Fetal therapies in congenital diaphragmatic hernia: a review of possibilities and practical challenges

Area of Science:

• Neonatal Medicine
• Developmental Biology
• Regenerative Medicine

Background:

• Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by pulmonary hypoplasia, leading to poor gas exchange and pulmonary hypertension.
• These pulmonary abnormalities significantly contribute to high mortality rates and long-term health issues in affected infants.
• Improving fetal lung development is a critical strategy for enhancing outcomes in CDH.

Purpose of the Study:

• To review current and emerging antenatal therapies for congenital diaphragmatic hernia.
• To evaluate the potential of pharmacologic agents and regenerative medicine approaches in addressing pulmonary hypoplasia.
• To highlight the need for novel strategies beyond current standards of care.

Main Methods:

• Review of existing literature on antenatal therapies for CDH, including surgical, pharmacologic, and regenerative approaches.
• Analysis of preclinical data from experimental CDH models investigating various therapeutic agents.
• Assessment of the evidence supporting Fetal Endoluminal Tracheal Occlusion (FETO) and its limitations.

Main Results:

• Fetal Endoluminal Tracheal Occlusion (FETO) has demonstrated improved survival in select CDH cases but has limitations in generalizability and impact on overall lung development.
• Pharmacologic agents, including corticosteroids and anti-inflammatory drugs, have been studied in experimental models with varying results.
• Regenerative medicine strategies, such as stem cell and extracellular vesicle administration, show promise for multi-targeted improvement of pulmonary hypoplasia.

Conclusions:

• While FETO offers benefits, complementary or alternative antenatal strategies are necessary for comprehensive treatment of CDH-related pulmonary hypoplasia.
• Pharmacologic interventions require further investigation for clinical application in CDH.
• Regenerative medicine approaches present a promising avenue for improving fetal lung development in CDH, with ongoing research focused on safety and efficacy.