Search

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]

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]

• 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]

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]

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]

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]

To evaluate the results in CDH patients subjected to a second course of ECMO at a single institution. Retrospective review of medical charts of patients treated for CDH and ECMO in our center since 1990 to December 2018 was performed. For patients subjected to a second course of ECMO and who survived to hospital discharge charts from follow up visits were also reviewed. From Jan 1990 until December 2018, 311 patients with CDH were treated in the department. 267 of these (86%) were discharged alive from the hospital and 81% (237/293) of the Swedish patients were alive by December 2018. 101 patients (32%) were subjected to ECMO treatment of whom 71 survived (70%). 22 patients underwent a second ECMO run and 13 of these survived to hospital discharge. Seven of the Swedish patients [ 19 ] were long-term survivors (37%). The vast majority was on V-A ECMO. It is possible to recannulate the right common carotid artery and internal jugular vein for a second course of venoarterial ECMO in CDH patients, who deteriorate severely after decannulation. Previous research has shown that long-term survivors subjected to ECMO twice reported similar frequencies of pulmonary, gastrointestinal, neurological and musculoskeletal sequelae as the long-term survivors, who needed ECMO support only once, and similar health-related quality of life. Regarding their psychosocial function, they scored within normal range in the behavioral, emotional and social scales domains. A second ECMO run may contribute to a higher survival and that the long-term morbidity among survivors is not more pronounced than among survivors after a single course of ECMO. It is therefore suggested that a second course of ECMO should be offered on the same indications as the first course. III Case series. [ABSTRACT FROM AUTHOR]

Although longer ECMO run times for patients with congenital diaphragmatic hernia (CDH) have been associated with worse outcomes, a large study has not been conducted to examine the risk factors for long ECMO runs. The Extracorporeal Life Support Organization (ELSO) Registry from 2000 to 2015 was used to identify predictors of long ECMO runs in CDH patients. A long run was any duration of ≥ 14 days. Multivariable logistic regression models were used to examine the association between demographics, pre-ECMO blood gas/ventilator settings, comorbid conditions, and therapies on long ECMO runs. There were 4730 CDH-infants examined. The largest association with long ECMO runs was on-ECMO repair (OR: 3.72, 95% CI: 3.013–4.602, p < 0.001) and the use of THAM (OR: 1.463, 95% CI: 1.062–2.016, p = 0.02). Each drop in pH quartile was associated with an increased risk of long ECMO run: pH ≥ 7.3 (reference), pH 7.2–7.9 (OR 1.24, 95% CI: 0.98–1.57, p = 0.07), pH 7.08–7.19 (OR 1.46, 95% CI: 1.17–1.84, p = 0.001), pH ≤ 7.07 (OR 1.64, 95% CI: 1.29–2.07, p < 0.001). We found a correlation between both pre-ECMO demographics/timing of repair and the subsequent risk of long ECMO runs, providing insight for both providers and parents about the risk factors for longer runs. Treatment Study. Level III. [ABSTRACT FROM AUTHOR]

Prosthetic patch (patch) and muscle flap (flap) techniques are utilized for severe congenital diaphragmatic hernia (CDH) repair; however, when performed on extracorporeal membrane oxygenation (ECMO), the risk of hemorrhage increases. We sought to compare bleeding complications between repair types. We retrospectively reviewed 2010–2016 on-ECMO CDH repairs. Twenty-nine patients met criteria: 13 patch (44.8%) and 16 flap (55.2%). Eight patch (61.5%) and 13 flap (81.2%) patients had left-sided defects (p = 0.223). All defects were Type C or D (Type C: patch 53.8%, flap 56.2%, p = 0.596). There was no difference in gestational age at delivery (patch 37.5 ± 0.9 weeks, flap 37.2 ± 1.3 weeks, p = 0.390) or age at repair (patch 7.46 ± 6.6 days, flap 6.00 ± 4.3 days, p = 0.476). Seven patch (53.8%) and 9 flap (56.2%) patients survived to discharge (p = 0.596). Estimated intraoperative blood loss was equivalent (patch 35.3 ± 53.9 mL, flap 24.2 ± 18.4 mL, p = 0.443). One patch patient (7.6%) and two (12.5%) flap patients required reoperation in the first 48 h for bleeding (p = 0.580). 48-h postoperative transfusions were the same for those that required reoperation (patch 282.0 mL/kg, flap 208.5 ± 21.9 mL/kg, p = 0.054) and those that did not (patch 120.7 ± 111.7 mL/kg, flap 118.4 ± 89.9 mL/kg, p = 0.561). On-ECMO bleeding complications are equivalent for both flap and patch CDH repair. Type III (retrospective comparative study) [ABSTRACT FROM AUTHOR]

"Early on-ECMO" repair of CDH entails repair within 48–72 h of cannulation in an effort to optimize pulmonary physiology, shorten ECMO duration, and, ultimately, improve survival. This study evaluated the effect of early on-ECMO repair as compared to leaving patients unrepaired during ECMO. The CDH Study Group database was queried for CDH patients requiring ECMO who either underwent repair within the first 72 h after cannulation or remained unrepaired on ECMO. Primary outcomes were survival to decannulation and ECMO duration. A total of 248 patients underwent early repair and 922 remained unrepaired on ECMO. The early repair group had increased risk factors for poor outcomes, including higher odds of cardiac defects and thoracic liver location, and lower odds of hernia sac presence. Nonetheless, ECMO survival for the early repair group was 87.1% compared to 78.4% in the unrepaired group (p = 0.002). However, the early repair group had a longer median ECMO duration than the unrepaired group (240.6 vs 196.8 h, p = 0.001). While early ECMO repair does not shorten ECMO duration, it results in increased survival to decannulation as compared to those unrepaired on ECMO. This suggests that there may be a physiologic benefit leading to increased ECMO survival in a subset of patients undergoing on-ECMO repair over those designated to undergo post-ECMO repair. Level III. [ABSTRACT FROM AUTHOR]

