Fetal Diagnosis and Therapy最新文献

Background: Fetal cardiac interventions (FCI) represent a groundbreaking advancement in maternal-fetal medicine, offering therapeutic strategies to address congenital heart defects (CHDs) in utero.

Summary: The indications, techniques, complications, and outcomes of the three most reported foetal cardiac interventions, namely foetal aortic valvuloplasty, foetal pulmonary valvuloplasty, and foetal atrial septal intervention, were systematically reviewed based on the published literature. The challenges and future directions of this field was also highlighted.

Key messages: Foetal cardiac interventions open the therapeutic opportunity of several severe congenital heart diseases. However, the selection of cases for best outcome is yet to be refined due to lack of randomized controlled trial.

Introduction: In this study, we aimed to investigate the expression of nuclear Yes-associated protein (nYAP), a molecule involved in mechanotransduction, during fetal lung development in a novel ex vivo mouse model of congenital diaphragmatic hernia (CDH) lung hypoplasia.

Methods: Pregnant CD1 mice were gavaged nitrofen at E8.5 to induce CDH lung hypoplasia. At E16.5, fetal lungs were harvested and cultured ex-vivo for 72hrs with or without tracheal occlusion (hypo-TO and hypo, respectively). Age-matched normal fetal lung controls (norm-TO and norm) were evaluated in parallel. Whole lungs at E16.5+3 were analyzed for nYAP and markers of distal epithelial differentiation by immunohistochemistry and quantitative gene expression.

Results: There was robust nYAP expression in norm-TO lungs. Analysis of the distal lung parenchyma in normal and hypoplastic lungs showed enhanced epithelial nYAP expression in the distal airways of both norm-TO and hypo-TO lungs relative to their respective controls. Hypo lungs had the lowest expression of nYAP among the groups. There was significantly increased expression of both Ctgf and Cyr61 in hypo-TO lungs compared to hypo lungs without tracheal occlusion (Ctgf: 1.57±0.43 and 1.02±0.23, p=0.016; Cyr61: 1.60±0.34 and 1.01±0.17, p=0.003).

Conclusion: In this ex vivo model, tracheal occlusion upregulates nYAP in both control and hypoplastic lungs during the canalicular stage of development, suggesting a critical role of mechanosensory response molecule in CDH lung hypoplasia.

Introduction: Skeletal dysplasias are genetically heterogeneous disorders characterized by high diagnostic complexity and major perinatal impact. Under current diagnostic guidelines, chromosomal microarray remains the recommended first-tier test for fetal anomalies. However, in suspected skeletal dysplasias-where sequencing provides a markedly higher diagnostic yield-starting with chromosomal microarray testing may delay diagnosis. Recent advances in next-generation sequencing, along with the 2022 International Society of Skeletal Dysplasias classification, now allow for earlier and more precise evaluation. We present a case of life-limiting osteogenesis imperfecta diagnosed prenatally through exome-sequencing, highlighting its efficiency and diagnostic advantage over chromosomal microarray analysis.

Case report: A 24-year-old primigravida was assessed during first-trimester screening in Cartagena, Colombia. Ultrasound at 13 weeks revealed multiple fetal anomalies suggestive of skeletal dysplasia. Chorionic villus sampling was performed, and molecular analysis with Exome Sequencing identified a heterozygous substitution NM_000088.3:c.1291G>T (p.Gly431Cys) in COL1A1, located in the triple helix domain of type I collagen. This variant was absent from genomic databases and showed previously documented glycine substitutions, being classified as "likely pathogenic." The patient opted for legal termination of pregnancy, and fetal histopathology confirmed osteogenesis imperfecta.

Conclusions: This novel COL1A1 variant reinforces the role of glycine substitutions in osteogenesis imperfecta. While chromosomal microarray remains first-tier, ES offers a faster and more efficient pathway for diagnosing suspected skeletal dysplasias, enhancing early counseling in resource-limited settings.

