Cardiac function in congenital diaphragmatic hernia.

Cardiac function is known to play critical role in the pathophysiological progression and ultimate clinical outcome of patients with congenital diaphragmatic hernia (CDH). While often anatomically normal, the fetal and neonatal heart in CDH can suffer from both right and left ventricular dysfunction. Here we explore the abnormal fetal heart, early postnatal right and left ventricular dysfunction, the interplay between cardiac dysfunction and pulmonary hypertension, evaluation and echocardiographic assessment of the heart, and therapeutic strategies for managing and supporting the pathophysiologic heart and CDH. Further, we take a common clinical scenario and provide clinically relevant guidance for the diagnosis and management of this complex process.

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is characterized by a developmental insult which compromises cardiopulmonary embryology and results in a diaphragmatic defect, allowing abdominal organs to herniate into the hemithorax. Among the significant pathophysiologic components of this condition is pulmonary hypertension (PH), alongside pulmonary hypoplasia and cardiac dysfunction. Fetal pulmonary vascular development coincides with lung development, with the pulmonary vasculature evolving alongside lung maturation. However, in CDH, this embryologic development is impaired which, in conjunction with external compression, stifle pulmonary vascular maturation, leading to reduced lung density, increased muscularization of the pulmonary vasculature, abnormal vascular responsiveness, and altered molecular signaling, all contributing to pulmonary arterial hypertension. Understanding CDH-associated PH (CDH-PH) is crucial for development of novel approaches and effective management due to its significant impact on morbidity and mortality. Antenatal and postnatal diagnostic methods aid in CDH risk stratification and, specifically, pulmonary hypertension, including fetal imaging and gas exchange assessments. Management strategies include lung protective ventilation, fluid optimization, pharmacotherapies including pulmonary vasodilators and hemodynamic support, and extracorporeal life support (ECLS) for refractory cases. Longitudinal re-evaluation is an important consideration due to the complexity and dynamic nature of CDH cardiopulmonary physiology. Emerging therapies such as fetal endoscopic tracheal occlusion and pharmacological interventions targeting key CDH pathophysiological mechanisms show promise but require further investigation. The complexity of CDH-PH underscores the importance of a multidisciplinary approach for optimal patient care and improved outcomes.

Fisiopatología de la hernia diafragmática congénita en el recién nacido / Pathophysiology of congenital diaphramatic hernia in the newborn

La hernia diafragmática congénita es una discontinuidad del diafragma con herniación de los órganos abdominales a la cavidad torácica, actualmente se postula una hipótesis dual para su origen. Su fisiopatología está determinada por la hipoplasia pulmonar, la hipertensión pulmonar y la disfunción ventricular, entender estos elementos es necesario para un adecuado manejo y la mejoría del pronóstico.

Congenital diaphragmatic hernia is a discontinuity of the diaphragm with herniation of the abdominal organs into the thoracic cavity, currently a dual hypothesis for its origin is postulated. Its pathophysiology is determined by pulmonary hypoplasia, pulmonary hypertension and ventricular dysfunction, understanding these elements is necessary for adequate management and improve prognosis.

Intestinal Air in the Mediastinum.

CASE PRESENTATION: A 74-year-old man, in excellent physical condition and doing regular intense cycling, was evaluated for transient episodes of thoracic discomfort over a period of several months. His medical history only included a right inguinal hernia, surgically treated, and an abdominal aortic aneurysm measured at 46 mm and treated medically. Physical examination did not reveal much information. The patient did not report gastroesophageal reflux, dysphagia, or history of digestive occlusion. The patient had normal weight and had no trauma history. He had no nicotine or alcohol-dependent behaviors. Vital signs were within normal values. Laboratory test results were normal. Functional status was normal, without anomalies of pulmonary function tests or arterial blood gases. The ECG did not reveal any anomaly.

Pulmonary hypertension is an important co-morbidity in developmental lung diseases of infancy: Bronchopulmonary dysplasia and congenital diaphragmatic hernia.

Bronchopulmonary dysplasia (BPD) following preterm birth and congenital diaphragmatic hernia (CDH) are both forms of developmental lung disease that may result in persistent pulmonary and pulmonary vascular morbidity in childhood. The pulmonary vascular disease (PVD) which accompanies BPD and CDH is due to developmental abnormalities and ongoing perinatal insults. This may be accompanied by evidence of elevated right heart pressures and pulmonary vascular resistance, leading to diagnosis of pulmonary hypertension (PH). The development of PH in these conditions is associated with increased morbidity and mortality in the vulnerable BPD and CDH populations. We present a review of PVD pathogenesis and evaluation in BPD and CDH and discuss management of related sequelae of PH co-morbidity for affected infants.

