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Purpose of review: Congenital diaphragmatic hernia (CDH) remains a significant challenge, particularly in severe cases with persistent pulmonary hypertension (PPHN) and hypoplastic lungs and heart. For patients unresponsive to conventional therapies, ECMO is required. While the surgical repair is relatively simple, determining the optimal timing for surgery in patients requiring ECMO is particularly challenging. This review explores the dilemma of surgical timing and proposes a two-staged approach: a reduction in herniated organs and the creation of a silo to relieve abdominal pressure before initiating ECMO, with defect closure following ECMO decannulation. Recent Findings: Studies support pre-, on-, and post-ECMO repair, each with its own risks and benefits. Pre-ECMO repair may enhance ECMO efficacy by relieving organ compression but poses risks due to instability. Post-ECMO repair is safer but may result in losing the chance to repair. On-ECMO repair has significant hemorrhage risks, but early repair with careful anticoagulation management is currently recommended. Recently, the author reported a successful case using a two-staged approach—reducing herniated organs and creating a silo before ECMO, followed by defect closure after ECMO decannulation—which suggests a potential alternative strategy for managing severe CDH. Summary: A two-staged approach may offer a solution for severe CDH patients requiring ECMO. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is readily prenatally diagnosed and associated with significant perinatal morbidity and mortality. Delivery at facilities with adequate resources for neonatal resuscitation, such as Children's Surgery Verification (CSV) centers, is recommended; however, disparities have been clinically noted. We aimed to characterize locoregional care of CDH and the impact of race and ethnicity. We conducted a population-based study using the Texas Inpatient Public Use Data File to identify infants <1 y-old with CDH based on international classification of diseases 9/10 codes (2013-2021). Only initial birth admissions in the Houston region were included. Data was analyzed using descriptive statistics and chi-squared analysis. We identified 257 newborns with CDH. While births were noted across 29 facilities, the majority were at the 2 CSV centers in Houston. There was no significant difference in illness severity, prematurity or insurance status by race. Black and 'other' patients were less likely to deliver at CSV facilities (Black 32% versus 'Other' 48% versus White 70% versus Asian 81%; P < 0.01), receive ECMO (Black 6% versus 'Other' 5% versus White 19% versus Asian 29%; P < 0.01) or undergo a CDH repair (Black 26% versus 'Other' 33% versus White 51% versus Asian 71%; P < 0.01) on their index admission and had lower average daily costs (Black $10,292 [$3219-25,021] versus 'Other' $9106 [$3617-15,672] versus White $12,906 [$9038-18,550] versus Asian $12,896 [$7469-23,817]; P < 0.05). Additionally, black and 'other' patients were more likely to be transferred (Black 23% versus 'Other' 28% versus White 12% versus Asian 14%; P < 0.05). None of the patients born at CSV centers transferred. Most Houston-born patients deliver at high-resource centers; however, Black and 'other' patients are less likely to deliver at CSV centers and more likely to require transfer during the critical neonatal period. This suggests a vulnerable population which may benefit from targeted intervention to improve prenatal care and delivery planning. [ABSTRACT FROM AUTHOR]

Purpose: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. Methods: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. Results: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8–28.6). The median GA at delivery was 37 weeks (IQR 34.4–37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). Conclusions: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population. A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression. Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use. Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO. • Surfactant administration is not associated with increased morbidity and mortality and may provide benefit to CDH patients that have undergone fetoscopic endoluminal tracheal occlusion. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) represents a population of high risk of major cardiopulmonary decompensation. Maintenance of patency of the patent ductus arteriosus (PDA), using intravenous prostaglandin, is a strategy used by some clinicians to decrease the risk of right ventricular dysfunction. A term infant with CDH presented with pulmonary hypertension unresponsive to aggressive hemodynamic support. Within 12 hours of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) initiation, circuit chugging occurred that was refractory to multiple volume boluses. Targeted neonatal echocardiography (TnECHO) revealed a high-volume left-to-right shunt across the PDA, resulting in decreased blood return to the right atrium. Interventions aimed at reducing the left-to-right PDA shunt led to the resolution of circuit chugging. This report highlights the unique challenge of VA-ECMO flow in the setting of a large PDA and the consequences of interventions, increasing PDA diameter or lowering pulmonary vascular resistance, on the magnitude of systemic-pulmonary shunting and systemic blood flow. TnECHO played a vital role in monitoring hemodynamics and guiding ECMO adjustments.

Purpose of review: Congenital diaphragmatic hernia (CDH) remains a significant challenge, particularly in severe cases with persistent pulmonary hypertension (PPHN) and hypoplastic lungs and heart. For patients unresponsive to conventional therapies, ECMO is required. While the surgical repair is relatively simple, determining the optimal timing for surgery in patients requiring ECMO is particularly challenging. This review explores the dilemma of surgical timing and proposes a two-staged approach: a reduction in herniated organs and the creation of a silo to relieve abdominal pressure before initiating ECMO, with defect closure following ECMO decannulation. Recent Findings: Studies support pre-, on-, and post-ECMO repair, each with its own risks and benefits. Pre-ECMO repair may enhance ECMO efficacy by relieving organ compression but poses risks due to instability. Post-ECMO repair is safer but may result in losing the chance to repair. On-ECMO repair has significant hemorrhage risks, but early repair with careful anticoagulation management is currently recommended. Recently, the author reported a successful case using a two-staged approach—reducing herniated organs and creating a silo before ECMO, followed by defect closure after ECMO decannulation—which suggests a potential alternative strategy for managing severe CDH. Summary: A two-staged approach may offer a solution for severe CDH patients requiring ECMO.

