Association between initial ventilation mode and hospital outcomes for severe congenital diaphragmatic hernia.

OBJECTIVE: To determine the association between initial delivery room (DR) ventilator (conventional mechanical ventilation [CMV] versus high frequency oscillatory ventilation [HFOV] and hospital outcomes for infants with severe congenital diaphragmatic hernia (CDH). STUDY DESIGN: Quasi-experimental design before/after introducing a clinical protocol promoting HFOV. The primary outcome was first blood gas parameters. Secondary outcomes included serial blood gas assessments, ECMO, survival, duration of ventilation, and length of hospitalization. RESULTS: First pH and CO2 were more favorable in the HFOV group (n = 75) than CMV group (n = 85), median (interquartile range (IQR)) pH 7.18 (7.03, 7.24) vs. 7.05 (6.93, 7.17), adjusted p-value < 0.001; median CO2 62.0 (46.0, 82.0) vs 85.9 (59.0, 103.0), adjusted p-value < 0.001. ECMO, survival, duration of ventilation, and length of hospitalization did not differ between groups in adjusted analysis. CONCLUSION: Among infants with severe CDH, initial DR HFOV was associated with improved early gas exchange with no adverse differences in hospital outcomes.

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 Delivery Room Resuscitation of Infants with Congenital Diaphragmatic Hernia Treated with Fetoscopic Endoluminal Tracheal Occlusion: Beyond the Balloon.

INTRODUCTION: Randomized controlled trials found that fetoscopic endoluminal tracheal occlusion (FETO) resulted in increased fetal lung volume and improved survival for infants with isolated, severe left-sided congenital diaphragmatic hernia (CDH). The delivery room resuscitation of these infants is particularly unique, and the specific delivery room events are largely unknown. The objective of this study was to compare the delivery room resuscitation of infants treated with FETO to standard of care (SOC) and describe lessons learned. METHODS: Retrospective single-center cohort study of infants treated with FETO compared to infants who met FETO criteria during the same period but who received SOC. RESULTS: FETO infants were more likely to be born prematurely with 8/12 infants born <35 weeks gestational age compared to 3/35 SOC infants. There were 5 infants who required emergent balloon removal (2 ex utero intrapartum treatment and 3 tracheoscopic removal on placental bypass with delayed cord clamping) and 7 with prenatal balloon removal. Surfactant was administered in 6/12 FETO (50%) infants compared to 2/35 (6%) in the SOC group. Extracorporeal membrane oxygenation use was lower at 25% and survival was higher at 92% compared to 60% and 71% in the SOC infants, respectively. CONCLUSION: The delivery room resuscitation of infants treated with FETO requires thoughtful preparation with an experienced multidisciplinary team. Given increased survival, FETO should be offered to infants with severe isolated left-sided CDH, but only in high-volume centers with the experience and capability of removing the balloon, emergently if needed. The neonatal clinical team must be skilled in managing the unique postnatal physiology inherent to FETO where effective interdisciplinary teamwork is essential. Empiric and immediate surfactant administration should be considered in all FETO infants to lavage thick airway secretions, particularly those delivered <48 h after balloon removal.

The Impact of Comprehensive Fetal Care on Mortality of Children With Congenital Diaphragmatic Hernia when Delivery is Co-located in a Pediatric Hospital.

BACKGROUND: We evaluated the impact of delivery at a comprehensive fetal care center co-located in a pediatric hospital on extracorporeal membrane oxygenation (ECMO) exposure and survivorship of children with CDH. METHODS: This retrospective study includes maternal-fetal dyads with a prenatal diagnosis of isolated CDH who received any prenatal care at a single fetal center between February 2006 and March 2021. The principal variables included: (1) delivery setting (children born in the pediatric hospital ["inborn"] vs. children who were delivered elsewhere ["outborn"]), (2) exposure to ECMO (yes vs. no), and (3) survival-at-discharge from birth hospitalization (yes vs. no). Multivariable logistic regression was used to evaluate the association between delivery setting and ECMO cannulation, and whether delivery setting moderates the association between exposure to ECMO and survival-at-discharge. RESULTS: Among 418 maternal-fetal dyads, 77.0% of children were inborn and 32.0% of children were exposed to ECMO during their index hospitalization. Inborn children had more severe prenatal prognostic indicators but had a 57% lower odds of extracorporeal than outborn children. In multivariable logistic regression, delivery setting moderated the association between exposure to ECMO and survival-at-discharge. Although there was no statistically significant difference in mortality between inborn and outborn children who were not exposed to ECMO, inborn children exposed to ECMO had a 6.86 (1.98, 23.74) increased odds of death and outborn children exposed to ECMO had a 17.71 (4.69, 66.87) increased odds of death when both were compared to non-cannulated outborn children. CONCLUSIONS: Comprehensive fetal care with delivery co-located in a pediatric hospital was associated with decreased exposure to ECMO and a survivorship advantage among children with CDH who required extracorporeal support. LEVEL OF EVIDENCE: Level III.

