Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia.

INTRODUCTION: The objective of this study was to evaluate the association between fetal cardiac deformation analysis (CDA) and cardiac function with severe adverse perinatal outcomes in fetuses with isolated left congenital diaphragmatic hernia (CDH). METHODS: CDA in each ventricle (contractility, size, and shape), evaluated by speckle tracking and novel FetalHQ software, and markers of cardiac function (E/A ratios, pulmonary and aortic peak systolic velocities, and sigmoid annular valve diameters), were evaluated in fetuses with isolated left CDH. Two evaluations were performed: at referral (CDA and function) and within 3 weeks of delivery (CDA). Severe adverse neonatal outcomes were considered neonatal death (ND) or survival with CDH-associated pulmonary hypertension (CDH-PH). Differences and associations between CDA, cardiac function, and severe adverse outcomes were estimated. RESULTS: Fifty fetuses were included, and seventeen (34%) had severe adverse neonatal outcomes (11 ND and 6 survivors with CDH-PH). At first evaluation, the prevalence of a small left ventricle was 34% (17/50) with a higher prevalence among neonates presenting severe adverse outcomes (58.8 [10/17] vs. 21.2% [7/33]; p = 0.01; OR, 5.03 [1.4-19.1; p = 0.01]) and among those presenting with neonatal mortality (8/11 [72.7] vs. 9/39 [23.0%]; p = 0.03; OR, 8.9 [1.9-40.7; p = 0.005]). No differences in cardiac function or strain were noted between fetuses with or without severe adverse outcomes. Within 3 weeks of delivery, the prevalence of small left ventricle was higher (19/34; 55.8%) with a more globular shape (reduced transverse/longitudinal ratio). A globular right ventricle was significantly associated with ND or survival with CDH-PH (OR, 14.2 [1.5-138.3]; p = 0.02). CONCLUSION: Fetuses with isolated CDH at risk of perinatal death or survival with CDH-PH had a higher prevalence of a small left ventricle and abnormal shape of the right ventricle.

Impact of Repeat Extracorporeal Life Support on Mortality and Short-term In-hospital Morbidities in Neonates With Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate the impact of repeat extracorporeal life support (ECLS) on survival and in-hospital outcomes in the congenital diaphragmatic hernia (CDH) neonates. BACKGROUND: Despite the widespread use of ECLS, investigations on multiple ECLS courses for CDH neonates are limited. METHODS: This is a retrospective cohort study of all ECLS-eligible CDH neonates enrolled in the Congenital Diaphragmatic Hernia Study Group registry between 1995 and 2019. CDH infants with estimated gestational age at birth <32 weeks and a birth weight <1.8 kg and/or with major cardiac or chromosomal anomalies were excluded. The primary outcomes were survival and morbidities during the index hospitalization. RESULTS: Of 10,089 ECLS-eligible CDH infants, 3025 (30%) received 1 ECLS course, and 160 (1.6%) received multiple courses. The overall survival rate for patients who underwent no ECLS, 1 ECLS course, and multicourse ECLS were 86.9±0.8%, 53.8±1.8%, and 43.1±7.7%, respectively. Overall ECLS survival rate is increased by 5.1±4.6% ( P =0.03) for CDH neonates treated at centers that conduct repeat ECLS compared with those that do not offer repeat ECLS. This suggests that there would be an overall survival benefit from increased use of multiple ECLS courses. Infants who did not receive ECLS support had the lowest morbidity risk, while survivors of multicourse ECLS had the highest rates of morbidities during the index hospitalization. CONCLUSIONS: Although survival is lower for repeat ECLS, the use of multiple ECLS courses has the potential to increase overall survival for CDH neonates. Increased use of repeat ECLS might be associated with improved survival. The potential survival advantage of repeat ECLS must be balanced against the increased risk of morbidities during the index hospitalization.

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.

Sex-Specific Differences in Congenital Diaphragmatic Hernia Mortality.

