Fetoscopic Endoluminal Tracheal Occlusion-Synergic Therapies in the Prenatal Treatment of Congenital Diaphragmatic Hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a relatively rare and severe developmental disease. Even with the most recent multidisciplinary therapies, the risk for neonatal mortality and morbidity remains high. Recent advancements in prenatal treatments, alongside experimental and clinical data, suggest that fetoscopic endoluminal tracheal occlusion (FETO) promotes lung development and offers a promising strategy against lung hypoplasia and pulmonary hypertension. It is the only existing direct mechanical therapy that intervenes in the regulation of pulmonary pressure. Its influence on lung development also interferes with tissue homeostasis and cell differentiation; it also enhances inflammation and apoptosis. Its physiopathology on cellular and molecular levels is still poorly understood. Unfortunately, the procedure also carries significant pregnancy-, maternal-, and fetus-related risks. Assessing a multifaceted intervention requires a collective view of all aspects. This scoping review uncovers potential materno-fetal procedure-related risks and highlights innovative solutions. Future research on lung development therapies in CDH may focus on the "dual hit" mechanism, combining molecular-targeting drugs and regenerative medicine with the mechanical nature of FETO for synergistic effects.

Keywords: congenital diaphragmatic hernia; fetoscopic endoluminal tracheal occlusion; lung development; materno-fetal; preterm birth; regenerative medicine.

Figure 1

Risks and complications associated with fetoscopic endoluminal tracheal occlusion (FETO), and potential synergistic treatments and improvements. Abbreviations: iPPROM—iatrogenic preterm prelabor rupture of membranes, PB—preterm birth, GI—gastrointestinal, PDE—phosphodiesterase.

Figure 2

Main FETO-associated molecular alterations. Abbreviations: Fgf10—fibroblast growth factor 10, FgfR2—fibroblast growth factor receptor 2, Spry2—Sprouty homolog 2, KGF—keratinocyte growth factor, EGFR—epithelial growth factor, RhoA—Ras homolog family member A, VEGF—vascular endothelial growth factor, TGF-β—transforming growth factor β, YAP—Yes-associated protein, STAT3—signal transducer and activator of transcription 3, IL—interleukin, DAMPs—damage associated molecular patterns, HSP—heat shock protein, ATP—adenosine triphosphate, TNF-α—tumor necrosis factor α, ROS—reactive oxygen species, miR—microRNAs, “+”—activation, “↑”—upregulation, “↓”—downregulation.