Mortality in Congenital Diaphragmatic Hernia: A Multicenter Registry Study of Over 5000 Patients Over 25 Years.

OBJECTIVE: To determine if risk-adjusted survival of patients with CDH has improved over the last 25 years within centers that are long-term, consistent participants in the CDH Study Group (CDHSG). SUMMARY BACKGROUND DATA: The CDHSG is a multicenter collaboration focused on evaluation of infants with CDH. Despite advances in pediatric surgical and intensive care, CDH mortality has appeared to plateau. Herein, we studied CDH mortality rates amongst long-term contributors to the CDHSG. METHODS: We divided registry data into 5-year intervals, with Era 1 (E1) beginning in 1995, and analyzed multiple variables (operative strategy, defect size, and mortality) to assess evolution of disease characteristics and severity over time. For mortality analyses, patients were risk stratified using a validated prediction score based on 5-minute Apgar (Apgar5) and birth weight. A risk-adjusted, observed to expected (O:E) mortality model was created using E1 as a reference. RESULTS: 5203 patients from 23 centers with >22years of participation were included. Birth weight, Apgar5, diaphragmatic agenesis, and repair rate were unchanged over time (all P > 0.05). In E5 compared to E1, minimally invasive and patch repair were more prevalent, and timing of diaphragmatic repair was later (all P < 0.01). Overall mortality decreased over time: E1 (30.7%), E2 (30.3%), E3 (28.7%), E4 (26.0%), E5 (25.8%) ( P = 0.03). Risk-adjusted mortality showed a significant improvement in E5 compared to E1 (OR 0.78, 95% CI 0.62-0.98; P = 0.03). O:E mortality improved over time, with the greatest improvement in E5. CONCLUSIONS: Risk-adjusted and observed-to-expected CDH mortality have improved over time.

Survival Benefit Associated With the Use of Extracorporeal Life Support for Neonates With Congenital Diaphragmatic Hernia.

OBJECTIVE: To measure the survival among comparable neonates with CDH supported with and without ECLS. SUMMARY OF BACKGROUND DATA: Despite widespread use in the management of newborns with CDH, ECLS has not been consistently associated with improved survival. METHODS: A retrospective cohort study was performed using ECLS-eligible CDH Study Group registry patients born between 2007 and 2019. The primary outcome was in-hospital mortality. Neonates who did and did not receive ECLS were matched based on variables affecting risk for the primary outcome. Iterative propensity score-matched, survival (Cox regression and Kaplan-Meier), and center effects analyses were performed to examine the association of ECLS use and mortality. RESULTS: Of 5855 ECLS-eligible CDH patients, 1701 (29.1%) received ECLS. "High-risk" patients were best defined as those with a lowest achievable first-day arterial partial pressure of CO2 of ≥60 mm Hg. After propensity score matching, mortality was higher with ECLS (47.8% vs 21.8%, odds ratio 3.3, 95% confidence interval 2.7-4.0, hazard ratio 2.3, P < 0.0001). For the subgroup of high-risk patients, there was lower mortality observed with ECLS (64.2% vs 84.4%, odds ratio 0.33, 95% confidence interval 0.17-0.65, hazard ratio 0.33, P = 0.001). This survival advantage was persistent using multiple matching approaches. However, this ECLS survival advantage was found to occur primarily at high CDH volume centers that offer frequent ECLS for the high-risk subgroup. CONCLUSIONS: Use of ECLS is associated with excess mortality for low- and intermediate-risk neonates with CDH. It is associated with a significant survival advantage among high-risk infants, and this advantage is strongly influenced by center CDH volume and ECLS experience.

Elevated proBNP levels are associated with disease severity, cardiac dysfunction, and mortality in congenital diaphragmatic hernia.