Support on Extracorporeal oxygenation membrane (ECMO) represents the last therapeutic option in the management of respiratory failure and pulmonary hypertension refractory to treatment in patients with congenital diaphragmatic hernia (CDH). The objective of this work was to present our experience of all the cases of CDH that we have transported on ECMO. Medical records of patients, national and international, with CDH transported by our service on ECMO from 1997 to 2018 were reviewed. During 22 years, we performed 40 ECMO transports of newborns with CDH, 39 primary and one secondary. In 10% (4/40) we transferred patients from their primary hospital after the implantation of cannulae and commencement of ECMO to another center abroad owing to the lack of beds in our unit. Twenty (50%) of the transports were from a foreign country. Median transport distance was 560 (428–1381) km and the median transport time was 4.5 (4.2–6.3) h. The mode of transport was ground ambulance in 20%, helicopter in 10%, fixed wing aircraft in 62.5% and ground ambulance in Freight aircraft in 7.5%. In 40% of the transports, 20 complications occurred. In one of every four transports with complications, more than one event occurred. Most frequent complication was loss of tidal volumes (35%) and in 30% of the complications another patient related event was recorded. Equipment failure occurred in 20%, and climate problems and transport vehicle problems in 15%. No deaths occurred during transport. Venoarterial ECMO was used in 39 of the 40 cases. Survival to discharge was 87% for the entire period and long-term survival was 77%. Long and short distance interhospital transports of CDH patients on ECMO can be performed safely. Despite occurrence of adverse events, the risk of mortality is very low. The personnel involved must be highly competent in intensive care, physiology and physics of ECMO, cannulation, intensive care transport and air transport medicine. They must also be trained to recognize risk factors in these patients. III Retrospective cohort study. [ABSTRACT FROM AUTHOR]

Studying the timing of repair in CDH is prone to confounding factors, including variability in disease severity and management. We hypothesized that delaying repair until post-ECMO would confer a survival benefit. Neonates who underwent CDH repair were identified within the ELSO Registry. Patients were then divided into on-ECMO versus post-ECMO repair. Patients were 1:1 matched for severity based on pre-ECMO covariates using the propensity score (PS) for the timing of repair. Outcomes examined included mortality and severe neurologic injury (SNI). After matching, 2,224 infants were included. On-ECMO repair was associated with greater than 3-fold higher odds of mortality (OR 3.41, 95% CI: 2.84–4.09, p < 0.01). The odds of SNI was also higher for on-ECMO repair (OR 1.49, 95% CI: 1.13–1.96, p < 0.01). A sensitivity analysis was performed by including the length of ECMO as an additional matching variable. On-ECMO repair was still associated with higher odds of mortality (OR 2.38, 95% CI: 1.96–2.89, p < 0.01). Results for SNI were similar but were no longer statistically significant (OR 1.33, 95% CI: 0.99–1.79, p = 0.06). Of the infants who can be liberated from ECMO and undergo CDH repair, there is a potential survival benefit for delaying CDH repair until after decannulation. Treatment Study III [ABSTRACT FROM AUTHOR]

Tracheal occlusion (TO) reverses pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH), but its mechanism of action remains poorly understood. Wnt signaling plays a critical role in lung development, but few studies exist. The purpose of our study was to a) confirm that our CDH rabbit model produced PH which was reversed by TO and b) determine the effects of CDH +/− TO on Wnt signaling. CDH was created in fetal rabbits at 23 days, TO at 28 days, and lung collection at 31 days. Lung body weight ratio (LBWR) and mean terminal bronchiole density (MTBD) were determined. mRNA and miRNA expression was determined in the left lower lobe using RT-qPCR. Fifteen CDH, 15 CDH + TO, 6 sham CDH, and 15 controls survived and were included in the study. LBWR was low in CDH, while CDH + TO was similar to controls (p = 0.003). MTBD was higher in CDH fetuses and restored to control levels in CDH + TO (p < 0.001). Reference genes TOP1, SDHA, and ACTB were consistently expressed within and between treatment groups. miR-33 and MKI67 were increased, and Lgl1 was decreased in CDH + TO. TO reversed pulmonary hypoplasia and stimulated early Wnt signaling in CDH fetal rabbits. Basic science, prospective. II. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the accuracy of fetal echocardiogram (ECHO) for detecting cardiac structural anomalies that may impact Extracorporeal Membrane Oxygenation (ECMO) candidacy in infants with Congenital Diaphragmatic Hernia (CDH). A retrospective review was performed on fetuses with CDH (January 2007–June 2017). Inclusion criteria were inborn and at least one prenatal and postnatal ECHO. ECHOs were evaluated for structural heart defects. Primary outcomes were accuracy of prenatal fetal ECHO and identify differences between prenatal and postnatal ECHO. Descriptive statistics and Chi-square analysis were performed. 131 inborn patients were identified. Mean gestational age of fetal ECHO was 26.6 ± 5.5 weeks. The median time to postnatal ECHO was DOL 1 [0–30]. Fetal ECHO had 92% accuracy, 83% sensitivity, 93% specificity, PPV of 95%, NPV of 92%, and a 90% accuracy for visualization of at least one pulmonary vein into the left atrium on the contralateral (non-CDH) side. Thirty-five percent of patients received ECMO, and 26% had an associated cardiac anomaly. All ECMO patients had an accurate structural fetal ECHO. Fetal ECHO is sufficient for identifying major structural heart defects at large volume centers with trained pediatric cardiologists and may be used to guide clinical management, particularly in regards to ECMO candidacy. Level III. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify management preferences that may exist in the care of infants with CDH receiving ECMO with emphasis on VV-ECMO. A survey was created to measure treatment preferences regarding ECMO use in CDH. The survey was distributed to all APSA and ELSO/Euro-ELSO members via e-mail. Survey results were summarized using descriptive statistics. The survey had 230 respondents. The survey participants were surgeons (75%), neonatologists/intensivists (23%), and "other" (2%). The mean annual center volume was 11.6(± 9.6) CDH cases, and the average number treated with ECMO was 4.5 (± 6.4) cases/yr. The most agreed upon criteria for ECMO initiation were preductal O 2 saturation < 80% refractory to ventilator manipulation and medical therapy (89%), oxygenation index > 40 (80%), severe air-leak (79%), and mixed acidosis (75%). Over 60% of respondents agreed the VV-ECMO would be optimum for average risk neonates. However, this preference diminished as the pre-ECMO level of cardiac support increased. When asked about why each respondent would choose VA-ECMO over VV-ECMO, the responses varied significantly between surgeons and non-surgeons. While there seem to be areas of consensus among practitioners, such as criteria for initiation of ECMO, this survey revealed substantial variation in individual practice patterns regarding the use of ECMO for CDH. Qualitative, Survey. IV. [ABSTRACT FROM AUTHOR]

