Risk factors for recurrence of congenital diaphragmatic hernia in the era of minimally invasive surgery.

Born under pressure: cardiac adaptation in congenital diaphragmatic hernia.

Congenital Diaphragmatic Hernia (CDH) is associated with significant cardiopulmonary morbidity. Pulmonary Hypertension (PH) and left ventricular (LV) dysfunction are major determinants of outcome. While the impact of CDH repair on pulmonary hemodynamics is recognized, comprehensive serial assessment of cardiac performance, specifically LV dimensions and function, surrounding surgical repair is limited. To characterize changes in LV dimensions, systolic/diastolic function, and global cardiac performance in neonates with CDH immediately before and within 48-72h after surgical repair. A prospective observational cohort study conducted between January 2022 and January 2025 in our tertiary center. Term neonates with isolated, left-sided Bochdalek CDH requiring surgical repair were included. Comprehensive transthoracic echocardiography (TTE) was performed at three time points: (1) Pre-Operative (Pre-Op): Within 24h before repair (after initial stabilization), (2) Early Post-Operative (E-Post-Op): 48-72h after completion of surgical repair. (3) One-month Post-Operative (M-Post-Op): One month after completion of surgical repair. Parameters measured from the LV and from the right ventricle (RV), Ventilator settings, inotrope score, and vasoactive-inotrope score (VIS) were recorded concurrently. Data were recorded and analyzed. Thirty neonates met the inclusion criteria (Median gestational age: 38 weeks [IQR 37-39], Birth weight: 3.0kg [IQR 2.7-3.3]). Significant PH was present pre-operatively in 70% (n = 21). Parameters of LV dimensions and function revealed: Left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD) (absolute and z-score) increased significantly early and one-month post-repair (p < 0.05*). Left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) decreased significantly in the early post-operative period, then increased again to their normal levels one-month post-repair (p < 0.05*). The decrease in LV systolic function correlated with higher peak Post-Op VIS (r = -0.45, p = 0.01). Improvement in LVEDD correlated with lower oxygen requirements at 7 days post-op (r = -0.38, p = 0.03). The mitral inflow E/A ratio decreased significantly early post-repair and then improved for one month (p = 0.004*), while the average E/e' ratio did not change significantly. Parameters reflecting RV systolic function improved immediately post-repair: Tricuspid annular plane systolic excursion (TAPSE) and Right Ventricular global longitudinal strain (RVGLS) increased significantly (p < 0.05*). Estimated systolic pulmonary artery pressure (ESPAP) decreased significantly (p = 0.002*) and ventricular septal flattening was significantly less common post-repair. Surgical repair of CDH induces significant acute changes in cardiac performance. While reduction of herniated viscera rapidly improves LV dimensions (indicating relief of compression) and RV function/PAP, it is also associated with a transient impairment in LV systolic function and altered diastolic relaxation pattern in the immediate post-operative period.

Targeted use of Prostaglandin E1 Therapy in "Duct-dependent" Congenital Diaphragmatic Hernia.

Non-invasive removal of the Smart tracheal occlusion device for fetal congenital diaphragmatic hernia: a single-arm, open-label, phase 1 study.

The next step towards lower complication rates in fetal therapy for congenital diaphragmatic hernia.

To assess for differences in congenital diaphragmatic hernia patient characteristics between those requiring single or multiple intubation attempts, and to determine the relationship between number of intubation attempts and time to intubation with outcomes. This was a retrospective cohort study of 205 infants with congenital diaphragmatic hernia born at Texas Children's Hospital. Patient demographics and severity numbers were compared to number of laryngoscopies as a surrogate for intubation attempts. Number of laryngoscopies and time to intubation were compared to clinical outcomes. Binary logistic regression and receiver operating characteristic curve analysis were used. There was no significant difference in baseline characteristics or CDH severity in those requiring single or multiple attempts. Greater number of intubation attempts was not associated with adverse outcomes but there was a significant association between longer time to successful intubation and mortality and higher risk of tracheostomy or death before discharge. Each additional minute before successful intubation was associated with 28% higher odds of mortality (p = 0.031) and 42% higher odds of tracheostomy or death before discharge (p = 0.006) CONCLUSION: Delayed time to intubation but not number of intubation attempts was associated with higher mortality and risk of tracheostomy or death in babies with CDH. Prenatal information including receipt of the FETO procedure, CDH severity markers, gestational age and birth weight cannot reliably be used to predict the likelihood of challenging intubations in infants with CDH.