The introduction of minimally invasive surgery (MIS) for repair of congenital diaphragmatic hernias (CDH) has reduced postoperative length of stay, postoperative opioid consumption, and provided a more esthetic repair. In adult abdominal surgery, minimally invasive techniques have been associated with decreased long-term rates of small bowel obstruction (SBO), although it is unclear if this benefit carries over into the pediatric population. Our objective was to evaluate the rates of SBO following open versus MIS CDH repair. Infants who underwent CDH repair between 2010 and 2021 were identified using the PearlDiver Mariner database. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate time to SBO by surgical approach (MIS versus open) while adjusting for mesh use, patient sex, and length of stay. Of 1033 patients that underwent CDH repair, 258 (25.0%) underwent a minimally invasive approach. The overall rate of SBO was 7.5% (n = 77). Rate of SBO following MIS repair was lower than open repair at 1 y (0.8% versus 5.1%), 3 y, (2.3% versus 9.0%), and 5 y (4.4% versus 10.1%, P = 0.004). Following adjustment, the rate of SBO following MIS repair remained significantly lower than open repair (adjusted hazard ratio: 0.37, 95% confidence interval: 0.18, 0.79). Following CDH repair, long-term rates of SBO are lower among patients treated with MIS approaches. Long-term risk of SBO should be considered when selecting surgical approach for CDH patients. • Less bowel obstruction associated with minimally invasive diaphragmatic hernia repair. • Mesh use in diaphragmatic hernia repair is associated with more bowel obstructions. • Risk of bowel obstruction should be considered when selecting surgical approach. [ABSTRACT FROM AUTHOR]

Objective: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). Methods: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. Results: The MSA was significantly higher in children who received ECMO therapy (p = 0.0054), as well as in children who developed CLD (p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy (p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). Conclusions: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters. [ABSTRACT FROM AUTHOR]

IntroductionCongenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics.Material and methodsAt 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h.ResultsCDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), p

The optimal role of high frequency jet ventilation (HFJV) in lung protective stabilization of congenital diaphragmatic hernia (CDH) remains uncertain. We aimed to describe our center's experience with HFJV as both a rescue (following failed stabilization with CMV) and primary ventilation mode in the management of CDH. Liveborn CDH patients treated from 2013 to 2021 in a single institution were reviewed. We compared 3 groups based on their primary and last ventilation mode prior to surgery: CMV (Group 1); HFJV (Group 2); and CMV/HFJV (Group 3). Outcomes included a composite primary outcome (≥1 of mortality, need for ECMO or need for supplemental O 2 at discharge), total invasive ventilation days and development of pneumothorax. A descriptive analysis including univariate group comparisons was performed. Multivariate logistic regression models investigating the relationship between mode of ventilation and the primary outcome adjusted by potentially confounding covariates were constructed. 56 patients (32 Group 1, 18 Group 2, 6 Group 3) were analyzed. Group 2 and 3 patients had more severe disease based on liver position, SNAP-II score, pulmonary hypertension severity, need for inotropic support, CDHSG defect size and need for patch repair. There were no group differences in survival, need for ECMO, or pneumothorax occurrence, although infants receiving HFJV required longer invasive ventilation and had a greater need for O 2 at discharge. Multivariate logistic regression revealed no associations between mode of ventilation and outcome. HFJV appears effective, both for CMV rescue and as a primary ventilation strategy in high risk CDH. Level of evidence : Level IV. • What is currently known? Lung protection for CDH includes high frequency ventilation. There is little evidence for the role of high frequency jet ventilation in CDH care. • What information is contained in this article? This article reports the largest experience to date with HFJV as a primary ventilatory mode in high risk CDH. [ABSTRACT FROM AUTHOR]

Fetal tracheal occlusion (TO) reverses the pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH), but its mechanism of action remains poorly understood. 'Omic' readouts capture metabolic and lipid processing function, which aid in understanding CDH and TO metabolic mechanisms. CDH was created in fetal rabbits at 23 days, TO at 28 days and lung collection at 31 days (Term ∼32 days). Lung-body weight ratio (LBWR) and mean terminal bronchiole density (MTBD) were determined. In a cohort, left and right lungs were collected, weighed, and samples homogenized, and extracts collected for non-targeted metabolomic and lipidomic profiling via LC–MS and LC–MS/MS, respectively. LBWR was significantly lower in CDH while CDH + TO was similar to controls (p = 0.003). MTBD was significantly higher in CDH fetuses and restored to control and sham levels in CDH + TO (p < 0.001). CDH and CDH + TO resulted in significant differences in metabolome and lipidome profiles compared to sham controls. A significant number of altered metabolites and lipids between the controls and CDH groups and the CDH and CDH + TO fetuses were identified. Significant changes in the ubiquinone and other terpenoid-quinone biosynthesis pathway and the tyrosine metabolism pathway were observed in CDH + TO. CDH + TO reverses pulmonary hypoplasia in the CDH rabbit, in association with a specific metabolic and lipid signature. A synergistic untargeted 'omics' approach provides a global signature for CDH and CDH + TO, highlighting cellular mechanisms among lipids and other metabolites, enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology and recovery. Basic Science, Prospective. II. • What is currently known about this topic? Congenital diaphragmatic hernia (CDH) is a life-threatening condition with a mortality rate of 20%. The primary cause of death is respiratory failure due to severe pulmonary hypoplasia and pulmonary hypertension. However, the pathophysiology of CDH remains poorly understood. • What new information is contained in this article? Within a rabbit model, we were able to highlight certain cellular mechanisms, including different lipids and other metabolites, that may be critical metabolic drivers in disease pathology and recovery of CDH. [ABSTRACT FROM AUTHOR]

IntroductionPulmonary hypertension (PH) is one of the major contributing factors to the high morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). The severity and duration of postnatal PH are an established risk factor for patient outcome; however, the early postnatal dynamics of PH have not been investigated. This study aims to describe the early course of PH in CDH infants, and its relation to established prognostic markers and outcome measures.MethodsWe performed a monocentric retrospective review of neonates with prenatally diagnosed CDH, who received three standardized echocardiographic examinations at 2–6 h, 24, and 48 h of life. The degree of PH was graded as one of three categories: mild/no, moderate, or severe PH. The characteristics of the three groups and their course of PH over 48 h were compared using univariate and correlational analyses.ResultsOf 165 eligible CDH cases, initial PH classification was mild/no in 28%, moderate in 35%, and severe PH in 37%. The course of PH varied markedly based on the initial staging. No patient with initial no/mild PH developed severe PH, required extracorporeal membrane oxygenation (ECMO)-therapy, or died. Of cases with initial severe PH, 63% had persistent PH at 48 h, 69% required ECMO, and 54% died. Risk factors for any PH included younger gestational age, intrathoracic liver herniation, prenatal fetoscopic endoluminal tracheal occlusion (FETO)-intervention, lower lung to head ratio (LHR), and total fetal lung volume (TFLV). Patients with moderate and severe PH showed similar characteristics, except liver position at 24- (p = 0.042) and 48 h (p = 0.001), mortality (p = 0.001), and ECMO-rate (p = 0.035).DiscussionTo our knowledge, this is the first study to systematically assess the dynamics of PH in the first postnatal 48 h at three defined time points. CDH infants with initial moderate and severe PH have a high variation in postnatal PH severity over the first 48 h of life. Patients with mild/no PH have less change in PH severity, and an excellent prognosis. Patients with severe PH at any point have a significantly higher risk for ECMO and mortality. Assessing PH within 2–6 h should be a primary goal in the care for CDH neonates.

