Parents-reported nutrition and feeding difficulties in infants with congenital diaphragmatic hernia after hospital discharge.

PURPOSE: Congenital diaphragmatic hernia (CDH) affects 1 in 3000-5000 newborns. In survivors, long-term complications include gastroesophageal reflux (GER), feeding difficulties, and failure to thrive. Data from the parents' perspective remain scarce. This study aims to report the prevalence and impact of feeding difficulties on CDH families after discharge. METHODS: National web-based survey amongst families with CDH infants in 2021. RESULTS: Caregivers of 112 CDH survivors participated. The baseline characteristics were representative with 54 % male, 83 % left-sided CDH, prenatal diagnosis in 83 %, and 34 % requiring extracorporeal membrane oxygenation. Most infants (81 %) were discharged within three months, with 62 % feeding by mouth, and 30 % requiring a feeding tube. Persisting feeding difficulties were experienced by 73 %, GER being the most common (66 %), followed by insufficient weight gain (64 %). After discharge, 41 % received medical support for failure to thrive. The primary-care pediatrician was consulted most frequently for information (61 %) and treatment of feeding difficulties (74 %). Therapeutic success was reported in 64 %. A cessation of symptoms was achieved in 89 % within three years. CONCLUSION: The majority of CDH infants had persistent feeding difficulties. This survey highlights the impact surrounding feeding problems on CDH families. Further studies and support systems are needed to raise the quality of life in CDH infants and their families.

Arterial hypertension in infants with congenital diaphragmatic hernia following surgical repair.

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension.   Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up. What is Known: • Due to decreasing mortality, morbidity is increasing in surviving CDH patients. • Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH. What is New: • There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication. • A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension.

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.

[Characteristics and Outcome of Neonates With Postnatally Diagnosed Congenital Diaphragmatic Hernia]. / Charakteristika und Outcomedaten von Neugeborenen mit pränatal nicht diagnostizierter angeborener Zwerchfellhernie.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is one of the most severe neonatal malformations with a mortality of 20-35%. Currently, the rate of prenatally recognized CDHs is 60-80%. This study investigated the characteristics and outcome data of children with prenatally unrecognized CDH. METHODS: Postnatally diagnosed CDH newborns treated at the University Hospital Bonn between 2012 and 2021 were included. Treatment and outcome data were compared according to type of maternity hospital, Apgar values, and between prenatally and postnatally diagnosed CDH. RESULTS: Of 244 CDH newborns, 22 were included. Comparison for birth in a facility with vs. without pediatric care showed for mortality: 9% vs. 27%, p=0.478; ECMO rate: 9% vs. 36%, p=0.300; age at diagnosis: 84 vs. 129 min, p=0.049; time between intubation and diagnosis: 20 vs. 86 min, p=0.019. Newborns in the second group showed significantly worse values for pH and pCO2. Furthermore, there was a tendency for higher mortality and ECMO rates in children with an Apgar score<7 vs.≥7. Children diagnosed postnatally were significantly more likely to have moderate or severe PH and tended to have cardiac dysfunction more often than those diagnosed prenatally. DISCUSSION: In our cohort, ca. one in 10 newborns received a postnatal CDH diagnosis. Birth in a facility without pediatric care is associated with later diagnosis, which may favor hypercapnia/acidosis and more severe pulm.

Hemolysis during Venovenous Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia: A Prospective Observational Study.

