Diaphragmatic Defects in Infants: Acute Management and Repair.

Congenital diaphragmatic hernia (CDH) is a complex and highly variable disease process that should be treated at institutions with multidisciplinary teams designed for their care. Treatment in the neonatal period focuses on pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Extracorporeal membrane oxygenation (ECMO) can be considered in patients refractory to medical management. Repair of CDH early during the ECMO course seems to improve mortality compared with other times for surgical intervention. The choice of surgical approach to CDH repair should consider the patient's physiologic status and the surgeon's familiarity with the operative approaches available, recognizing the pros/cons of each technique.

A clinical consensus guideline for nutrition in infants with congenital diaphragmatic hernia from birth through discharge.

OBJECTIVE: To develop a consensus guideline to meet nutritional challenges faced by infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: The CDH Focus Group utilized a modified Delphi method to develop these clinical consensus guidelines (CCG). Topic leaders drafted recommendations after literature review and group discussion. Each recommendation was sent to focus group members via a REDCap survey tool, and members scored on a Likert scale of 0-100. A score of > 85 with no more than 25% outliers was designated a priori as demonstrating consensus among the group. RESULTS: In the first survey 24/25 recommendations received a median score > 90 and after discussion and second round of surveys all 25 recommendations received a median score of 100. CONCLUSIONS: We present a consensus evidence-based framework for managing parenteral and enteral nutrition, somatic growth, gastroesophageal reflux disease, chylothorax, and long-term follow-up of infants with CDH.

Mechanical ventilation in special populations.

Optimal respiratory support can only be achieved if the ventilator strategy utilized for each individual patient at any given point in the evolution of their disease process is tailored to the underlying pathophysiology. The critically ill newborn infant requires individualized patient care when it comes to mechanical ventilation. This can only occur if the clinician has a good understanding of the different pathophysiologies of a variety of conditions that can lead to respiratory failure. In this chapter we describe the key pathophysiological features of bronchopulmonary dysplasia, meconium aspiration syndrome and lung hypoplasia syndromes with emphasis on congenital diaphragmatic hernia. We review available evidence to guide management an provide specific recommendations for pathophysiologically-based mechanical ventilation support.

Exploring new perspectives on congenital diaphragmatic hernia: A comprehensive review.

Congenital diaphragmatic hernia (CDH) represents a developmental anomaly that profoundly impacts the embryonic development of both the respiratory and cardiovascular systems. Understanding the influences of developmental defects, their origins, and clinical consequences is of paramount importance for further research and the advancement of therapeutic strategies for this condition. In recent years, groundbreaking studies in the fields of metabolomics and genomics have significantly expanded our knowledge regarding the pathogenic mechanisms of CDH. These investigations introduce novel diagnostic and therapeutic avenues. CDH implies a scarcity of available information within this domain. Consequently, a comprehensive literature review has been undertaken to synthesize existing data, providing invaluable insights into this rare disease. Improved comprehension of the molecular underpinnings of CDH has the potential to refine diagnostic precision and therapeutic interventions, thus potentially enhancing clinical outcomes for CDH patients. The identification of potential biomarkers assumes paramount significance for early disease detection and risk assessment in CDH, facilitating prompt recognition and the implementation of appropriate interventions. The process of translating research findings into clinical practice is significantly facilitated by an exhaustive literature review. It serves as a pivotal step, enabling the integration of novel, more effective diagnostic and therapeutic modalities into the management of CDH patients.