BACKGROUND: Cardiac dysfunction is a key determinant of outcome in congenital diaphragmatic hernia (CDH). Pro-b-type natriuretic peptide (proBNP) is used as a prognosticator in heart failure and cardiomyopathy. We hypothesized that proBNP levels would be associated with ventricular dysfunction and high-risk disease in CDH. METHODS: Patients in the CDH Study Group (CDHSG) from 2015-2019 with at least one proBNP value were included. Ventricular function was determined using echocardiograms from the first 48 h of life. RESULTS: A total of 2,337 patients were identified, and 212 (9%) had at least one proBNP value. Of those, 3 (1.5%) patients had CDHSG stage A defects, 58 (29.6%) B, 111 (56.6%) C, and 24 (12.2%) D. Patients with high-risk defects (Stage C/D) had higher proBNP compared with low-risk defects (Stage A/B) (14,281 vs. 5,025, p = 0.007). ProBNP was significantly elevated in patients who died (median 14,100, IQR 4,377-22,900 vs 4,911, IQR 1,883-9,810) (p<0.001). Ventricular dysfunction was associated with higher proBNP than normal ventricular function (8,379 vs. 4,778, p = 0.005). No proBNP value was both sensitive and specific for ventricular dysfunction (AUC=0.61). CONCLUSION: Among CDH patients, elevated proBNP was associated with high-risk defects, ventricular dysfunction, and mortality. ProBNP shows promise as a biomarker in CDH-associated cardiac dysfunction.

Surgical Repair of Congenital Diaphragmatic Hernia After Extracorporeal Membrane Oxygenation Cannulation: Early Repair Improves Survival.

OBJECTIVE: To determine the optimal timing of congenital diaphragmatic hernia (CDH) repair after extracorporeal membrane oxygenation (ECMO) cannulation. SUMMARY BACKGROUND DATA: The timing of CDH repair after ECMO cannulation remains a controversial topic due to studies with low power or strong selection bias. METHODS: This is a 2-aim retrospective cohort study based on the CDH Study Group registry for the period of 2007-2017. Aim 1-Compare On versus After ECMO repair. Aim 2-Compare Early versus Late repair on ECMO. In order to minimize selection bias and account for non-repairs, subjects in each aim were stratified into study groups based on their treatment center's characteristics. In each aim, the study groups were matched based on propensity score (PS). The main outcomes included mortality rate and incidence of non-repair. RESULTS: In aim 1, 136 patients remained in each group after PS matching. Compared to the After ECMO group, patients in the On ECMO group demonstrated a lower mortality rate, hazard ratio (HR) 0.54 (0.38, 0.77) (P < 0.001), and lower incidence of non-repair, 5.9% versus 33.8% (P < 0.001). In aim 2, 77 patients remained in each group after PS matching. Compared to the Late group, Early repair of CDH on ECMO was associated with a lower mortality rate, HR 0.51 (0.33, 0.77) (P = 0.002), and lower incidence of non-repair, 9.1% versus 44.2% (P < 0.001). CONCLUSIONS: The approach of early repair after ECMO cannulation is associated with improved survival compared to delayed surgical correction.

Cornelia de Lange syndrome and congenital diaphragmatic hernia.

PURPOSE: There is a known association between Cornelia de Lange syndrome (CdLS) and congenital diaphragmatic hernia (CDH), with CDH being the cause of death in 5%-20% of CdLS cases. We aimed to identify and describe patients with CDLS and CDH. We hypothesized that CdLS would be associated with high-risk CDH and poor outcomes. METHODS: CDH Study Group patients from 1995 to 2019 were included. Those with CdLS were reviewed retrospectively. Rates of repair and outcomes were compared between patients with and without CdLS. RESULTS: We identified 9,251 CDH patients. Of those, 21 had confirmed CdLS. CdLS patients had a lower birth weight (2.2±0.57 kg) than non-CdLS patients (2.9±0.64 kg) (p<0.001). 5-min Apgar scores were lower in CdLS patients (6, 4-7) than non-CdLS patients (7, 5-8) (p=0.014). Only 33% of CdLS patients underwent diaphragmatic repair compared to 84.2% of non-CdLS patients (p<0.001). Mortality was 76% for CdLS patients compared with 29% for non-CdLS patients (p<0.001). Of the 7 CdLS patients who underwent repair, 5 survived to hospital discharge. CONCLUSIONS: Infants with CdLS and CDH have a poor prognosis. However, CdLS patients who undergo repair can survive to discharge; therefore, the concomitant diagnosis of CdLS and CDH is not necessarily a contraindication to repair. Early recognition of these anomalies can assist with counseling and prognostication. TYPE OF STUDY: Retrospective comparative study LEVEL OF EVIDENCE: III.

