Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

OBJECTIVES: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. METHODOLOGY: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). RESULTS: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). CONCLUSION: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

A comparative analysis of the Vasoactive-Inotropic Score, the Vasoactive-Ventilation-Renal Score, and the Oxygenation Index as outcome predictors in infants with a congenital diaphragmatic hernia.

OBJECTIVES: To date, different severity scores and indices are available to predict outcome in infants with a congenital diaphragmatic hernia (CDH). The Oxygenation Index (OI) and the Vasoactive-Inotropic Score (VIS) has already been evaluated in the CDH population. The Vasoactive-Ventilation-Renal (VVR) Score was recently evaluated as new severity score in several studies on infants with need for cardiac surgery. The score was shown to outperform the VIS and OI as outcome predictors in these infants, but no data are available regarding the evaluation of the VVR Score in CDH infants. PATIENTS AND METHODS: This was a retrospective single-center analysis at the University Children's Hospital, Bonn, Germany, during the study period from January 2019 until December 2022. Of 108 CDH infants treated at our institution, a final cohort of 100 neonates met the inclusion criteria. INCLUSION CRITERIA: diagnosis of CDH (right-sided, left-sided, or bilateral). EXCLUSION CRITERIA: early mortality (before surgical correction of the diaphragm), palliative care after birth, no available data for OI, VIS, and VVR Score calculation. The OI, the VIS, and the VVR Score were calculated at three selected timepoints: at 48-72 h after birth (T1), before surgery (T2), and after surgery (T3). MAIN RESULTS: The primary clinical endpoint (in-hospital mortality) was reached in 21% of the infants. Infants surviving to discharge were allocated to group A, infants with fatal outcome to group B. In the univariate analysis, the OI was significantly higher in infants allocated to group B at T2 (p < .001), and T3 (p < .001). The VIS was significantly higher only at T1 in infants allocated to group B (p = .001). The VVR Score was significantly higher at T1 (p = .017), and at T3 (p = .002) in infants not surviving to discharge. In the multivariate analysis, the OI at T2 + T3 (p < .001), the VIS at T1 (p = .048), and the VVR Score at T1 + T3 (p = .023, and p = .048, respectively) remained significantly associated with in-hospital mortality. The OI presented the highest area under the curve (AUC) at T2 and T3 (T2:0.867, p = .001; T3:0.833, p = .000) regarding the primary endpoint in the overall cohort. In the subgroup of infants without need for extracorporeal membrane oxygenation (ECMO) therapy (n = 60) the VVR Sore presented the best performance with an AUC of 0.942 (p = .000) at T3. CONCLUSION: The severity scores OI, VIS, and VVR-Score are independent predictors of in-hospital mortality in CDH infants. The OI seems to outperform the VIS and VVR-Score as outcome predictor immediately before and after CDH surgery, whereas the VVR Score presented the best performance in the subgroup of CDH infants without need for ECMO and mild-to-moderate CDH defects.

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.

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.

Intravenous sildenafil for treatment of early pulmonary hypertension in preterm infants.

Data is lacking on the effect of continuous intravenous sildenafil treatment in preterm infants with early pulmonary hypertension (PH), especially in very low birth weight (VLBW) infants. Preterm infants (< 37 weeks of gestational age) with intravenous sildenafil treatment and diagnosis of PH between 01/12 and 12/21 were retrospectively screened for analysis. The primary clinical endpoint was defined as response to sildenafil according to the improvement of the oxygenation index (OI), the saturation oxygenation pressure index (SOPI) and PaO2/FiO2-ratio. Early-PH was defined as diagnosis < 28 day of life (DOL). 58 infants were finally included, with 47% classified as very low birth weight (VLBW) infants. The primary endpoint was reached in 57%. The likelihood to die during in-hospital treatment was more than three times higher (72 vs 21%, p < 0.001) in infants without response to sildenafil. The echocardiographic severity of PH and right-ventricular dysfunction (RVD) decreased significantly from baseline to 24 h (p = 0.045, and p = 0.008, respectively). Sildenafil treatment leads to significant improvement of the oxygenation impairment in 57% of the preterm infants, with similar response rates in VLBW infants. Intravenous sildenafil treatment is associated with a significant decrease of the PH-severity and RVD.

