RARE DISEASE
Congenital diaphragmatic hernia
Congenital diaphragmatic hernia
Congenital diaphragmatic hernia
Synonyms: CDH
Synonyms: CDH
Synonyms: CDH
Drug discovery
2
drugs
With orphan designations
Overview
Congenital Diaphragmatic Hernia (CDH) is a congenital defect characterized by incomplete diaphragm formation, allowing abdominal organs to herniate into the chest. This impairs pulmonary development, leading to pulmonary hypoplasia, hypertension, and respiratory failure. Prenatal diagnosis via ultrasound/MRI enables risk stratification. Management includes fetal endoscopic tracheal occlusion (FETO) for severe cases, postnatal stabilization with gentle ventilation, ECMO, and delayed surgical repair. Long-term complications include chronic lung disease, reflux, and neurodevelopmental delays [1][5][13].
Therapies
Prenatal: FETO for severe CDH (improves lung growth via tracheal occlusion) [1][8][16].
Postnatal: Gentle ventilation, inhaled nitric oxide, ECMO (used in 25–30% of cases), and delayed surgical repair after cardiorespiratory stabilization [3][13][17].
Long-term: Multidisciplinary follow-up for pulmonary, nutritional, and neurodevelopmental sequelae [1][6][19].
Categories: rare abdominal surgical diseases, rare developmental anomalies during embryogenesis, rare respiratory diseases, rare surgical thoracic diseases
Research Papers
2,240 drug discovery papers about Congenital diaphragmatic hernia, with 7 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,240 drug discovery papers about Congenital diaphragmatic hernia, with 7 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-06 | Bioprinting of BSA membranes with C2C12 and NIH 3T3 pre-cellularized PLGA microscaffold : a step toward diaphragmatic hernia patches.
The diaphragm is a physical barrier separating the thoracic and abdominal cavities. Its physiological function is fundamental to pulmonary ventilation. Congenital diaphragmatic hernia (CDH) is a malformation that leaves a hole in the diaphragm during fetal development. Synthetic nondegradable membranes are currently used for the repair of diaphragm holes. However, these membranes do not help cells to adhere and proliferate. There is a need for biodegradable membranes composed of muscular and fibroblast cells to replicate a simplified diaphragmatic tissue. We thus developed a biocompatible and biodegradable salt-compacted albumin membrane. C2C12 myoblasts were bioprinted as central spokes, surrounded by a ring of NIH 3T3 fibroblasts, onto albumin membranes. We used bioink based on methacrylated collagen and hyaluronic acid, containing porous poly(D,L-lactic-co-glycolic acid) solid microscaffolds to protect myoblast and fibroblast cells against mechanical stress during extrusion printing. We found that metabolic activity of C2C12 myoblast increased by 215% in the presence of a polylysine-coated microscaffolds, compared to those cultured without microscaffolds. Microscaffolds loaded with C2C12 and NIH 3T3 cells increased viability (30% and 15%) and cell activity (527% and 567%) either after co-culture (5.6% increased viability and 588% cell activity) bioprinting on albumin membrane, compared to cells in bioink without microscaffolds. Cell-loaded microscaffolds embedded in bioink enhance C2C12 to NIH3T3 cross-migration on albumin membrane. This work is a preliminary proof of concept of cellularization of myoblasts and fibroblasts by extrusion bioprinting on a new biodegradable albumin membrane designed for diaphragmatic hernia patches.
2026-08-06 | Vasopressin for hemodynamic support in neonates: current evidence and clinical applications.
To systematically map and synthesize the available evidence on the use of vasopressin for hemodynamic support in neonates. We conducted a scoping review to synthesize available data on indications, dosing, clinical effects, and safety. Twelve studies were included (one randomized trial, eleven observational), encompassing heterogeneous neonatal populations. Vasopressin was primarily used as rescue therapy in refractory shock, including sepsis, persistent pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. Dosing regimens varied widely. Most studies reported improvements in mean arterial blood pressure, with some demonstrating reduced vasoactive support and improved oxygenation. Effects on urine output were variable. Safety reporting was inconsistent; hyponatremia was the most commonly described adverse event, while serious ischemic complications were rarely reported. Vasopressin may improve short-term hemodynamic parameters, but evidence is limited and heterogeneous, with insufficient data to guide optimal use.
2026-07-30 | Transamniotic stem cell therapy (TRASCET).