Treatment Facility Case Volume and Disparities in Outcomes of Congenital Diaphragmatic Hernia Cases.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a life-threatening, prenatally diagnosed congenital anomaly. We aim to characterize care and outcomes of infants with CDH in Texas and the impact of treating facilities volume of care. METHODS: Retrospective cohort study using a state-wide Hospital Inpatient Discharge Public Use Data File was conducted (2013-2021). Neonates and infants <1 year of age were included using CDH ICD-9/ICD-10 codes. Neonates transferred to an outside hospital were excluded to avoid double-counting. Descriptive statistics, chi-square and logistic regression analysis were performed. RESULTS: Of 1314 CDH patient encounters identified, 728 (55%) occurred at 5 higher volume centers (HVC, >75 cases), 326 (25%) at 9 mid-volume centers (MVC, 20-75 cases) and 268 (20%) at 79 low volume centers (LVC, <20 cases). HVC had lower mortality rates (18%, MVC 22% vs LVC 27%; p = 0.011) despite treating sicker patients (extreme illness severity: HVC 71%, MVC 62% vs LVC 50%; p < 0.001) with longer length-of-stay (p < 0.001). Extracorporeal membrane oxygenation was used in 136 (10%) and provided primarily at HVC. LVC treated proportionately more non-white Hispanic patients (p < 0.001) and patients from counties along the Mexican border (p < 0.001). The predicted probability of mortality in CDH patients decreases with higher treatment facility CDH case volume, with a 0.5% decrease in the odds of mortality for every additional CDH case treated (p < 0.001). CONCLUSIONS: Patients treated in HVC have significantly lower mortality despite increased severity. Our data suggest minority populations may be disproportionately treated at LVC associated with worse outcomes. TYPE OF STUDY: Retrospective Prognosis Study. LEVEL OF EVIDENCE: Level II.

Pathogenesis and Physiologic Mechanisms of Neonatal Pulmonary Hypertension: Preclinical Studies.

Neonatal pulmonary hypertension (PH) is a devastating disorder of the pulmonary vasculature characterized by elevated pulmonary vascular resistance and mean pulmonary arterial pressure. Occurring predominantly because of maldevelopment or maladaptation of the pulmonary vasculature, PH in neonates is associated with suboptimal short-term and long-term outcomes because its pathobiology is unclear in most circumstances, and it responds poorly to conventional pulmonary vasodilators. Understanding the pathogenesis and pathophysiology of neonatal PH can lead to novel strategies and precise therapies. The review is designed to achieve this goal by summarizing pulmonary vascular development and the pathogenesis and pathophysiology of PH associated with maladaptation, bronchopulmonary dysplasia, and congenital diaphragmatic hernia based on evidence predominantly from preclinical studies. We also discuss the pros and cons of and provide future directions for preclinical studies in neonatal PH.

Comorbidities and Late Outcomes in Neonatal Pulmonary Hypertension.

Long-term outcomes of persistent pulmonary hypertension of newborn (PPHN) depend on disease severity, duration of ventilation, and associated anomalies. Congenital diaphragmatic hernia survivors may have respiratory morbidities and developmental delay. The presence of PPHN is associated with increased mortality in hypoxic-ischemic encephalopathy, though the effects on neurodevelopment are less clear. Preterm infants can develop pulmonary hypertension (PH) early in the postnatal course or later in the setting of bronchopulmonary dysplasia (BPD). BPD-PH is associated with higher mortality, particularly within the first year. Evidence suggests that both early and late PH in preterm infants are associated with neurodevelopmental impairment.

Quality of life in congenital diaphragmatic hernia survivors treated at a non-ECMO centre from 1998 to 2015: a cross-sectional study.

BACKGROUND: Survival of infants with congenital diaphragmatic hernia (CDH) has increased and more insight is warranted on the long-term issues of this condition. METHODS: We conducted a cross-sectional study on consecutively born infants with CDH treated at a non-extracorporeal membrane oxygenation centre (ECMO) from 1998 to 2015. Quality of life was evaluated using the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL(4.0)) Questionnaire and an interview was conducted to assess for CDH-related morbidity. RESULTS: 71 eligible CDH survivors were identified and 51 consented to participate: aged 5-21 years, 28 (54.9%) male, 42 (82.4%) with left-sided hernias, 10 (19.6%) needed patch repair, median length of stay in hospital was 27.96 days (IQR 18.54-61.56). Forty-nine completed the questionnaire with a median PedsQL total score for participants of 82.6 vs 83.7 of the total proxy parent score (p=0.04). Total score was significantly lower for participants aged 5-12 years compared with participants aged 13-21 years (p=0.04); however, when reported by domains, only the physical score remained significantly lower (p=0.048). Two (4.1%) participants' and 8 (16.7%) proxy parents' scores were below 70 and considered at risk of impaired quality of life. We identified the presence of CDH-related morbidity in our population, and confirmed an association between respiratory morbidity and lower PedsQL scores (p=0.04). CONCLUSION: We report an overall good quality of life in our population with CDH. However, a lower physical score was noted when compared with a national Danish cohort and individuals at risk of reduced quality of life were recognised. Structured follow-up programmes to identify and ensure early management of CDH-related issues may prevent a negative impact on quality of life.