Abstract Background For infants with severe congenital diaphragmatic hernia (CDH) stabilized with extracorporeal membrane oxygenation (ECMO), early repair on ECMO improves outcome; however when compared to operative repair after ECMO, repair on ECMO is associated with increase bleeding risk and need for blood product transfusions. Methods A retrospective review of 54 patients with CDH placed on ECMO prior to CDH repair was performed. For the subset of patients repaired on ECMO, analysis comparing those repaired early (within 48 h of cannulation) and late (beyond 48 h) on ECMO was performed. Outcomes of interest included survival to discharge, days on ECMO, and postoperative blood product utilization. Results When compared to those patients repaired prior to 48 h of ECMO initiation, 57.7% of patients survived versus 40.9% of late repair patients. For those repaired early, blood product utilization was significantly less. Early repair patients received a median of 72 mL/kg packed red blood cells (PRBC) and 75 mL/kg platelets compared to 151.9 mL/kg and 98.7 mL/kg, respectively (p < 0.05 respectively). There was no difference in median days on ECMO (p = 0.38). Conclusion Our data supports prior reports of improved outcome with repair with 48 h of ECMO initiation and suggests early repair on ECMO is associated with less bleeding and decreased blood product requirement in the postoperative period.

Peripherally inserted central catheter (PICC) lines are used routinely in neonates requiring prolonged drugs and parenteral nutrition and complications are usually infectious, mechanical, or thrombotic in nature. Spontaneous extravascular migration is extremely rare, and presentation with large volume chest tube output even rarer. We present a case involving a neonate on extracorporeal membrane oxygenation (ECMO) after congenital diaphragmatic hernia (CDH) repair and discuss management strategies.

Newborns with congenital diaphragmatic hernia (CDH) can have complex respiratory problems which are worsened by ventilatory induced lung injury. Neurally adjusted ventilator assist (NAVA) is a potentially promising ventilation mode for this population, as it can result in improved patient-ventilator interactions and provision of adequate gas exchange at lower airway pressures. A literature review was undertaken to provide an overview of NAVA and examine its role in the management of infants with CDH. NAVA in neonates has been used in CDH infants who were stable on ventilatory support or being weaned from mechanical ventilation and was associated with a reduction in the level of respiratory support. There is, however, limited evidence regarding the efficacy of NAVA in infants with CDH, with only short-term benefits being investigated. A prospective, multicentre study with long term follow-up is required to appropriately assess NAVA in this population. [ABSTRACT FROM AUTHOR]

Background: Congenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect, leading to herniation of abdominal organs into the chest, lung compression, and impaired lung development, often resulting in pulmonary hypertension and lung hypoplasia. Prenatal imaging techniques like ultrasound and MRI provide anatomical predictors of outcomes, but their limitations necessitate novel biomarkers for better prognostic accuracy., Objective: This study aims to identify unique circulating maternal, fetal, and neonatal microRNAs (miRNAs) that can distinguish CDH pregnancies from healthy controls and assess their potential as markers of disease severity., Study Design: We conducted a prospective study involving third-trimester maternal blood, amniotic fluid, cord blood, and neonatal blood samples from pregnancies complicated by CDH and healthy controls. miRNA expression was analyzed using RNA-sequencing, and random forest analysis identified miRNAs distinguishing CDH survivors from non-survivors. Pathway enrichment analyses were performed to explore the biological relevance of differentially expressed miRNAs., Results: Significant miRNA expression differences were observed between CDH and control samples across all sample types. In infant blood, 148 miRNAs were up-regulated, and 36 were down-regulated in CDH cases. Pathway analysis revealed that dysregulated miRNAs in CDH targeted pathways related to protein binding, transcription regulation, and signaling pathways implicated in pulmonary hypertension and lung hypoplasia. Random forest analysis identified miRNAs in maternal blood (miR-7850-5p&#95;L-1R+2, miR-942-3p, and miR-197-3p) that distinguished CDH survivors from non-survivors, with an ROC area under the curve of 1.0., Conclusion: Circulating miRNAs in maternal blood offer promising biomarkers for predicting CDH outcomes. miRNAs from infant blood provide mechanistic insights and potential targets for therapeutic intervention in critical pathways of pulmonary hypertension and lung hypoplasia. Further studies with larger cohorts are needed to validate these findings and explore the clinical application of miRNA biomarkers in CDH management., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

In patients affected by CDH, survival beyond the neonatal period continues to increase thanks to technological and pharmacological improvements. Conversely, patients, families and caregivers are more and more frequently facing “new” complex late comorbidities, including chronic pulmonary and cardiac dysfunctions, neurodevelopmental challenges, and specific nutritional requirements, that often require ongoing long-term medical or surgical care. Therefore, late morbidity is now a key focus in clinical care of CDH. The aims of this paper are to stress some of the most important “unsolved problems” for CDH patients at long-term follow-up.

TITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that Titf1 null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this study, we aim to evaluate the role of TITF1 in the pathogenesis of congenital diaphragmatic hernia (CDH) in humans. We investigated TITF1 expression in human trachea and lungs and performed direct mutation analysis in a CDH population. We studied 13 human fetuses at 14 to 24 weeks of gestation. Five μm sections were fixed in paraformaldehyde and incubated with anti-TITF1 primary antibody. Positive staining was visualized by biotinylated secondary antibody. We also performed TITF1 screening on genomic DNA extracted from peripheral blood of 16 patients affected by CDH and different degrees of PH, searching for mutations, insertions, and/or deletions, by sequencing the exonic regions of the gene. Histochemical studies showed positive brown staining of fetal follicular thyroid epithelium, normal fetal trachea, and normal fetal lung bronchial epithelium. Fetal esophageal wall was immunohistochemically negative. Molecular genetic analysis showed complete identity between the sequences obtained and the Wild Type (WT) form of the gene in all cases. No mutation, insertion and/or deletion was detected. Although TITF1 is expressed in the human fetal lung and has been considered to have a role in the pathogenesis of PH in CDH, the results of our study do not support the hypothesis that TITF1 mutations play a key role in the etiopathogenesis of CDH. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia is a life-threatening anomaly with the high mortality rate in infancy. Very rarely they remain silent and manifest in the adult life. Once they manifest, the symptoms vary and are not easy to diagnose. The entity also has associated problems in the form of hypoplastic lungs and loss of domain of the abdomen. In such cases, the diagnosis is most often based on clinical suspicion and radiological confirmation. The treatment options are open abdominothoracic procedures or laparoscopic procedures. Once hernia is reduced, the defect is closed and should be reinforced with prosthetic mesh. Here we present a case of congenital diaphragmatic hernia in a teenager presenting with cardiac symptoms. The challenges faced in managing the case are discussed.

Congenital diaphragmatic hernia (CDH) is a complex disease associated with pulmonary hypoplasia and pulmonary hypertension. Great strides have been made in our ability to care for CDH patients, specifically in the prenatal improvement of lung volume and morphology with fetoscopic endoluminal tracheal occlusion (FETO). While the anatomic effects of FETO have been described in-depth, the changes it induces at the cellular and molecular level remain a budding area of CDH research. This review will delve into the cellular and molecular effects of FETO in the developing lung, emphasize areas in which further research may improve our understanding of CDH, and highlight opportunities to optimize the FETO procedure for improved postnatal outcomes.

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly, whose presentation is complicated by pulmonary hypertension (PH), pulmonary hypoplasia, and myocardial dysfunction, each of which have significant impact on short-term clinical management and long-term outcomes. Despite many advances in therapy and surgical technique, optimal CDH management remains a topic of debate, due to the variable presentation, complex pathophysiology, and continued impact on morbidity and mortality. One of the more recent management strategies is the use of prostaglandin E1 (PGE1) infusion in the management of PH associated with CDH. PGE1 is widely used in the NICU in critical congenital cardiac disease to maintain ductal patency and facilitate pulmonary and systemic blood flow. In a related paradigm, PGE1 infusion has been used in situations of supra-systemic right ventricular pressures, including CDH, with the therapeutic intent to maintain ductal patency as a “pressure relief valve” to reduce the effective afterload on the right ventricle (RV), optimize cardiac function and support pulmonary and systemic blood flow. This paper reviews the current evidence for use of PGE1 in the CDH population and the opportunities for future investigations.

Surgical repair of the diaphragm is essential for survival in congenital diaphragmatic hernia (CDH). There are many considerations surrounding the operation – why the operation matters, optimal timing of repair and its relation to extracorporeal life support (ECLS) use, minimally invasive versus open approaches, and strategies for reconstruction. Surgery is both affected by, and affects, the physiology of these infants and is an important factor in determining long-term outcomes. Here we discuss the evidence and provide insight surrounding this complex decision making, technical pearls, and outcomes in repair of CDH. [ABSTRACT FROM AUTHOR]

Objective: To determine how blood gas exchange is altered during the transition in the first hour of life in infants with congenital diaphragmatic hernia (CDH).Study Design: This was a prospective observational cohort study evaluating arterial blood gas (ABG) samples and ventilator support in 34 infants with CDH in the first hour of life. Infants were stratified into mild, moderate, and severe CDH. The first ABG was compared with the umbilical cord ABGs and response to intervention evaluated on subsequent ABGs among infants with different CDH severities.Results: Infants were intubated at a median of 120 seconds (range 50-240 seconds) and ABGs obtained at a median of 6 minutes (IQR 4, 8 minutes), 16 minutes (IQR 13.5, 22.5 minutes), and 60 minutes (IQR 56, 64 minutes). Compared with the cord ABG, first ABG mean partial pressure of carbon dioxide (PaCO2) increased from 49.8 mm Hg to 82.1 mm Hg, mean base deficit decreased from -2.2 to -7.3, and mean pH from 7.298 to 7.060. With ventilator adjustments, second mean PaCO2 decreased to 76.7 mm Hg and third mean PaCO2 48.5 mm Hg. When stratified, with all CDH severities PaCO2 increased abruptly, remained elevated in moderate and severe CDH, and improved in all severities by 60 minutes after delivery.Conclusions: Gas exchange is markedly altered in the first hour of life in infants with CDH with abrupt onset of acidemia and a mixed respiratory and metabolic acidosis. Early implementation of adequate cardiopulmonary support may contribute to more timely stabilization of gas exchange. [ABSTRACT FROM AUTHOR]

ObjectiveIn patients with a congenital diaphragmatic hernia (CDH), postoperative small bowel obstruction (SBO) is a life-threatening event. Literature reports an incidence of SBO of 20% and an association with patch repair and ECMO treatment. Adhesions develop due to peritoneal damage and underly various biochemical and cellular processes. This longitudinal cohort study is aimed at identifying the incidence of SBO and the risk factors of surgical, pre-, and postoperative treatment.MethodsWe evaluated all consecutive CDH survivors born between January 2009 and December 2017 participating in our prospective long-term follow-up program with a standardized protocol.ResultsA total of 337 patients were included, with a median follow-up of 4 years. SBO with various underlying causes was observed in 38 patients (11.3%) and significantly more often after open surgery (OS). The majority of SBOs required surgical intervention (92%). Adhesive SBO (ASBO) was detected as the leading cause in 17 of 28 patients, in whom surgical reports were available. Duration of chest tube insertion [odds ratio (OR) 1.22; 95% CI 1.01–1.46, p = 0.04] was identified as an independent predictor for ASBO in multivariate analysis. Beyond the cut-off value of 16 days, the incidence of serous effusion and chylothorax was higher in patients with ASBO (ASBO/non-SBO: 2/10 vs. 3/139 serous effusion, p = 0.04; 2/10 vs. 13/139 chylothorax, p = 0.27). Type of diaphragmatic reconstruction, abdominal wall closure, or ECMO treatment showed no significant association with ASBO. A protective effect of one or more re-operations has been detected (RR 0.16; 95% CI 0.02–1.17; p = 0.049).ConclusionThoracoscopic CDH repair significantly lowers the risk of SBO; however, not every patient is suitable for this approach. GoreTex®-patches do not seem to affect the development of ASBO, while median laparotomy might be more favorable than a subcostal incision. Neonates produce more proinflammatory cytokines and have a reduced anti-inflammatory capacity, which may contribute to the higher incidence of ASBO in patients with a longer duration of chest tube insertion, serous effusion, chylothorax, and to the protective effect of re-operations. In the future, novel therapeutic strategies based on a better understanding of the biochemical and cellular processes involved in the pathophysiology of adhesion formation might contribute to a reduction of peritoneal adhesions and their associated morbidity and mortality.

