Semin Fetal Neonatal Med
. 2025 Aug 22:101656.
doi: 10.1016/j.siny.2025.101656. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/40877055/
Fetal therapies in congenital diaphragmatic hernia: a review of possibilities and practical challenges
Adriana Dekirmendjian 1, Fabian Doktor 2, Lina Antounians 2, Augusto Zani 3
Affiliations Expand
- PMID: 40877055
- DOI: 10.1016/j.siny.2025.101656
Abstract
Congenital diaphragmatic hernia (CDH) is characterized by pulmonary hypoplasia. CDH lungs exhibit an inflammatory signature with impaired growth, maturation, and vascularization, which postnatally result in altered gas exchange and pulmonary hypertension. These pulmonary abnormalities are drivers of poor survival and long-term morbidity. Improving lung development before birth remains a key strategy to enhance outcomes, and several antenatal therapies have emerged to address this need. These include surgical procedures, pharmacologic agents, and regenerative approaches. Fetal Endoluminal Tracheal Occlusion has shown the most robust evidence, improving survival in selected CDH cases. However, concerns about its generalizability, complications, and its limited effect on overall lung development have underscored the need for complementary or alternative strategies. A wide range of pharmacologic agents, some of which are in clinical use while others remain experimental, has been studied in experimental CDH models, such as corticosteroids, anti-inflammatory drugs and vasoactive medications. In parallel, regenerative medicine strategies via the antenatal administration of stem cells or their derivatives (extracellular vesicles) offer promise through multi-targeted mechanisms that address several aspects of pulmonary hypoplasia. Encouraging preclinical results provide a promising basis for advancing these regenerative therapies toward clinical application, with ongoing investigations focused on establishing their safety, efficacy, and feasibility.
Keywords: Exosome; Fetal surgery; Pediatric surgery; Pulmonary hypertension; Pulmonary hypoplasia.
Copyright © 2025. Published by Elsevier Ltd.
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