Feasibility of bedside portable MRI in neonates and children during ECLS.

Magnetic resonance imaging (MRI) is the preferred neuroimaging technique in pediatric patients. However, in neonates and instable pediatric patients accessibility to MRI is often not feasible due to instability of patients and equipment not being feasible for MRI. Low-field MRI has been shown to be a feasible neuroimaging tool in pediatric patients. We present the first four patients receiving bedside high-quality MRI during ECLS treatment. We show that it is safe and feasible to perform bedside MRI in this patient population. This opens the route to additional treatment decisions and may guide optimized treatment in these patients.

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

CA125: a novel cardiac biomarker for infants with congenital diaphragmatic hernia.

BACKGROUND: The carbohydrate antigen 125 (CA125) was proven as a robust biomarker for risk stratification in adults with heart failure. This is the first study analyzing CA125 in a cohort of infants with congenital diaphragmatic hernia (CDH). METHODS: Sixty-eight infants with CDH, treated at the University Children's Hospital Bonn (Germany), between January 2018 and February 2021, were prospectively enrolled for analysis. CA125 values were measured at the following timepoints: 6,12, 24, 48 h, and during ECMO daily from day 1 to day 7. RESULTS: In infants not surviving to discharge, CA125 values were significantly higher at day 1 (6, 12, and 24 h). Infants with subsequent need for ECMO presented significantly higher CA125 values at 12 h of life. During ECMO, CA125 values measured at day 1 were significantly higher in infants not surviving to discharge. In the ROC analysis, a CA125 value of ≥10 U/ml was calculated as optimal cut-off for the prediction of ECMO and in-hospital mortality. CA125 values correlated significantly with the severity of PH and ventricular dysfunction. CONCLUSIONS: CA125 values correlate significantly with echocardiographic markers of PH and ventricular dysfunction and correlate significantly with parameters of disease severity (need for ECMO, mortality). IMPACT: CA125 was proven as robust cardiac biomarker in adult cohorts. Information about the utility as a biomarker in neonatal cohorts is lacking. This is the first study analyzing CA125 as a cardiac biomarker in a cohort of infants with congenital diaphragmatic hernia (CDH). CA125 correlates significantly with markers of echocardiographic assessment (PH and ventricular dysfunction) in infants with CDH and helps to identify infants at high risk for ECMO and in-hospital mortality. The results underline the need for the inclusion of cardiac biomarkers in the clinical routine in neonates at risk for cardiopulmonary failure.

NT-proBNP and Zlog-transformed NT-proBNP values predict extubation failure in critically ill neonates with pulmonary hypertension and ventricular dysfunction.