Introduction Twin-twin transfusion syndrome (TTTS) may complicate triplet pregnancies with a monochorionic component; however, data on fetoscopic laser ablation (FLA) in this setting remain limited. This study evaluated perinatal outcomes in TTTS-affected triplet pregnancies with at least one monochorionic placenta treated with FLA, and compared these with monochorionic diamniotic (MC/DA) twin pregnancies. Methods We retrospectively reviewed 42 triplet pregnancies complicated by TTTS treated with FLA. Of these, 25 were dichorionic triamniotic (DC/TA, 59.5%) and 17 were monochorionic triamniotic (MC/TA, 40.5%). Antenatal, procedural, and neonatal outcomes were compared with those of 1072 MC/DA twin pregnancies treated with FLA at the same centre. Categorical and continuous variables were compared using the Chi-square/Fisher's exact test and Mann-Whitney U test, respectively; with p < 0.05 considered statistically significant. Proportions are presented with 95% confidence intervals, and subgroup analyses were considered exploratory. Results Quintero stage distribution did not differ significantly between cohorts, and gestational age (GA) at FLA was 20.3 weeks (IQR 18.7-22.3) in triplets and 20.4 weeks (IQR 18.4-23.1) in twins. Procedural complications in triplets were infrequent and did not differ significantly from twins. PPROM rates and laser time did not differ significantly. Survival of unaffected triplet was 88.1%. Among TTTS-affected pairs within triplets, dual neonatal survival was 61.9%, with at least one survivor in 85.7%. Dual survival was more frequent in MC/TA (70.6%) than in DC/TA (56.0%) triplets. Survival outcomes were not statistically different from those of MC/DA twins (dual: 70.1%, at least one 91.6%. The median GA at delivery was 31.8 weeks in triplets and 32.3 weeks in twins. Conclusions Triplet pregnancies with TTTS treated with FLA showed no statistically significant differences in antenatal and neonatal outcomes to MC/DA twins, with high survival rates and low complication rates reported.

Split cord malformation (SCM) is an uncommon congenital anomaly of the spinal cord in which the neural tube is longitudinally divided into two hemicords, separated by a fibrous, cartilaginous, or osseous septum. Historically described as diastematomyelia or diplomyelia, the current unified classification proposed by Pang et.al distinguishes two main subtypes: type I, characterized by two hemicords within separate dural sacs separated by a rigid spur, and type II, in which hemicords share a single dural sac and are separated by a fibrous band. Composite SCM, with multiple non-contiguous lesions, is exceedingly rare. Although SCM is most often recognized in childhood following neurological symptoms or cutaneous stigmata, advances in fetal ultrasonography and magnetic resonance imaging (MRI) now permit prenatal diagnosis. This shift carries significant implications for obstetric counseling, delivery planning, and multidisciplinary coordination of perinatal care. While surgical correction in infancy remains the mainstay of treatment, the increasing ability to detect SCM in utero has prompted discussion of fetal therapy. Unlike open spina bifida, however, SCM is primarily a tethering disorder rather than a defect of neural tube closure, and no evidence currently supports fetal intervention. This review summarizes embryology, classification, epidemiology, clinical features, diagnostic strategies, and management of SCM, with special emphasis on prenatal imaging, obstetric considerations, and future prospects for fetal therapy.

Introduction We present a case of spontaneous premature ductus arteriosus (DA) closure following modified interstitial laser ablation (ILA) of a giant chorangioma (GC) in a fetus with evidence of hydrops. Case presentation A 26-week ultrasound revealed a 10-cm GC in the posteriorly located placenta with signs of fetal hydrops, polyhydramnios, and elevated middle cerebral artery peak systolic velocity (MCA PSV) of 1.9 MoM. Preoperative fetal echocardiogram showed elevated combined cardiac output (753 ml/kg/min) without structural abnormalities. Modified ILA targeting the branches of the feeder artery with an extended-pulse technique (30 seconds at 40 Watts) followed by intrauterine fetal transfusion were performed without complications. On post-operative day (POD) 1, new onset of ductus venosus flow reversal was noted, which was attributed to post-procedural hemodynamics. Fetal echocardiography on POD 5 suggested constriction of DA; follow-up confirmed complete DA closure and secondary right heart dysfunction. The pregnancy was managed expectantly with at least weekly echocardiograms. Digoxin and hyperoxygenation for fetal heart failure did not change DA caliber. Acetaminophen and fluoxetine were discontinued without improvement. After an uncomplicated term cesarean delivery (indication: breech), the female neonate was discharged home on day of life 3. Currently, the child is 6 months old and healthy. Conclusion Modified ILA for GC followed by expectant management of associated DA closure yielded a term delivery with a favorable outcome.