OBJECTIVE: To compare disease severity and mortality differences between female and male patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We queried the CDH Study Group (CDHSG) database for CDH neonates managed between 2007 and 2018. Female and males were compared in statistical analyses using t tests, χ² tests, and Cox regression, as appropriate (P ≤ .05). RESULTS: There were 7288 CDH patients, of which 3048 (41.8%) were female. Females weighed less on average at birth than males (2.84 kg vs 2.97 kg, P < .001) despite comparable gestational age. Females had similar rates of extracorporeal life support (ECLS) utilization (27.8% vs 27.3%, P = .65). Although both cohorts had equivalent defect size and rates of patch repair, female patients had increased rates of intrathoracic liver herniation (49.2% vs 45.9%, P = .01) and pulmonary hypertension (PH) (86.6% vs 81.1%, P < .001). Females had lower survival rates at 30-days (77.3% vs 80.1%, P = .003) and overall lower survival to discharge (70.2% vs 74.2%, P < .001). Subgroup analysis revealed that increased mortality was significant among those who underwent repair but were never supported on ECLS (P = .005). On Cox regression analysis, female sex was independently associated with mortality (adjusted hazard ratio 1.32, P = .02). CONCLUSION: After controlling for the established prenatal and postnatal predictors of mortality, female sex remains independently associated with a higher risk of mortality in CDH. Further study into the underlying causes for sex-specific disparities in CDH outcomes is warranted.

Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia.

BACKGROUND: Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited. METHODS: This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses. RESULTS: Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05-4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11-5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use. CONCLUSIONS: Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration. IMPACT: Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited. The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use. Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use. Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.

Syndromic congenital diaphragmatic hernia: Current incidence and outcome. Analysis from the congenital diaphragmatic hernia study group registry.

BACKGROUND: The aim of this study was to describe the incidence of Congenital Diaphragmatic Hernia, CDH, associated with known or clinically suspected syndromes, and the postnatal outcomes from a large database for CDH. METHODS: Data from the multicenter, multinational database on infants with CDH (Congenital Diaphragmatic Hernia Study Group Registry) born from 1996 to 2020 were analyzed. Patients with known or suspected syndromes were grouped and outcome data were analyzed and compared to those without syndromic features. RESULTS: A total of 12,553 patients were entered in the registry during the study period, and 421 had reported known syndromes, representing 3.4% of all CDH cases in the registry. A total of 50 different associated syndromes were reported. In addition to those with clinically suspected genetic conditions, a total rate of genetic syndromes with CDH was 8.2%. The overall survival to discharge for syndromic CDH was 34% and for non-syndromic CDH was 76.7%. The most common were syndromes Fryns syndrome (19.7% of all syndromes, 17% survival), trisomy 18 or Edward syndrome (17.5%, 9% survival), trisomy 21 or Down syndrome (9%, 47% survival), trisomy 13 or Patau syndrome (6.7%, 14% survival), Cornelia de Lange syndrome (6.4% of all syndromes, 22% survival) and Pallister-Killian syndrome (5.5% of all syndromes, 39.1% survival). In addition, 379 cases had reported chromosomal anomalies and 233 cases had clinically suspected syndromes, based on two more dysmorphic features or malformations in addition to CDH, but without molecular diagnosis. The syndromic CDH group had lower birth weight and gestational age at birth and increased incidence of bilateral CDH (2.9%) and rates of non-repair (53%). The length of hospital stay was longer, and larger number of patients needed O2 at 30 days. Extracorporeal life support was used only in 15% of the cases. Those who underwent surgical repair had survival to discharge rates of 73%. CONCLUSION: Syndromic CDH is rare and only 3.4% of the reported cases of CDH have a known syndrome or association, but, if including patients with two dysmorphic features malformations, in addition to CDH, altogether as many as 8.2% have a diagnosed or suspected genetic condition. These children have with lower survival rates. Given higher rates of non-repair and decreased extracorporeal life support use, along with a high early mortality, decision-making regarding goals of care clearly influences outcomes. Survival varies depending on the genetic cause. Early genetic diagnosis is important and may influence the decision-making.

Center Volume and Survival Relationship for Neonates With Congenital Diaphragmatic Hernia Treated With Extracorporeal Life Support.