Congenital Diaphragmatic Hernia at a Non-ECMO Center in Jordan.

OBJECTIVES: We studied the clinical characteristics and outcomes of neonates with congenital diaphragmatic hernia (CDH) admitted to a non-extracorporeal membrane oxygenation (ECMO) center. METHODS: A retrospective chart review of neonates with CDH admitted to a University Hospital, in Amman, Jordan, between 2005 and 2019. Demographic characteristics and their management details were extracted and factors associated with survival were analyzed. RESULTS: A total of 28 neonates born with CDH were included; their survival rate was 39.3%. Onset of respiratory distress, pre-operative ventilation, and length of hospitalization were significantly associated with mortality. Survival after surgery was significantly associated with a higher gestational age and a longer hospital stay. CONCLUSION: Our study showed a high mortality rate for CDH patients. Decreasing the health inequity and improved clinical interventions could improve outcomes.

Respiratory function testing for guiding ventilator mode conversion in congenital diaphragmatic hernia.

INTRODUCTION: For patients with a congenital diaphragmatic hernia, conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) are used in initial ventilatory management. HFOV has recently been recommended as a rescue therapy; however, we use HFOV for initial ventilation management, with a preoperative challenge test for CMV conversion and respiratory function testing at the time of CMV conversion. We aimed to compare patient characteristics between CMV conversion- and HFOV-preferred treatment groups. METHODS: Ventilator settings and blood gases were retrospectively evaluated pre- and post-CMV conversion, and respiratory function tests for compliance of the respiratory system (Crs) and for resistance of the respiratory system (Rrs) were performed during the trial to CMV conversion. RESULTS: No differences were observed between the CMV conversion- and HFOV-preferred groups regarding gestational age, birth weight, and observed/expected lung area-to-head circumference ratios. The median Crs (ml/cmH2 O/kg) and Rrs (cmH2 Oï½¥kg/L/s) in the CMV conversion- and HFOV-preferred groups was 0.42 versus 0.53 (p = .44) and 467 versus 327 (p = .045), respectively. The pre and posttrial amount of change in blood gas levels and ventilator parameters in the CMV conversion- and HFOV-preferred groups were as follows: mean airway pressure, -2.0 versus 0 cmH2 O; partial pressure of carbon dioxide, 6.1 versus 2.9 Torr; alveolar-arterial oxygen difference, -39.5 versus -50 Torr; and oxygenation index, -1.0 versus -0.6; respectively. CONCLUSION: Respiratory function tests were useful in tailoring ventilator settings. Patients with high Rrs values responded better to CMV conversion.

Study protocol for a randomised cross-over trial of Neurally adjusted ventilatory Assist for Neonates with Congenital diaphragmatic hernias: the NAN-C study.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers oxygen pressures in proportion to electrical signals of the diaphragm. The proportional assistance can be adjusted by the clinician to reduce the patient's work of breathing. Several case series of infants with congenital diaphragmatic hernias (CDH) have shown that NAVA may reduce oxygenation index and mean airway pressures. To date, no clinical trial has compared NAVA to standard methods of mechanical ventilation for babies with CDH. METHODS: The aim of this dual-centre randomised cross-over trial is to compare post-operative NAVA with assist control ventilation (ACV) for infants with CDH. If eligible, infants will be enrolled for a ventilatory support tolerance trial (VSTT) to assess their suitability for randomisation. If clinically stable during the VSTT, infants will be randomised to receive either NAVA or ACV first in a 1:1 ratio for a 4-h period. The oxygenation index, respiratory severity score and cumulative sedative medication use will be measured. DISCUSSION: Retrospective studies comparing NAVA to ACV in neonates with congenital diaphragmatic hernia have shown the ventilatory mode may improve respiratory parameters and benefit neonates. To our knowledge, this is the first prospective cross-over trial comparing NAVA to ACV. TRIAL REGISTRATION: NAN-C was prospectively registered on ClinicalTrials.gov NCT05839340  Registered on May 2023.

Oxygen saturation index: an adjunct for oxygenation index in congenital diaphragmatic hernia.