Introduction: Fetoscopic endoluminal tracheal occlusion (FETO) has demonstrated neonatal survival and pulmonary hypertension benefits in patients with severe congenital diaphragmatic hernia (CDH). This study describes early childhood outcomes of patients treated with FETO compared to a contemporary cohort of non-FETO patients.

Methods: A single center, retrospective cohort study evaluated patients with a prenatal diagnosis of isolated severe left CDH at a single center from September 2016 through January 2023. Severe CDH was defined as liver herniation with an ultrasound observed/expected lung to head ratio < 30%. Outcomes were assessed by specialists within a multidisplinary follow up clinic and are reported as descriptive statistics.

Results: Twelve patients underwent FETO and 35 did not (non-FETO). Ninety-one percent of FETO and 75% of non-FETO patients survived to 24 months of age. Amongst surviving patients, 100% of FETO and 72% of non-FETO patients had a 24 month clinic follow up assessment. At that time, 45% of FETO patients and 33% of non-FETO patients were feeding exclusively by mouth. Nine percent of FETO, and 22% of non-FETO patients required respiratory support. No FETO patients required pulmonary hypertension (PH) medications while 22% of non-FETO patients required PH medications. Eighty-three percent and 57% of surviving FETO and non-FETO patients, respectively, had at least one neurodevelopment assessment during the 6,12, or 24 month time points. Despite higher frequency of prematurity amongst FETO patients, similar neurodevelopmental scores were observed in both groups.

Conclusions: FETO patients received pulmonary hypertension medications less frequently and had similar outcomes in feeding, respiratory management, and neurodevelopment as non-FETO patients.

Objective: To assess the longitudinal intrathoracic changes after pleuroamniotic shunting in fetuses with massive unilateral or bilateral hydrothorax.

Methods: The presence of intrafetal fluid effusions, and the observed/expected lung-to-head ratio (O/E-LHR) of both lungs were weekly evaluated in a cohort of fetuses with severe hydrothorax treated pleuro-amniotic shunting (PAS) in a single reference center in Mexico. Severe fetal hydrothorax was diagnosed as an accumulation of fluid within the fetal pleural space accompanied with severe bilateral lung compression, mediastinal shift, polyhydramnios, and/or hydrops. The longitudinal changes in intrafetal fluid effusions, and pulmonary growth were analyzed by survival and multilevel analysis against weeks after fetal intervention.

Results: Fifty-six pregnancies with severe fetal hydrothorax were treated with PAS at a median gestational age of 30.1 (range, 20.8-36.1) weeks. After shunting, all cases were longitudinally analyzed and in whom a total of 332 scans were performed (median 6, range 2-16). A complete disappearance of hydrops and hydrothorax was observed at a median interval of 1.6 and 5.9 weeks after PAS, respectively. A progressive increase in lung growth were observed, becoming normal O/E-LHR at on average 7.0 weeks after PAS.

Conclusion: Fetal pleuro-amniotic shunting promotes disappearance of all fetal fluid effusions, and a normalization of the pulmonary growth after fetal intervention.

Introduction: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) is the most severe form of α-thalassemia, typically caused by homozygous deletion of α-globin genes. However, rare non-deletional variants, such as Hemoglobin (Hb) Agrinio, can also produce a lethal phenotype.

Case presentation: We report a case of homozygous Hb Agrinio (HBA2:c.89T>C, p.Leu30Pro) diagnosed prenatally in a fetus of Bulgarian origin presenting with hydrops and severe anemia at 23 weeks of gestation. Following diagnosis, the pregnancy was managed with five intrauterine transfusions, resulting in resolution of hydrops and prolongation of pregnancy to term. The neonate was delivered at 37+3 weeks, required transient respiratory and cardiovascular support, and remains clinically stable at three months of age under regular transfusion therapy.

Conclusion: To our knowledge, this is only the second reported case of BHFS resulting from homozygous Hb Agrinio successfully managed with intrauterine transfusions, and uniquely, the first to achieve term delivery. This case highlights the importance of considering unstable α-globin variants in the differential diagnosis of unexplained fetal hydrops in an at risk population. Early diagnosis and timely intrauterine transfusions can significantly improve the perinatal outcomes in these cases.