Volatile Organic Compounds, Bacterial Airway Microbiome, Spirometry and Exercise Performance of Patients after Surgical Repair of Congenital Diaphragmatic Hernia.

The aim of this study was to analyze the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance in congenital diaphragmatic hernia (CDH) patients compared to healthy age and sex-matched controls. A total of nine patients (median age 9 years, range 6-13 years) treated for CDH were included. Exhaled VOCs were measured by GC-MS. Airway microbiome was determined from deep induced sputum by 16S rRNA gene sequencing. Patients underwent conventional spirometry and exhausting bicycle spiroergometry. The exhaled VOC profile showed significantly higher levels of cyclohexane and significantly lower levels of acetone and 2-methylbutane in CDH patients. Microbiome analysis revealed no significant differences for alpha-diversity, beta-diversity and LefSe analysis. CDH patients had significantly lower relative abundances of Pasteurellales and Pasteurellaceae. CDH patients exhibited a significantly reduced Tiffeneau Index. Spiroergometry showed no significant differences. This is the first study to report the VOCs profile and airway microbiome in patients with CDH. Elevations of cyclohexane observed in the CDH group have also been reported in cases of lung cancer and pneumonia. CDH patients had no signs of impaired physical performance capacity, fueling controversial reports in the literature.

Prenatal stomach position predicts gastrointestinal morbidity at 2 years in fetuses with left-sided congenital diaphragmatic hernia.

OBJECTIVE: The long-term morbidity associated with isolated left-sided congenital diaphragmatic hernia (CDH) has been described previously. However, antenatal criteria impacting gastrointestinal morbidity (GIM) are not yet defined. The objective of this study was to evaluate the effect of fetal stomach position on the risk of GIM at 2 years of age in children with left-sided CDH. METHODS: This was a retrospective, observational multicenter cohort study of data obtained from January 2010 to January 2014, that included patients whose fetus had isolated left-sided CDH, with or without fetal endoscopic tracheal occlusion (FETO). Prenatal maternal, fetal and pediatric data were collected. Fetal stomach position was evaluated a posteriori by two observers, using ultrasound images at the level of the four-chamber view of the heart that had been obtained to calculate the observed-to-expected lung-area-to-head-circumference ratio (O/E-LHR). Fetal stomach position was graded as follows: Grade 1, stomach not visualized; Grade 2, stomach visualized anteriorly, next to the apex of the heart, with no structure in between the stomach and the sternum; Grade 3, stomach visualized alongside the left ventricle of the heart, and abdominal structures anteriorly; or Grade 4, as Grade 3 but with stomach posterior to the level of the atrioventricular heart valves. The primary outcome was GIM at 2 years of age, assessed in a composite manner, including the occurrence of gastroesophageal reflux disease, need for gastrostomy, duration of parenteral and enteral nutrition and persistence of oral aversion. Regression analysis was performed in order to investigate the effect of O/E-LHR, stomach position and FETO on various GIM outcome variables. RESULTS: Forty-seven patients with fetal left-sided CDH were included in the analysis. Thirteen (27.7%) infants did not meet the criterion of exclusive oral feeding at 2 years of age. Fetal stomach position grade was associated significantly and independently with the duration of parenteral nutrition (odds ratio (OR), 19.86; P = 0.031) and persistence of oral aversion at 2 years (OR, 3.40; P = 0.006). On multivariate analysis, O/E-LHR was predictive of the need for prosthetic patch repair, but not for GIM. FETO did not seem to affect the risk of GIM at 2 years. CONCLUSION: In isolated left-sided CDH, fetal stomach position is the only factor that is predictive of GIM at 2 years of age. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Weight gain velocity and adequate amount of nutrition for infants with congenital diaphragmatic hernia.