Predicting lethal pulmonary hypoplasia in congenital diaphragmatic hernia (CDH): Institutional experience combined with CDH registry outcomes.

BACKGROUND: The Severe Pulmonary Hypoplasia and Evaluation for Resuscitative Efforts (SPHERE) protocol was developed to attempt to identify CDH patients with likely lethal pulmonary hypoplasia. We present our experience with this protocol and utilize the CDH Registry to critically assess the protocol. METHODS: SPHERE patients identified based on prenatal imaging (10/2009-1/2018) were offered ECMO if meeting postnatal physiologic criteria, while others received comfort measures. Within the CDH Registry, patients with suspected severe CDH were identified and separated into "passed" (lowest pCO2 ≤100) versus "failed" (lowest pCO2 >100) groups. RESULTS: Of 23 SPHERE patients, 57% (13/23) passed criteria for ECMO and survival was 46% (6/13) in that cohort. Of 4912 patients in the CDH Registry, 265 met criteria. There was no difference in survival rates between those that "passed" (122/227; 54%) versus "failed" (18/38; 47%). However, the latter had longer ECMO runs and more required ventilator/ECMO support at 30 days. Amongst survivors, the "failed" group had longer hospital stays and more frequently required tube feeds at discharge. CONCLUSIONS: The SPHERE protocol did not predict mortality in the CDH Registry. However, our data suggest resource utilization is significant when unable to reach pCO2 ≤100 despite resuscitation. Morbidity remains high in this group. LEVEL OF EVIDENCE: Level III ANNOTATION OF CHANGES: Institutional Review Board Approval at University of Michigan (HUM00031524 and HUM00044010) TYPE OF STUDY: Retrospective Review.

Congenital diaphragmatic hernia and associated omphalocele: a study from the CDHSG registry.

BACKGROUND: Congenital Diaphragmatic Hernia (CDH) associated with Omphalocele is a rare condition, and only a few case reports are available in the literature. Both conditions are associated with some degree of pulmonary hypoplasia. We hypothesize that the combination of CDH with Omphalocele might be associated with poorer outcomes. AIM: The aim of this study was to describe the incidence of this association and postnatal outcomes from the largest database available for CDH. METHODS: Data from the multicenter, multinational database on infants with CDH (CDHSG Registry) born from 2007 to 2018 was analyzed. RESULTS: A total of 5730 entries were made into the registry during the study period. The incidence of Omphalocele associated with CDH was 0.63% (36 out of 5730). When comparing posterolateral Bochdalek hernias with Omphalocele (CDH + O) to CDH without Omphalocele (CDH-), CDH + O were born at significantly younger gestational ages. They were sicker directly after birth with significantly lower APGARs at all time points, but received ECMO significantly less often. The distribution of left vs right side or the defect size did not differ but CDH + O required patch in a significantly larger extent. CDH + O had surgical repair significantly later and had significantly higher rates of non-repairs and significantly lower survival rates. The morbidity was significantly higher with longer hospital stays and higher requirements for O2 at 30 DOL. DISCUSSION: CDH associated with Omphalocele is a rare but more severe condition with higher mortality and morbidity rates. Newborns with these combined conditions can be difficult to stabilize or might pose complicated management problems due to pulmonary hypertension and/or pulmonary hypoplasia. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level I.

Early CDH repair on ECMO: Improved survival but no decrease in ECMO duration (A CDH Study Group Investigation).

PURPOSE: "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. METHODS: 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. RESULTS: 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). CONCLUSION: 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 OF EVIDENCE: Level III.

Risk-stratification enables accurate single-center outcomes assessment in congenital diaphragmatic hernia (CDH).