• Raised intra-abdominal pressure is observed in neonates post CDH repair. • The timing of intra-abdominal hypertension has strong correlation with the duration of ventilatory support post CDH repair. • The timing of intra-abdominal hypertension has moderate correlation with the time taken to establish feeding post CDH repair. • Intra vesical pressure is an accurate minimally invasive method to monitor intra-abdominal pressure. Increased intra-abdominal pressure (IAP) is seen in patients after congenital diaphragmatic hernia (CDH) repair owing to reduction of thoracic contents into the relatively smaller abdominal cavity. In infants, IAP ≥11 mmHg is considered intra-abdominal hypertension (IAH). We aim to determine the incidence of IAH and its relationship with duration of ventilatory support, and gastrointestinal function post CDH repair. We prospectively recruited all neonates who had CDH repair in four hospitals in Malaysia from June 2018 to October 2020. Intra vesical pressure was used as a proxy for IAP and was measured for 5 consecutive days post surgery. The daily median value was used for analysis. We categorized IAP as <11 mmHg (no IAH), 11–15 mmHg (IAH), and >15 mmHg (severe IAH). Incidence of IAH, its effects on the duration of ventilatory support, and gastrointestinal function were studied. There were 24 neonates included in this study. They were operated between day 1 and 6 of life (median: 4 days old). IAH was detected within the first 3 days post surgery, with 83% occurring on day one. Those requiring ventilatory support for more than 3 days contributed the largest proportion of IAH (n = 17, 71%). There was strong correlation between days of IAH and duration of ventilation (p < 0.001, r = 0.70). There was moderate correlation between days of IAH and duration taken to achieve full enteral feeding (p < 0.005, r = 0.70). IAP measurement is a safe and useful adjunct in post CDH monitoring and in predicting ventilatory support requirements and the time needed to establish feeding. [ABSTRACT FROM AUTHOR]

Tracheal occlusion (TO) is a fetal treatment option for congenital diaphragmatic hernia. It aims to reduce lung hypoplasia and hypertension by occluding the trachea with a subsequent increase in pulmonary pressure. However, how TO affects lung pressure is unknown, and no devices are available for its measurement. We developed an implantable device for real-time wireless monitoring and long-term logging of lung pressure in ovine fetuses. The device comprised a microcontroller unit, two pressure sensors, an inertial measurement unit (IMU), a radio frequency unit, and an antenna. In vitro and in vivo tests were performed to evaluate device performances. A diaphragmatic hernia was created in ovine fetuses via hysterotomy. Nine devices were implanted at 100 days of gestation and remained until delivery (~142 d). One pressure sensor measured pressure in the amniotic sac and the other in the fetal trachea. In vitro pressure accuracy was median (interquartile range) 0.31% (0.1%). In vitro device lifetime was ~60 days. The in vivo device recording time was 26.0 (3.9) days and it was well tolerated by the fetus and the ewe. Data telemetry operated throughout the device lifetime. At delivery, amniotic fluid, device encapsulation, and lamb skin did not present evidence of damages. Pressure data in four lambs were analyzed. Fast pressure changes due to the spontaneous fetal activity and long-term mean pressure changes resulting from TO were detected. The IMU allowed for the assessment of changes in fetal position. This device allows long-term monitoring of mean lung pressure, spontaneous breathing activity, and movements in physiological and pathological ovine fetal models. [ABSTRACT FROM AUTHOR]

Background: For infants with severe congenital diaphragmatic hernia (CDH) stabilized with extracorporeal membrane oxygenation (ECMO), early repair on ECMO improves outcome; however when compared to operative repair after ECMO, repair on ECMO is associated with increase bleeding risk and need for blood product transfusions. Methods: A retrospective review of 54 patients with CDH placed on ECMO prior to CDH repair was performed. For the subset of patients repaired on ECMO, analysis comparing those repaired early (within 48 h of cannulation) and late (beyond 48 h) on ECMO was performed. Outcomes of interest included survival to discharge, days on ECMO, and postoperative blood product utilization. Results: When compared to those patients repaired prior to 48 h of ECMO initiation, 57.7% of patients survived versus 40.9% of late repair patients. For those repaired early, blood product utilization was significantly less. Early repair patients received a median of 72 mL/kg packed red blood cells (PRBC) and 75 mL/kg platelets compared to 151.9 mL/kg and 98.7 mL/kg, respectively (p < 0.05 respectively). There was no difference in median days on ECMO (p = 0.38). Conclusion: Our data supports prior reports of improved outcome with repair with 48 h of ECMO initiation and suggests early repair on ECMO is associated with less bleeding and decreased blood product requirement in the postoperative period. [ABSTRACT FROM AUTHOR]

To evaluate the enteral feeding requirements, including caloric provisions, of infants with CDH in relation to growth patterns. A retrospective observational study was conducted on infants with CDH between August 2012 and March 2017. Electronic medical records were reviewed to extract detailed infant feeding data and anthropometric measurements at monthly intervals until discharge. Statistical methods of analysis included generalized linear models, Pearson correlation coefficient, Analysis of variance (ANOVA), Kruskal-Wallis, Wilcoxon rank sum, and Fisher's Exact tests. Among 149 infants with CDH, 45% (n = 67) met criteria for malnutrition at discharge. Maternal human milk (HM) was initiated in 95% of infants (n = 142) and continued in 79% of infants (n = 118) at discharge. Overall, 50% received fortification of feeds, including 60% (n = 89) of formula fed infants compared to only 21% (n = 31) of HM fed infants (p <0.001). Infants fed formula had lower weight-for-length z-scores at discharge compared to those fed HM. Infants receiving HM demonstrated improved growth compared to formula fed infants. However, higher calorie feeding regimens need to be initiated earlier to improve growth velocity. Prompt recognition of malnutrition and growth failure with aggressive supplementation may improve the overall growth of infants with CDH and has the potential to improve long term neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

