Prenatal Diagnosis最新文献

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities (NDDRSB) is an extremely rare but severe disorder. Here, we describe the case of a 24-week-old fetus from a Chinese family with healthy parents. The fetus presented with hydrops fetalis and abnormal limb posturing. Chromosomal microarray analysis revealed that the fetus had a heterozygous 17p12 deletion, which is associated with hereditary neuropathy with liability to pressure palsies. Trio-based exome sequencing (ES) analysis revealed that the deletion was inherited from the father, who has a normal phenotype. Trio-based ES identified a novel nonsense variant (c.229C>T, p.Q77*) and a rare nonsense variant (c.325C>T, p.R109*) in the mediator complex subunit 11 (MED11) gene. Both parents were heterozygous carriers for one of the variants in MED11. This is the first study to report the presence of hydrops fetalis and abnormal limb posturing phenotypes in fetuses with MED11 variants. These results expand the prenatal phenotypic spectrum of NDDRSB, which is helpful for genetic counseling and early prenatal diagnosis of fetuses with ultrasound abnormalities. In addition, the novel c.229C>T variant expands the spectrum of MED11 variants.

Objective: We examined the role of myofibroblasts in regulating Cx43 and collagen structure in iatrogenic preterm amniotic membrane (AM) defects subjected to mechanical stimulation.

Method: Preterm AM specimens were collected from women undergoing planned preterm caesarean section after in utero intervention for correction of spina bifida by open fetal surgery (n = 4 patients; preterm delivery at 34 + 0 weeks to 35 + 0 weeks). Control specimens taken 5 cm away from the open fetal surgery defect site were compared with wound edge AM. In separate experiments, the effects of mechanical stimulation and co-treatment with Cx43 antisense on matrix and repair proteins were examined. Specimens were immunostained to detect αSMA and Cx43 in myofibroblasts and counterstained with DAPI to quantify nuclei shape. The direction of collagen fibrils in the wound edge region was examined by SHG imaging. Markers for matrix (collagen, elastin, GAG), inflammation (PGE₂) and repair (TGFβ₁) were examined by RT-qPCR and biochemical assays.

Results: In iatrogenic preterm AM specimens, the diameter of the open fetal surgery defect ranged between 3.5 and 7.5 cm. At the wound edge of the open fetal surgery defect, αSMA positive myofibroblasts had deformed nuclei and showed abundant Cx43 localized in the cell bodies or formed plaques. In the fibroblast layer, collagen had degenerated in some regions or had polarity near the wound edge. In preterm AM defects, mechanical stimulation and Cx43 antisense increased the levels of collagen and elastin but not GAG or PGE₂ release. Mechanical stimulation increased Cx43 and TGFβ₁ gene expression.

Conclusion: In open fetal surgery defects, myofibroblasts were elongated with collagen fibrils that either degenerated or had polarity. Whilst cells produced substantially higher Cx43 in the fibroblast than in the epithelial layer, they formed plaques, which may prevent migration and delay healing. Mechanical stimulation of preterm AM enhanced matrix repair proteins and the mechanotransduction should be explored to understand how Cx43 contributes to membrane integrity.

Background: Down syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level.

Methods: Amniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 17^3/7 and 24^0/7 weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites.

Results: Fifty differential metabolites, including L-glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS-DA model, FDR-adjusted p-value < 0.05, and |log₂FC| > log₂(1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS-DA model and FDR-adjusted p-value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00.

Conclusions: Our results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS.

Objective: This study aims to assess the diagnostic value of post-mortem radiographic imaging compared with prenatal ultrasound in suspected fetal skeletal dysplasias in a large Finnish cohort.

Method: Prenatal ultrasound findings and their association with post-mortem radiographic imaging were evaluated in a cohort of 36 fetuses with prenatally suspected skeletal dysplasia.