To assess whether vasoactive-inotropic score (VIS) during early life was predictive of outcomes for infants with congenital diaphragmatic hernia and to determine whether VIS differed by defect size and laterality. Retrospective single-center cohort study of 206 infants with CDH. VIS was calculated at 6, 12, 24, 48 and 72 h of life as well as at repair, 24 h and 48 h-post repair. Higher VIS scores at all time points were associated with an increased risk of mechanical ventilation at 28 days of life (p < 0.02). VIS in the first 24 h was associated with an increased risk ECMO or death (p < 0.001) and tracheostomy or death (p < 0.02). VIS did not differ between left and right defects, but larger defects had higher scores. Early-life VIS scores at 6, 12 and 24 h have predictive value for extended duration of mechanical ventilation, ECMO, tracheostomy or death.

To examine national trends in bivalirudin use among neonates with congenital diaphragmatic hernia (CDH) supported with extracorporeal membrane oxygenation (ECMO) and to evaluate its association with mortality and morbidity. Preliminary data suggest that first-line anticoagulation of the ECMO circuit with bivalirudin, a direct thrombin inhibitor, may improve outcomes in neonates with CDH. This multicenter retrospective cohort study used data from 48 United States children's hospitals from January 1, 2016, to December 31, 2023. The analytic cohort included neonates with CDH supported with ECMO. Patients were categorized by anticoagulant exposure: bivalirudin or unfractionated heparin. The primary outcome was in-hospital mortality. Secondary outcomes included anticoagulant utilization and anticoagulant-associated morbidity. Multivariable logistic regression models were constructed after exclusion of extreme high-volume center outliers. Among 1,049 neonates, bivalirudin use increased significantly over time, from 9.6% in 2016 to 48.0% in 2023. In the final cohort of 820 neonates, 398 died in hospital (48.5% mortality). Median hospital charges were higher among neonates receiving bivalirudin [$876,054 (IQR, $652,735 - $1,366,728)] compared with heparin [$577,326 (IQR, $384,468 - $871,769); P<0.0001]. Bivalirudin use was not associated with in-hospital mortality [adjusted odds ratio (aOR), 1.08, 95% CI, 0.42-2.82; P=0.87], bleeding (aOR, 1.43, 95% CI, 0.54-3.82; P=0.47), thrombosis (aOR, 1.88; 95% CI, 0.65-5.41; P=0.24), or neurologic complications (aOR, 2.00; 95% CI, 0.81-4.91; P=0.13). Among neonates with CDH supported with ECMO, bivalirudin use increased substantially over the study period and was associated with higher hospital charges but not with improved survival or reduced ECMO-related morbidity compared with unfractionated heparin.

Serum biomarkers of right ventricular (RV) fibrosis associate with adverse outcomes in right heart conditions. Urinary protein profiling may be preferable in critically ill infants, but its feasibility is unknown. We sought to characterize the urinary proteome in conditions affecting the RV-Tetralogy of Fallot (TOF) and congenital diaphragmatic hernia (CDH)-and to explore the impact of surgery. Urine from 53 infants (19 CDH, 17 TOF, 17 controls) was analyzed in this prospective single-center pilot study. Protein detection and quantification were performed by mass spectrometry with data-independent acquisition. Groups were compared via Voom/Limma in R, and significantly different proteins were surveyed for pathway enrichment. Pre-operatively, both CDH and TOF samples clustered away from controls. Post-operatively, TOF normalized towards controls, whereas CDH remained segregated. In CDH, proteins that differed significantly from controls and changed with surgery were clustered into cell-cell adhesion/junction, complement activation, and immune regulation. In TOF, post-operatively upregulated proteins were critical to prostanoid/prostaglandin metabolism, purine metabolism, and glutathione metabolism/oxidative stress, while post-operatively normalized proteins were critical to extracellular matrix organization and platelet regulation. RV pathologies demonstrate distinct urinary proteomic signatures. Future studies should investigate associations between urinary biomarkers, RV function, and clinical outcomes. Serum biomarkers of right ventricular (RV) fibrosis associate with adverse outcomes in tetralogy of Fallot (TOF), but data are limited in other RV pathologies including congenital diaphragmatic hernia (CDH). Urinary proteomics may be preferable to blood sampling in critically ill infants, but the feasibility is unknown. We demonstrated that urinary proteins in TOF and CDH differ from healthy controls. TOF proteins broadly normalize post-operatively, while the abnormal CDH proteome persists, indicating that surgery does not modify the underlying physiology in CDH. These data provide a foundation to study associations between urinary proteomics and RV function.