We present a rare case of congenital diaphragmatic hernia (CDH) with intrathoracic stomach associated with a congenital short esophagus (CSE) prenatally diagnosed in a male fetus. The unusual hernia appeared right-sided but did not contain liver, instead containing stomach, small and large bowel, and spleen. The infant was delivered preterm at 32 weeks gestation. At 9 days of age, the spleen, small bowel, and large bowel were reduced into the abdominal cavity. The stomach was only partially reduced because of the CSE. Gastropexy and a gastrostomy were also performed. The diaphragmatic defect was fixed around the stomach, which later presented problems requiring another surgery. Additional operations: 1. Tracheostomy placed (3 months) 2. Stomach repositioned more into the abdominal cavity and gastrostomy redone (8 months) 3. Duodenoplasty (postoperative small bowel obstruction) (9 months). Outcome: The patient is currently alive at 11 years old and continues with a gastrostomy tube (g-tube) and tracheostomy dependent. Lessons: To the best of our knowledge, this patient is the longest surviving patient with CDH and intrathoracic stomach caused by CSE. Early diagnosis and continued monitoring remain a key feature to survival.

Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility in utero have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.

Objective: Valid postnatal prediction parameters for neonates with congenital diaphragmatic hernia (CDH) are lacking, but recently, the chest radiographic thoracic area (CRTA) was proposed to predict survival with high sensitivity. Here, we evaluated whether the CRTA correlated with morbidity and mortality in neonates with CDH and was able to predict these with higher sensitivity and specificity than prenatal observed-to-expected (O/E) lung-to-head ratio (LHR).Methods: In this retrospective cohort study, all neonates with CDH admitted to our institution between 2013 and 2019 were included. The CRTA was measured using the software Horos (V. 3.3.5) and compared with O/E LHR diagnosed by fetal ultrasonography in relation to outcome parameters including survival, extracorporeal membrane oxygenation (ECMO) support, and chronic lung disease (CLD).Results: In this study 255 neonates were included with a survival to discharge of 84%, ECMO support in 46%, and 56% developing a CLD. Multiple regression analysis demonstrated that the CRTA correlates significantly with survival (p = 0.001), ECMO support (p < 0.0001), and development of CLD (p = 0.0193). The CRTA displayed a higher prognostic validity for survival [area under the curve (AUC) = 0.822], ECMO support (AUC = 0.802), and developing a CLD (AUC = 0.855) compared with the O/E LHR.Conclusions: Our data suggest that the postnatal CRTA might be a better prognostic parameter for morbidity and mortality than the prenatal O/E LHR.

In neonates, pulmonary diseases such as bronchopulmonary dysplasia and other chronic lung diseases (CLDs) pose significant challenges due to their complexity and high degree of morbidity and mortality. This review discusses the etiology, pathophysiology, clinical presentation, and diagnostic criteria for these conditions, as well as current management strategies. The review also highlights recent advancements in understanding the pathophysiology of these diseases and evolving strategies for their management, including gene therapy and stem cell treatments. We emphasize how supportive care is useful in managing these diseases and underscore the importance of a multidisciplinary approach. Notably, we discuss the emerging role of personalized medicine, enabled by advances in genomics and precision therapeutics, in tailoring therapy according to an individual's genetic, biochemical, and lifestyle factors. We conclude with a discussion on future directions in research and treatment, emphasizing the importance of furthering our understanding of these conditions, improving diagnostic criteria, and exploring targeted treatment modalities. The review underscores the need for multicentric and longitudinal studies to improve preventative strategies and better understand long-term outcomes. Ultimately, a comprehensive, innovative, and patient-centered approach can enhance the quality of care and outcomes for neonates with CLDs., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, El-Atawi et al.)

Purpose: In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. Methods: We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right–left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. Results: Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. Conclusion: O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. Level of evidence: Level III, retrospective comparative study. [ABSTRACT FROM AUTHOR]

To identify factors associated with gastrostomy tube (GT) placement in infants with congenital diaphragmatic hernia (CDH). Retrospective cohort study of 114 surviving infants with CDH at a single tertiary care neonatal intensive care unit from 2010–2019. Prenatal, perinatal and postnatal characteristics were compared between patients who were discharged home with and without a GT. Prenatal imaging was available for 50.9% of the cohort. Logistic regression was used to assess the association between GT placement and pertinent clinical factors. ROC curves were generated, and Youden's J statistic was used to determine optimal predictive cutoffs for continuous variables. Elastic net regularized regression was used to identify variables associated with GT placement in multivariable analysis. GT was placed in 43.9% of surviving infants with CDH. Prenatal variables predictive of GT placement were percent predicted lung volume (PPLV) <21%, total lung volume (TLV) <30 ml, lung-head ratio (LHR) <1.2 or observed to expected LHR (O/E LHR) <55%. Infants who required a GT were diagnosed earlier prenatally (23.6 ± 3.4 vs. 26.4 ± 5.6 weeks). Patients whose stomach was above the diaphragm on prenatal ultrasound (up) had a higher odds of GT placement compared to those with stomachs below the diaphragm (down) position by a factor of 2.9 (95% CI: 1.25, 7.1); p = 0.0154. Postnatally, infants with GT had lower Apgar scores at 1 and 5 min, longer lengths of stay and higher proportion of flap closures. Infants with a type C or D defect and extracorporeal membrane oxygenation (ECMO) were associated with increased odds of needing a GT. Postnatal association included being NPO for >12 days, need for transpyloric (TP) feeds for >10 days, >14 days to transition to a 30 min bolus feed, presence of gastro-esophageal reflux (GER), chronic lung disease and pulmonary hypertension. In multivariable analysis, duration of NPO, time to TP feeds, transition to 30 min bolus feeds remained significantly associated with GT placement after adjusting for severity of pulmonary hypertension (PH), GER diagnosis and sildenafil treatment. Identification of risk factors associated with need for long-term feeding access may improve timing of GT placement and prevent prolonged hospitalization related to feeding issues. Level II (Retrospective Study) [ABSTRACT FROM AUTHOR]

Purpose: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). Methods: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. Results: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. Conclusions: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR. [ABSTRACT FROM AUTHOR]