Abstract Background The benefits to early repair (< 72 h postcannulation) of infants with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO) are increasingly recognized. Yet it is not known if even earlier repair (< 24 h) results in comparable or improved patient outcomes. The goal of this study was to compare "super-early" (< 24 h) to early repair (24-72 h) of CDH patients on ECMO. Methods A retrospective review of infants with CDH placed on ECMO (2004–2017; n = 72) was performed. Data collected on the patients repaired while on ECMO within 72 h of cannulation (n = 33) included pre- and postnatal disease severity stratification variables and postnatal outcomes. Comparison groups were those patients repaired within 24 h of cannulation (n = 14) and those repaired between 24 and 72 h postcannulation (n = 19). Results Patients undergoing "super-early" (< 24 h) repair had an average survival of 71.4% compared to the average survival of 59.7% in the early repair group. Pre- and postnatal variables predicting disease severity were not significantly different between the groups. Mean hospital stays, ventilator days, and cannulation days were statistically similar between the groups. Conclusions Repair of patients with CDH patients on ECMO at less than 24 h postcannulation achieves outcomes that are comparable to those of repair between 24 and 72 h. While the present data suggest that there is not a "too early" time point for CDH repair on ECMO, larger multicenter studies are needed to validate our findings and determine the overall benefits. Type of study Retrospective comparative study. Level of evidence Level III. [ABSTRACT FROM AUTHOR]

Abstract Purpose To identify technical modifications concerning factors that may lower the risk of recurrence following thoracoscopic repair of congenital diaphragmatic hernia (CDH). Methods All CDH patients who underwent thoracoscopic repair from April 2003 to September 2017 were retrospectively reviewed. Some of the more recently treated patients underwent technically modified repairs with underlay and overlay buttresses. Results Sixty-eight patients underwent thoracoscopic repair of a diaphragmatic hernia that presented either neonatally (n = 52) or beyond the neonatal period (> 1 month) (n = 16). At our institution, the minimally invasive surgical approach is considered for clinically stable CDH patients, who are likely to have type A or B defects. 21 patients had a sac-type defect. Forty-seven patients with type A defect had primary closure, buttressed in 6 cases. In 21 patients, the type B defect was repaired with a patch, buttressed in 11 patients. Median follow-up was 36 months (IQR 9–45). Recurrence occurred in 13 patients (overall 19% recurrence rate); all had a neonatally presented defect (25% vs. 0%, p = 0.03). Patients with a sac-type defect had a lower recurrence rate than patients with no hernia sac (5% vs. 26%, p = 0.05). Recurrence complicated 7 of 47 (15%) patients after primary closure and 6 of 21 (29%) patients with patch repair; none of the 17 cases with buttressed repairs had a recurrence. Conclusions Due to a higher rate of recurrence following thoracoscopic CDH repair compared to the standard open approach, we suggest a sandwich-type buttress repair with underlay and overlay components for both primary and patch repairs. Level of Evidence Level III cohort study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Congenital diaphragmatic hernia remains a complex disease with significant morbidity and mortality. Hypercarbia is a common derangement in this population, which often requires escalating ventilator support. By decreasing airway turbulence and enhancing CO2 removal, inhaled helium-oxygen mixture (heliox) has the potential to improve ventilation and thereby decrease ventilator support and its associated lung injury. METHODS: Retrospective cohort review of all neonates with congenital diaphragmatic hernia treated at Rady Children's Hospital San Diego during 2011-2015. Clinical characteristics were compared between the infants who were treated with heliox and those who did not receive this intervention. To analyze the effect of heliox in the subgroup that received this treatment, ventilator settings and arterial blood gas values were compared before and after starting heliox by using paired t tests. RESULTS: During the study period, 45 neonates with congenital diaphragmatic hernia were admitted to our neonatal ICU, 28 received heliox, and 27 were analyzed. During heliox treatment, ... levels decreased from 68 to 49 mm Hg (P < .001), amplitude decreased from 33 to 23 cm H2O (P < .001), ventilator frequency decreased from 28 to 23 breaths/min (P = .02), ... decreased from 0.52 to 0.40 (P < .01), and pH increased from 7.3 to 7.4 (P < .001). CONCLUSIONS: The addition of heliox to the standard practice of permissive hypercapnia facilitated improvement in gas exchange, which allowed a decrease in ventilator settings and oxygen exposure, both of which are known to contribute to lung injury in this population. A prospective trial is needed to more clearly define the acute and longterm impacts of this treatment. [ABSTRACT FROM AUTHOR]

Purpose Survivors of congenital diaphragmatic hernia (CDH) face high morbidity. We studied the neurodevelopmental outcomes of CDH survivors at a single institution. Methods CDH survivors born July 2006–March 2016 at a free-standing children's hospital were reviewed. Neurodevelopment was assessed using the Peabody Developmental Motor Scales (PDMS-2) broken into gross, fine, and total motor quotients. Data collected included prenatal variables (liver herniation, defect laterality, observed:expected total fetal lung volume (o:eTFLV) on MRI), birth demographics (sex, race, estimated gestational age (EGA), birth weight (BtWt), 5 min APGAR, associated anomalies), and therapies/hospital course (HFOV/HFJV, ECMO, timing of repair, pulmonary hypertension (PHTN) severity, length of stay, ventilator days). Variables were analyzed using mixed linear modeling. Results Sixty-eight children were included. Most patients had left-sided CDH (55/68, 81%) without liver herniation (42/68, 62%). ECMO utilization was 25/68 (37%). The mean [95% confidence interval] gross motor quotient for the entire cohort was 87 [84–91], fine motor quotient was 92 [88–96], and total motor quotient was 88 [84–93], representing below average, average, and below average functioning, respectively. o:eTFLV predicted fine motor quotient among prenatal variables. Associated anomalies and ECMO use predicted all quotients in the final model. Conclusions Associated anomalies and ECMO use predict neurodevelopmental delay in CDH survivors. Type of Study Retrospective observational study; Prognostic. Level of Evidence II. [ABSTRACT FROM AUTHOR]

