check the origin of both pulmonary arteries.

A review of application of stem cell therapy in the management of congenital heart disease.

Research on stem cells has been rapidly growing with impressive breakthroughs. Although merely a few of the laboratory researches have successfully transited to the clinical trial phase, the application of stem cells as a therapeutic option for some currently incapacitating diseases hold fascinating potentials. This review emphasis the various opportunities for the application of stem cell in the treatment of fetal diseases. First, we provide a brief commentary on the common stem cell strategy used in the treatment of congenital anomalies, thereafter we discuss how stem cell is being used in the management of some fetal disorders.

Melatonin treatment in fetal and neonatal diseases.

This literature review aims to address the main scientific findings on oxidative stress activity in different gestational disorders, as well as the function and application of melatonin in the treatment of fetal and neonatal changes. Oxidative stress has been associated with the etiopathogenesis of recurrent miscarriages, preeclampsia, intrauterine growth restriction, and stillbirth. Both, the exacerbated consumption of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and the increased synthesis of reactive oxygen species, such as superoxide, peroxynitrite, and hydrogen peroxide, induce phospholipid peroxidation and endothelial dysfunction, impaired invasion and death of trophoblast cells, impaired decidualization, and remodeling of maternal spiral arteries. It has been postulated that melatonin induces specific biochemical responses that regulate cell proliferation in fetuses, and that its antioxidant action promotes bioavailability of nitric oxide and, thus, placental perfusion and also fetal nutrition and oxygenation. Therefore, the therapeutic action of melatonin has been the subject of major studies that aim to minimize or prevent different injuries affecting this pediatric age group, such as intrauterine growth restriction, encephalopathy, chronic lung diseases, retinopathy of prematurity Conclusion: the results antioxidant and indicate that melatonin is an important therapy for the clinical treatment of these diseases.

Twin Reversed Arterial Perfusion Sequence: Assessing the Role of the Correct Imaging Modality in a Rare Clinical Entity.

Acardiac twin formation is a rare anomaly. It is one of the most extreme complications of monozygotic twin pregnancies. Such occurrences are brought about when a normal twin donates blood to an abnormal twin through its umbilical arteries via vascular anastomoses at the level of the placenta, which is termed as twin reversed arterial perfusion sequence (TRAPS). Twin reversed arterial perfusion sequence is considered a rare variant of twin-to-twin transfusion syndrome. Due to the considerable blood transfer from the healthy twin to the parasitic one, cardiac failure can ensue in the healthy twin. The mortality of the acardiac twin is 100%. We present an obstetric case of a South Asian female, whose serial ultrasound scans consistently displayed a heterogeneous mass, initially labeled a teratoma. This was postoperatively diagnosed as an acardiac twin due to TRAPS. Thus, we would like to highlight the importance of umbilical artery Doppler in the prompt diagnosis of TRAPS so timely management may be undertaken to prevent morbidity and/or mortality of the normal twin.

Normal Intracranial Translucency Values During the First Trimester of Gestation in a Latin American Population.

OBJECTIVES: The purpose of this study was to establish intracranial translucency reference values in healthy fetuses from a Latin American population. METHODS: This work was a cross-sectional retrospective correlational study. A review of sonographic reports from women between gestational ages of 11 weeks and 13 weeks 6 days at 2 health institutes in Bogota, Colombia, whose fetuses had a crown-rump length of 45 to 84 mm was conducted between January 1, 2010, and December 31, 2012. Women with multiple fetuses or with a deceased fetus were excluded. RESULTS: Data corresponding to 1520 obstetric sonographic examinations were included in the statistical analysis. The crown-rump length was between 45 and 84 mm, with a median of 65 mm (interquartile range, 58-73 mm). The median intracranial translucency was 1.7 mm (interquartile range, 1.4-2.2 mm). Different percentiles (1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th) were established for each crown-rump length value. A correlation between crown-rump length and intracranial translucency was found, which seemed to be linear. The intracranial translucency value was not significantly correlated with the frontomaxillary angle but was correlated with nuchal translucency, nasal bone length, and metopic suture length. CONCLUSIONS: We present normal intracranial translucency values in the first trimester of single gestations with live fetuses in a Latin American population. These values are similar to those described in other populations. The intracranial translucency value was linearly correlated with crown-rump length in fetuses between gestational ages of 11 weeks and 13 weeks 6 days, which is consistent with previous publications, although these data cannot be interpreted independently.

Prenatal and Postnatal MR Findings of a Congenital Hemangioma: A Case Report

Hemangiomas are common benign soft tissue tumors found in pediatrics. Knowledge of prenatal image findings for hemangiomas can be essential for ensuring optimal antepartum and postpartum care. In this study, we provide a report the MR findings of a congenital hemangioma in the posterior neck region, which was different from the pre and postnatal image findings as well as a literature review.