OBJECTIVES: Critically ill neonates with a history of pulmonary hypertension (PH) or ventricular dysfunction are at risk to experience an extubation failure (EF) after liberation from mechanical ventilation (MV). Due to insufficient data from neonatal cohorts, it remains unclear whether NT-proBNP is an appropriate biomarker to predict EF in this cohort. The Zlog-transformation of NT-proBNP (further named NT-proBNPZlog ) is an additional tool to optimize the interpretation of NT-proBNP since absolute NT-proBNP values are varying with the age of these infants. PATIENTS AND METHODS: This was a retrospective single-center analysis at the University Children's Hospital, Bonn, Germany, during the study period from January 2020 until December 2021. Forty-three neonates met the inclusion criteria and were screened for study participation. INCLUSION CRITERIA: prolonged (>24 h) MV with at least one extubation attempt, with a history of PH and/or ventricular dysfunction in the echocardiographic assessment at admission to the neonatal intensive care unit or during the period of MV, NT-proBNP measurements before (max. 24 h, baseline) and after (max. 24 h, follow-up) the first extubation attempt. The primary clinical endpoint was defined as EF with need for reintubation (0-72 h). Neonates with an EF were allocated to group A and neonates with successful liberation from MV to group B. MAIN RESULTS: The primary clinical endpoint (EF) was reached in 21% (nine infants). Absolute mean NT-proBNP values (NT-proBNPabs ) at baseline did not differ significantly in infants of group A and B (6931 vs. 7136 pg/ml, p = 0.227). NT-proBNPZlog values at baseline (2.35 vs. 1.57, p = 0.073) tended to higher values in group A. NT-proBNPabs values measured at follow-up were significantly higher in infants allocated to group A (11120 vs. 7570 pg/ml, p = 0.027). Likewise, NT-proBNPZlog values at follow-up were significantly higher in infants allocated to group A (3.05 vs. 1.93, p = 0.009). NT-proBNPabs values at follow-up and NT-proBNPZlog values at baseline correlated significantly with the severity of PH. Regarding the receiver operating characteristic-analysis, a NT-proBNPabs value at follow-up of ≥4622 pg/ml was calculated as optimal cut-off value for the prediction of EF (area under the curve [AUC] 0.742, p = 0.001). A NT-proBNPZlog value at baseline of ≥1.63 and at follow-up of ≥2.14 was calculated as optimal cut-off for the prediction of EF (AUC: 0.690/p = 0.027, and 0.781/p = 0.000, respectively). CONCLUSION: NT-proBNPabs and NT-proBNPZlog might be valuable biomarkers for the prediction of EF in critically ill neonates. The Zlog-transformation of NT-proBNP allows an age-independent interpretation of NT-proBNP and should be considered for clinical routine.

Heart rate control with landiolol hydrochloride in infants with ventricular dysfunction and pulmonary hypertension.

AIMS: Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort-acting beta-blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure. METHODS AND RESULTS: This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35 weeks of GA (Group A) and born at >35 weeks of GA (Group B). Tachycardia was defined depending on GA (<35 weeks of GA: >170 b.p.m.; ≥ 35 weeks of GA: >150 b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24 h of landiolol treatment. Twenty-nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3-24) h. The median starting dose of landiolol was 8.8 (3.9-25.3) µk/kg/min, with a median dosing during the first 24 h of landiolol treatment of 9.9 (2.8-35.4) µk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4-44.4) µk/kg/min. The right ventricular dysfunction improved significantly in both groups 24 h after onset of landiolol infusion (P = 0.001 in Group A and P = 0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24 h after onset of landiolol infusion in infants of Group B (P = 0.004 and P = 0.006, respectively). The severity of PH improved significantly after 24 h in infants of Group A (P < 0.001). During landiolol treatment, no severe drug-related adverse event was noted. CONCLUSIONS: The use of landiolol hydrochloride for HR control of non-arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH.

Comparative performance data for multiplex SARS-CoV-2 serological assays from a large panel of dried blood spot specimens.

The extent of the COVID-19 pandemic will be better understood through serosurveys and SARS-CoV-2 antibody testing. Dried blood spot (DBS) samples will play a central role in large scale serosurveillance by simplifying biological specimen collection and transportation, especially in Canada. Direct comparative performance data on multiplex SARS-CoV-2 assays resulting from identical DBS samples are currently lacking. In our study, we aimed to provide performance data for the BioPlex 2200 SARS-CoV-2 IgG (Bio-Rad), V-PLEX SARS-CoV-2 Panel 2 IgG (MSD), and Elecsys Anti-SARS-CoV-2 (Roche) commercial assays, as well as for two highly scalable in-house assays (University of Ottawa and Mount Sinai Hospital protocols) to assess their suitability for DBS-based SARS-CoV-2 DBS serosurveillance. These assays were evaluated against identical panels of DBS samples collected from convalescent COVID-19 patients (n = 97) and individuals undergoing routine sexually transmitted and bloodborne infection (STBBI) testing prior to the COVID-19 pandemic (n = 90). Our findings suggest that several assays are suitable for serosurveillance (sensitivity >97% and specificity >98%). In contrast to other reports, we did not observe an improvement in performance using multiple antigen consensus-based rules to establish overall seropositivity. This may be due to our DBS panel which consisted of samples collected from convalescent COVID-19 patients with significant anti-spike, -receptor binding domain (RBD), and -nucleocapsid antibody titers. This study demonstrates that biological specimens collected as DBS coupled with one of several readily available assays are useful for large-scale COVID-19 serosurveillance.