Prenatal observed/expected lung–to-head ratio (O/E LHR) by ultrasound correlates with postnatal mortality for congenital diaphragmatic hernia (CDH) patients. The aim of this study is to determine if O/E LHR correlates with pulmonary hypertension (PH) outcomes for CDH patients. Methods A single center retrospective chart review was performed for CDH neonates from January 1, 2006, to December 31, 2015, (REB #1000053124) to include prenatal O/E LHR, liver position, first arterial blood gas, repair type, echocardiogram (ECHO), and lung perfusion scan (LPS) results up to 5 years of age. Results Of 153 newborns, 123 survived (80.4%), 58 (37.9%) had prenatal O/E LHR, and 42 (27.5%) had postnatal ECHO results. High mortality risk neonates (O/E LHR ≤ 45%) correlated with higher right ventricular systolic pressure (RVsp) at birth. Generally PH resolved by age 5 years. LPS results did not change over time ( p > 0.05) regardless of initial PH severity, suggesting that PH resolution did not correlate with increased ipsilateral lung perfusion to offload the right ventricle. Conclusion Prenatal prognostic markers correlated with initial PH severity for CDH newborns, but PH resolved over time despite fixed perfusion bias to the lungs. These results suggest favorable PH outcomes for CDH patients who survive beyond infancy. Type of Study Retrospective Cohort Study. Level of Evidence 3b [ABSTRACT FROM AUTHOR]

Background Right-sided congenital diaphragmatic hernias (CDH) and bigger defect sizes have been associated with poorer outcomes. Aim The aim of this study was to evaluate right- and left-sided CDH in terms of size, survival, associated anomalies, and morbidity. Material and methods We used information from a multicenter, multinational database including patients with CDH born between 2007 and 2015. All infants with data on defect side were included for this analysis. We compared differences in outcomes between right- and left-sided CDH. Further analysis on the association between side, size of the defect, and outcome was performed. Results A total of 3754 cases of CDH were entered in the registry between January 2007 and September 2015, with an overall survival of 71%. Of those, 598 (16%) were right-sided and 3156 left-sided, with a survival rate of 67% and 72%, respectively. Right-sided CDH had a larger proportion of C and D defects (p < 0.001 and 0.04, respectively). Survival rates for the same size defect were similar, independent of the side of the defect. Multivariable logistic regression analysis with survival as dependent variable identified a significant correlation with defect size, but not side. Conclusions The higher proportion of large defects (C & D) in right-sided CDH, not the side itself, accounts for the reported poorer survival in right-sided CDH. Level of evidence Level I for a prognosis study – This is a high-quality, prospective cohort study with 99% of patients followed to the study end point (death or discharge). [ABSTRACT FROM AUTHOR]

Background Improvements in the clinical management of CDH have led to overall improved reported result from single institutions. However, population-based studies have highlighted a hidden mortality. Aim To explore the incidence in Sweden and to address the hidden mortality for CDH during a 27-year period in a population-based setting. Materials and methods This is a population based cohort study that includes all patients diagnosed with CDH that were registered in the National Patient Register, the Medical Birth Register, the Register of Congenital Malformations and the Register for Causes of Death between 1987 and 2013. The mortality rates were calculated based on the number deaths divided by the number of live born cases. The hidden mortality was defined as the number of CDH cases that were not born (because of TOP or IUFD), cases of neonatal demise during birth or demise the same day of birth in patients who were in peripheral institutions and who never reached tertiary centers. Results In total, 861 CDH patients were born in Sweden between 1987 and 2013, which corresponds to an incidence of 3.0 born CDH per 10,000 live births. When adding the cases of TOP and IUFD, the total incidence of CDH in Sweden was 3.5/10,000 live born. The mortality rate between 1987 and 2013 was 36%: 44% during the first time period 1987–1999 and 27% in the later period 2000–2013. The hidden mortality in the second period was 30%, resulting in a total mortality rate of 45%. Conclusion The incidence of CDH during a 27-year period remained unchanged in the population. However, we observed a decrease in the prevalence because of the increasing numbers of TOP. A significant hidden mortality exists, with overall mortality rate of 45% for CDH in this population. Level of evidence II (cohort). [ABSTRACT FROM AUTHOR]

