先天性横隔膜ヘルニア

Maternal-fetal surgery has advanced rapidly, offering targeted prenatal interventions that can improve outcomes for conditions such as myelomeningocele, sacrococcygeal teratoma, congenital diaphragmatic hernia, lung lesions, lower urinary tract obstruction, and twin-twin transfusion syndrome. This review summarizes current fetal therapies, patient selection, contraindications, and maternal risks, emphasizing the need for multidisciplinary evaluation. Emerging innovations, including fetoscopic repair techniques, stem cell and gene-based therapies, and tissue engineering, highlight the expanding potential of fetal intervention. Ethical frameworks remain essential to ensure that maternal autonomy and safety are prioritized while pursuing fetal benefit.

Extracellular vesicles (EVs) are lipid bilayer-delimited nanoparticles released by cells to act as mediators of intercellular communication during organ development, injury, and repair. EVs carry cargo (bioactive proteins, lipids, and nucleic acids) that reflects the status of the parent cell and is transferred to recipient cells to regulate biological processes, such as inflammation, immune responses, and tissue regeneration. These properties have made EVs promising tools for investigating disease pathogenesis, improving diagnostic and prognostic accuracy, and developing cell-free regenerative therapies for conditions characterized by dysregulation of multiple biological pathways. EVs are particularly relevant in diseases that affect the pediatric population where pathogenesis often remains poorly understood, access to affected tissues is limited, and treatment options are frequently inadequate. This review summarizes current evidence on EV applications in fetal and neonatal disorders, including necrotizing enterocolitis, congenital diaphragmatic hernia, and bronchopulmonary dysplasia, and highlights emerging data in biliary atresia, spina bifida, short bowel syndrome, and Hirschsprung's disease. In this age group, human milk and amniotic fluid represent particularly attractive biologically accessible sources of EVs, combining therapeutic potential with feasibility of clinical application. Building on robust preclinical evidence, the field is now advancing toward clinical translation, but several aspects still need to be addressed such as cargo heterogeneity, scalability of production, dosing, biodistribution, safety, and regulatory standardization. Herein, we discuss the translational challenges and future directions that will shape the clinical application of EVs in perinatal conditions.

Congenital diaphragmatic hernia (CDH) is a rare anomaly with an incidence of 1 in 3000 live births and characterized by defective closure of the diaphragm, lung hypoplasia, and pulmonary vascular remodeling. Although several genes associated with the occurrence of CDH, no clear genetic component has been identified. Previously, we showed that CDH patients have vascular abnormalities already early in development, and that perivascular cells are affected in CDH. In the current study, we focused on early abnormalities in the nitrofen-induced CDH mouse model. Transcriptome analysis of FACS-sorted perivascular and endothelial cell populations from lungs of control and experimental mouse CDH revealed a high similarity in GO terms of differentially expressed genes (DEGs) between these populations, suggesting a disturbed interaction between endothelial cells and pericytes. The disturbed interaction is the basis for the aberrant development of the pulmonary vasculature in CDH. Furthermore, the RNA sequence data revealed reduced expression of the Kruppel like factor 4 (Klf4) gene in endothelial cells of CDH, which was confirmed with protein expression analysis. Furthermore, we show that KLF4 is an important up stream regulator of genes associated with vascular development and confirm that members of the NOTCH signaling pathway are differentially expressed, indicating that NOTCH signaling is disturbed in CDH. Collectively, our data support the importance of KLF4 in pulmonary angiogenesis and contribute to our previous data that pulmonary vessels in CDH patients are already affected before birth, which in turn may impact therapeutic strategies to reduce pulmonary hypertension associated with CDH.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a challenging neonatal surgical condition associated with significant morbidity and mortality. Thoracoscopic repair has emerged as a minimally invasive alternative to conventional open repair in selected patients. AIM: The aim of this study is to share our experience in the surgical management of CDH and to compare postoperative outcomes between thoracoscopic repair and open laparotomy. MATERIALS AND METHODS: A retrospective analysis of six patients with CDH managed surgically at a tertiary care center was performed. Demographic data, antenatal diagnosis, pulmonary arterial hypertension (PAH), surgical approach, ventilator requirement, initiation of enteral feeding, duration of analgesia, hospital stay, and follow-up outcomes were evaluated. RESULTS: All patients had left-sided Bochdalek hernias. Three patients underwent thoracoscopic repair, and three underwent open laparotomy. Thoracoscopic repair was associated with a reduced ventilator requirement, earlier initiation of enteral feeds, shorter duration of intravenous analgesia, and reduced hospital stay. One mortality occurred in the laparotomy group. No patient required extracorporeal membrane oxygenation (ECMO) or patch repair. Conclusion: Thoracoscopic repair of CDH, when performed in carefully selected patients, is safe and associated with improved short-term postoperative outcomes compared to open repair.

INTRODUCTION: The detrimental effect of congenital heart disease (CHD) on congenital diaphragmatic hernia (CDH) survival is well known. However, estimates of survival and of extracorporeal membrane oxygenation (ECMO) utilization in CDH associated with critical congenital heart defects (CCHD) have not been described. Accurate data will enable prognostication for prenatal counseling and possibly expansion of the indications for fetal intervention. METHODS: The Pediatric Health Information System (PHIS) was queried for all infants born with CDH between 2017-2023 using ICD-10 diagnostic codes for CDH, CHD, and CCHD. Pearson chi-square test and logistic regression were used to assess relationships between diagnostic codes and use of ECMO or mortality. RESULTS: There were 4,691 NICU admissions for CDH. Of these, 3,580 (76.3%) were also diagnosed with any CHD, and 488 (10.4%) with any CCHD. Patients diagnosed with CDH and CCHD were significantly more likely to die (52%, p <0.01) and undergo open cardiac repair (34.6%, p <0.01) upon index admission compared to those with isolated CDH. However, there were no significant differences in the use of ECMO cannulation, duration of ECMO or likelihood of CDH repair on ECMO. CONCLUSION: Despite similar rates of ECMO utilization, mortality in this cohort is 50%; more than three times the rate of the non-CCHD cohort. 75% of deaths in infants with CDH and CCHD occurred without ECMO, suggesting that ECMO may have been considered futile. These data have important ramifications for prenatal consultation and perhaps on the role of fetal intervention in this cohort with few other therapeutic options.