PURPOSE: Growth retardation is a severe morbidity in infants with congenital diaphragmatic hernia (CDH). This study aimed to determine when catch-up growth starts in infants with CDH and to determine the adequate amount of nutrition required during catch-up growth. METHODS: This was a multicenter retrospective cohort study involving neonates with isolated CDH (born 2006-2010; n = 98). Weight gain velocity (WGV) was calculated using body weight Z-scores. The minimum required weight gain was defined as WGV ≥ 0. Patients were dichotomized into severe and non-severe cases according to diaphragmatic defects. RESULTS: Average monthly WGV changed from < 0 to ≥ 0 at 2 months of age. Total caloric intake at 2 months of age was lower when the WGV between 1 and 3 months was < 0 in both severe cases [122 (95% confidence interval (CI) 116-128) vs. 97 (95% CI 84-110) kcal/kg/day, p = 0.02] and non-severe cases [115 (95% CI 110-120) vs. 99 (95% CI 87-111) kcal/kg/day, p < 0.001)]. CONCLUSION: Catch-up growth started at approximately 2 months of age. During this period, total caloric intake of > 122 kcal/kg/day was needed to avoid decreases in the body weight Z-score in severe cases.

Growth from Birth to 30 months for Infants Born with Congenital Gastrointestinal Anomalies and Disorders.

OBJECTIVE: This study aimed to investigate growth among neonates with gastrointestinal disorders. STUDY DESIGN: Inclusion criteria included neonates with gastroschisis, omphalocele, intestinal atresia, tracheoesophageal fistula, Hirschsprung's disease, malabsorption disorders, congenital diaphragmatic hernia, and imperforate anus born between 2010 and 2018. Anthropometrics were collected for the first 30 months, and a subgroup analysis was performed for gastroschisis infants. RESULTS: In 61 subjects, 13% developed severe growth failure within the first month. One-, four-, and nine-month weight and length z-scores were less than birth weight in all infants (p < 0.05). In infants with gastroschisis, a similar pattern was observed for weight z-scores only (p < 0.05). From birth to 15 months, head circumference z-score increased over time in all infants (p = 0.001), while in gastroschisis infants, weight, length, and head circumference z-scores increased over time (p < 0.05). CONCLUSION: In a cohort of infants with gastrointestinal disorders, growth failure was followed by catch-up growth.

Congenital diaphragmatic hernias: Severe defect grade predicts the need for fundoplication.

Over one-third of infants with congenital diaphragmatic hernia (CDH) eventually require a Nissen fundoplication (NF). We examined pre- and intraoperative predictors for need of a NF in children undergoing CDH repair to elucidate, which patients will need a later NF.A retrospective analysis of all consecutive patients undergoing CDH repair at our institution from 2008 to 2018 was performed. Patients who underwent a NF were compared to those who did not (noNissen). Logistic regression analysis was performed to find independent predictors for NF in patients undergoing CDH repair. Severe Defect Grade was defined as defect >50% of the hemidiaphragm and intrathoracic liver.One hundred twenty-six patients were included, 42 (33%) underwent NF at a median of 61 days after CDH repair. Intrathoracic liver was more frequent in the NF (71%) versus noNissen (45%) group (P = .008). Absence of >50% of the hemidiaphragm was more frequent in the NF group (76% vs 31%, P < .001). Severe Defect Grade emerged as independent predictor for NF (odds ratio 7, 95% confidence interval 3-16, P < .001).Severe Defect Grade emerged as independent predictor for NF after CDH repair.

Impacts of Respiratory Muscle Training on Respiratory Functions, Maximal Exercise Capacity, Functional Performance, and Quality of Life in School-Aged Children with Postoperative Congenital Diaphragmatic Hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a birth defect affecting the respiratory functions, functional performance, and quality of life (QOL) in school-aged children. Rarely have studies been conducted to evaluate the impacts of respiratory muscle training on school-aged children with postoperative CDH. The current study was designed to evaluate the impacts of respiratory muscle training on respiratory function, maximal exercise capacity, functional performance, and QOL in these children. METHODS: This study is a randomized control study. 40 children with CDH (age: 9-11 years) were assigned randomly into two groups. The first group conducted an incentive spirometer exercise combined with inspiratory muscle training (study group, n = 20), whereas the second group conducted only incentive spirometer exercise (control group, n = 20), thrice weekly for twelve consecutive weeks. Respiratory functions, maximal exercise capacity, functional performance, and pediatric quality of life inventory (PedsQL) were assessed before and after the treatment program. Results. Regarding the posttreatment analysis, the study group showed significant improvements in all outcome measures (FVC%, p < 0.001; FEV1%, p = 0.002; VO2max, p = 0.008; VE/VCO2 slope, p = 0.002; 6-MWT, p < 0.001; and PedsQL, p < 0.001), whereas the control group did not show significant changes (p > 0.05). CONCLUSION: Respiratory muscle training may improve respiratory functions, maximal exercise capacities, functional performance, and QOL in children with postoperative CDH. Clinical commendations have to be considered to include respiratory muscle training in pulmonary rehabilitation programs in children with a history of CDH.

Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia.

OBJECTIVE: Abnormal pulmonary vasculature directly affects the development and progression of congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension (PH). Though overarching structural and cellular changes in CDH-affected pulmonary arteries have been documented, the precise role of the extracellular matrix (ECM) in the pulmonary artery (PA) pathophysiology remains undefined. Here, we quantify the structural, compositional, and mechanical CDH-induced changes in the main and distal PA ECM and investigate the efficacy of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as a therapy to ameliorate pathological vascular ECM changes. METHODS: Pregnant Sprague-Dawley rodents were administered nitrofen to induce CDH-affected pulmonary vasculature in the offspring. A portion of CDH-affected pups was treated with intravenous infusion of MSC-EVs (1 × 1010 /mL) upon birth. A suite of histological, mechanical, and transmission electron microscopic analyses were utilized to characterize the PA ECM. RESULTS: The CDH model main PA presented significantly altered characteristics-including greater vessel thickness, greater lysyl oxidase (LOX) expression, and a relatively lower ultimate tensile strength of 13.6 MPa compared to control tissue (25.1 MPa), suggesting that CDH incurs ECM structural disorganization. MSC-EV treatment demonstrated the potential to reverse CDH-related changes, particularly through rapid inhibition of ECM remodeling enzymes (LOX and MMP-9). Additionally, MSC-EV treatment bolstered structural aspects of the PA ECM and mitigated pathological disorganization as exhibited by increased medial wall thickness and stiffness that, while not significantly altered, trends away from CDH-affected tissue. CONCLUSIONS: These data demonstrate notable ECM remodeling in the CDH pulmonary vasculature, along with the capacity of MSC-EVs to attenuate pathological ECM remodeling, identifying MSC-EVs as a potentially efficacious therapeutic for CDH-associated pulmonary hypertension.

Extracellular Vesicles Attenuate Nitrofen-Mediated Human Pulmonary Artery Endothelial Dysfunction: Implications for Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) leads to pathophysiologic pulmonary vasoreactivity. Previous studies show that mesenchymal stromal cell-derived extracellular vesicles (MSCEv) inhibit lung inflammation and vascular remodeling. We characterize MSCEv and human pulmonary artery endothelial cell (HPAEC) interaction, as well as the pulmonary artery (PA) response to MSCEv treatment. HPAECs were cultured with and without exposure to nitrofen (2,4-dichloro-phenyl-p-nitrophenylether) and treated with MSCEv. HPAEC viability, architecture, production of reactive oxygen species (ROS), endothelial dysfunction-associated protein levels (PPARγ, LOX-1, LOX-2, nuclear factor-κB [NF-κB], endothelial NO synthase [eNOS], ET-1 [endothelin 1]), and the nature of MSCEv-cellular interaction were assessed. Newborn rodents with and without CDH (nitrofen model and Sprague-Dawley) were treated with intravascular MSCEv or vehicle control, and their PAs were isolated. Contractility was assessed by wire myography. The contractile (KCL and ET-1) and relaxation (fasudil) responses were evaluated. HPAEC viability correlated inversely with nitrofen dose, while architectural compromise was directly proportional. There was a 2.1 × increase in ROS levels in nitrofen HPAECs (P < 0.001), and MSCEv treatment attenuated ROS levels by 1.5 × versus nitrofen HPAECs (P < 0.01). Nitrofen-induced alterations in endothelial dysfunction-associated proteins are shown, and exposure to MSCEv restored more physiologic expression. Nitrofen HPAEC displayed greater MSCEv uptake (80% increase, P < 0.05). Adenosine, a clathrin-mediated endocytosis inhibitor, decreased uptake by 46% (P < 0.05). CDH PA contraction was impaired with KCL (108.6% ± 1.4% vs. 112.0% ± 1.4%, P = 0.092) and ET-1 (121.7% ± 3.0% vs. 131.2% ± 1.8%, P < 0.01). CDH PA relaxation was impaired with fasudil (32.2% ± 1.9% vs. 42.1% ± 2.2%, P < 0.001). After MSCEv treatment, CDH PA contraction improved (125.9% ± 3.4% vs. 116.4 ± 3.5, P = 0.06), and relaxation was unchanged (32.5% ± 3.2% vs. 29.4% ± 3.1%, P = 0.496). HPAEC exposure to nitrofen led to changes consistent with vasculopathy in CDH, and MSCEv treatment led to a more physiologic cellular response. MSCEv were preferentially taken up by nitrofen-treated cells by clathrin-dependent endocytosis. In vivo, MSCEv exposure improved PA contractile response. These data reveal mechanisms of cellular and signaling alterations that characterize MSCEv-mediated attenuation of pulmonary vascular dysfunction in CDH-associated pulmonary hypertension.