OBJECTIVES: Literature is emerging regarding the role of center volume as an independent variable contributing to improved outcomes. A higher volume of index procedures may be associated with decreased morbidity and mortality. This association has not been examined for the subgroup of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS). Our study aims to examine the risk-adjusted association between center volume and outcomes in CDH-ECLS neonates, hypothesizing that higher center volume confers a survival advantage. DESIGN: Multicenter, retrospective comparative study using the Extracorporeal Life Support Organization database. SETTING: One hundred twenty international pediatric centers. PATIENTS: Neonates with CDH managed with ECLS from 2000 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort included 4,985 neonates with a mortality rate of 50.6%. For the 120 centers studied, mean center volume was 42.4 ± 34.6 CDH ECLS cases over the 20-year study period. In an adjusted model, higher ECLS volume was associated with lower odds of mortality: odds ratio (OR) 0.995 (95% CI, 0.992-0.999; p = 0.014). For an increase in one sd in volume, that is, 1.75 cases annually, the OR for mortality was lower by 16.7%. Volume was examined as a categorical exposure variable where low-volume centers (fewer than 2 cases/yr) were associated with 54% higher odds of mortality (OR, 1.54; 95% CI, 1.03-2.29) compared with high-volume centers. On-ECLS complications (mechanical, neurologic, cardiac, hematologic metabolic, and renal) were not associated with volume. The likelihood of infectious complications was higher for low- (OR, 1.90; 95% CI, 1.06-3.40) and medium-volume (OR, 1.87; 95% CI, 1.03-3.39) compared with high-volume centers. CONCLUSIONS: In this study, a survival advantage directly proportional to center volume was observed for CDH patients managed with ECLS. There was no significant difference in most complication rates. Future studies should aim to identify factors contributing to the higher mortality and morbidity observed at low-volume centers.

Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?

INTRODUCTION: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. METHODS: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. RESULTS: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59-5.73) positive and 0.27 (95% CI 0.08-0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. CONCLUSION: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.

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.

Extracorporeal Life Support for Respiratory Failure in Patients With Electronic Cigarette or Vaping Product Use-Associated Lung Injury.

OBJECTIVES: Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support. DESIGN: We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. SETTING: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. PATIENTS: Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. MEASUREMENTS AND MAIN RESULTS: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. CONCLUSIONS: Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

In-Hospital Morbidities for Neonates with Congenital Diaphragmatic Hernia: The Impact of Defect Size and Laterality.

OBJECTIVE: To determine in-hospital morbidities for neonates with right-sided congenital diaphragmatic hernia (R-CDH) compared with those with left-sided defects (L-CDH) and to examine the differential effect of laterality and defect size on morbidities. STUDY DESIGN: This retrospective, multicenter, cohort study from the international Congenital Diaphragmatic Hernia Study Group registry collected data from neonates with CDH surviving until hospital discharge from 90 neonatal intensive care units between January 1, 2007, and July 31, 2020. Major pulmonary, cardiac, neurologic, and gastrointestinal morbidities were compared between neonates with L-CDH and R-CDH, adjusted for prenatal and postnatal factors using logistic regression. RESULTS: Of 4123 survivors with CDH, those with R-CDH (n = 598 [15%]) compared with those with L-CDH (n = 3525 [85%]) had an increased odds of pulmonary (1.7; 95% CI, 1.4-2.2, P < .0001), cardiac (1.4; 95% CI, 1.1-1.8; P = .01), gastrointestinal (1.3; 95% CI, 1.1-1.6; P = .01), and multiple (1.6; 95% CI, 1.2-2.0; P < .001) in-hospital morbidities, with a greater likelihood of morbidity with increasing defect size. There was no difference in neurologic morbidities between the groups. CONCLUSIONS: Neonates with R-CDH and a larger defect size are at an increased risk for in-hospital morbidities. Counseling and clinical strategies should incorporate knowledge of these risks, and approach to neonatal R-CDH should be distinct from current practices targeted to L-CDH.