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.

[Therapy and Outcome of Neonates with Congenital Diaphragmatic Hernia and Congenital Heart Defects]. / Therapie und Outcome von Neugeborenen mit kongenitaler Zwerchfellhernie und angeborenen Herzfehlern.

Die Mortalität von Patienten mit isoliert auftretenden angeborenen Zwerchfellhernien liegt in spezialisierten Zentren bei 20-40%. Wesentliche, das Outcome beeinflussende Faktoren, sind die bestehende Lungenhypoplasie, eine daraus resultierende pulmonale Hypertonie, sowie das Vorliegen weiterer Fehlbildungen. Begleitfehlbildungen wie angeborene Herzfehler treten bei ca. 18% aller Neonaten mit Zwerchfellhernie auf. Schwere angeborene Herzfehler wie das hypoplastische Linksherz Syndrom zeigen sich in ca. 8% der Fälle. In einer retrospektiven Analyse des Patientenkollektivs unserer Klinik zwischen 01/2012 und 12/2018 wurde das prä- und postnatale Management, sowie das Outcome von Neugeborenen mit der Kombination aus angeborenen Herzfehlern und Zwerchfellhernien untersucht. Im Studienzeitraum wurden in unserer Klinik 156 Neugeborene mit Zwerchfellhernie behandelt. Bei 10 Patienten (6,4%) lag zusätzlich ein schwerer, bei 11 Patienten (7,1%) ein moderater Herzfehler vor. 6/21 Patienten verstarben im Verlauf des Krankenhausaufenthaltes, davon 3 am ersten Lebenstag. Es zeigte sich eine deutlich geringere Mortalität bei Patienten mit Zwerchfellhernie und moderatem Herzfehler im Vergleich zu schwerem Herzfehler (9 vs. 50%). Besonders hoch lag die Mortalität bei Kindern mit einem univentrikulären Herzen. Trotz einer deutlich reduzierten Prognose bei der Kombination aus angeborenem Herzfehler und Zwerchfellhernie muss nicht generell mit einer infausten Prognose gerechnet werden. In spezialisierten Zentren kann ein kurativer Ansatz erfolgen.The mortality of patients with isolated congenital diaphragmatic hernia (CDH) in specialized centers is 20-40%. The main factors influencing the outcome are the underlying pulmonary hypoplasia, the resulting pulmonary hypertension and the presence of other malformations. Concomitant malformations such as congenital heart defects occur in around 18% of all neonates with a diaphragmatic hernia. Serious congenital heart defects such as hypoplastic left heart syndrome occur in approximately 8% of cases. In a retrospective analysis of the patient collective of our hospital between 01/2012 and 12/2018, the prenatal and postnatal management as well as the outcome of newborns with a combination of congenital heart defects and diaphragmatic hernias were examined. During the study period, 156 newborns with diaphragmatic hernias were treated at our institution. In 10 patients (6.4%) there was also a severe, and in 11 patients (7.1%) a moderate heart defect. 6/21 patients died during their hospital stay, 3 of them on the first day of life. There was a significantly lower mortality in patients with diaphragmatic hernia and moderate heart defects compared to severe heart defects (9 vs. 50%). The mortality in children with a univentricular heart was particularly high. Despite a significantly reduced prognosis for the combination of congenital heart defects and diaphragmatic hernia, generally a poor prognosis does not have to be expected. A curative approach can be achieved in specialized centers.