Prevalence and patterns of executive function, adaptive function, and behavioral outcomes in preschool and school age children with congenital diaphragmatic hernia.

BACKGROUND: Executive function, adaptive function, and behavioral outcomes in congenital diaphragmatic hernia (CDH) survivors have not been well studied. AIM: To evaluate executive and neurobehavioral dysfunction in preschool and early school-aged children with CDH. STUDY DESIGN: Retrospective cohort study. SUBJECTS: All eligible CDH survivors ages 3 to 7 years enrolled in our follow-up program between February 2020 and February 2021. OUTCOME MEASURES: The Behavior Rating Inventory of Executive Function (BRIEF), the Adaptive Behavior Assessment System, 2nd Edition (ABAS-II), and the Child Behavior Checklist (CBCL) were used to assess functional and behavioral outcomes. Summary scores were compared to standard population norms. RESULTS: A total of 100 patients were enrolled during the study period. Of those, 73 parents completed at least one of the questionnaires, resulting in completion of the BRIEF, ABAS-II, and CBCL for 63, 68, and 63 patients, respectively. Preschool children had normal executive function (BRIEF-P) while global executive composite (P = 0.012) and the emotional regulation index (P = 0.010) for school age patients (BRIEF-2) were worse. CDH survivors had favorable adaptive functioning (ABAS-II). Mean CBCL scores for preschool attention problems (P = 0.018), school age attention problems (P = 0.001), and attention deficits hyperactivity problems (P = 0.027) were significantly worse. Prematurity, surrogate markers of disease severity, non-white race, and public insurance status were associated with worse neurobehavioral dysfunction in bivariable analysis. CONCLUSIONS: The majority of preschool and school age CDH survivors have age-appropriate executive, adaptive and behavioral functioning. CDH survivors, however, have lower executive function and attention scores compared with the general population.

Update on Management and Outcomes of Congenital Diaphragmatic Hernia.

Infants with congenital diaphragmatic hernia (CDH) benefit from comprehensive multidisciplinary teams that have experience in caring for the unique and complex issues associated with CDH. Despite prenatal referral to specialized high-volume centers, advanced ventilation strategies and pulmonary hypertension management, and extracorporeal membrane oxygenation, mortality and morbidity remain high. These infants have unique and complex issues that begin in fetal and infant life, but persist through adulthood. Here we will review the literature and share our clinical care pathway for neonatal care and follow up. While many advances have occurred in the past few decades, our work is just beginning to continue to improve the mortality, but also importantly the morbidity of CDH.

Birth Admission Length-of-Stay and Hospital Readmission in Children With Congenital Diaphragmatic Hernia.

BACKGROUND: The objective of this study was to identify factors associated with prolonged birth admission length of stay (LOS) and to evaluate the association between these characteristics and readmission in the year following discharge for children with congenital diaphragmatic hernia (CDH). METHODS: This was a single-center retrospective cohort study of children with isolated CDH born in the Special Delivery Unit and admitted to the Newborn/Infant Intensive Care Unit at Children's Hospital of Philadelphia from April 2008 to August 2019. Birth admission hospitalization was categorized into 3 groups (≤35, 36-75, and >76 days) based on the data distribution. Participant factors included gestational age (days), side of CDH (right/left), liver position (up/down), CDH repair technique (open/minimally invasive), exposure to extracorporeal membrane oxygenation, lung-to-head circumference ratio, and feeding tube at discharge. Chi-squared, t-tests and analysis of variance were used to examine bivariable associations between participant characteristics, birth admission LOS and readmission in the year following initial hospital discharge. Multivariable logistic regression was used to evaluate factors associated with readmission. RESULTS: Children hospitalized ≥76 days at birth had 4.33 (95% CI: 1.2, 15.2) higher odds of readmission than those admitted for ≤35 days. Children with a non-operative feeding tube at discharge had 4.12 (895% CI: 1.6, 10.5) higher odds of readmission when compared to those with no feeding tube at discharge. CONCLUSIONS: Longer birth hospitalization and non-operative feeding tube are associated with increased readmissions in the year after discharge. LEVEL OF EVIDENCE: Level III.