Inborn Versus Outborn Delivery in Neonates With Congenital Diaphragmatic Hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a morbid and potentially fatal condition that challenges providers. The aim of this study is to compare outcomes in neonates with prenatally diagnosed CDH that are inborn (delivered in the institution where definitive care for CDH is provided) versus outborn. METHODS: Prenatally diagnosed CDH cases were identified from the Congenital Diaphragmatic Hernia Study Group (CDHSG) database between 2007 and 2019. Using risk adjustment based on disease severity, we compared inborn versus outborn status using baseline risk and multivariable logistic regression models. The primary endpoint was mortality and the secondary endpoint was need for extracorporeal life support (ECLS). RESULTS: Of 4195 neonates with prenatally diagnosed CDH, 3087 (73.6%) were inborn and 1108 (26.4%) were outborn. There was no significant difference in birth weight, gestational age, or presence of additional congenital anomalies. There was no difference in mortality between inborn and outborn infants (32.6% versus 33.8%, P = 0.44) or ECLS requirement (30.9% versus 31.5%, P = 0.73). Among neonates requiring ECLS, outborn status was a risk factor for mortality (OR 1.51, 95% CI 1.13-2.01, P = 0.006). After adjusting for post-surgical defect size, which is not known prenatally, outborn status was no longer a risk factor for mortality for infants requiring ECLS. CONCLUSIONS: Risk of mortality and need for ECLS for inborn CDH patients is not different to outborn infants. Future studies should be directed to establishing whether highest risk infants are at risk for worse outcomes based on center of birth.

Isolated aortic arch anomalies are associated with defect severity and outcome in patients with congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) patients often have suspected isolated aortic arch anomalies (IAAA) on imaging. The purpose of this work was to describe the incidence and outcomes of CDH + IAAA patients. METHODS: Cardiovascular data were collected for infants from the CDH Study Group born between 2007 and 2019. IAAA were defined as coarctation of aorta, hypoplastic aortic arch, interrupted aortic arch, and aortic aneurysmal disease on early, postnatal echocardiography. Patients with major cardiac malformations and/or chromosomal abnormalities were excluded. Primary outcomes included the rate of aortic intervention, rates of extracorporeal life support (ECLS) utilization, and mortality. RESULTS: Of 6357 CDH infants, 432 (7%) were diagnosed with a thoracic aortic anomaly. Of these, 165 were diagnosed with IAAA, most commonly coarctation of the aorta (n = 106; 64%) or hypoplastic aortic arch (n = 58; 35%). CDH + IAAA patients had lower birthweights (3 kg vs. 2.9 kg) and Apgar scores (7 vs. 6) than patients without IAAA (both χ2 p < 0.001). CDH + IAAA were less likely to undergo diaphragm repair (72 vs. 87%, p < 0.001), and overall mortality was higher for CDH + IAAA infants (58 vs. 24%, p < 0.001). When controlling for defect size, birth weight, and Apgar, IAAA were significantly associated with mortality (OR 3.3, 95% CI 2.2-5.0; p < 0.01) but not associated with ECLS (OR 0.98, 95% CI 0.65-1.50; p = 0.90). Only 17% (n = 28) of CDH + IAAA patients underwent aortic intervention. CONCLUSIONS: IAAA in CDH are associated with increased mortality. This often simply reflects severity of the defect and thoracic anatomic derangement, as opposed to unique aortic pathology, given few CDH + IAAA patients undergo aortic intervention.

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.

Injury Severity, Arrival Physiology, Coagulopathy, and Outcomes Among the Youngest Trauma Patients.

BACKGROUND: Although physiologic differences exist between younger and older children, pediatric trauma analyses are weighted toward older patients. Trauma-induced coagulopathy, determined by rapid thrombelastography (rTEG), is a predictor of outcome in trauma patients, but the significance of rTEG values among very young trauma patients remains unknown. Our objective was to identify the prehospital or physiologic factors, including rTEG values, that were associated with mortality in trauma patients younger than 5 y old. MATERIALS AND METHODS: Patients younger than 5 y old that met the highest-level trauma activation criteria at an academic children's hospital from 2010-2016 were included. Data regarding demographics, pre-hospital management, laboratory values, injury severity, and outcome were queried. Univariate and multivariate analyses were performed comparing survivors and non-survivors. RESULTS: A total of 356 patients were included. 60% were male, and the median age was 3 y (IQR 1-4). Overall mortality was 13% (n = 45); brain injury (91%) and hemorrhage (9%) were the causes of death. Compared to survivors, rTEG values in nonsurvivors showed longer activated clotting time and slower speed of clot formation. Clot strength was also decreased in nonsurvivors. On stepwise regression modeling, rTEG values were not significant predictors of mortality. Admission base deficit, arrival temperature, and head injury severity were identified as independent predictors of mortality. CONCLUSIONS: While rTEG identified coagulopathy in trauma patients < 5 y old, it was not an independent predictor of mortality. Our findings suggest that trauma providers should pay close attention to admission base deficit, arrival temperature, and head injury severity when managing the youngest trauma patients.