BackgroundCongenital diaphragmatic hernia is an important cause of neonatal morbidity and mortality, primarily because of pulmonary hypoplasia and pulmonary hypertension. Early postnatal risk stratification may improve prognostication and guide escalation of care. We aimed to identify early postnatal predictors of mortality and to derive a simple bedside mortality risk score for neonates with isolated congenital diaphragmatic hernia.MethodsWe conducted a retrospective cohort study of newborns with isolated congenital diaphragmatic hernia admitted to a tertiary-care NICU within 6h of life between 2004 and 2025. Clinical and physiologic variables, including Day-1 oxygenation, inotrope requirement and preoperative pneumothorax, were extracted from the medical records. Receiver operating characteristic analysis and Firth penalized logistic regression were performed. A bedside score, the Neonatal Congenital Diaphragmatic Hernia Mortality Risk Score (NCMRS-6), was derived from early predictors and internally evaluated using bootstrap resampling.Results66 newborns were included, of whom 52 (78.8%) survived to discharge. Non-survivors had a significantly higher Day-1 oxygenation index than survivors (median 64.0 vs 6.3; p < 0.001) and more frequent inotropic requirement (100% vs 40.4%; p < 0.001). Preoperative pneumothorax was also more common among non-survivors (46.2% vs 7.7%; p = 0.003). Day-1 oxygenation index alone showed excellent discrimination for mortality (area under the curve 0.945). The NCMRS-6, combining Day-1 oxygenation index tiers, inotrope requirement, and preoperative pneumothorax, demonstrated an area under the curve of 0.964 (95% confidence interval 0.894-1.000). A threshold of at least four points yielded 92.3% sensitivity and 90.4% specificity.ConclusionsDay-1 oxygenation index, inotrope requirement and preoperative pneumothorax are important early predictors of mortality in isolated congenital diaphragmatic hernia. The NCMRS-6 is a simple bedside risk-stratification tool with promising discriminatory ability, but external validation is required before broader clinical application.

Correlation of Oxygen Saturation Index with Oxygenation Index in Congenital Diaphragmatic Hernia: in A Secondary Analysis of a Randomized Clinical Trial.

Minimally invasive surgery (MIS) for congenital diaphragmatic hernia (CDH) has previously been associated with higher recurrence rates and uncertain indications compared with open surgery. Since 2017, the Japanese Congenital Diaphragmatic Hernia Study Group (JCDHSG) has implemented a standardized national protocol, potentially improving perioperative management and surgical outcomes. This multicenter retrospective study analyzed 1,081 infants who underwent definitive CDH surgery at 15 tertiary centers in Japan between 2007 and 2023. Patients were categorized by surgical approach and period: early-period MIS (≤ 2016, n = 62), late-period MIS (≥ 2017, n = 109), early-period open (≤ 2016, n = 536), and late-period open (≥ 2017, n = 374). In-hospital mortality was assessed for the "Intended-MIS" group (including conversions), while surgical outcomes and recurrence were evaluated for the "Complete-MIS" group (successfully completed procedures without conversion). In the Intended-MIS group, the conversion rate dropped significantly from 29% in the early period to 10% in the late period (p < 0.01). Compared with the early period, the late-period MIS group had lower severity indices (oxygenation index < 8: 76.6% vs. 93.3%, p = 0.012; Terui category 3: 11.4% vs. 1.1%, p = 0.007). In the Complete-MIS group, early postoperative recovery improved, with a higher rate of ventilator weaning within 7days (20% vs. 58.3%, p < 0.001). The recurrence rate at discharge in the Complete-MIS group decreased significantly (8.2% vs. 1.0%, p = 0.044), while remaining unchanged in the open surgery group. In-hospital mortality in the Intended-MIS group was eliminated in the late period (3.2% vs. 0%, p = 0.252). Following nationwide protocol implementation, MIS for CDH has evolved into a safe and effective alternative to open surgery in carefully selected neonates. Improved patient selection based on physiologic severity, stabilization of technical proficiency, and advances in perioperative management have led to earlier respiratory recovery and a significant reduction in recurrence.

