Prenatal Diagnosis最新文献

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: 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.

Objectives: To determine the additional detection rate (DR) and the residual risk (RR) of combined cell-free DNA (cfDNA) screening for aneuploidies (not including copy number variants) and 25 dominant single-gene disorders (SGD) in pregnancies with sonographic abnormalities.

Method: One hundred sixteen singleton pregnant women with abnormal fetal ultrasounds from week 12 were included in the study. They underwent combined cfDNA analysis, while exome sequencing and karyotyping were performed as reference standards. The results of the cfDNA analysis were compared with diagnostic genetic tests.

Results: The positive rate of cfDNA analysis was 15/116 (12.9%), with a positive predictive value of 13/15 (86.7%). The incremental DR of combined cfDNA screening for aneuploidies and 25 SGD compared with cfDNA testing for aneuploidies in fetuses with sonographic anomalies was 22.9%. The RR of cfDNA analysis for aneuploidies and pathogenic/likely pathogenic gene variants, after excluding cfDNA testing-detectable findings, was 2/101 (2.0%). The DR of cfDNA analysis for genetic aberrations in pregnancies with abnormal ultrasound was 13/35 (37.1%) compared with diagnostic testing.

Conclusion: In fetuses with sonographic anomalies, the additional DR of combined cfDNA analysis for aneuploidies and 25 SGD was remarkable at 22.9% compared with cfDNA testing for aneuploidies; the overall RR of combined cfDNA analysis was approximately 2.0%. It is essential to provide detailed genetic counseling before using cfDNA analysis in these pregnancies.

Objective: This study explored prenatal ultrasound markers in patients with anorectal malformations (ARMs).

Methods: All patients treated for ARM in our institution from January 2014 to December 2021 with an available expert fetal anomaly scan (eFAS) were reviewed. The eFAS images were assessed to evaluate the fetal anus, specifically by identifying hyperechoic anal mucosa surrounded by hypoechoic anal sphincter, referred to as "target sign" (TS). Furthermore, indirect signs of ARM were assessed and correlated with postnatal clinical symptoms.

Results: Of the 115 patients treated for ARM, 32 mothers underwent eFAS. TS was assessed in 22 fetuses, of which 17 (77.3%) had an absent or abnormal TS. Of the patients with a postnatally confirmed complex type of ARM, 90% had an absent or abnormal TS. One or more indirect signs of ARM were found in 16 out of 32 fetuses (50.0%), comprising echogenic bowel (n = 3), echogenic meconium (n = 2), dilated intestines (n = 7), echo-lucent cavity behind the urinary bladder (n = 4), abnormal external genitalia (n = 6), and polyhydramnios (n = 5).

Conclusion: This retrospective cohort study provides valuable insights into the potential role of TS assessment and indirect signs in the prenatal diagnosis of ARM. Future studies should further validate our findings and elicit whether TS assessment should be incorporated into prenatal screening protocols.