Risk Factors for Hemolysis During Extracorporeal Life Support for Congenital Diaphragmatic Hernia.

BACKGROUND: Neonates receiving extracorporeal life support (ECLS) for congenital diaphragmatic hernia (CDH) require prolonged support compared with neonates with other forms of respiratory failure. Hemolysis is a complication that can be seen during ECLS and can lead to renal failure and potentially to worse outcomes. The purpose of this study was to identify risk factors for the development of hemolysis in CDH patients treated with ECLS. METHODS: The Extracorporeal Life Support Organization database was used to identify infants with CDH (2000-2015). The primary outcome was hemolysis (plasma-free hemoglobin >50 mg/dL). Potentially associated variables were identified in the data set. Descriptive statistics and a series of nested multivariable logistic regression models were used to identify associations between hemolysis and demographic, pre-ECLS, and on-ECLS factors. RESULTS: There were 4576 infants with a mortality of 52.5%. The overall mean rate of hemolysis was 10.5% during the study period. In earlier years (2000-2005), the hemolysis rates were 6.3% and 52.7% for roller versus centrifugal pumps, whereas in later years (2010-2015), they were 2.9% and 26.5%, respectively. The fully adjusted model demonstrated that the use of centrifugal pumps was a strong predictor of hemolysis (odds ratio: 6.67, 95% confidence interval: 5.14-8.67). In addition, other risk factors for hemolysis included low 5-min Apgar score, on-ECLS complications (renal, metabolic, and cardiovascular), and duration of ECLS. CONCLUSIONS: In our cohort of CDH patients receiving ECLS over 15 y, the use of centrifugal pumps increased over time, along with the rate of hemolysis. Patient- and treatment-level risk factors were identified contributing to the development of hemolysis.

A Multicenter Study of Nutritional Adequacy in Neonatal and Pediatric Extracorporeal Life Support.

BACKGROUND: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population. MATERIALS AND METHODS: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support. RESULTS: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%). CONCLUSIONS: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications.

Early Left Ventricular Dysfunction and Severe Pulmonary Hypertension Predict Adverse Outcomes in "Low-Risk" Congenital Diaphragmatic Hernia.

OBJECTIVES: Given significant focus on improving survival for "high-risk" congenital diaphragmatic hernia, there is the potential to overlook the need to identify risk factors for suboptimal outcomes in "low-risk" congenital diaphragmatic hernia cases. We hypothesized that early cardiac dysfunction or severe pulmonary hypertension were predictors of adverse outcomes in this "low-risk" congenital diaphragmatic hernia population. DESIGN: This is a retrospective cohort study using data from the Congenital Diaphragmatic Hernia Study Group registry. "Low-risk" congenital diaphragmatic hernia was defined as Congenital Diaphragmatic Hernia Study Group defect size A/B without structural cardiac and chromosomal anomalies. Examined risk factors included left ventricular dysfunction, right ventricular dysfunction, and severe pulmonary hypertension on the first postnatal echocardiogram. The primary outcome was composite adverse events, defined as either death, extracorporeal membrane oxygenation utilization, oxygen requirement on day 30 of life, or hospitalization greater than or equal to 8 weeks. Multivariable adjustment was performed with logistic regression and inverse probability weighting. SETTING: Neonatal index hospitalization for congenital diaphragmatic hernia. PATIENTS: "Low-risk" congenital diaphragmatic hernia infants born between January 2015 and December 2018. INTERVENTIONS: First postnatal echocardiogram performed within 24 hours from birth. MEASUREMENTS AND MAIN RESULTS: Seven-hundred seventy-eight patients were identified as "low-risk" congenital diaphragmatic hernia. Left ventricular dysfunction, right ventricular dysfunction, and severe pulmonary hypertension were present in 10.8%, 20.5%, and 57.5%, respectively. The primary outcome occurred in 21.3%. Death occurred in 3.0% and 9.1% used extracorporeal membrane oxygenation. On unadjusted analysis, all three risk factors were associated with the primary outcome. On all multivariable adjustment methods, left ventricular dysfunction and severe pulmonary hypertension remained significant predictors of adverse outcomes while right ventricular dysfunction no longer demonstrated any effect. CONCLUSIONS: Early left ventricular dysfunction and severe pulmonary hypertension are independent predictors of adverse outcomes among "low-risk" congenital diaphragmatic hernia infants. Early recognition may lead to interventions that can improve outcome in this at-risk cohort.

