Extracellular Vesicles and Their miRNA Content in Amniotic and Tracheal Fluids of Fetuses with Severe Congenital Diaphragmatic Hernia Undergoing Fetal Intervention

Infants with congenital diaphragmatic hernia (CDH) are at high risk of postnatal mortality due to lung hypoplasia and arterial pulmonary hypertension. In severe cases, prenatal intervention by fetal endoscopic tracheal occlusion (FETO) can improve survival by accelerating lung growth. However, postnatal mortality remains in the range of about 50% despite fetal treatment, and there is currently no clear explanation for this different clinical response to FETO. We evaluated the concentration of extracellular vesicles (EVs) and associated microRNA expression in amniotic and tracheal fluids of fetuses with CDH undergoing FETO, and we examined the association between molecular findings and postnatal survival. We observed a higher count of EVs in the amniotic fluid of non-survivors and in the tracheal fluid sampled in utero at the time of reversal of tracheal occlusion, suggesting a pro-inflammatory lung reactivity that is already established in utero and that could be associated with a worse postnatal clinical course. In addition, we observed differential regulation of four EV-enclosed miRNAs (miR-379-5p, miR-889-3p; miR-223-3p; miR-503-5p) in relation to postnatal survival, with target genes possibly involved in altered lung development. Future research should investigate molecular therapeutic agents targeting differentially regulated miRNAs to normalize their expression and potentially improve clinical outcomes.

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Prenatal Diagnosis and Management of a Rare Central Tendon Defect Type of Congenital Diaphragmatic Hernia with a Massive Pericardial Effusion

Case Reports in Obstetrics and Gynecology ◽

10.1155/2020/6798253 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Inas Babic ◽

Haifa Al-Jobair ◽

Osama Al Towaijri ◽

Huda Al-Shammary ◽

Merna Atiyah ◽

...

Keyword(s):

Pericardial Effusion ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Neonatal Morbidity ◽

Lung Hypoplasia ◽

Defect Type ◽

Tendon Defect ◽

Prenatal Diagnostic ◽

Large Pericardial Effusion ◽

Prenatal Intervention

The central tendon defect type of congenital diaphragmatic hernia (CDH) is extremely rare and usually associated with a significant pericardial effusion. Prenatal diagnostic ultrasound features of this quite rare entity remain often overlooked or misdiagnosed. There is a dearth of literature about the role of prenatal intervention, often through an elective pericardiocentesis, for the prevention of lung hypoplasia and to decrease the overall neonatal morbidity and mortality. To the best of our knowledge, till date, there is only one case that was subjected to a prenatal intervention. Here, we present a second case of a central tendon defect type of CDH with a large pericardial effusion that was subjected to a prenatal transthoracic pericardiocentesis. Although smooth intubation and ventilation were performed immediately after birth, the infant suffered for several months from respiratory instability. Laparoscopic central tendon hernia repair was performed, and neonate was discharged home at seven months of age. Although prenatal pericardiocentesis may facilitate smoother postnatal intubation and ventilation, its broader effect on respiratory function is uncertain and still remains elusive.

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Antenatal prediction of lung volume and in-utero treatment by fetal endoscopic tracheal occlusion in severe isolated congenital diaphragmatic hernia

Seminars in Fetal and Neonatal Medicine ◽

10.1016/j.siny.2008.08.010 ◽

2009 ◽

Vol 14 (1) ◽

pp. 8-13 ◽

Cited By ~ 66

Author(s):

Jan A. Deprest ◽

Andreas W. Flemmer ◽

Eduard Gratacos ◽

Kypros Nicolaides

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Lung Volume ◽

In Utero ◽

Tracheal Occlusion

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OC37: The hyperoxygenation test for fetal pulmonary artery reactivity before and after in utero unplugging in fetuses with severe congenital diaphragmatic hernia that underwent fetoscopic endoluminal tracheal occlusion