Introduction Despite improvements of neonatal intensive care, mortality among patients born with congenital diaphragmatic hernia (CDH), remains high, and there is a significant late mortality in this cohort. Objective The aim of this study was to evaluate the causes of death among 251 consecutive CDH patients treated at our institution during the last 26 years period. Methods Retrospective review of all causes of death between 1990 and 2015 of the CDH cohort prospectively collected in a database. Results Of the 251 CDH patients treated in our department since 1990, 49 were not alive by the end of 2015. Thirty-six patients (14%) died before discharge, and 13 (5%) after the first care event. The mean age at death was 262 days (± 653 days, median 34 days). Eighty six % (42 cases) of the fatalities occurred during the first year of life, more than half of the patients died before 1 month of age and only 13% after the age of 1 year (7 patients) (late mortality). The causes of early mortality (before 1 year of age) were mainly cardio-respiratory, whereas GI complications occurred in the late mortality group. Conclusion The most common cause of death among CDH patients is respiratory insufficiency and associated pulmonary hypertension, and most of the fatalities occur before 1 year of age. Among older patients, gastrointestinal morbidity as cause of death is highly represented. Level of evidence: II. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is the most common indication for ECLS in neonatal respiratory failure. The ultimate purpose of ECLS is to grant cardiopulmonary support, allowing time for operative intervention and optimization of cardiopulmonary function as the pathophysiologic processes of pulmonary hypertension, pulmonary hypoplasia, and ventricular dysfunction either improve or resolve. In CDH, ECLS plays a crucial role in the management of the most challenging patients, facilitating postnatal stabilization, allowing a ventilation strategy which minimizes barotrauma and volutrauma, and permitting treatment of and recovery from pulmonary hypertension and/or cardiac dysfunction. Understanding the nuances of CDH patients, which differ from other forms of neonatal respiratory failure, and the benefits of ECLS for these infants, is crucial for effective management. CDH patients present distinct challenges. Every aspect of ECLS, from mode of support and anticoagulation medication to pump selection, ventilation strategy, pulmonary hypertension management, and the weaning process, requires meticulous consideration. ECLS for CDH serves as a bridge to making informed decisions, granting clinicians stability and time to manage / recover from specific pathophysiologic consequences, and it offers the potential for survival among even the most challenging and complex patients. As overall care and management for infants with CDH receiving ECLS continue to improve, the focus has shifted toward managing survivor morbidity. Given the multisystem nature of the disease, this requires significant experience, expertise, and multidisciplinary teamwork to optimize long-term outcomes for these patients. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate the association of observed/expected (O/E) lung-to-head ratio (LHR) with long-term morbidity for isolated fetal congenital diaphragmatic hernia (CDH) patients in a single institution. Methods We performed a retrospective study of prenatally diagnosed CDH from 18 to 38 weeks of gestation (01/2002–04/2010). Two cohorts of O/E LHR were defined (22.6–45%, 45.1–78.3%) based upon previous studies. Survivors with at least 1-year follow-up of prospectively collected long-term morbidity assessments were included. Results O/E LHR was available in 43 survivors (median 40%, range 22.8–78.3%). Follow-up data were available in 41 survivors (M:F = 24:17, left CDH = 39/41). Median follow-up was 6.5 years (1–11 years). Height/weight trajectories were similar between the two cohorts, with the majority below the 50th centile. There were no differences between the two cohorts by age 3 years for Bayley scales (developmental domains) and/or REEL-3 (language development). In addition, V/Q scans in the two cohorts demonstrated similar degrees of mismatch (mean delta V/Q = 35.4 versus 31.3). Conclusions In fetuses with isolated CDH, a reduction in O/E LHR does not predict a worse outcome in long-term follow-up. There is no association between a lower O/E LHR and a reduction in REEL-3 or Bayley score nor V/Q mismatch. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The coexistence of congenital diaphragmatic hernia (CDH) with esophageal atresia (EA) has only been reported occasionally in literature. Series of patients from a single institution with comparison of different postnatal therapeutic approaches have not been reported. We describe our management in this unique cohort of patients and discuss the procedures that can lead to successful outcomes in this association of congenital anomalies. Methods The surgical approaches and outcome of six neonates with CDH associated with EA and distal tracheo-esophageal fistula (TEF) are discussed. Results Five newborns were treated surgically, while one patient with trisomy 18 only received palliative treatment. In four patients TEF was ligated during laparotomy for CDH repair. Secondary surgery was performed for correction of EA via thoracotomy after 4–6 weeks (primary anastomosis in two patients, Foker’s-technique in one patient, one patient deceased prior to secondary surgery). All three surviving patients required fundoplication due to severe gastro-esophageal reflux during the first year of life. Two patients also required dilatation for anastomotic stricture. In one preterm infant correction of both malformations was accomplished during one surgical intervention. The herniated organs were eventrated and temporarily placed into a silastic bag to allow a mediastinal shift to the left. Thus a continuous ventilation of the right lung with minimal compression and sufficient oxygenation was possible during esophageal repair via a right-sided thoracotomy and extrapleural approach. No further surgery was required so far. Conclusions Definitive surgical correction in newborns with CDH and EA was so far accomplished with multiple surgical interventions. Ligation of TEF via an abdominal approach with repair of CDH followed by delayed repair of EA is prone to stenosis and gastro-esophageal reflux due to loss of esophageal length. With a new combination of established surgical methods a single-staged correction of both malformations is possible. This new approach might help to preserve sufficient length of esophagus to accomplish primary anastomosis without tension and therefore avoid long-term morbidity and repetitive surgeries. [ABSTRACT FROM AUTHOR]

Objective: To measure and evaluate the effects of tracheal dimensions on survival and ventilation in a large series of infants with congenital diaphragmatic hernia (CDH) treated antenatally with fetal endoluminal tracheal occlusion (FETO). Study design: Tracheal dimensions on chest radiograph (CR) were measured by 2 blinded radiologists. Survival, day 1 best oxygenation index and duration of ventilation, continuous positive airway pressure, and hospital stay were recorded. Survivors with a minimum 12-month follow-up were longitudinally compared for incidence of gastroesophageal reflux, chest infections, chest deformities, and hernia recurrence. Results: Seventy infants with CDH (41 who underwent FETO) were treated between 2004 and 2010. Hernia repair was performed in 26 infants without FETO (8 with patch repair) and 35 infants with FETO (26 with patch repair; P = .0015). Infants with FETO had a wider trachea than those without FETO at T1 (P < .0001) and between T1 and the carina (P < .0001). Tracheal diameter was similar in survivors and nonsurvivors in the FETO group. Tracheal size was not correlated with day 1 best oxygenation index in the FETO group (R 2 = 0.17) or the non-FETO group (R 2 = 0.07). There were no between-group differences in duration of mechanical ventilation (P = .30), continuous positive airway pressure (P = .20), or hospital stay (P = .30). In the longitudinal study, tracheal widths were larger on the last CR than on preoperative CR in patients without FETO (T1, P = .02; widest point, P = .001; carina, P = .0001), and for patients with FETO at the widest point (P < .0001) and at the carina (P < .0001), but not at T1 (P = .12). There were no differences in clinical variables between the FETO and non-FETO groups. Conclusion: FETO has a significant impact on tracheal size of infants with CDH; however, tracheal size does not affect survival or the requirement for early respiratory support. [Copyright &y& Elsevier]

Abstract: Background/Purpose: We determined the incidence of sensorineural hearing loss (SNHL; >20dB at any frequency) in a contemporary cohort of congenital diaphragmatic hernia (CDH) survivors at a single tertiary care center and identified potential risk factors for SNHL. Methods: From 2000 through 2011, clinical and audiologic data were collected on 122 surgically-repaired Bochdalek CDH patients. CDH defect size, duration of ventilation, and cumulative aminoglycoside treatment were used for multivariate logistic regression. Results: Incidence of SNHL was 7.4% (9/122). We identified one significant independent predictor of SNHL: cumulative length of aminoglycoside treatment (P <.001; OR 1.44, 95% CI: 1.13–1.83). Conclusions: Over the last decade, the incidence of SNHL in our CDH patients is low compared to previous reports in the literature (7.4%) and is not associated with CDH defect size or the need for extracorporeal membrane oxygenation. Prolonged duration of aminoglycoside treatment increases the risk of SNHL independent of defect size and duration of ventilation. [Copyright &y& Elsevier]

Abstract: Background/Purpose: The purpose of this paper was to examine the effect of prenatal counseling in the Advanced Fetal Care Center (AFCC) on the well-being of parents of infants with congenital diaphragmatic hernia (CDH). Methods: From 2008 through 2012, 26 mothers and fathers of surgically repaired CDH patients who received prenatal counseling at our institution, and 15 who received no prenatal counseling, each completed the Short-Form 36 version 1 (SF-36v1) at the appropriate time points: prenatal, two weeks, and six months post-surgery. Results: Parents in both groups did not differ by demographic characteristics. Patients who received prenatal counseling had significantly longer ventilatory time and length of stay (LOS) in the ICU and in the hospital compared to those who did not receive prenatal counseling (all P <.01). Mothers and fathers had similar SF-36v1 mental and physical component summary (MCS, PCS) post-surgery scores when compared by counseling status. Prenatal MCS scores for mothers and fathers (47 vs. 41; P =.24) were similar to those at six months post-surgery (47 vs. 47; P =.90). Conclusions: When hospital LOS was controlled between groups stratified by AFCC counseling status, MCS scores were comparable prenatally and were sustained at six months post-surgery for both parents. These findings may reflect the support services parents received beginning in the prenatal period. [Copyright &y& Elsevier]