Transamniotic stem cell therapy (TRASCET) constitutes the least invasive approach to prenatal stem cell delivery described to date. This strategy is largely based on the recently discovered active transport of donor cells from the amniotic fluid to the placenta directly through the amnio-placental interface. From a simple amniocentesis, via the placenta, donor cells of different phenotypes can reach the fetal circulation and virtually any fetal anatomical site, including, and particularly, the fetal bone marrow. As a result, TRASCET has shown broad therapeutic potential in an assortment of animal models. First reported experimentally only a little over a decade ago, it has yet to be attempted clinically, though clinical translation may be imminent. Much of TRASCET's appeal lies in the fact that, in large part, it constitutes a form of replenishment therapy based on the magnification of naturally occurring processes in the distinctive environment of the maternal-fetal unit. Despite significant experimental advances, much promise and perhaps excessive publicity, most cell-based therapies have yet to deliver meaningful large-scale impact to patient care. The few exceptions have been therapies based on the amplification of the normal biological role played by donor cells in their natural environment. TRASCET falls in that category. Further, while fetal stem cells possess unique characteristics when compared with postnatal stem cells, so does the fetus when compared with any other age group, converging into a scenario that enables therapeutic paradigms exclusive to prenatal life. This review summarizes the biological basis, diversity of applications and operability of the TRASCET principle.
2026-07-24 | Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.
To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. PROSPERO: CRD420261325458.
2026-07-21 | Extracellular vesicles in perinatal conditions: A minimally invasive approach to regenerative medicine.
Extracellular vesicles (EVs) are lipid bilayer-delimited nanoparticles released by cells to act as mediators of intercellular communication during organ development, injury, and repair. EVs carry cargo (bioactive proteins, lipids, and nucleic acids) that reflects the status of the parent cell and is transferred to recipient cells to regulate biological processes, such as inflammation, immune responses, and tissue regeneration. These properties have made EVs promising tools for investigating disease pathogenesis, improving diagnostic and prognostic accuracy, and developing cell-free regenerative therapies for conditions characterized by dysregulation of multiple biological pathways. EVs are particularly relevant in diseases that affect the pediatric population where pathogenesis often remains poorly understood, access to affected tissues is limited, and treatment options are frequently inadequate. This review summarizes current evidence on EV applications in fetal and neonatal disorders, including necrotizing enterocolitis, congenital diaphragmatic hernia, and bronchopulmonary dysplasia, and highlights emerging data in biliary atresia, spina bifida, short bowel syndrome, and Hirschsprung's disease. In this age group, human milk and amniotic fluid represent particularly attractive biologically accessible sources of EVs, combining therapeutic potential with feasibility of clinical application. Building on robust preclinical evidence, the field is now advancing toward clinical translation, but several aspects still need to be addressed such as cargo heterogeneity, scalability of production, dosing, biodistribution, safety, and regulatory standardization. Herein, we discuss the translational challenges and future directions that will shape the clinical application of EVs in perinatal conditions.
2026-08-06 | Bioprinting of BSA membranes with C2C12 and NIH 3T3 pre-cellularized PLGA microscaffold : a step toward diaphragmatic hernia patches.
The diaphragm is a physical barrier separating the thoracic and abdominal cavities. Its physiological function is fundamental to pulmonary ventilation. Congenital diaphragmatic hernia (CDH) is a malformation that leaves a hole in the diaphragm during fetal development. Synthetic nondegradable membranes are currently used for the repair of diaphragm holes. However, these membranes do not help cells to adhere and proliferate. There is a need for biodegradable membranes composed of muscular and fibroblast cells to replicate a simplified diaphragmatic tissue. We thus developed a biocompatible and biodegradable salt-compacted albumin membrane. C2C12 myoblasts were bioprinted as central spokes, surrounded by a ring of NIH 3T3 fibroblasts, onto albumin membranes. We used bioink based on methacrylated collagen and hyaluronic acid, containing porous poly(D,L-lactic-co-glycolic acid) solid microscaffolds to protect myoblast and fibroblast cells against mechanical stress during extrusion printing. We found that metabolic activity of C2C12 myoblast increased by 215% in the presence of a polylysine-coated microscaffolds, compared to those cultured without microscaffolds. Microscaffolds loaded with C2C12 and NIH 3T3 cells increased viability (30% and 15%) and cell activity (527% and 567%) either after co-culture (5.6% increased viability and 588% cell activity) bioprinting on albumin membrane, compared to cells in bioink without microscaffolds. Cell-loaded microscaffolds embedded in bioink enhance C2C12 to NIH3T3 cross-migration on albumin membrane. This work is a preliminary proof of concept of cellularization of myoblasts and fibroblasts by extrusion bioprinting on a new biodegradable albumin membrane designed for diaphragmatic hernia patches.