OBJECTIVE: To investigate the incidence of hemolysis and its association with outcome in neonates with congenital diaphragmatic hernia (CDH) requiring venovenous extracorporeal membrane oxygenation (ECMO) treatment using a Medos Deltastream circuit with a DP3 pump, a hilite 800 LT oxygenator system, and a »' tubing. STUDY DESIGN: Plasma free hemoglobin (PFH) was prospectively measured once daily during ECMO using spectrophotometric testing. Patients (n = 62) were allocated into two groups according to presence or absence of hemolysis. Hemolysis was defined as PFH ≥ 50 mg/dL on at least 2 consecutive days during ECMO treatment. Hemolysis was classified as either moderate with a maximum PFH of 50-100 mg/dL or severe with a maximum PFH >100 mg/dL. RESULTS: Hemolysis was detected in 14 patients (22.6%). Mortality was 100% in neonates with hemolysis compared with 31.1% in neonates without hemolysis (P < .001). In 21.4% hemolysis was moderate and in 78.6% severe. Using multivariable analysis, hemolysis (hazard ratio: 6.8; 95%CI: 1.86-24.86) and suprasystemic pulmonary hypertension (PH) (hazard ratio: 3.07; 95%CI: 1.01-9.32) were independently associated with mortality. Hemolysis occurred significantly more often using 8 French (Fr) cannulae than 13 Fr cannulae (43% vs 17%; P = .039). Cutoff for relative ECMO flow to predict hemolysis were 115 ml/kg/ minute for patients with 8 Fr cannulae (Area under the curve [AUC] 0.786, P = .042) and 100 ml/kg/ minute for patients with 13 Fr cannulae (AUC 0.840, P < .001). CONCLUSIONS: Hemolysis in CDH neonates receiving venovenous ECMO is independently associated with mortality.

Dynamics of pulmonary hypertension severity in the first 48†h in neonates with prenatally diagnosed congenital diaphragmatic hernia.

Introduction: Pulmonary hypertension (PH) is one of the major contributing factors to the high morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH). The severity and duration of postnatal PH are an established risk factor for patient outcome; however, the early postnatal dynamics of PH have not been investigated. This study aims to describe the early course of PH in CDH infants, and its relation to established prognostic markers and outcome measures. Methods: We performed a monocentric retrospective review of neonates with prenatally diagnosed CDH, who received three standardized echocardiographic examinations at 2-6 h, 24, and 48 h of life. The degree of PH was graded as one of three categories: mild/no, moderate, or severe PH. The characteristics of the three groups and their course of PH over 48 h were compared using univariate and correlational analyses. Results: Of 165 eligible CDH cases, initial PH classification was mild/no in 28%, moderate in 35%, and severe PH in 37%. The course of PH varied markedly based on the initial staging. No patient with initial no/mild PH developed severe PH, required extracorporeal membrane oxygenation (ECMO)-therapy, or died. Of cases with initial severe PH, 63% had persistent PH at 48 h, 69% required ECMO, and 54% died. Risk factors for any PH included younger gestational age, intrathoracic liver herniation, prenatal fetoscopic endoluminal tracheal occlusion (FETO)-intervention, lower lung to head ratio (LHR), and total fetal lung volume (TFLV). Patients with moderate and severe PH showed similar characteristics, except liver position at 24- (p = 0.042) and 48 h (p = 0.001), mortality (p = 0.001), and ECMO-rate (p = 0.035). Discussion: To our knowledge, this is the first study to systematically assess the dynamics of PH in the first postnatal 48 h at three defined time points. CDH infants with initial moderate and severe PH have a high variation in postnatal PH severity over the first 48 h of life. Patients with mild/no PH have less change in PH severity, and an excellent prognosis. Patients with severe PH at any point have a significantly higher risk for ECMO and mortality. Assessing PH within 2-6 h should be a primary goal in the care for CDH neonates.

Percutaneous, ultrasound-guided single- and multisite cannulation for veno-venous extracorporeal membrane oxygenation in neonates.

AIMS: Extracorporeal membrane oxygenation (ECMO) is a widely used technique to support neonates with severe respiratory failure. Data on percutaneous, ultrasound-guided veno-venous (VV) ECMO cannulation in neonates is still scarce. Aim of this study was to describe our institutional experience with ultrasound-guided percutaneous, VV ECMO cannulation in neonates with severe respiratory failure. METHODS: Neonates receiving ECMO support at our department between January 2017 and January 2021 were retrospectively identified. Patients receiving VV ECMO cannulation performed by the percutaneous Seldinger technique by single- or multisite cannulation were analyzed. RESULTS: A total of 54 neonates received ECMO cannulation performed by the percutaneous Seldinger technique. In 39 patients (72%) a 13 French bicaval dual-lumen cannula was inserted and in 15 patients (28%) two single-lumen cannulae were used. Cannulae positioning using the multisite approach was in all cases as desired. The tip of the 13 French cannula was located in the IVC in 35/39 patients, in four patients position was too proximal but did not dislocate during the ECMO run. One (2%) preterm neonate (weight 1.75 kg) developed a cardiac tamponade which was successfully managed with drainage. Median duration of ECMO was 7 days (interquartile range: 5-16 days). Forty-four patients (82%) were successfully weaned from ECMO and in 31/44 (71%) the ECMO cannulae were removed with a delay of 0.9-7.2 days (median 2.8 days) after weaning without noticing complications. CONCLUSIONS: A correct cannula placement using the ultrasound-guided percutaneous Seldinger technique, for both single- and multisite cannulation, seems feasible in most neonatal patients receiving VV ECMO.