Abstract: Congenital diaphragmatic hernias (CDH) are rare congenital anomalies occurring in 1:5000 live births with a wide range of clinical presentations. The Morgagni hernia is the rarest of these defects with the hernia presenting anteriorly, most commonly on the right. Factors found to predict mortality in infants presenting with CDH include prenatal diagnosis, early gestational age, low birth weight, large diaphragmatic defect, associated congenital anomalies, and low APGAR scores. We present the case of a 27-week gestational age premature girl weighing 460 g who required urgent repair of a Morgagni diaphragmatic hernia and a review of the current literature on the topic. To the best of our knowledge, this is the smallest infant to undergo repair of this CDH reported to date. [Copyright &y& Elsevier]

Abstract: Background/Purpose: Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. Eyes absent 1 (Eya1) and sine oculis homebox 1 (Six1) have been identified as essential components of the gene network that regulates foetal lung development. Eya1 and Six1 are expressed in distal epithelial tips of branching airways as well as in surrounding mesenchymal cells, highlighting their important role during branching morphogenesis. Lungs of Eya1−/− and Six1−/− knockouts display PH with reduced epithelial branching, appearing to be arrested in the pseudoglandular stage. We hypothesized that Eya1 and Six1 expression is decreased in branching airways of nitrofen-induced PH. Methods: Time-mated rats received either nitrofen or vehicle on E9.5. Foetal lungs were dissected on E15.5 and divided into control and nitrofen groups, whereas lungs harvested on E18.5 were divided into controls, PH without CDH [PH(−)], and PH with CDH [PH(+)]. Pulmonary gene expression levels of Eya1 and Six1 were analyzed by quantitative real-time PCR. Immunofluorescence staining was performed to investigate Eya1 and Six1 protein expression and localization by confocal laser scanning microscopy (CLSM). Results: Relative mRNA expression of Eya1 and Six1 was significantly decreased in PH(−) and PH(+) on E18.5 compared to controls. CLSM confirmed markedly diminished immunofluorescence of Eya1 and Six1 in distal airway epithelium as well as in surrounding mesenchymal cells of nitrofen-induced PH on E18.5 compared to controls. Conclusions: Downregulation of Eya1 and Six1 gene expression in nitrofen-induced PH suggests that decreased Eya1 and Six1 expression during the late pseudoglandular stage may interfere with epithelial branching and distal airway maturation, thus resulting in PH. [Copyright &y& Elsevier]

Abstract: Background/purpose: Congenital diaphragmatic hernia (CDH) remains a significant cause of neonatal death. A wide spectrum of disease severity and treatment strategies makes comparisons challenging. The objective of this study was to create a standardized reporting system for CDH. Methods: Data were prospectively collected on all live born infants with CDH from 51 centers in 9 countries. Patients who underwent surgical correction had the diaphragmatic defect size graded (A–D) using a standardized system. Other data known to affect outcome were combined to create a usable staging system. The primary outcome was death or hospital discharge. Results: A total of 1,975 infants were evaluated. A total of 326 infants were not repaired, and all died. Of the remaining 1,649, the defect was scored in 1,638 patients. A small defect (A) had a high survival, while a large defect was much worse. Cardiac defects significantly worsened outcome. We grouped patients into 6 categories based on defect size with an isolated A defect as stage I. A major cardiac anomaly (+) placed the patient in the next higher stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78% stage III, 58% stage IV, 39% stage V, and 0% for non-repair. Conclusions: The size of the diaphragmatic defect and a severe cardiac anomaly are strongly associated with outcome. Standardizing reporting is imperative in determining optimal outcomes and effective therapies for CDH and could serve as a benchmark for prospective trials. [Copyright &y& Elsevier]

Abstract: Purpose: To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2years of age. Methods: This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2years of age. Results: BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93±15, 95±16, and 95±11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97±14, 94±16, 93±13, 97±10, and 94±14. For the BSID-III, supplemental oxygen at 28days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion: CDH patients on average have lower developmental scores at 2years of age compared to the norm. A need for ECMO, oxygen at 28days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays. [Copyright &y& Elsevier]

Abstract: Introduction: Functional residual capacity (FRC) and lung clearance index (LCI) are sensitive parameters for early detection of airway disease in infancy. The closed helium dilution method has been applied to assess lung volume and ventilation inhomogeneity (VI) in spontaneously breathing infants. Aims: The aims of this study were as follows: (1) to assess applicability of the helium gas dilution technique in mechanically ventilated infants with high-risk congenital diaphragmatic hernia (CDH) and to evaluate changes in breathing patterns, lung volume, and VI during the first days of life before and after surgery, and (2) to analyze the possible correlation between changes in lung volume, cerebral hemodynamics, and oxygenation before and after surgical correction of CDH through near-infrared spectroscopy (NIRS) monitoring. Methods: Lung function tests were performed by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique. For all babies, three acceptable FRC and LCI measurements were collected for each test (mean and SD of three measurements were calculated) before surgery (T 0), 24h after surgery (T 1) during mechanical ventilation, and within 24h after extubation in spontaneous breathing (T 2). Cerebral and splanchnic hemodynamics were continuously monitored by NIRS during mechanical ventilation to evaluate relationships between changes in lung volume and capillary–venous oxyhemoglobin saturation in tissues. Fraction of inspired oxygen delivered was adjusted to keep oxygen saturation between 90% and 95%. Results: Thirteen CDH infants were studied; median GA=38weeks (range 35–41) and median BW=3000g (range 1850–3670). FRC and LCI significantly improved after extubation when compared with pre-surgical values. No differences were found in tidal volume (Vt) and NIRS monitoring before and after surgery and after extubation. Neither LCI nor FRC was correlated with NIRS values. Conclusions: Helium gas dilution technique is an applicable and reliable technique to measure lung volumes and ventilation inhomogeneity also in ventilated infants. NIRS is a non-invasive technique to monitor tissue oxygenation during surgery and mechanical ventilation. In CDH newborns these preliminary data show an improvement in both FRC and LCI after extubation. [Copyright &y& Elsevier]

