Prenatal Diagnosis最新文献

Objective: To evaluate phenotype and genotype characteristics of fetuses and children with upper limb anomalies.

Method: Retrospective cohort study of a prenatal and postnatal cohort with upper limb anomalies from January 2007 to December 2021 in a Fetal Medicine Unit. Prenatally on ultrasound suspected upper limb anomalies, such as transverse and longitudinal reduction defects, polydactyly, and syndactyly, and postnatally identified children referred to the Congenital Hand Team were evaluated separately.

Results: The prenatal group included 199 pregnancies: 64 transverse and 19 longitudinal reduction defects, 103 polydactylies, and 13 cases with syndactyly. The majority of cases with longitudinal reduction defects (n = 10, 52.6%), polydactyly (n = 62, 60.2%), and syndactyly (n = 10, 76.9%) were non-isolated, as opposed to transverse reduction defects, which were generally isolated (n = 41, 64.1%). The postnatal cohort included 362 children with upper limb anomalies with 49 transverse and 22 longitudinal reduction defects, 226 polydactylies, and 65 syndactylies. Chromosomal or monogenic abnormalities were identified in 76/199 (38.2%) cases of the prenatal cohort and in 31/362 (8.6%) cases of the postnatal cohort.

Conclusion: Prenatal identification of minor defects of the digits is a challenge, with more postnatal than prenatal cases. The majority of cases with isolated anomalies in both groups had no underlying chromosomal or monogenic cause, nor were they associated with a syndrome, as compared to the non-isolated cases. Conducting structural anomaly scans and genetic counseling are crucial to assess the risk of genetic abnormalities.

Objective: To explore the personal experiences of women faced with the decision to continue a triplet pregnancy or undergo multifetal pregnancy reduction.

Methods: A qualitative study with semi-structured interviews was conducted between October 2021 and April 2023. Participants included women who continued a triplet pregnancy, and those who underwent multifetal pregnancy reduction from triplet to twins or singletons, 1-6 years post-decision. Interviews focused on: (1) the decision-making process, and (2) the emotional aspects and psychological impact of the decision. Thematic analysis was used to identify patterns, involving familiarization, defining themes, and producing the final report.

Results: Data saturation was achieved after 16 interviews, revealing two main themes: (1) maternal intuition as a guiding force, and (2) navigating the crossroads: coping and reflection on the decision. These themes illustrate an interplay between maternal intuition and intrinsic feelings in the decision whether to perform multifetal pregnancy reduction, seemingly less influenced by external factors. Mothers who adhere to their intuition (15/16) have a low likelihood of experiencing regret. Despite the inclination to share and seek support, a persistent taboo surrounds the topic of multifetal pregnancy reduction. The findings also emphasize a considerable gap in aftercare for women, regardless of their decision.

Conclusion: There is a need for improved care and support for parents facing the decision of continuing a triplet pregnancy or deciding on multifetal pregnancy reduction. Efforts should focus on fostering open societal dialog about this taboo subject, and addressing the gap in aftercare to provide comprehensive support to women post-decision and post-birth, thereby establishing a more supportive and compassionate framework.

Fetal lower urinary tract obstruction (LUTO) encompasses a spectrum of rare congenital anomalies affecting the fetal urinary system, leading to significant morbidity and mortality. This condition, arising from various anatomical anomalies such as posterior urethral valves (PUV), urethral atresia, and cloacal malformations, disrupts normal urine flow, resulting in secondary complications such as pulmonary hypoplasia and renal impairment. Current management strategies, including fetal vesicoamniotic shunting (VAS) and fetal cystoscopy, aim to alleviate obstruction and mitigate associated risks. While VAS has been a longstanding intervention, fetal cystoscopy presents a promising alternative by enabling direct visualization and targeted treatment of urinary tract obstructions. However, fetal cystoscopy is not without challenges, including technical complexities and risks associated with invasive procedures. This review explores the rationale, indications, technical considerations, outcomes, and future innovations of fetal cystoscopy in managing LUTO. It highlights the critical role of accurate diagnosis, patient selection, and procedural expertise in optimizing fetal and maternal outcomes. Despite existing challenges, ongoing advancements in technology and clinical practice hold the potential for further enhancing the safety and efficacy of fetal cystoscopy, underscoring its evolving role in prenatal care.

Objective: This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT.

Method: We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked.

Results: A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p < 0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5 Mb in size, and nine (13.85%) were between 5 and 10 Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p < 0.05).

Conclusions: Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

Variants of the ACTG2 gene cause autosomal dominant ACTG2 visceral myopathy, a disorder of smooth muscle dysfunction of the bladder and gastrointestinal system. Bladder involvement can behave as fetal megacystis (FM). We report four prenatal cases of ACTG2 visceral myopathy. All four cases presented with FM identified by ultrasound in the second trimester. All had invasive genetic investigations during pregnancy, and trio exome sequencing revealed likely pathogenic or pathogenic ACTG2 variants in the fetuses. Three of the four variants were de novo, and one was inherited form mother who had symptoms of smooth muscle dysfunction since childhood. ACTG2 visceral myopathy is the most concern in fetuses with isolated second-trimester megacystis. Genetic diagnosis of single gene disorders associated with FM is useful in parental counseling, pregnancy management and risk assessment of recurrence in future pregnancy.

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.