Objective·To analyze the postoperative pulmonary function of children with congenital diaphragmatic hernia (CDH) and explore the related factors affecting the recovery of pulmonary function. Methods·The medical data of children with CDH who were treated in the Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and underwent infant pulmonary function test (IPFT) from November 2016 to November 2020 were retrospectively reviewed. According to the type of ventilatory dysfunction in the examination, the children were divided into restrictive group, obstructive group, mixed group and healthy group. The differences in prenatal diagnosis, diagnostic gestational week, observed/expected lung-to-head ratio (O/E LHR), birth weight, 1 min Apgar score, hernia side, liver-up, use of patch during operation, duration of mechanical ventilation, length of hospital stay, month age at the time of IPFT and postoperative follow-up time in each group were analyzed. The pulmonary function results of the first-time test were analyzed in the diagnosis of whether the gestational age was less than 25 weeks, whether there was a liver-up and whether the patch was used during the operation. The difference between the results of the first and last test was analyzed. Results·Fourty-two children were included in the analysis. A total of 96 tests were conducted in patients. Sixteen cases underwent IPFT once, and 26 cases had 2 or more tests. There were significant differences in month age at the time of IPFT and postoperative follow-up time among the restrictive (n=6), obstructive (n=68), mixed (n=9) and healthy (n=13) groups (P=0.004, P=0.002). Overall, the tidal volume per kg of body weight (TV/kg), and tidal expiratory flow 50% remaining tidal volume (TEF50%) in children with diagnosis of gestational age less than 25 weeks were lower (P=0.022, P=0.043), TEF75% and TEF50% in children with liver-up were lower (both P=0.040), and TEF50% and TEF25% in children with use of patch during operation were lower (P=0.034, P=0.020). The higher the O/E LHR, the higher the ratio of time to peak tidal expiratory flow to total expiratory time (TPEF/TE) and the ratio of volume at peak tidal expiratory flow to expiratory tidal volume (VPEF/VE) (r=0.393, P=0.005; r=0.324, P=0.023). The less the duration of mechanical ventilation, the higher the TPEF/TE and VPEF/VE (r=-0.377, P=0.000; r=-0.314, P=0.002). Within 1 month after operation, obstructive ventilatory dysfunction occurred 6 times (46.2%), and obstructive ventilatory dysfunction was found 49 times (77.8%) 3 months after operation. In patients who received IPFT twice or more, with the increase of follow-up time, TV/kg, TEF75%, TEF50% and TEF25% in the last IPFT were higher than those in the first test (P=0.001, P=0.003, P=0.001, P=0.000), and the respiratory rate decreased (P=0.010). Conclusion·The tidal respiratory function of CDH children diagnosed before the first 25 weeks of pregnancy, with liver-up and intraoperative patch use is even worse. The main manifestation of early and late postoperative ventilatory dysfunction is obstruction. With the passage of time of postoperative follow-up, the pulmonary function of children with CDH is improved. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect that presents as either an isolated diaphragm defect or as part of a complex disorder with a wide array of anomalies (complex CDH). Some patients with complex CDH display distinct craniofacial anomalies such as craniofrontonasal dysplasia or craniosynostosis, defined by the premature closure of cranial sutures. Using clinical whole exome sequencing (WES), we found a BCL11B missense variant in a patient with a left-sided congenital diaphragmatic hernia as well as sagittal suture craniosynostosis. We applied targeted sequencing of BCL11B in patients with craniosynostosis or with a combination of craniosynostosis and CDH. This resulted in three additional BCL11B missense mutations in patients with craniosynostosis. The phenotype of the patient with both CDH as well as craniosynostosis was similar to the phenotype of previously reported patients with BCL11B missense mutations. Although these findings imply that both craniosynostosis as well as CDH may be associated with BCL11B mutations, further studies are required to establish whether BCL11B variants are causative mutations for both conditions or if our finding was coincidental.

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research.

TITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that Titf1 null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this study, we aim to evaluate the role of TITF1 in the pathogenesis of congenital diaphragmatic hernia (CDH) in humans. We investigated TITF1 expression in human trachea and lungs and performed direct mutation analysis in a CDH population. We studied 13 human fetuses at 14 to 24 weeks of gestation. Five μm sections were fixed in paraformaldehyde and incubated with anti-TITF1 primary antibody. Positive staining was visualized by biotinylated secondary antibody. We also performed TITF1 screening on genomic DNA extracted from peripheral blood of 16 patients affected by CDH and different degrees of PH, searching for mutations, insertions, and/or deletions, by sequencing the exonic regions of the gene. Histochemical studies showed positive brown staining of fetal follicular thyroid epithelium, normal fetal trachea, and normal fetal lung bronchial epithelium. Fetal esophageal wall was immunohistochemically negative. Molecular genetic analysis showed complete identity between the sequences obtained and the Wild Type (WT) form of the gene in all cases. No mutation, insertion and/or deletion was detected. Although TITF1 is expressed in the human fetal lung and has been considered to have a role in the pathogenesis of PH in CDH, the results of our study do not support the hypothesis that TITF1 mutations play a key role in the etiopathogenesis of CDH.