Early postnatal changes of circulating N-terminal-pro-B-type natriuretic peptide in neonates with congenital diaphragmatic hernia.

BACKGROUND: Severity of lung hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction are major contributors to mortality in congenital diaphragmatic hernia (CDH). Therefore, early assessment and management is important to improve outcome. NT-proBNP is an established cardiac biomarker with only limited data for early postnatal risk assessment in CDH newborns. AIMS: To investigate the correlation of NT-proBNP at birth, 6 h, 12 h, 24 h, and 48 h with PH and cardiac dysfunction and the prognostic information of NT-proBNP for the use of ECMO support or mortality. SUBJECTS: 44 CDH newborns treated at our institution (December 2014-October 2017) were prospectively enrolled. OUTCOME MEASURES: Primary clinical endpoint was either need for ECMO or death within the first 48 h (group A). Infants not receiving ECMO support were allocated to group B. Mortality was tested as secondary endpoint. RESULTS: NT-proBNP levels measured at 6 h, 12 h, 24 h and 48 h postpartum correlated significantly with PH severity following NICU admission and at 24 h, and with severity of cardiac dysfunction at birth, 24 h, 48 h and after 7 days of life. There was no difference in NT-proBNP levels between survivors and non-survivors. NT-proBNP levels were significantly higher in group A at 6 h (p = 0.007), 12 h (p = 0.036), and 24 h (p = 0.007), but not at birth (p = 0.785) or 48 h (p = 0.15) compared to group B. CONCLUSION: NT-proBNP analysis in the first 48 h of life may be useful to assess PH and cardiac dysfunction in CDH newborns and to predict the need for ECMO support.

An intriguing case of post-operative respiratory failure from an occult diaphragmatic hernia- be aware of the masquerader.

Though respiratory complications after cardiac surgery for congenital heart disease are common, and malformations of the diaphragm can be expected in these patients, the presence of an occult diaphragmatic defect unrecognisible preoperatively and complicating the post operative course is very rare and need a high index of suspicion for diagnosis in the setting of post operative respiratory failure. We present here a case of post operative respiratory failure from a delayed presenting diaphragmatic hernia in a 2-month-old boy who underwent corrective surgery for Taussig bing anomaly and hypoplastic aortic arch. Surgical repair of the diaphragmatic defect and reduction of the bowel loops to the abdomen resulted in rapid weaning from ventilation and recovery with subsequent discharge from hospital.

Extra-Corporeal Membrane Oxygenation for Neonatal Respiratory Support.

To review our experience with Extra-Corporeal Membrane Oxygenation (ECMO) for respiratory support in neonates. From 1989 to 2018 2114 patients underwent respiratory ECMO support, with 764 (36%) neonates. Veno-Venous (V-V) cannulation was used in 428 (56%) neonates and Veno-Arterial (V-A) in 336 (44%). Historically V-V ECMO was our preferred modality, but due to lack of suitable cannula in the last 7 years V-A was used in 209/228 (92%) neonates. Mean and inter-quartile range of ECMO duration was 117 hours (inter-quartile range 90 to 164 hours). Overall 724 (95%) neonates survived to ECMO decannulation, with 640 (84%) hospital discharge. Survival varied with underlying diagnosis: meconium aspiration 98% (354/362), persistent pulmonary hypertension 80% (120/151), congenital diaphragmatic hernia 66% (82/124), sepsis 59% (35/59), pneumonia 86% (6/7), other 71% (43/61). Survival was 86% with V-V and 80% with V-A cannulation, better than ELSO Registry with 77% V-V and 63% V-A. Major complications: cerebral infarction/hemorrhage in 4.7% (31.1% survival to discharge), renal replacement therapy in 17.6% (58.1% survival to discharge), new infection in 2.9%, with negative impact on survival (30%). Following a circuit design modification and subsequent reduction in heparin requirement, intracerebral hemorrhage decreased to 9/299 (3.0%) radiologically proven cerebral infarction/hemorrhage. We concluded (1) outcomes from neonatal ECMO in our large case series were excellent, with better survival and lower complication rate than reported in ELSO registry. (2) These results highlight the benefits of ECMO service in high volume units. (3) The similar survival rate seen in neonates with V-A and V-V cannulation differs from the ELSO register; this may reflect the change in cannulation enforced by lack of suitable V-V cannula and all neonates undergoing V-A cannulation.