The EXTra-uterine Environment for Neonatal Development (EXTEND) - future treatment for prematurity and potentially other congenital disease.

Long-term follow-up after surgery for congenital anomalies: A time to complication analysis.

OBJECTIVES:To evaluate neonatal and pediatric extracorporeal membrane oxygenation (ECMO) referrals and transfers to a high-volume center and optimize the process of ECMO referrals and decision-making.DESIGN:This retrospective study analyzed ECMO referrals, focusing on various patient parameters during the request, transport, use of ECMO, and outcome. Data were grouped into transferred and nontransferred neonates and children.SETTING:This study analyzes ECMO referrals and transfers to the Clinic of Neonatology and Pediatric Intensive Care at an ECMO center between 2015 and 2023.PATIENTS:A total of 348 neonatal and pediatric ECMO referrals were included in the analysis.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Neonates were transferred at a higher rate (79/189 patients, 41.8%) than pediatric patients (40/159 patients, 25.2%). The leading neonatal diagnoses (data available n = 164) were meconium aspiration syndrome (59/164 patients, 36%), congenital diaphragmatic hernia (35/164 patients, 21.3%), and persistent pulmonary hypertension (27/164 patients, 16.5%). In pediatric patients (data available n = 133), viral pneumonia was most common (61/133 patients, 45.9%). A significant association (Kruskal-Wallis test) was found between the Vasoactive-Inotropic Score (VIS) and ECMO initiation for transferred patients (p < 0.05), as well as a higher oxygenation index (OI, calculated immediately after the transfer) in ECMO groups of transferred patients (p < 0.001; t test). Most transfers (82/107 patients, 76.6%) were performed by helicopter. Neonatal ECMO survival was 90.2% (37/41 patients; vs. Extracorporeal Life Support Organization [ELSO] 69%); pediatric ECMO survival was 57.1% (4/7 patients; vs. ELSO 64%).CONCLUSIONS:Structured referral processes, early telemedical contact, and standardized networks may improve ECMO outcomes and resource use. VIS and OI could be valuable tools for ECMO decision-making.

Congenital diaphragmatic hernia is a critical neonatal condition frequently associated with growth impairment. Nutritional strategies to support adequate growth remain poorly defined. To evaluate the association between caloric and protein intake, timing of parenteral and enteral nutrition, and changes in anthropometric z-scores during neonatal hospitalization in infants with congenital diaphragmatic hernia. Retrospective cohort study including infants with congenital diaphragmatic hernia who underwent surgical repair at a single center between 2018 and 2023. Data were collected from birth to discharge or 12th week of hospitalization. Weekly deltas in anthropometric z-scores-weight-for-age, length-for-age, and head circumference-for-age-were calculated. Daily caloric and protein intakes were estimated and averaged weekly; timing of parenteral and enteral nutrition and disease-related factors were obtained and associations with anthropometric z-score deltas were analyzed. A total of 117 infants were included. Overall, 65% experienced z-score declines ≥0.8 across all anthropometric z-scores. Receiver operating characteristic (ROC) curve analysis identified a caloric intake of 113 kcal/kg/day as predictive of positive weight-for-age z-score deltas (area under curve 0.67) with improved specificity at 118 kcal/kg/day. In multivariable linear mixed-effects model, higher caloric intake (p < 0.001) and longer duration of mechanical ventilation (p = 0.01) were independently associated with positive weekly weight-for-age z-score deltas. Additionally, higher caloric intake was independently associated with positive weekly head circumference-for-age z-score deltas (p = 0.02). Growth impairment during hospitalization was highly prevalent among infants with congenital diaphragmatic hernia. A caloric intake of at least 113 kcal/kg/day, with an optimal threshold near 118 kcal/kg/day, may help prevent further deterioration in weight status.

