Development of a prediction nomogram for 1-month mortality in neonates with congenital diaphragmatic hernia.

OBJECTIVES: Although many prognostic factors in neonates with congenital diaphragmatic hernia (CDH) have been described, no consensus thus far has been reached on which and how many factors are involved. The aim of this study is to analyze the association of multiple prenatal and postnatal factors with 1-month mortality of neonates with CDH and to construct a nomogram prediction model based on significant factors. METHODS: A retrospective analysis of neonates with CDH at our center from 2013 to 2022 was conducted. The primary outcome was 1-month mortality. All study variables were obtained either prenatally or on the first day of life. Risk for 1-month mortality of CDH was quantified by odds ratio (OR) with 95% confidence interval (CI) in multivariable logistic regression models. RESULTS: After graded multivariable adjustment, six factors were found to be independently and consistently associated with the significant risk of 1-month mortality in neonates with CDH, including gestational age of prenatal diagnosis (OR, 95% CI, P value: 0.845, 0.772 to 0.925, < 0.001), observed-to-expected lung-to-head ratio (0.907, 0.873 to 0.943, < 0.001), liver herniation (3.226, 1.361 to 7.648, 0.008), severity of pulmonary hypertension (6.170, 2.678 to 14.217, < 0.001), diameter of defect (1.560, 1.084 to 2.245, 0.017), and oxygen index (6.298, 3.383 to 11.724, < 0.001). Based on six significant factors identified, a nomogram model was constructed to predict the risk for 1-month mortality in neonates with CDH, and this model had decent prediction accuracy as reflected by the C-index of 94.42%. CONCLUSIONS: Our findings provide evidence for the association of six preoperational and intraoperative factors with the risk of 1-month mortality in neonates with CDH, and this association was reinforced in a nomogram model.

Timing of magnetic resonance imaging in pregnancy for outcome prediction in congenital diaphragmatic hernia.

PURPOSE: To evaluate the impact of the timing of MRI on the prediction of survival and morbidity in patients with CDH, and whether serial measurements have a beneficial value. METHODS: This retrospective cohort study was conducted in two perinatal centers, in Germany and Italy. It included 354 patients with isolated CDH having at least one fetal MRI. The severity was assessed with the observed-to-expected total fetal lung volume (o/e TFLV) measured by two experienced double-blinded operators. The cohort was divided into three groups according to the gestational age (GA) at which the MRI was performed (< 27, 27-32, and > 32 weeks' gestation [WG]). The accuracy for the prediction of survival at discharge and morbidity was analyzed with receiver operating characteristic (ROC) curves. Multiple logistic regression analyses and propensity score matching examined the population for balance. The effect of repeated MRI was evaluated in ninety-seven cases. RESULTS: There were no significant differences in the prediction of survival when the o/e TFLV was measured before 27, between 27 and 32, and after 32 WG (area under the curve [AUC]: 0.77, 0.79, and 0.77, respectively). After adjustment for confounding factors, it was seen, that GA at MRI was not associated with survival at discharge, but the risk of mortality was higher with an intrathoracic liver position (adjusted odds ratio [aOR]: 0.30, 95% confidence interval [95%CI] 0.12-0.78), lower GA at birth (aOR 1.48, 95%CI 1.24-1.78) and lower o/e TFLV (aOR 1.13, 95%CI 1.06-1.20). ROC curves showed comparable prediction accuracy for the different timepoints in pregnancy for pulmonary hypertension, the need of extracorporeal membrane oxygenation, and feeding aids. Serial measurements revealed no difference in change rate of the o/e TFLV according to survival. CONCLUSION: The timing of MRI does not affect the prediction of survival rate or morbidity as the o/e TFLV does not change during pregnancy. Clinicians could choose any gestational age starting mid second trimester for the assessment of severity and counseling.

Congenital Diaphragmatic Hernia Patients with Left Heart Hypoplasia and Left Ventricular Dysfunction Have Highest Odds of Mortality.