Aim: The optimal gestational age (GA) at delivery and mode of delivery (MoD) for pregnancies with fetal congenital diaphragmatic hernia (CDH) is undetermined. The impact of early term (37–38 weeks 6 days) versus full term (39–40 weeks 6 days) and MoD on immediate neonatal outcomes in prenatally diagnosed isolated CDH cases was evaluated. Material and Methods: A retrospective chart review of pregnancies evaluated and delivered with the prenatal diagnosis of CDH between July 1, 2008, and December 31, 2018. The primary outcome was survival to hospital discharge. Secondary outcomes included neonatal intensive care unit (NICU) length of stay (LOS), extracorporeal membrane oxygenation (ECMO) requirement and need for supplemental oxygen at day 30 of life. Results: A total of 296 patients were prenatally evaluated for CDH and delivered in a single center during the study period. After applying exclusion criteria, data were available on 113 women who delivered early term and 72 women who delivered full term. Survival to hospital discharge was comparable between the 2 groups – 83.2% in the early term versus 93.1% in the full term (p = 0.07; 95% CI of 0.13–1.04). No difference was observed in any other secondary outcomes. MoD was stratified into spontaneous vaginal, induced vaginal, unplanned cesarean and scheduled cesarean delivery with associated neonatal survival rates of 74.2, 90.6, 89.7 and 88.2%, respectively, p = 0.13. The 5-min Apgar score was higher in the elective cesarean group (7.94) followed by the induced vaginal delivery group (7.8) compared to 7.17 and 7.18 in the spontaneous vaginal and unplanned cesarean groups, respectively (p = 0.03). The GA and MoD did not influence survival to hospital discharge nor NICU LOS in multivariate analysis. Conclusions: Though there were no significant differences in neonatal outcomes for early term compared to full term deliveries of CDH neonates, a trend toward improved survival rates and lower ECMO requirements in the full term group may suggest an underlying importance GA at delivery. Further studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Bochdalek hernia is an inherited posterior lateral defect in the diaphragm that allows the abdominal organs to herniate into the thoracic cavity. In addition to being the most prevalent variety of congenital diaphragmatic hernia (CDH), it is also the type that is observed on the left hemithorax the majority of the time. Ectopic kidney is an uncommon condition, and the occurrence of ectopic intrathoracic kidney is even more uncommon, accounting for only a few of all the cases of renal ectopias. The occurrence of intrathoracic kidney associated with Bochdalek hernia is infrequent among adult individuals and is typically an incidental finding. A 52-year-old obese female patient presented to the pulmonology outpatient unit and reported experiencing the symptoms of coughing, wheezing, and difficulty in breathing since three years. A chest radiograph revealed an elevated dome of the diaphragm on the right side. A computed tomography (CT) of the chest revealed a defect in the posterior aspect of the right hemi-diaphragm with herniation of the right kidney and retroperitoneal fat into the right hemi-thorax. CT urography showed normal size and enhancement of the intrathoracic kidney with prompt excretion of contrast into the pelvicalyceal system. With regard to the small size of the hernia and considering the absence of complications on CT urography, a conservative treatment was proposed to the patient. The patient was followed up every year. There was no occurrence of renal complications during the follow-up period. When evaluating patients with 'elevated hemi-diaphragm' or thoracic 'mass', it is essential to check for the presence of intrathoracic kidney to avoid undesirable surgical procedures and image-guided biopsies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kummari et al.)

Congenital diaphragmatic hernia (CDH) is a complex and highly variable disease process that should be treated at institutions with multidisciplinary teams designed for their care. Treatment in the neonatal period focuses on pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Extracorporeal membrane oxygenation (ECMO) can be considered in patients refractory to medical management. Repair of CDH early during the ECMO course seems to improve mortality compared with other times for surgical intervention. The choice of surgical approach to CDH repair should consider the patient's physiologic status and the surgeon's familiarity with the operative approaches available, recognizing the pros/cons of each technique., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-602/coif). A.A.B. receives royalties from UpToDate and in-kind donation of fetoscopy sheath equipment from Karl Storz. J.L.M. is supported by Janssen Research and Development, LLC; serves as a Data Safety Monitoring Board member for FETO, and on the Executive Board of the North American Fetal Therapy Network. The other authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Congenital diaphragmatic hernias (CDH) confer substantial morbidity and mortality. Genetic defects, including chromosomal anomalies, copy number variants, and sequence variants are identified in ~30% of patients with CDH. A genetic etiology is not yet found in 70% of patients, however there is a growing number of genetic syndromes and single gene disorders associated with CDH. While there have been two reported individuals with X‐linked Opitz G/BBB syndrome with MID1 mutations who have CDH as an associated feature, CDH appears to be a much more prominent feature of a SPECC1L‐related autosomal dominant Opitz G/BBB syndrome. Features unique to autosomal dominant Opitz G/BBB syndrome include branchial fistulae, omphalocele, and a bicornuate uterus. Here we present one new individual and five previously reported individuals with CDH found to have SPECC1L mutations. These cases provide strong evidence that SPECC1L is a bona fide CDH gene. We conclude that a SPECC1L‐related Opitz G/BBB syndrome should be considered in any patient with CDH who has additional features of hypertelorism, a prominent forehead, a broad nasal bridge, anteverted nares, cleft lip/palate, branchial fistulae, omphalocele, and/or bicornuate uterus. [ABSTRACT FROM AUTHOR]

Background: Failure to thrive (FTT) is a common underlying condition in patients with Congenital diaphragmatic hernia (CDH). The aim of current study was to evaluate nutritional status and growth pattern in CDH patients. Methods: In current study, we investigated a total of 146 CDH patients who had undergone surgery in Dr. Sheikh Hospital, Mashhad, Iran between April 2006 to November 2013. Due to inaccessibility or lack of cooperation by some parents, 61 cases completed the study. Demographic and anthropometric data along with postoperative complications were taken into consideration. Results: Among the 61 studied cases, 32.7% had died during the initial 6-months after surgery. The mean age of participants was 24.21 ± 30.26 months. According to Z-score classification of weight for height following surgery, 7.3% had severe malnutrition, 4.8% moderate malnutrition and 24.3% mild malnutrition while 51.2% were normal. While current evaluation indicates that the majority of subjects were in the normal range. Conclusion: Most children with congenital diaphragmatic hernia had a normal growth following surgery; however, few cases experienced a reduced growth rate in the early years of their life. Highlighting the need for additional calories to prevent FTT and other complications are recommended.

Abstract Background Newborns with congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) might experience breastfeeding difficulties. The aim of this study was to detect the prevalence of breastfeeding in newborns with CDH and EA at different time points. Methods We performed an epidemiological study and retrospective survey on the prevalence of breastfeeding in CDH and EA affected newborns. We identified 40 CDH and 25 EA newborns who were fed through breastfeeding procedures according to WHO categorized definitions, and compared the breastfeeding procedures at the beginning of hospitalization and at three months of life. Results Although all the mothers attempted breastfeeding after birth, only 44 (67.7%) were still breastfeeding at the time of discharge. Exclusive breastfeeding was successful for only 19 (29%) mothers. The rate of exclusive breastfeeding at three months of life did not differ statistically from discharge and between the two groups of study. Conclusion A large percentage of mothers of children with CDH and EA who breastfed at the beginning of hospitalization did not continue at three months. It would be important to increase the breastfeeding rate in CDH and EA affected newborns by following specific steps for vulnerable infants and sustaining breastfeeding after discharge.