To describe mortality, surgical treatment, and hospitalization patterns in children with congenital diaphragmatic hernia (CDH) using population-based data, linked to congenital anomaly registries across Europe. This cohort study used nine EUROCAT registries in five countries (Denmark, Finland, Italy, Spain, and the United Kingdom) linked to routinely collected hospital and mortality data. Children born alive with CDH between 2005 and 2014 were included and followed until age 5 in hospital data or age 10 in death data, with the final follow-up the end of 2015. Analyses were conducted for all CDH cases and separately for isolated CDH (CDH without additional major congenital anomalies). Standardized data processing and meta-analysis methods were used to generate pooled estimates of mortality, surgical interventions, and hospital stays. Among 567 children with CDH, most were isolated CDH. First year survival was 74.5% for isolated CDH, ranging from 63% to 83% between registries. Similar survival was noted for all children with CDH. Most deaths occurred within the first week. Mortality rates plateaued after infancy, with no deaths recorded after age 5. The median age at surgery was approximately 2 weeks, although this varied by region. Median hospital length of stay in infancy varied from 14 to 29 days between regions. In children with CDH, mortality is highest in the neonatal period, with long-term survival stabilizing after infancy. No deaths occurred after age 5 years. Regional differences in mortality and surgical timing highlight the value of population-based, harmonized data for benchmarking and international comparisons.

To evaluate the impact of cardiac lesions on outcomes to discharge in infants with congenital diaphragmatic hernia (CDH). Retrospective analysis of infants with CDH identified in the Children's Hospitals Neonatal Database (CHND) from 2010 to 22. Patients were stratified into groups based on associated congenital heart disease (CHD): (1) noCHD (2) CDH + atrial, ventricular septal defects (avCHD); (3) CDH + severe CHD (sevCHD). Among 2940 neonates with CDH, 570 (19%) had CHD (453 avCDH, 117 sevCHD). CHD of any severity was associated with small for gestational age at birth, a 5 minute Apgar <5, and additional anomalies or syndromes (p < 0.05 for all). Mechanical ventilation days, use of extra-corporeal membrane oxygenation, length of stay, and mortality increased with CHD severity (p < 0.005). Home medical needs were more frequent in infants with associated CHD (p < 0.001). Comorbid CHD of any severity adds complexity and risk to patients with CDH.

Congenital diaphragmatic hernia (CDH) is a rare malformation with high neonatal mortality. Although advances in management have improved survival rates, long-term morbidity remains substantial, and its impact on the health care system, particularly hospital readmissions, remains poorly described. To describe the incidence, causes, and factors associated with hospital readmission and late mortality after discharge from the primary stay. This nationwide retrospective cohort study was conducted from 2012 to 2024 and used data from the French National Health Data System, capturing nationwide health insurance claims and hospital discharge records in France. Participants were children with CDH who underwent surgical repair within the first 6 months of life, and were discharged alive from the primary stay. Data were analyzed from January to October 2025. The main outcomes were readmission to an acute care facility within 3 years after discharge and death during follow-up. Factors associated with readmission were identified using multivariable analysis. Of the 1028 included infants (median [IQR] birth weight, 3050 [2720-3410] g; 849 [82.6%] with full-term birth; 630 [61.3%] male infants), 753 had at least 3 years of follow-up (median [IQR] time of follow-up, 6.2 [2.6-9.1] years), constituting the overall sample size for the primary analysis. Of them, 546 children (72.5%) were readmitted at least once, and 182 (24.2%) required intensive care. At 3 years, 208 (38.0%), 112 (20.5%), and 127 (23.3%) children had experienced at least 1 readmission for respiratory causes, gastrointestinal and/or nutritional issues, and CDH-related surgical complications, respectively. Preterm birth (incidence rate ratio [IRR], 1.32; 95% CI, 1.10-1.60), associated congenital anomalies (IRR, 1.31; 95% CI, 1.13-1.53), a primary stay longer than 1 month (IRR, 1.50; 95% CI, 1.27-1.76), oxygen therapy at discharge (IRR, 2.14; 95% CI, 1.55-2.99), and enteral feeding at discharge (IRR, 2.21; 95% CI, 1.83-2.68) were independently associated with readmission. Fourteen late deaths (14 of 1028 infants [1.4%]) were recorded, attributable to CDH-related complications or associated comorbidities in half of cases. Enteral feeding at discharge was also independently associated with late mortality (hazard ratio, 5.09; 95% CI, 1.33-19.48). In this cohort study of 1028 children with CDH, nearly three-quarters were readmitted within 3 years, but late mortality was low. Although enteral feeding at discharge likely reflected CDH severity, it may also represent a potentially modifiable target that warrants further investigation to improve outcomes.