OBJECTIVES: To describe the scope of left ventricular (LV) dysfunction and left heart hypoplasia (LHH) in infants with congenital diaphragmatic hernia (CDH), to determine associations with CDH severity, and to evaluate the odds of extracorporeal membrane oxygenation (ECMO) and death with categories of left heart disease. STUDY DESIGN: Demographic and clinical variables were collected from a single-center, retrospective cohort of patients with CDH from January 2017 through May 2022. Quantitative measures of LV function and LHH were prospectively performed on initial echocardiograms. LHH was defined as ≥2 of the following: z score ≤ -2 of any left heart structure or LV end-diastolic volume <3 mL. LV dysfunction was defined as shortening fraction <28%, ejection fraction <60%, or global longitudinal strain <20%. The exposure was operationalized as a 4-group categorical variable (LV dysfunction +/-, LHH +/-). Logistic regression models evaluated associations with ECMO and death, adjusting for CDH severity. RESULTS: One hundred eight-two patients (80.8% left CDH, 63.2% liver herniation, 23.6% ECMO, 12.1% mortality) were included. Twenty percent demonstrated normal LV function and no LHH (LV dysfunction-/LHH-), 37% normal LV function with LHH (LV dysfunction-/LHH+), 14% LV dysfunction without LHH (LV dysfunction+/LHH-), and 28% both LV dysfunction and LHH (LV dysfunction+/LHH+). There was a dose-response effect between increasing severity of left heart disease, ECMO use, and mortality. LV dysfunction+/LHH + infants had the highest odds of ECMO use and death, after adjustment for CDH severity [OR (95% CI); 1.76 (1.20, 2.62) for ECMO, 2.76 (1.63, 5.17) for death]. CONCLUSIONS: In our large single-center cohort, patients with CDH with LV dysfunction+/LHH + had the highest risk of ECMO use and death.

The Association of Prenatal Diagnoses with Mortality and Long-Term Morbidity in Children with Specific Isolated Congenital Anomalies: A European Register-Based Cohort Study.

OBJECTIVES: To compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally. METHODS: Population-based registers' data were linked to hospital and mortality databases. RESULTS: Children whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06). CONCLUSIONS: Our findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed.

Risk Factors for Preoperative Pneumothorax in Neonates With Isolated Left-Sided Congenital Diaphragmatic Hernia: An International Cohort Study.

BACKGROUND: We aimed to investigate the clinical characteristics and outcomes of patients with isolated left-sided congenital diaphragmatic hernia (CDH) who developed preoperative pneumothorax and determine its risk factors. METHODS: We performed an international cohort study of patients with CDH enrolled in the Congenital Diaphragmatic Hernia Study Group registry between January 2015 and December 2020. The main outcomes assessed included survival to hospital discharge and preoperative pneumothorax development. The cumulative incidence of pneumothorax was estimated by the Gray test. The Fine and Gray competing risk regression model was used to identify the risk factors for pneumothorax. RESULTS: Data for 2858 neonates with isolated left-sided CDH were extracted; 224 (7.8%) developed preoperative pneumothorax. Among patients with a large diaphragmatic defect, those with pneumothorax had a significantly lower rate of survival to discharge than did those without. The competing risks model demonstrated that a patent ductus arteriosus with a right-to-left shunt flow after birth (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.21-2.63; p = 0.003) and large defects (HR: 1.65; 95% CI: 1.13-2.42; p = 0.01) were associated with an increased risk of preoperative pneumothorax. Significant differences were observed in the cumulative incidence of pneumothorax depending on defect size and shunt direction (p < 0.001). CONCLUSIONS: Pneumothorax is a significant preoperative complication associated with increased mortality in neonates with CDH, particularly in cases with large defects. Large diaphragmatic defects and persistent pulmonary hypertension were found to be risk factors for preoperative pneumothorax development. LEVEL OF EVIDENCE: LEVEL Ⅲ Retrospective Comparative Study.

Pulmonary Artery Measurements as Postnatal Prognostic Tool in Right Congenital Diaphragmatic Hernia.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is a rare and often fatal congenital anomaly, primarily attributed to lung hypoplasia, which is associated with small branch pulmonary artery (PA). This study investigated whether postnatal PA measurements obtained through echocardiography are associated with mortality or the extracorporeal membrane oxygenation (ECMO) requirement in neonates with RCDH. METHODS: A retrospective study was conducted on neonates with RCDH born between 2008 and 2022. Echocardiography was performed on the day of birth. The diameter of the main PA (MPA) was measured at the maximal dimension, and the diameters of the left PA (LPA) and right PA (RPA) were measured at the bifurcation. The primary outcome was mortality or ECMO requirement. Parameters, including the LPA:MPA ratio, RPA:MPA ratio, Nakata index, McGoon ratio, and ejection fraction (EF), were analyzed and compared with the observed-to-expected lung-to-head ratio (o/e LHR), initial blood gas, and defect size as predictive values. RESULTS: Among 39 neonates with RCDH, 25 (64.1 %) survived without ECMO. The non-survivor or ECMO group exhibited lower o/e LHR, reduced EF, smaller LPA and RPA diameters, and larger MPA diameter than survivors. Lower LPA:MPA ratio, Nakata index, McGoon ratio, and higher initial PaCO2 were associated with adverse outcomes. Notably, the LPA:MPA ratio showed the highest predictive capability (area under the curve, 0.983; p < 0.001). CONCLUSION: The LPA:MPA ratio is a promising postnatal predictor of mortality or ECMO requirement in neonates with RCDH. Additionally, Nakata index, McGoon ratio, and initial PaCO2 are significantly correlated with outcomes. LEVEL OF EVIDENCE: This is a level III. TYPE OF STUDY: Prognostic study.