2026-08-06 | Vasopressin for hemodynamic support in neonates: current evidence and clinical applications.
To systematically map and synthesize the available evidence on the use of vasopressin for hemodynamic support in neonates. We conducted a scoping review to synthesize available data on indications, dosing, clinical effects, and safety. Twelve studies were included (one randomized trial, eleven observational), encompassing heterogeneous neonatal populations. Vasopressin was primarily used as rescue therapy in refractory shock, including sepsis, persistent pulmonary hypertension of the newborn, and congenital diaphragmatic hernia. Dosing regimens varied widely. Most studies reported improvements in mean arterial blood pressure, with some demonstrating reduced vasoactive support and improved oxygenation. Effects on urine output were variable. Safety reporting was inconsistent; hyponatremia was the most commonly described adverse event, while serious ischemic complications were rarely reported. Vasopressin may improve short-term hemodynamic parameters, but evidence is limited and heterogeneous, with insufficient data to guide optimal use.
2026-07-30 | Transamniotic stem cell therapy (TRASCET).
Transamniotic stem cell therapy (TRASCET) constitutes the least invasive approach to prenatal stem cell delivery described to date. This strategy is largely based on the recently discovered active transport of donor cells from the amniotic fluid to the placenta directly through the amnio-placental interface. From a simple amniocentesis, via the placenta, donor cells of different phenotypes can reach the fetal circulation and virtually any fetal anatomical site, including, and particularly, the fetal bone marrow. As a result, TRASCET has shown broad therapeutic potential in an assortment of animal models. First reported experimentally only a little over a decade ago, it has yet to be attempted clinically, though clinical translation may be imminent. Much of TRASCET's appeal lies in the fact that, in large part, it constitutes a form of replenishment therapy based on the magnification of naturally occurring processes in the distinctive environment of the maternal-fetal unit. Despite significant experimental advances, much promise and perhaps excessive publicity, most cell-based therapies have yet to deliver meaningful large-scale impact to patient care. The few exceptions have been therapies based on the amplification of the normal biological role played by donor cells in their natural environment. TRASCET falls in that category. Further, while fetal stem cells possess unique characteristics when compared with postnatal stem cells, so does the fetus when compared with any other age group, converging into a scenario that enables therapeutic paradigms exclusive to prenatal life. This review summarizes the biological basis, diversity of applications and operability of the TRASCET principle.
2026-07-24 | Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.
To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. PROSPERO: CRD420261325458.
2026-07-21 | Extracellular vesicles in perinatal conditions: A minimally invasive approach to regenerative medicine.
Extracellular vesicles (EVs) are lipid bilayer-delimited nanoparticles released by cells to act as mediators of intercellular communication during organ development, injury, and repair. EVs carry cargo (bioactive proteins, lipids, and nucleic acids) that reflects the status of the parent cell and is transferred to recipient cells to regulate biological processes, such as inflammation, immune responses, and tissue regeneration. These properties have made EVs promising tools for investigating disease pathogenesis, improving diagnostic and prognostic accuracy, and developing cell-free regenerative therapies for conditions characterized by dysregulation of multiple biological pathways. EVs are particularly relevant in diseases that affect the pediatric population where pathogenesis often remains poorly understood, access to affected tissues is limited, and treatment options are frequently inadequate. This review summarizes current evidence on EV applications in fetal and neonatal disorders, including necrotizing enterocolitis, congenital diaphragmatic hernia, and bronchopulmonary dysplasia, and highlights emerging data in biliary atresia, spina bifida, short bowel syndrome, and Hirschsprung's disease. In this age group, human milk and amniotic fluid represent particularly attractive biologically accessible sources of EVs, combining therapeutic potential with feasibility of clinical application. Building on robust preclinical evidence, the field is now advancing toward clinical translation, but several aspects still need to be addressed such as cargo heterogeneity, scalability of production, dosing, biodistribution, safety, and regulatory standardization. Herein, we discuss the translational challenges and future directions that will shape the clinical application of EVs in perinatal conditions.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Congenital diaphragmatic hernia.
2 orphan drug designations for Congenital diaphragmatic hernia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Rhizobium rhizogenes, lipopolysaccharide | other | EMA | 2023-07-25 | — | Crazy Science & Business S.L. |
Sildenafil | small molecules | EMA | 2017-06-20 | — | Avivia Beheer BV |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.