Congenital diaphragmatic hernia (CDH) is a devastating condition characterized by incomplete closure of the diaphragm and herniation of abdominal organs into the chest. As a result, fetuses have pulmonary hypoplasia, whose severity is the main determinant of poor outcome. The pathogenesis of pulmonary hypoplasia secondary to CDH is at least in part explained by lack or dysregulation of miRNAs that are known to regulate lung developmental processes. Herein, we report that intra-amniotic administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC-EVs) rescues lung growth and maturation in a fetal rat model of CDH. To understand which fetal lung cells and biological pathways are affected by AFSC-EVs, we conducted whole lung single nucleus RNA-sequencing. We discovered that CDH lungs have a multilineage inflammatory signature with macrophage enrichment, and confirmed these findings in autopsy samples of lungs from human fetuses with CDH. Transcriptomic analysis of CDH fetal rat lungs also showed that AFSC-EV treatment reduced macrophage density and inflammation to normal levels. Analyzing the miRNAs contained in the AFSC-EV cargo with validated mRNA targets, we found that the downregulated genes in AFSC-EV treated CDH lungs were involved in inflammatory response and immune system processes. This study reports a single cell atlas of normal and hypoplastic CDH fetal rat lungs and provides evidence that AFSC-EVs restore lung development by addressing multiple pathophysiological aspects of CDH.

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Congenital mature teratomas of the umbilical cord are extremely rare. We report on a girl who presented with a ruptured omphalocele and a 7 cm mass connected to the umbilicus, which we resected on the first day of life. Histology revealed mature umbilical cord teratoma . On the 29th day of life, a secondary laparotomy was necessary to address the associated intestinal malformations (megaduodenum, stenotic small bowel with duplication and malrotation). After a prolonged hospital stay, we discharged the patient in age-appropriate conditions. Antenatal diagnosis of an umbilical cord tumor can be challenging in the presence of an omphalocele. Given the high prevalence of associated malformations, the finding of umbilical cord teratoma should be followed by a detailed and comprehensive neonatal workup for additional abnormalities.

Introduction: The etiology of congenital diaphragmatic hernia (CDH) remains unknown and only 10-30% of patients have a genetic cause. Seasonal variation is known to contribute to the development of some congenital anomalies. Our aim was to investigate whether CDH births have seasonal variation. Material and Methods: A literature review was conducted for CDH and seasonality. Moreover, data from the CDH International Patient Registry Database were collected for babies with due dates between 2008 and 2014. Due dates were used to determine seasonal distribution of births. Birth rates per month in USA and Canada were extracted from publicly available databases. Data were analyzed using ANOVA and contingency tables. Results: Firstly, the literature review revealed 11 articles, of which 3 were eligible for inclusion. These studies reported conflicting results on seasonality of CDH. Secondly, we extracted due dates from the CDH International Patient Registry Database (1,259 patients) and found that there were fewer due dates in winter months (12.1±4 patients/month) than in summer (16.7±6 patients/month; p=0.011) and fall months (16.3±5 patients/month; p=0.022). Although this trend was similar to that of all births in USA and Canada, a lower incidence was observed in winter for CDH babies (20.2%) than for the general population (24.1%, p= 0.0012). CDH survival rate did not vary by season. Conclusions: This study provides evidence for a seasonal variation of CDH births. No causative link was established between CDH development and seasonality. Population-based studies with a focus on exposome data are needed to explain seasonal variation in CDH.