Ductus arteriosus flow predicts outcome in neonates with congenital diaphragmatic hernia.

OBJECTIVE: To investigate whether the pattern of flow through the ductus arteriosus (DA) is associated with the need for extracorporeal membrane oxygenation support (ECMO) or death in neonates with congenital diaphragmatic hernia (CDH). DESIGN: Retrospective observational study. SETTING: German level III Neonatal Intensive Care Unit. PARTICIPANTS: 139 CDH neonates were born between March 2009 and May 2021. METHODS: DA flow pattern was assessed in echocardiograms obtained within 24 h of life by measuring flow time and velocity time integral (VTI) for both left-to-right (LR) and right-to-left (RL) components of the ductal shunt. A VTI ratio (VTILR/VTIRL) < 1.0 and an RL relative flow time (Flow timeRL/(Flow timeLR+Flow timeRL)) >33% were defined as markers of abnormal flow patterns. The primary outcome was the need for ECMO. The secondary outcome was death. RESULTS: 72 patients (51.8%) had a VTI ratio <1.0, 73 (52.5%) an RL relative flow time >33%. 59 patients (42.4%) had an alteration of both values. Need for ECMO was present in 37.4% (n = 52), while 19.4% (n = 27) died. A VTI ratio <1.0 had the highest diagnostic accuracy for the need for ECMO, (sensitivity 82.7%, specificity 66.7%, negative predictive value [NPV] 86.6%, and positive predictive value [PPV] 59.7%) as well as for death (sensitivity 77.8%, specificity 54.5%, NPV 91.0%, and PPV 29.2%). Patients with VTI ratio <1.0 were 4.7 times more likely to need ECMO and 3.3 times more likely to die. VTI ratio values correlated significantly with pulmonary hypertension (PH) severity (r = -0.516, p < 0.001). CONCLUSIONS: A VTI ratio <1.0 is a valuable threshold to identify high-risk CDH neonates. For improved risk stratification, other parameters-for example, left ventricular cardiac dysfunction-should be combined with DA flow assessment.

Echocardiographic Assessment of Pulmonary Hypertension in Neonates with Congenital Diaphragmatic Hernia Using Pulmonary Artery Flow Characteristics.

Background: Assessment of pulmonary hypertension (PH) is essential in neonates with congenital diaphragmatic hernia (CDH). Echocardiography is widely established to quantify PH severity, but currently used parameters have inherent limitations. The aim of our study was to investigate the prognostic utility of the index of the pulmonary artery acceleration time to the right ventricular ejection time (PAAT:ET) in CDH neonates assessed using echocardiography. Methods: PAAT:ET values were prospectively measured in CDH neonates on admission, on day of life (DOL) 2 and DOL 5−7. Optimal cut-off values to predict mortality and need for ECMO were calculated and PAAT:ET values were compared between non-ECMO survivors, ECMO-survivors, and ECMO-non-survivors. Results: 87 CDH neonates were enrolled and 39 patients required ECMO therapy. At baseline, PAAT:ET values were significantly lower in ECMO patients compared to non-ECMO patients (p < 0.001). ECMO survivors and ECMO non-survivors had similar values at baseline (p = 0.967) and DOL 2 (p = 0.124) but significantly higher values at DOL 5−7 (p = 0.003). Optimal PAAT:ET cut-off for predicting ECMO was 0.290 at baseline and 0.310 for predicting non-survival in patients on ECMO at DOL 5−7. Conclusion: PAAT:ET is a feasible parameter for early risk assessment in CDH neonates.

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.