Exploratory Assessment of Levosimendan in Infants With Congenital Diaphragmatic Hernia.

OBJECTIVES: Infants with congenital diaphragmatic hernia frequently suffer from cardiac dysfunction and pulmonary hypertension during the postnatal course. With the use of the inodilator levosimendan, a therapeutic approach is available in situations with catecholamine-refractory low-cardiac-output failure and severe pulmonary hypertension. DESIGN: Retrospective single-center cohort study. SETTING: University-based, tertiary-care children's hospital neonatal ICU. PATIENTS: Cohort of 24 infants with congenital diaphragmatic hernia and levosimendan therapy, without underlying major cardiac defect, treated at the University Children´s Hospital Bonn, Germany, between January 2017 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-four infants with congenital diaphragmatic hernia were treated with levosimendan (41% of hospitalized congenital diaphragmatic hernia infants in the study period). In 88%, the congenital diaphragmatic hernia was left-sided. The median observed-to-expected lung-to-head ratio was 36%. About 60% of the infants were supported with venovenous extracorporeal membrane oxygenation and the mortality was 38% (9/24 infants). Levosimendan administration was associated with improvement of pulmonary hypertension severity (p = 0.013 and p = 0.000) and right ventricular dysfunction (p = 0.011 and p = 0.000) at 24 hours and 7 days after treatment. Similarly, the prevalence of left ventricular dysfunction decreased from 50% at baseline to 10% after 7 days (p = 0.026). A significant reduction in the peak inspiratory pressure was observed after drug application (p = 0.038) and a significant decrease of the Vasoactive-Inotropic Score was apparent (p = 0.022). A relevant arterial hypotension as a drug-related adverse event occurred in one patient. CONCLUSIONS: This is the first study exploring clinical and hemodynamic changes after levosimendan treatment in a cohort of infants with congenital diaphragmatic hernia. An association of levosimendan application and an improvement in pulmonary hypertension, right ventricular, and left ventricular dysfunction were observed within 7 days after drug infusion. However, due to the retrospective design of this study, the results should be interpreted carefully.

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.

Prediction of ECMO and Mortality in Neonates with Congenital Diaphragmatic Hernia Using the SNAP-II Score.

BACKGROUND: The mortality of neonates with congenital diaphragmatic hernia (CDH) ranges between 20 and 40% even in specialized high-volume centers. The Score for Neonatal Acute Physiology-II (SNAP-II Score) could facilitate the decision about supportive therapies in CDH newborns. METHODS: The SNAP-II score consists of the variables arterial blood pressure, pH, PaO2:FiO2, body temperature, diuresis, and seizure activity and was calculated at an age of 12 h. RESULTS: 101 CDH newborns treated in our institution between 2009 and 2017 were included in the study. A SNAP-II score ≥ 28 was calculated as cutoff for predicting mortality (AUC 0.876; 95% CI: 0.795-0.957). The mortality rate was 52.9% with a SNAP-II score ≥ 28, and 5.9% with a SNAP-II score<28. Sensitivity and specificity for predicting mortality was 81.8 and 79.7%, the negative predicting value (NPV) was 94.0%, the positive predicting value (PPV) 52.9%. The optimal cutoff for predicting ECMO was ≥ 22 (AUC 0.895; 95% CI: 0.836-0.954). Sensitivity and specificity for predicting ECMO therapy was 90.7, and 63.8%, the NPV was 90.2%, and the PPV was 65% respectively. The SNAP-II score was independently associated with mortality [OR 1.126 (95% CI: 1.050-1.207)] and the need for ECMO therapy [OR 1.243 (95% CI: 1.106-1.397)]. CONCLUSION: The SNAP-II score is strongly associated with mortality and the need for ECMO therapy in CDH newborns and should be implemented in the risk stratification of these infants.