Ventricular Dysfunction Is a Critical Determinant of Mortality in Congenital Diaphragmatic Hernia.

Rationale: Congenital diaphragmatic hernia (CDH) is an anomaly with a high morbidity and mortality. Cardiac dysfunction may be an important and underrecognized contributor to CDH pathophysiology and determinant of disease severity.Objectives: Our aim was to investigate the association between early, postnatal ventricular dysfunction and outcome among infants with CDH.Methods: Multicenter, prospectively collected data in the CDH Study Group (CDHSG) registry, abstracted between 2015 and 2018, were evaluated. Ventricular function on early echocardiograms, defined as obtained within the first 48 hours of life, was categorized into four hierarchical groups: normal function, right ventricular dysfunction only (RVdys), left ventricular dysfunction only (LVdys), and combined RV and LV dysfunction (RV&LVdys). Univariate, multivariate, and Cox proportional hazards regression analyses were performed.Measurements and Main Results: Cardiac function data from early echocardiograms were available for 1,173 (71%) cases and categorized as normal in 711 (61%), RVdys in 182 (15%), LVdys in 61 (5%), and combined RV&LVdys in 219 (19%) cases. Ventricular dysfunction was significantly associated with prenatal diagnosis, CDHSG stage, intrathoracic liver, and patch repair (all P < 0.001). Survival varied by category: normal function, 80%; RVdys, 74%; LVdys, 57%; and RV&LVdys, 51% (P < 0.001). The adjusted risk of death (hazard ratio) for cases with LVdys was 1.96 (95% confidence interval [CI], 1.29-2.98; P = 0.020) and for cases with RV&LVdys was 2.27 (95% CI, 1.77-2.92; P = 0.011). All cardiac dysfunction categories were associated with use of extracorporeal membrane oxygenation (P < 0.005).Conclusions: Early ventricular dysfunction occurs frequently in CDH and is an independent determinant of severity and clinical outcome.

Establishing a regional pediatric trauma preventable/potentially preventable death rate.

PURPOSE: Although trauma is the leading cause of death for the pediatric population, few studies have addressed the preventable/potentially preventable death rate (PPPDR) attributable to trauma. METHODS: This is a retrospective study of trauma-related death records occurring in Harris County, Texas in 2014. Descriptive and Chi-squared tests were conducted for two groups, pediatric and adult trauma deaths in relation to demographic characteristics, mechanism of injury, death location and survival time. RESULTS: There were 105 pediatric (age < 18 years) and 1738 adult patients. The PPPDR for the pediatric group was 21.0%, whereas the PPPDR for the adult group was 37.2% (p = 0.001). Analysis showed fewer preventable/potentially preventable (P/PP) deaths resulting from any blunt trauma mechanism in the pediatric population than in the adult population (19.6% vs. 48.4%, p < 0.001). Amongst the pediatric population, P/PP traumatic brain injury (TBI) were more common in the youngest age range (age 0-5) vs. the older (6-12 years) pediatric and adolescent (13-17 years) patients. CONCLUSION: Our results identify areas of opportunities for improving pediatric trauma care. Although the overall P/PP death rate is lower in the pediatric population than the adult, opportunities for improving initial acute care, particularly TBI, exist.