BACKGROUND: Management of CDH is highly variable from center to center, as are patient outcomes. The purpose of this study was to examine risk-stratified survival and extracorporeal membrane oxygenation (ECMO) rates at a single center, and to determine whether adverse outcomes are related to patient characteristics or management. METHODS: A retrospective single-center review of CDH patients was performed, and outcomes compared to those reported by the CDH Study Group (CDHSG) registry. Patient demographics, disparities, and clinical characteristics were examined to identify unique features of the cohort. A model derived using the registry that estimates probability of ECMO use or death in CDH newborns was used to risk-stratify patients and assess mortality rates. Observed over expected (O/E) ECMO use rates were calculated to measure whether "excess" or "appropriate" ECMO use was occurring. RESULTS: There were 81 CDH patients treated between 2004-2017, and 5034 in the CDHSG registry. Mortality in ECMO-treated patients was higher than the registry. Socioeconomic variables were not significantly associated with outcomes. The strongest predictors of mortality were ECMO use and early blood gas variables. The risk model accurately predicted ECMO use with a c-statistic of 0.79. Compared with the registry, the disparity in mortality rates was greatest for moderate-risk patients. O/E ECMO use was highest in low and moderate-risk patients. CONCLUSIONS: ECMO use is a more consistent predictor of mortality than CDH severity at a single center, and there is relative overuse of ECMO in lower-risk patients. Risk stratification allows for more accurate institutional assessment of mortality and ECMO use, and other centers could consider such an adjusted analysis to identify opportunities for outcomes improvement. LEVEL OF EVIDENCE: III.

Prenatally versus postnatally diagnosed congenital diaphragmatic hernia - Side, stage, and outcome.

AIM: To compare outcomes between prenatally and postnatally diagnosed CDH in a large multicenter database of prospectively collected data and evaluate factors associated with poorer outcome for prenatally diagnosed CDH. MATERIAL AND METHODS: We used information from the multicenter, multinational CDH Study Group database on patients born between 2007 and 2015. We compared differences between prenatally and postnatally diagnosed CDH with respect to survival, side, size, ECMO needs, associated major cardiac malformations and liver position. RESULTS: 3746 cases of CDH were entered in the registry between 2007 and 2015, with an overall survival of 71%. Of those, 68% had a prenatal diagnosis. Survival rates were significantly better in the postnatally diagnosed group, 83 vs 65%. There was a higher proportion of bigger defect sizes, C and D, in the prenatally diagnosed group, but the survival rates were similar when patients were stratified by defect size. The rate of ECMO utilization was higher overall in the prenatally diagnosed group, 33 vs 22%, but it was similar within similar defect sizes. Right-sided defects are more commonly missed at prenatal screening than left-sided CDH, 53 vs 35% (p < 0.0001). CONCLUSIONS: Prenatally diagnosed CDH is associated with larger defect sizes compared to those with a postnatal diagnosis, and consequently have higher morbidity and mortality. Right-sided CDH are more often missed at prenatal ultrasound. The increasing rate of prenatal detection requires a clear understanding of accurate risk stratification, in order to counsel families and to provide appropriate perinatal management. LEVEL OF EVIDENCE: 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).

Evaluating the utility of the "late ECMO repair": a congenital diaphragmatic hernia study group investigation.

PURPOSE: Optimal timing of congenital diaphragmatic hernia (CDH) repair in patients requiring extracorporeal membrane oxygenation (ECMO) remains controversial. The "late ECMO repair" is an approach where the patient, once deemed stable for decannulation, is repaired while still on ECMO to enable expeditious return to ECMO if surgery induces instability. The goal of this study was to investigate the potential benefit of this approach by evaluating the rate of return to ECMO after repair. METHODS: The CDH Study Group database was used to analyze CDH patients requiring ECMO support. The primary outcome was return to ECMO within 72 h of CDH repair among those repaired following ECMO decannulation ("post-ECMO" patients). Secondary outcomes were death within 72 h of repair and cumulative death and return to ECMO rate. RESULTS: A total of 668 patients were repaired post-ECMO decannulation. Six patients (0.9%) in the post-ECMO group required return to ECMO within 72 h of surgery and a total of 19 (2.8%) died or returned to ECMO within 72 h of surgery. CONCLUSION: The rate of return to ECMO and death following CDH repair is extremely low and does not justify the risks inherent to "on-ECMO" repair. Patients stable to come off ECMO should undergo repair after decannulation.