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study.

OBJECTIVES: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. DESIGN: Retrospective cohort study. SETTING: Multicentre study in large referral centres. POPULATION: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. METHODS: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). MAIN OUTCOME MEASURE: Survival to discharge. RESULTS: We included 53 infants born at 30+4 (interquartile range 29+1 -31+2 ) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07-1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88-1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). CONCLUSIONS: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival.

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.

Increased N-terminal Pro-B-Type Natriuretic Peptide during Extracorporeal Life Support Is Associated with Poor Outcome in Neonates with Congenital Diaphragmatic Hernia.

OBJECTIVES: To evaluate the prognostic information derived from the daily measurements of N-terminal pro-B-type natriuretic peptide (proBNP) in neonates with congenital diaphragmatic hernia undergoing extracorporeal life support (ECLS). STUDY DESIGN: Plasma proBNP was prospectively measured daily during the first week of ECLS using an electrochemiluminescence immunoassay. Patients (n = 63) were allocated according to outcome: survivors (group 1, n = 35); nonsurvivors with successful weaning (defined as survival for >12 hours after ECLS discontinuation) (group 2, n = 16); nonsurvivors with unsuccessful weaning (group 3, n = 12). ProBNP kinetics were compared using Kruskal-Wallis testing and correlated with pulmonary hypertension and cardiac dysfunction on echocardiography using the Spearman correlation coefficient. RESULTS: Infants in group 3 presented significantly higher proBNP values from day 3 to day 6 compared with group 1 and 2. Overall mortality among patients with the highest proBNP values on day 1 was 30.6% compared with 63% in those patients with at least 1 higher value on day 2 to day 7. In patients with a late increase (day 4 to day 7) in proBNP the mortality was 70%, compared with 32.6% in those with proBNP below the value on day 1. Weaning failure was 35% in patients with a late increase and 11.6% in those without a late increase. ProBNP correlated significantly with pulmonary hypertension and cardiac dysfunction before and during ECLS. CONCLUSIONS: Absolute proBNP values are associated with weaning failure but not overall mortality in neonates with congenital diaphragmatic hernia undergoing ECLS. Echocardiographic findings correlate well with proBNP values.

Intrapulmonary artery Doppler to predict mortality and morbidity in fetuses with mild or moderate left-sided congenital diaphragmatic hernia.

OBJECTIVES: In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. METHODS: This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 . RESULTS: Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size. CONCLUSIONS: In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

BACKGROUND: Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. METHODS: In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. RESULTS: The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). CONCLUSIONS: In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Thoracoscopic repair of congenital diaphragmatic hernia in neonates: findings of a multicenter study in Japan.

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

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.

Does the Presence of a Hernia Sac Improve Survival in Newborns with Congenital Diaphragmatic Hernia? A United Kingdom Single-Center Experience.

INTRODUCTION: A developing body of literature suggests that the presence of a hernia sac in fetuses with congenital diaphragmatic hernia (CDH) may indicate improved prognosis. By examining a large cohort of CDH newborns admitted to a single United Kingdom specialist center, we aimed to establish if presence of hernia sac is a robust predictor of improved survival. MATERIALS AND METHODS: All CDH patients admitted to a single center were recruited. Postneonatal presentations and Morgagni hernias were excluded. Demographics, defect type, laterality, survival, and hernia recurrence were recorded. RESULTS: In this study, 192 CDH newborns were managed from 1997 to 2017; 39 were excluded (10 Morgagni and 29 postneonatal); 22 (14%) neonates had a hernia sac. Survival in patients with a hernia sac was 21/22 (95%) versus 107/124 (86%) in cases without hernia sac (p = 0.2). There was no difference in hernia sac proportion by gender (male:female 15 vs. 13.2%, p = 0.8). CONCLUSION: In contrast to studies showing a survival advantage, albeit with smaller patient numbers, we report a statistical nonsignificant benefit of hernia sac. Better survival outcomes at this specialist center with CDH patients without a hernia sac than reported in other published studies are likely responsible for the lack of statistical significance observed, despite a larger cohort. National and international CDH registries yielding "big data" may provide further answers on the utility of a CDH hernia sac as a new prognostic scoring tool.