Abstract: Congenital diaphragmatic hernia (CDH) is a congenital anomaly that presents with a broad spectrum of severity that is dependent upon components of pulmonary hypoplasia and pulmonary hypertension. While advances in neonatal care have improved the overall survival of CDH in experienced centers, mortality and morbidity remain high in a subset of CDH infants with severe CDH. Prenatal predictors have been refined for the past two decades and are the subject of another review in this issue. So far, all randomized trials comparing prenatal intervention to standard postnatal therapy have shown no benefit to prenatal intervention. Although recent non-randomized reports of success with fetoscopic endoluminal tracheal occlusion (FETO) and release are promising, prenatal therapy should not be widely adopted until a well-designed prospective randomized trial demonstrating efficacy is performed. The increased survival and subsequent morbidity of CDH survivors has resulted in the need to provide resources for the long-term follow up and support of the CDH population. [Copyright &y& Elsevier]

Abstract: Background: Congenital diaphragmatic hernia (CDH) can be repaired on or off extracorporeal membrane oxygenation (ECMO). In many centers, operating off ECMO is advocated to prevent bleeding complications. We aimed to compare surgery-related bleeding complications between repair on or off ECMO. Methods: All patients with CDH repair and ECMO treatment between January 1, 1995, and May 31, 2008, were retrospectively reviewed. Tranexamic acid was routinely given to all patients repaired on ECMO for 24 hours perioperatively after 2003. Extra-fluid expansion, transfusion, or relaparotomy caused by postoperative bleeding were scored as surgery-related bleeding complications and were related to the Extracorporeal Life Support Organization (ELSO) registry. We used χ 2 test and t test for statistics. Results: Demographic data and surgery-related bleeding complications in the on-ECMO group were not significantly different compared with the off-ECMO group (P = .331) in our institute. In contrast, more surgery-related bleeding complications were reported by ELSO in their on-ECMO group (P < .0001). Conclusion: In contrast to the data from the ELSO registry, we did not observe significantly more surgery-related bleeding complications after CDH repair on ECMO. Using a specific perioperative hemostatic treatment enabled us to perform CDH repair on ECMO with a low frequency of bleeding complications, thereby taking advantage of having the physiologic benefits of ECMO available perioperatively. [Copyright &y& Elsevier]

Abstract: Purpose: Thoracoscopic congenital diaphragmatic hernia (CDH) repair is increasingly reported. A significant intraoperative acidosis secondary to the pneumocarbia, as well as an increased recurrence rate, are possible concerns. Our aim was to review our early experience of the technique. Methods: A prospective and retrospective data collection was carried out on all patients undergoing either an open or thoracoscopic CDH repair for a 4-year period. Preoperative blood gas values were identified at various stages of the operative procedure. A pH of 7.2 was considered to be a significant acidosis. The duration of surgery, complications, and recurrence rates were also recorded. Data were analyzed using the Mann-Whitney U test, and a P value of .05 or less was considered significant. Results: Twenty-two patients were included. One death occurred before surgery. Twelve patients underwent thoracoscopic repair (8 neonatal), and 9 underwent open repair (8 neonatal). There were 9 left-sided defects in the thoracoscopic group and 9 in the open group. Operative time was longer in the thoracoscopic group compared to the open group (median, 135 vs 93.5 minutes; P = .02). Neonates undergoing thoracoscopic repair were heavier compared to the open group (median, 3.9 vs 2.9 kg; P = .05), and their preoperative requirements for ventilation and inotropes were comparable. However, the association between those patients who required preoperative inotropes and those who required a patch repair was statistically significant P = .03. Two patients in each group developed an intraoperative acidosis. A further patient in the thoracoscopic group had a severe acidosis present at the beginning of surgery. There was no statistical difference in pH values or recurrence rate between the 2 groups. All recurrences were in patients requiring patch repairs. No postoperative mortality occurred. Conclusions: We present our early experience of thoracoscopic CDH repair. Our results from thoracoscopic repair appear similar to the open procedure performed over the same period. No clear difference in intraoperative pH or recurrence rate has been demonstrated in our series. There is a need for a multicenter prospective study to establish the longer term outcome of this technique. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study was to identify mortality risk factors in children with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO) and generate a prediction score for those at a very high risk for mortality. Methods: Data on first ECMO runs of all neonates with CDH, between January 1997 and June 2007, were obtained from the Extracorporeal Life Support Organization registry (N = 2678). The data were split into “training data (TD)” (n = 2006) and “validation data” (n = 672). The primary outcome analyzed was in-hospital mortality. Modified Poisson regression was used for analyses. Results: Overall in-hospital mortality among 2678 neonates (males, 57%; median age at ECMO, 1 day) was 52%. The univariate and multivariable analyses were performed using TD. An empirically weighted mortality prediction score was generated with possible scores ranging from 0 to 35 points. Of 69 who scored 14 or higher in the TD, 62 died (positive predictive value [PPV], 90%), of 37 with 15 or higher, 35 died (PPV, 95%), of 23 with 16 or higher, 22 died (PPV, 96%). A cut-off point of 15 was chosen and was tested using the separate validation dataset. In validation data, the cut-off point 15 had a PPV of 96% (23 died of 24). Conclusion: Scoring 15 or higher on the prediction score identifies neonates with CDH at a very high risk for mortality among those managed with ECMO and could be used in surgical decision making and counseling. [Copyright &y& Elsevier]