Extracorporeal Membrane Oxygenation (ECMO) Risk Stratification in Newborns with Congenital Diaphragmatic Hernia (CDH).

BACKGROUND: A means for early postnatal stratification of ECMO risk in CDH newborns could be used to comparatively assess the utilization and outcomes of ECMO use between centers. While multiple CDH mortality risk calculators are available, no validated tool exists specifically for prediction of ECMO use. The purpose of this study was to derive and validate an ECMO risk stratification model. METHODS: The study population was obtained from CDH Study Group registry for the period between 2007 and 2016. Only centers offering ECMO were included. The cohort was restricted to ECMO candidates and then divided into derivation and validation sets. Using all relevant perinatal predictors in the registry, univariate analysis was performed for the composite outcome of ECMO use or death without ECMO use. The model was derived using the derivation cohort with multivariable logistic regression and automatic stepwise forward selection (P < 0.05 for qualifying variables), and a c-statistic was obtained. The model was then tested on the validation cohort. Sample reuse validation and bootstrap validation were performed. The validated model was then tested for accuracy on CDH subgroups. RESULTS: There were 1992 patients in the derivation cohort. Four significant variables were identified in the final ECMO risk model: 1-min and 5-min Apgar scores and highest and lowest post-ductal partial pressure of CO2 during the first 24 h of life. The model c-statistic was 0.824 which was confirmed with cross-validation and bootstrap optimism correction. The validation cohort c-statistic was 0.823 (N = 993). The model had good discrimination for left and right CDH, inborn and outborn patients, patients born before and after 2011, and high and low volume centers. The model performed significantly better for postnatally diagnosed patients. CONCLUSIONS: This study represents proof-of-concept that a risk model can accurately estimate the probability of ECMO use in CDH newborns. This stratification could assist centers as a metric for assessment of ECMO usage and outcomes. Refinement and prospective validation of this model should be carried out prior to clinical application. LEVEL OF EVIDENCE: 3.

Aggressive Surgical Management of Congenital Diaphragmatic Hernia: Worth the Effort?: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: The objectives of this study were (i) to evaluate infants with congenital diaphragmatic hernia (CDH) that do not undergo repair, (ii) to identify nonrepair rate by institution, and (iii) to compare institutional outcomes based on nonrepair rate. BACKGROUND: Approximately 20% of infants with CDH go unrepaired and the threshold to offer surgical repair is variable. METHODS: Data were abstracted from a multicenter, prospectively collected database. Standard clinical variables, including repair (or nonrepair), and outcome were analyzed. Institutions were grouped based on volume and rate of nonrepair. Preoperative mortality predictors were identified using logistic regression, expected mortality for each center was calculated, and observed /expected (O/E) ratios were computed for center groups and compared by Kruskal-Wallis ANOVA. RESULTS: A total of 3965 infants with CDH were identified and 691 infants (17.5%) were not repaired. Nonrepaired patients had lower Apgar scores (P < 0.05) and increased incidence of anomalies (P < 0.0001). Low-volume centers ("Lo", n=44 total, < 10 CDH pts/yr) and high-volume centers ("Hi", n = 21) had median nonrepair rates of 19.8% (range 0%-66.7%) and 16.7% (5.1%-38.5%), respectively. High-volume centers were further dichotomized by rate of nonrepair (HiLo = 5.1-16.7% and HiHi = 17.6-38.5%), leaving 3 groups: HiLo, HiHi, and Lo. Predictors of mortality were lower birth weight, lower Apgar scores, prenatal diagnosis, and presence of congenital anomalies. O/E ratios for mortality in the HiLo, HiHi, and Lo groups were 0.81, 0.94, and 1.21, respectively (P < 0.0001). For every 100 CDH patients, HiLo centers have 2.73 (2.4-3.1, 95% confidence interval) survivors beyond expectation. CONCLUSIONS: There are significant differences between repaired and nonrepaired CDH infants and significant center variation in rate of nonrepair exists. Aggressive surgical management, leading to a low rate of nonrepair, is associated with improved risk-adjusted mortality.