Results: Prenatal ultrasound performed well in detecting skeletal dysplasias and severe forms of the disease. Additional radiographic imaging was performed post-mortem in 16/27 terminated pregnancies. Post-mortem X-ray and 3D-CT detected several features not seen with US. They were superior to US in identifying spinal and thoracic anomalies and performed better in discovering fractures and deformities of long bones. In addition, disease-specific findings became more accurate with X-ray/CT, especially in the group of true skeletal dysplasias (14/18, 77.8%). Post-mortem X-ray and CT increased phenotypic data and facilitated interpretation of genetic findings.

Conclusion: Post-mortem X-ray and CT offer additional information supporting the diagnostic process. Detailed phenotypic data are important in interpreting the results of genetic analyses and in assessing the recurrence risk in future pregnancies. Complementary imaging methods including post-mortem radiography are therefore recommended.

Objective: To investigate the exome sequencing (ES) detection rate among fetuses with congenital anomalies and describe the rates in the setting of multiple versus isolated anomalies, perinatal autopsy, and family history of a previously affected child.

Methods: A single-center retrospective chart review was conducted on 397 anomalous fetuses that underwent ES from May 2012 through December 2023. Medical record review included demographics, imaging, and genetic testing.

Results: The overall ES diagnostic rate was 34.3%. The rate of diagnosis was 31.6% in fetuses with a single anomaly and 42.6% in fetuses with 4 or more major organ systems involved. Of the fetuses with a single anomaly, lymphatic, craniofacial, skeletal, and neurological anomalies had the highest diagnostic rate on ES. 38.6% of deceased fetuses who underwent autopsy had a genetic diagnosis. Additionally, families who had a previously affected child had a 45.5% diagnostic rate.

Conclusions: ES is an important tool that should be offered in pregnancies affected with congenital abnormalities or at the time of fetal demise or termination. The diagnostic rate of ES in the prenatal setting is also highly dependent on comprehensive phenotyping. With diagnostic ES results, reproductive technology and testing options are available in subsequent pregnancies.

Objective: Prenatal detection and genetic diagnosis of congenital upper limb anomalies is particularly challenging due to both anatomical and technological factors. Hereby, we present a cross-sectional description of clinical and genetic findings in a 188-patient cohort.

Method: In this retrospective study, we present 188 cases with prenatally or postnatally detected upper limb anomalies, either isolated, associated with other anomalies, or syndromic. Patients were examined in four tertiary care centers in South London and Kent from 2012 to 2023.

Results: Anomalies were prenatally detected in 158/188 patients (84%), with positional defects (37), polydactyly (34) and transverse defects (25) as the most frequent. 63/188 patients (58%) received a genetic diagnosis of aneuploidy (36), Copy Number Variant (9), or monogenic disorder (18). In 39 out of 103 prenatally tested patients (38%), this diagnosis was given prenatally, contributing to termination of the pregnancy in 23 cases.

Conclusion: Through a cross-sectional description of 188 cases with congenital upper limb anomalies, we discuss prenatal ultrasound detection (in terms of numbers and accuracy) and genetic diagnosis.

Objective: The aim of the current study was to reveal ultrasonographic and clinical features, prenatal-postnatal outcomes and prognostic risk factors of fetal volvulus.

Method: This retrospective study evaluated all cases of fetal volvulus diagnosed between 2018 and 2024 at the Perinatology center of Zeynep Kamil Women and Children Diseases Training and Research Hospital. In the vast majority of cases, the pediatric surgery team confirmed the conclusive diagnosis of volvulus during the postnatal period. The cohort was divided into two groups, the "survivor" and "deceased", in order to compare the outcome and to evaluate factors determining the outcome.

Result: A total of 26 cases of fetal volvulus were followed up in our perinatology center which were confirmed by postnatal pediatric surgery or autopsy. Termination of pregnancy in two cases and intrauterine fetal death in one case were observed. Twenty-three cases reached live birth. Preterm labor, fetal growth restriction, ascites and decreased intestinal peristalsis were significantly more common in the deceased group. Neonatal death in five cases (19.2%), infant death in four cases (15.3%) and short gut syndrome in three cases (11.5%) were long term outcomes.

Conclusion: Overall mortality rate may increase when fetal growth restriction, ascites, and decreased intestinal peristalsis are present with volvulus.