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.2897 ◽

2006 ◽

Vol 28 (4) ◽

pp. 369-370

Author(s):

E. Done ◽

J. Jani ◽

D. Van Schoubroeck ◽

A. Debeer ◽

J. Deprest

Keyword(s):

Pulmonary Artery ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

In Utero ◽

Tracheal Occlusion ◽

Before And After

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Knowledge Gaps in the Fetal to Neonatal Transition of Infants With a Congenital Diaphragmatic Hernia

Frontiers in Pediatrics ◽

10.3389/fped.2021.784810 ◽

2021 ◽

Vol 9 ◽

Author(s):

Philip L. J. DeKoninck ◽

Emily J. J. Horn-Oudshoorn ◽

Ronny Knol ◽

Kelly J. Crossley ◽

Irwin K. M. Reiss

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Transition Period ◽

Adverse Outcomes ◽

Lung Hypoplasia ◽

Future Research ◽

Knowledge Gaps ◽

Physiological Adaptations ◽

Interesting Approach ◽

Neonatal Transition

Clinical research for infants born with a congenital diaphragmatic hernia (CDH) has until recently mainly focused on advances in prenatal and postnatal treatment. However, during the early perinatal transition period there are major physiological adaptations. For most infants these changes will happen uneventfully, but for CDH infants this marks the beginning of serious respiratory complications. In recent years, there is emerging evidence that the clinical management during the perinatal stabilization period in the delivery room may influence postnatal outcomes. Herein, we discuss major knowledge gaps and novel concepts that aim to optimize fetal to neonatal transition for infants with CDH. One such novel and interesting approach is performing resuscitation with an intact umbilical cord, the efficacy of this procedure is currently being investigated in several clinical trials. Furthermore, close evaluation of neonatal physiological parameters in the first 24 h of life might provide early clues concerning the severity of lung hypoplasia and the risk of adverse outcomes. We will provide an overview of trending concepts and discuss potential areas for future research.

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Congenital Diaphragmatic Hernia: More than Just a Lung Problem

Austin Journal of Surgery ◽

10.26420/austinjsurg.2021.1274 ◽

2021 ◽

Vol 8 (4) ◽

Author(s):

Emam D ◽

◽

Van der Veeken L ◽

El Badry A ◽

Elattar A ◽

...

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Lung Hypoplasia ◽

Short Term ◽

Mortality And Morbidity ◽

Abdominal Organs ◽

Increased Risk ◽

Prenatal Intervention ◽

The Cost ◽

Neurodevelopmental Problems

Congenital Diaphragmatic Hernia (CDH) is a rare congenital anomaly characterized by a defect in the diaphragm, which permits abdominal organs to herniate into the thorax. This causes lung hypoplasia and at birth, children with CDH experience respiratory distress and pulmonary hypertension. Despite optimal neonatal treatment, CDH is still associated with a high mortality and morbidity. In severe cases, Fetal Intervention (FETO) may alter the natural course of this disease. Herein we describe the rationale, action mechanism and technique to perform this intervention. Despite hope giving results, this technique remains investigational for left sided CDH. However, an increased survival may come at the cost of increased morbidity. Children born with CDH are at increased risk for long and short-term morbidity, including neurodevelopmental problems. Until now, there are still uncertainties about the severity and prevalence of neurologic morbidity. Furthermore, it remains uncertain if these problems are already present prenatally and if a prenatal intervention influence this.

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Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.2.769 ◽

1999 ◽

Vol 87 (2) ◽

pp. 769-775 ◽

Cited By ~ 39

Author(s):

Yoshihiro Kitano ◽

Paul Davies ◽

Daniel von Allmen ◽

N. Scott Adzick ◽

Alan W. Flake

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Rat Model ◽

Weight Ratio ◽

Lung Parenchyma ◽

Lung Hypoplasia ◽

Lung Growth ◽

Lung Weight ◽

Pregnant Rats ◽

Tracheal Occlusion

Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death ( day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.

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