Right versus left congenital diaphragmatic hernia - What's the difference?

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).

Treatment Strategies for Congenital Diaphragmatic Hernia: Change Sometimes Comes Bearing Gifts.

OBJECTIVE: To report treatment strategies' evolution and its impact on congenital diaphragmatic hernia (CDH) outcome. DESIGN: Registry-based cohort study using the CDH Study Group database, 1995-2013. SETTING: International multicenter database. PATIENTS: CDH patients entered into the registry. Late presenters or patients with very incomplete data were excluded. Patients were divided into three Eras (1995-2000; 2001-2006; 2007-2013). MAIN OUTCOME MEASURES: Treatment strategies and outcomes. One-way ANOVA, X2 test, and X2 test for trend were used. A Sydak-adjusted p < 0.0027 was considered significant. Prevalence or mean (SE) are reported. RESULTS: Patients: 8,603; included: 7,716; Era I: 2,146; Era II: 2,572; Era III: 2,998. From Era I to Era III, significant changes happened. Some severity indicators such as gestational age, prevalence of prenatal diagnosis, and inborn patients significantly worsened. Also, treatment strategies such as the use of prenatal steroids and inhaled nitric oxide, age at operation, prevalence of minimal access surgery, and the use of surfactant significantly changed. Finally, length of hospital stay became significantly longer and survival to discharge slightly but significantly improved, from 67.7 to 71.4% (p for trend 0.0019). CONCLUSION: Treatment strategies for patients registered since 1995 in the CDH Study Group significantly changed. Survival to discharge slightly but significantly improved.

Congenital diaphragmatic hernia: The role of multi-institutional collaboration and patient registries in supporting best practice.

Among congenital malformations, congenital diaphragmatic hernia (CDH) is distinguished by its relatively low occurrence rate, need for resource intensive, integrated multidisciplinary care, and widespread variation in practice and outcome. Although randomized controlled trials (RCTs) are considered the gold standard for generating evidence, they are poorly suited to the study of a condition like CDH due to challenges in illness severity adjustment, unpredictability in clinical course and the impact limitations of studying a single intervention at a time. An alternative to RCTs for comparative effectiveness research for CDH is the patient registry, which aggregates multi-institutional condition-specific patient level data into a large CDH-specific database for the dual purposes of collaborative research and quality improvement across participating sites. This article discusses patient registries from the perspective of structure, data collection and management, and privacy protection that guide the use of registry data to support collaborative, multidisciplinary research. Two CDH-specific registries are described as illustrative examples of the "value proposition" of registries in improving the evidence basis for best practices for CDH.

Factors associated with early recurrence after congenital diaphragmatic hernia repair.

BACKGROUND: The purpose of this study was to identify patient and treatment characteristics associated with early (in hospital) hernia recurrence after congenital diaphragmatic hernia (CDH) repair. METHODS: Data from the Congenital Diaphragmatic Hernia Study Group registry were queried from 2007 to 2015. Recurrence of the diaphragmatic hernia after initial repair and prior to death or discharge was determined at the time of reoperation. Minimally invasive surgery (MIS) approaches included laparoscopy or thoracoscopy, and open approaches consisted of laparotomy or thoracotomy. Multivariate regression analysis was performed. RESULTS: Of 3984 patients, 3332 (84%) underwent CDH repair. 76 (2.3%) patients had an early recurrence. The rate of recurrence was less variable over time for patients undergoing laparotomy vs thoracoscopy (range: 1.1-3.7% vs 1.7-8.9% annually). Timing of repair, whether performed after, during, or before ECMO did not significantly alter recurrence rates (0% vs 4.2% vs 3.0%, p=0.116). Larger defect size (C: OR 4.3, 95% CI 1.2-15.4; D: OR 7.1, 95% CI 1.7-29.1) and an MIS approach (OR 3.2, 95% CI 1.7-6.0) were the only independent predictors of recurrence. CONCLUSION: Larger defect size and an MIS approach were associated with higher rates of early recurrence, while ECMO use and timing of repair with ECMO were not. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: II.