Quantitative Measures of Right Ventricular Size and Function by Echocardiogram Correlate with Cardiac Catheterization Hemodynamics in Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively. RESULTS: Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n = 31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n = 24, 45%) and/or intravenous treprostinil (n = 16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15 mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status. CONCLUSIONS: Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.

Extracorporeal Membrane Oxygenation for Neonates With Congenital Diaphragmatic Hernia: Prevalence of Seizures and Outcomes.

OBJECTIVES: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective, descriptive case series. SETTING: Neonatal ICU (NICU) in a quaternary care institution. PATIENTS: All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074). CONCLUSIONS: Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population.

Treprostinil in Neonates with Congenital Diaphragmatic Hernia-Related Pulmonary Hypertension.

OBJECTIVE: To describe our experience with treprostinil, evaluate correlations with cardiac function, and assess for adverse effects in neonates with congenital diaphragmatic hernia-related pulmonary hypertension (CDH-PH). STUDY DESIGN: A retrospective review of a single-center prospective registry at a quaternary care children's hospital. Patients included in the study had CDH-PH treated with treprostinil between April 2013 and September 2021. Assessed outcomes were brain-type natriuretic peptide levels and quantitative echocardiographic parameters collected at baseline, 1 week, 2 weeks, and 1 month after treprostinil initiation. Right ventricular (RV) function was assessed by tricuspid annular plane systolic excursion Z-score and speckle tracking echocardiography (global longitudinal and free wall strain). Septal position and left ventricular (LV) compression were assessed by eccentricity index and M-mode Z-scores. RESULTS: Fifty-one patients were included, with an average expected/observed lung-to-head ratio of 28.4 ± 9.0%. Most patients required extra-corporeal membrane oxygenation (n = 45, 88%). Survival to hospital discharge was 31/49 (63%). Treprostinil was initiated at a median age of 19 days with a median effective dose of 34 ng/kg/minute. Median baseline brain-type natriuretic peptide level decreased from 416.9 pg/mL to 120.5 pg/mL after 1 month. Treprostinil was associated with improved tricuspid annular plane systolic excursion Z-score, RV global longitudinal strain, RV free wall strain, LV eccentricity index, and LV diastolic and systolic dimensions, reflecting less compression by the RV, regardless of ultimate patient survival. No serious adverse effects were recorded. CONCLUSIONS: In neonates with CDH-PH, treprostinil administration is well tolerated and is associated with improved RV size and function.

Enteral nutrition support for infants with pulmonary hypoplasia: A qualitative evaluation of caregiver and provider perspectives.

BACKGROUND: Enteral nutrition is a critical intervention that supports the growth of children with pulmonary hypoplasia (PH). We explored the experiences of caregivers and providers caring for children with PH to better understand gaps in knowledge transfer and identify barriers and facilitators to caregiving to inform interventions that may improve support. METHODS: This qualitative study included 10 interviews with caregivers and 10 clinical team members at a single integrated care program for children with PH. An inductive and iterative coding strategy was employed to produce a codebook. After cluster analysis, themes were generated to capture participant sentiments. RESULTS: Themes were defined along a care continuum (1) initiation, (2) adaptation, and (3) maintenance that represented distinct phases of adjustment to enteral nutrition support (1) in the perinatal period and initial neonatal intensive care unit (NICU) admission, (2) from discharge planning through the family's first days at home and establishment of a stable feeding regime, and (3) through long-term follow-up and weaning. Notable subthemes included uncertainty, partnerships in training, and obstacles to adaptation. CONCLUSIONS: Among children with PH, the caregiver-provider relationship during the perinatal and NICU course is critical to promoting caregiver adaptation to the needs of the child. Ongoing considerations to support resource alignment and transition to a stable feeding regimen may facilitate caregiver adjustment to a "new normal," culminating in successful growth and/or weaning. These findings will inform interventions focused on training curricula, discharge planning, and the provision of follow-up in the context of an integrated care program for PH.