Therapy at 30 days of life predicts lung function at 6 to 12 months in infants with congenital diaphragmatic hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is associated with variable degrees of lung hypoplasia. Pulmonary support at 30 days postnatal age was found to be the strongest predictor of inpatient mortality and morbidity among CDH infants and was also associated with higher pulmonary morbidity at 1 and 5 years. It is not known, however, if there is a relationship between the need for medical therapy at 30 days of life and subsequent abnormalities in lung function as reflected in infant pulmonary function test (iPFT) measurements. OBJECTIVE: We hypothesized that CDH infants who require more intensive therapy at 30 days would have more abnormal iPFT values at the time of their first infant pulmonary function study, reflecting the more severe spectrum of lung hypoplasia. METHODS: A single-institution chart review of all CDH survivors who were enrolled in a Pulmonary Hypoplasia Program (PHP) through July 2019, and treated from 2002 to 2019 was performed. All infants were divided into groups based on their need for noninvasive (supplemental oxygen, high flow therapy, noninvasive mechanical ventilation) or invasive (mechanical ventilation, extracorporeal membrane oxygenation) respiratory assistance, bronchodilators, diuretic use, and pulmonary hypertension (PH) therapy (inhaled and/or systemic drugs) at 30 days. Descriptive and statistical analyses were performed between groups comparing subsequent lung function measurements. RESULTS: A total of 382 infants (median gestational age [GA] 38.4 [interquartile range (IQR) = 37.1-39] weeks, 41.8% female, 70.9% Caucasian) with CDH were enrolled in the PHP through July 2019, and 118 infants underwent iPFT. The median age of the first iPFT was 6.6 (IQR = 5.3-11.7) months. Those requiring any pulmonary support at 30 days had a higher functional residual capacity (FRC) (z) (P = .03), residual volume (RV) (z) (P = .008), ratio of RV to total lung capacity (RV/TLC) (z) (P = .0001), and ratio of FRC to TLC (FRC/TLC) (z) (P = .001); a lower forced expiratory volume at 0.5 seconds (FEV0.5) (z) (P = .03) and a lower respiratory system compliance (Crs) (P = .01) than those who did not require any support. Similarly, those requiring diuretics and/or PH therapy at 30 days had higher fractional lung volumes, lower forced expiratory flows and Crs than infants who did not require such support (P < .05). CONCLUSIONS: Infants requiring any pulmonary support, diuretics and/or PH therapy at 30 postnatal days have lower forced expiratory flows and higher fractional lung volumes, suggesting a greater degree of lung hypoplasia. Our study suggests that the continued need for PH, diuretic or pulmonary support therapy at 30 days can be used as additional risk-stratification measurements for evaluation of infants with CDH.

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is a neonatal pathology in which intrathoracic herniation of abdominal viscera via diaphragmatic defect results in aberrant pulmonary and cardiovascular development. Despite decades of study and many advances in the diagnosis and treatment of CDH, morbidity and mortality remain high, largely due to pulmonary hypertension (PH), along with pulmonary hypoplasia and cardiac dysfunction. In patients with CDH, hypoplastic pulmonary vasculature and alterations in multiple molecular pathways lead to pathophysiologic pulmonary vasculopathy and, for severe CDH, sustained, elevated pulmonary arterial pressures. This review addresses the multiple anatomic and physiologic changes that underlie CDH-associated PH (CDH-PH), along with the multimodal treatment strategies that exist currently and future therapies currently under investigation.