OBJECTIVE: Our objective was to investigate the correlation of Oxygen Saturation Index (OSI) with Oxygenation Index (OI) and determine OSImax values that could predict need for ECMO and death in Congenital Diaphragmatic Hernia (CDH). STUDY DESIGN: This is a retrospective cohort study of infants with CDH admitted to a tertiary level VI NICU. Pearson's correlation coefficient and simple linear regression analysis were used to investigate the OSI: OI correlation, and logistic regression analysis to investigate OSImax values that predicted need for ECMO and death. RESULTS: Among the 180 infants, OSImax value of >13 at 6 h of life (HOL) best predicted need for ECMO and death. There was a strong correlation between OSI: OI paired values (r = 0.876, p < 0.001). The linear regression equation was OI = -2.4 + 2.4(OSI). CONCLUSION: OSI could be used as a valuable adjunct to OI in the clinical management of newborn infants with CDH.

Sustained inflation improves initial lung aeration in newborn rabbits with a diaphragmatic hernia.

BACKGROUND: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH. METHODS: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging. RESULTS: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV. CONCLUSION: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit. IMPACT: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH.

Prenatal MRI assessment of mediastinal shift angle as a feasible and effective risk stratification tool in isolated right-sided congenital diaphragmatic hernia.

OBJECTIVES: To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. METHODS: Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). RESULTS: MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781-1.000)), PH (0.828, 95%CI: (0.661-0.994)), and ECMO therapy (0.813, 95%CI: (0.645-0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. CONCLUSIONS: We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. CLINICAL RELEVANCE STATEMENT: Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. KEY POINTS: • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management.

Spontaneous breathing in selected neonates with very mild congenital diaphragmatic hernia.

AIMS: Current treatment guidelines recommend immediate postnatal intubation in all neonates with congenital diaphragmatic hernia (CDH). This study aimed to investigate the feasibility and outcomes of a spontaneous breathing approach (SBA) versus immediate intubation in neonates with prenatally diagnosed very mild CDH. METHODS: A retrospective study was conducted comparing neonates with very mild CDH (left-sided, liver-down, observed-to-expected lung-to-head ratio ≥45%) undergoing SBA and matched controls receiving standard treatment. Data on early echocardiographic findings, respiratory support, length of hospital stay, and clinical outcomes were analyzed. RESULTS: Of 151 CDH neonates, eight underwent SBA, while 31 received standard treatment. SBA was successful in six of eight patients. SBA patients had shorter length of stay (14 vs. 30 days, p = .005), mechanical ventilation (3.5 vs. 8.7 days, p = .011), and oxygen supplementation (3.2 vs. 9.3 days, p = .013) compared to matched controls. Echocardiographic evidence of pulmonary hypertension and cardiac dysfunction were significantly lower in SBA neonates after admission but similar before surgical repair. The SBA group tolerated enteral feeding earlier (day of life 7 vs. 16, p = .019). CONCLUSIONS: SBA appears feasible and beneficial for prenatally diagnosed very mild CDH. It was associated with a shortened hospital stay supportive therapies. However, larger trials are needed to confirm these findings and determine optimal respiratory support.

The role of point-of-care ultrasound in the management of neonates with congenital diaphragmatic hernia.

In the last few years, current evidence has supported the use of point-of-care ultrasound (POCUS) for a number of diagnostic and procedural applications. Considering the valuable information that POCUS can give, we propose a standardized protocol for the management of neonates with a congenital diaphragmatic hernia (CDH-POCUS protocol) in the neonatal intensive care unit. Indeed, POCUS could be a valid tool for the neonatologist through the evaluation of 1) cardiac function and pulmonary hypertension; 2) lung volumes, postoperative pleural effusion or pneumothorax; 3) splanchnic and renal perfusion, malrotations, and/or signs of necrotizing enterocolitis; 4) cerebral perfusion and eventual brain lesions that could contribute to neurodevelopmental impairment. In this article, we discuss the state-of-the-art in neonatal POCUS for which concerns congenital diaphragmatic hernia (CDH), and we provide suggestions to improve its use. IMPACT: This review shows how point-of-care ultrasound (POCUS) could be a valid tool for managing neonates with congenital diaphragmatic hernia (CDH) after birth. Our manuscript underscores the importance of standardized protocols in neonates with CDH. Beyond the well-known role of echocardiography, ultrasound of lungs, splanchnic organs, and brain can be useful. The use of POCUS should be encouraged to improve ventilation strategies, systemic perfusion, and enteral feeding, and to intercept any early signs related to future neurodevelopmental impairment.