Minimally Invasive vs Open Congenital Diaphragmatic Hernia Repair: Is There a Superior Approach?

BACKGROUND: The minimally invasive surgery (MIS) approach for congenital diaphragmatic hernia (CDH) repair remains controversial. Our objective was to compare outcomes and complications of the MIS and open approaches, with risk-stratification of patients based on defect size and key patient characteristics. STUDY DESIGN: The multinational CDH Study Group (CDHSG) registry was queried for the period from 2007 to 2015. Patient demographics and operative details, including the CDHSG Staging System defect size (A to D), were reviewed. Open cases consisted of laparotomy and thoracotomy; MIS repairs included laparoscopy and thoracoscopy. Outcomes included length of stay (LOS) for patients surviving to discharge, hernia recurrence, and adhesive small bowel obstruction (SBO) requiring surgery. Regression analyses were performed. Odds ratios (ORs) with 95% CIs were derived. RESULTS: A total of 3,067 CDH patients underwent open (n = 2,579; 84%) or MIS (n = 488; 16%) repair. Patients undergoing open repair were more likely to be diagnosed prenatally, be premature, have lower 5-minute Apgar scores, and have major cardiac anomalies (all p < 0.001). Among MIS repairs, 79% were low risk (size A and B) defects vs 50% among open repairs (p < 0.001). Patients undergoing MIS repair experienced shorter overall median LOS, higher recurrence rates, and fewer SBO. With multivariable regression adjusting for defect size and key patient characteristics, an MIS approach was significantly associated with decreased LOS (mean -13.4 days; 95% CI -18 to -8.8 days), increased recurrences (OR 3.10; 95% CI 1.91 to 5.04), and decreased SBO (OR 0.19; 95% CI 0.06 to 0.60). CONCLUSIONS: After risk-stratification of CDH patients, an MIS approach was independently associated with decreased LOS and SBO, but higher recurrence rates.

Bilateral congenital diaphragmatic hernia: prognostic evaluation of a large international cohort.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a lethal birth defect, which occurs in 1:2000-3000 live births. Bilateral CDH is a rare form (1%), with a high mortality. This study presents the outcomes of the largest cohort of bilateral CDH patients. METHODS: The records of patients with bilateral CDH from the Congenital Diaphragmatic Hernia Registry born between 1995 and 2015 were retrospectively analyzed to identify parameters associated with mortality. RESULTS: Eighty patients with a bilateral CDH were identified. Overall mortality was 74% (n=59). Apgar scores at 1 and 5min were statistically lower in the non-survivors compared to the survivors (median 3.0 and 5.0, versus 6.5 and 8.0, respectively, p<0.001). All survivors were repaired (n=21), compared to 22% of the non-survivors (n=17). The type of repair was equally divided in the survivors (52% primary versus 48% patch), while non-survivors were mainly patch repaired (82% versus 12%). Nineteen were treated with extracorporeal membrane oxygenation (ECMO) (24%), only three of them survived. When calculating the risk on mortality for the patients who lived until repair, ECMO had an adjusted odds ratio for mortality of 10.8 (95% CI: 2.0-57.7) and patch repair 5.2 (95% CI: 0.8-34.9). CONCLUSIONS: The treatment of bilateral CDH patients remains challenging with a high mortality rate. Lower Apgar-scores, ECMO (probably as a surrogate for the severity of disease), and patch repair were negatively associated with outcome. LEVEL OF EVIDENCE: Level IV study.

The Congenital Diaphragmatic Hernia Study Group Registry.

Congenital diaphragmatic hernia (CDH) is a rare anomaly with an incidence between 1/2,500 and 1/3,000 live births. The rarity of the disease makes it difficult to design powerful studies leading to accurate and meaningful evidence. For rare diseases, the development of multicenter international registries may help in collecting data and give an overall picture of the disease. In this review, we will describe the development of the CDH study group, we will describe its work methodology, and the results obtained since its birth in 1995.