Longitudinal B-Type Natriuretic Peptide Levels Predict Outcome in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective study of 49 infants with CDH, classifying the cohort by respiratory status at 56 days, based on a proposed definition of bronchopulmonary dysplasia for infants ≥32 weeks' gestation: good outcome (alive with no respiratory support) and poor outcome (ongoing respiratory support or death). BNP levels were available at age 1-5 weeks. Longitudinal BNP trends were assessed using mixed-effects modeling. Receiver operating characteristic curves were generated to identify BNP cutoffs maximizing correct outcome classification at each time point. The time to reach BNP cutoff by outcome was assessed using Kaplan-Meier curves for weeks 3-5. RESULTS: Twenty-nine infants (59%) had a poor outcome. Infants with a poor outcome were more likely than those with a good outcome to have liver herniated into the thorax (90% vs 50%; P = .002) and to undergo nonprimary repair (93% vs 35%; P < .001). Mixed-effects modeling demonstrated a differing decline in BNP over time by outcome group (P = .003 for interaction). BNP accurately predicted outcome at 3-5 weeks (area under the curve, 0.81-0.82). BNP cutoffs that maximized correct outcome classification decreased over time from 285 pg/mL at 3 weeks to 100 pg/mL at 4 weeks and 48 pg/mL at 5 weeks. Time to reach the cutoffs of 100 pg/mL and 48 pg/mL were longer in the poor outcome group (log-rank P = .006 and <.0001, respectively). CONCLUSIONS: Elevated BNP accurately predicts poor outcome in infants with CDH at age 3-5 weeks, with declining cutoffs over 3-5 weeks of age.

Survival and Developmental Outcomes of Neonates Treated with Extracorporeal Membrane Oxygenation: A 10-Year Single-Center Experience.

OBJECTIVE: To evaluate the associations between the primary indication for extracorporeal membrane oxygenation (ECMO) in neonates and neurodevelopmental outcomes at 12 and 24 months of age. STUDY DESIGN: This is a retrospective cohort study of neonates treated with ECMO between January 2006 and January 2016 in the Children's Hospital of Philadelphia newborn/infant intensive care unit. Primary indication for ECMO was classified as medical (eg, meconium aspiration syndrome) or surgical (eg, congenital diaphragmatic hernia). Primary study endpoints were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Groups were compared with standard bivariate testing and multivariable regression. RESULTS: A total of 191 neonates met the study's inclusion criteria, including 96 with a medical indication and 95 with a surgical indication. Survival to discharge was 71%, with significantly higher survival in the medical group (82% vs 60%; P = .001). Survivors had high rates of developmental therapies and neurosensory abnormalities. Developmental outcomes were available for 66% at 12 months and 70% at 24 months. Average performance on the Bayley-III was significantly below expected population normative values. Surgical patients had modestly lower the Bayley-III scores over time; most notably, 15% of medical infants and 49% of surgical infants had motor delay at 24 months (P = .03). CONCLUSIONS: In this single-center cohort, surgical patients had lower survival rates and higher incidence of motor delays. Strategies to reduce barriers to follow-up and improve rates of postdischarge developmental surveillance and intervention in this high-risk population are needed.

Optimal timing of surgery in infants with prenatally diagnosed isolated left-sided congenital diaphragmatic hernia: a multicenter, cohort study in Japan.

PURPOSE: To date, there is no compelling evidence of the optimal timing of surgery for congenital diaphragmatic hernia (CDH). This study aimed to establish the optimal timing of surgery in neonates with isolated left-sided CDH. METHODS: This multicenter cohort study enrolled 276 patients with isolated left-sided CDH at 15 institutions. Based on the timing of surgery, the patients were classified into four groups [< 24 h (G1), 24-47 h (G2), 48-71 h (G3), and ≥ 72 h (G4)]. The clinical outcomes were compared among the groups using a logistic regression model, after adjusting for potential confounders, such as disease severity. RESULTS: Multivariate analyses showed that G2 also had a lower mortality rate than the other groups. In mild and severe cases, there were no significant differences in mortality across the four groups. In moderate cases, G2 resulted in significantly increased survival rates, compared with G1. CONCLUSION: The study results suggest that surgery within 24 h of birth is not recommended for patients with moderate severity CDH, that there is no benefit in the delay of surgery for more than 72 h in mild severity CDH patients, and that there is no definite optimal time to perform surgery in severe cases of CDH.