Abstract: Purpose: The high incidence of cardiac malformations in humans and animal models with congenital diaphragmatic hernia (CDH) is well known. The precise molecular mechanisms underlying cardiac maldevelopment in CDH are still unclear. It has been reported that GATA4 and GATA6, members of the GATA transcription factor family, act cooperatively to regulate cardiovascular development, and the levels of cardiac GATA4 and GATA6 are important regulators of cardiomyocyte proliferation, cardiac morphogenesis, and embryo survival. In addition, the GATA4/GATA6 double heterozygous mutant embryo model displayed a spectrum of cardiovascular malformations similar to those seen in human CDH and nitrofen-induced animal models, including ventricular and aortopulmonary septal defects and thin ventricular myocardium. To test the hypothesis that expression of GATA4 and GATA6 is reduced in early stages of gestation in a CDH hypoplastic heart, we investigated the expression of GATA4 and GATA6 in the hearts of nitrofen-treated rats in early gestation. Wnt2, bone morphogenetic protein 4 (BMP4), and myocyte enhancer factor 2C (MEF2C) were also investigated as GATA4/6 target genes involved in cardiogenesis. Materials and Methods: Fetal rat hearts of normal (n = 7) and nitrofen-treated (n = 7) dams were harvested on embryonic day 13. The expression of GATA4, GATA6, Wnt2, BMP4, and MEF2C was analyzed in each heart by real-time reverse transcription–polymerase reaction. Results: The gene expression of GATA4, GATA6, Wnt2, BMP4, and MEF2C on embryonic day 13 were significantly reduced (P < .05) in the hearts of nitrofen-treated animals compared with normal hearts of equivalent age. Conclusion: Decreased expression of GATA4 and GATA6 and their target genes in the developing fetal heart may perturb the delicate regulation of cardiovascular development, resulting in cardiovascular malformations in the nitrofen rat model. [Copyright &y& Elsevier]

Congenital Diaphragmatic Hernia (CDH) is a congenital disorder with an incidence of 1 in 2500 live births. Respiratory distress of newborns with CDH is the result of pulmonary hypoplasia and pulmonary hypertension. Hypoplastic lungs are characterized by a decreased number of airways with smaller airspaces, whereas the combination of a decreased number of vascular branches and an increased adventitia and medial thickness of the pulmonary arterial walls result in pulmonary hypertension. The appearance of the CDH lungs suggests that its complete formation is stalled during development. Understanding the basic mechanisms of lung development is mandatory to unravel the origin of CDH. Although the histological abnormalities in CDH lungs have been well described, less is known about the underlying molecular mechanisms. In this review we will discuss the current molecular and genetic background of lung formation, as well as a reflection of this knowledge towards CDH. [Copyright &y& Elsevier]

The use of extracorporeal membrane oxygenation (ECMO) has revolutionized the care of the critical infant born with a congenital diaphragmatic hernia (CDH). In some respects, this is surprising given our current lack of understanding regarding optimal preoperative ventilation strategy, identification of patients most likely to benefit from ECMO, and the correct timing of hernia repair for the infant treated with ECMO. Historically, repair of CDH was considered one of the few true pediatric surgical emergencies. Mortality, however, was high. In the 1970s, ECMO was first utilized as a rescue therapy following repair of CDH when conventional methods failed. In the 1980s, advancements in neonatal intensive care and an understanding of the pathophysiology of pulmonary hypertension associated with CDH led to a strategy involving preoperative stabilization and delayed surgical intervention. Historical reviews demonstrate an improvement of survival in infants treated with ECMO from 56% to 71%. This paper will outline the advances in the care of the CDH patient and the approach used for treatment with ECMO. [Copyright &y& Elsevier]

Extracorporeal membrane oxygenation (ECMO) has been offered as a life-saving technology to newborns with respiratory and cardiac failure refractory to maximal medical therapy. ECMO has been used in treatment of neonates with a variety of cardio-respiratory problems, including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis/pneumonia, respiratory distress syndrome (RDS), air leak syndrome, and cardiac anomalies. For this group of high-risk neonates with an anticipated mortality rate of 80% to 85%, ECMO has an overall survival rate of 84%, with recent data showing nearly 100% survival in many diagnostic groups. This article reviews the current selection criteria for ECMO and the clinical management of neonates on ECMO, and discusses the long-term outcome of neonates treated with ECMO. [Copyright &y& Elsevier]

Neonatal extracorporeal support is most often required for neonatal hypoxemic respiratory failure, usually accompanied by persistent pulmonary hypertension of the newborn (PPHN). PPHN is a clinical syndrome that results from the failure of pulmonary vascular transition to extrauterine life. Infants typically present shortly after birth with respiratory distress and cyanosis, but a structurally normal heart. The incidence of PPHN is estimated at 0.2% of live-born term infants. Respiratory failure and hypoxemia in the term newborn result from a heterogeneous group of disorders, and the therapeutic approach and response often depend on the underlying disease. PPHN can largely be thought of as one of three types: (1) the abnormally constricted pulmonary vasculature which is the most common type and includes diagnoses such as meconium aspiration syndrome, respiratory distress syndrome, and sepsis; (2) the structurally abnormal vasculature, which is often termed idiopathic PPHN; or (3) the hypoplastic vasculature such as is seen in congenital diaphragmatic hernia, or alveolar capillary dysplasia, a rare malformation of lung development. The pathophysiology of each type is dependent on the point in gestation when the normal transition to extrauterine life fails. This article will discuss the known pathophysiology in PPHN and new treatment modalities. [Copyright &y& Elsevier]

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. 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). The patient is currently alive at 11 years old and continues with a gastrostomy tube (g-tube) and tracheostomy dependent. 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. [ABSTRACT FROM AUTHOR]

Endothelial colony-forming cells (ECFCs) are decreased in the cord blood of preterm infants with moderate-to-severe bronchopulmonary dysplasia. We quantified ECFCs from infants with congenital diaphragmatic hernia, a neonatal disorder with severe lung hypoplasia. Unlike newborns who develop bronchopulmonary dysplasia, those with congenital diaphragmatic hernia had increased and highly-proliferative cord blood ECFCs. [Copyright &y& Elsevier]

Background Undescended testes (UDT) is a common abnormality treated by pediatric surgeons. Embryological development of the genitourinary ridge is in close proximity with the pleuroperitoneal fold. The purpose of this paper is to describe the association between congenital diaphragmatic hernia (CDH) and UDT. Materials/methods As part of the DHREAMS (Diaphragmatic Hernia Research and Exploration: Advancing Molecular Science) study ( www.cdhgenetics.com ), all living children had tissue banked and analyzed for common genetic mutations and had a health assessment performed by telephone consultation with the parents at two years of age. The incidence of UDT was then compared to clinical and genetic findings previously identified. Results Sixty-five males had complete information from their 2 year health assessment. Of these, twelve (18%) had a UDT repaired by the time of the 2 year assessment. Of the twelve who had a repair, no child had a unilateral UDT which was contralateral to the side of the CDH. There were no differences in rate or number of mutations of any of the genes we checked as part of our study. Conclusion It appears that a deficiency of diaphragm tissue may affect the first or transabdominal phase of the testicular descent, leading to an increased incidence of UDT. [ABSTRACT FROM AUTHOR]