http://repub.eur.nl/res/aut/26735/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37681/ 2012-10-01T00:00:00Z Pulmonary hypertension associated with congenital diaphragmatic hernia is still one of the major challenges in neonatal intensive care units. Several relevant pathways in its pathogenesis have been described and studied, but the absence of well-designed randomized controlled trials and the scattered data on the pharmacokinetics and pharmacodynamics of most of the drugs used in these patients hamper progress significantly. This review aims to give an overview of current management strategies in the antenatal and neonatal phase, and provides founded clinical recommendations. http://repub.eur.nl/res/pub/33446/ 2011-05-01T00:00:00Z Background: Congenital diaphragmatic hernia (CDH) is a life threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. Objective: To identify genomic alterations that contribute to the development of diaphragmatic defects. Methods: A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations was screened for genomic alterations by array comparative genomic hybridisation or single nucleotide polymorphism based copy number analysis. Results: Genomic alterations that were likely to have contributed to the development of CDH were identified in 8 patients. Inherited deletions of ZFPM2 were identified in 2 patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was identified in a patient with a partial pentalogy of Cantrellphenotype.Conclusion: Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. These data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH related genes on chromosomes 16p11.2, 11q23-24 and 13q12, and suggest a possible role for FZD2 and Wnt signalling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects. http://repub.eur.nl/res/pub/23545/ 2011-04-01T00:00:00Z Introduction: The lung-to-head ratio (LHR), measured by ultrasound, and the fetal lung volume (FLV), measured by MRI, are both used to predict survival and need for extra corporeal membrane oxygenation (ECMO) in infants with congenital diaphragmatic hernia (CDH). The aim of this study is to determine whether MRI measurements of the FLV, in addition to standard ultrasound measurements of the LHR, give better prediction of chronic lung disease, mortality by day 28 and need for ECMO. Materials and methods: Patients with unilateral isolated CDH born between January 2002 and December 2008 were eligible for inclusion. LHR and FLV were expressed as observed-to-expected values (O/E LHR and O/E FLV). Univariate and multivariate analyses were performed. Receiver operating characteristic curves were constructed and areas under the curve (AUC) were calculated to determine predictive values. Results: 90 patients were included in the analysis. Combined measurement of the O/E LHR and O/E FLV gave a slightly better prediction of chronic lung disease (AUC = 0.83 and AUC = 0.87) and need for ECMO therapy (AUC = 0.77 and AUC = 0.81) than standard ultrasound measurements of the O/E LHR alone. Combined measurement of the O/E LHR and O/E FLV did not improve prediction of early mortality (AUC = 0.90) compared to measurement of the O/E LHR alone (AUC = 0.89). An intrathoracal position of the liver was independently associated with a higher risk of early mortality (p < 0.001), chronic lung disease (p = 0.007) and need for ECMO therapy (p = 0.001). Discussion: Chronic lung disease and need for ECMO therapy are slightly better predicted by combined measurement of the O/E LHR and the O/E FLV. Early mortality is very well predicted by measurement of the O/E LHR alone. Conclusion: Clinical relevance of additional MRI measurements may be debated. http://repub.eur.nl/res/pub/34247/ 2011-02-01T00:00:00Z Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with a high rate of mortality and morbidity. Objective: Our aim was to determine a possible effect of standardized treatment on outcome in infants with CDH. Methods: All prenatally diagnosed patients with unilateral CDH born alive between January 2006 and December 2009 at the Erasmus MC or the University Hospital Mannheim were eligible for inclusion. Patients who underwent a fetal tracheal occlusion were excluded. From November 1, 2007, all CDH patients were treated according to a standardized treatment protocol. Patients were divided into two chronological groups according to their date of birth: without standardized treatment (group 1, Jan 2006-Oct 2007) and with standardized treatment (group 2, Nov 2007-Dec 2009). Outcome measures were mortality by day 28, bronchopulmonary dysplasia (BPD), defined as oxygen dependency at day 28, and need for extracorporeal membrane oxygenation (ECMO) therapy. Uni- and multivariate analyses were performed. Results: 167 patients were included. By day 28, 18% of the infants had died. Of the patients who were alive at day 28, 49% had BPD. An ECMO procedure was performed in 31% of the patients. Overall mortality for all included patients was 22%. In group 1, overall mortality was 33% and in group 2 overall mortality was 12% (p = 0.004). A standardized treatment protocol was independently associated with a reduced risk for mortality by day 28 (OR 0.28, 95% CI 0.11-0.68). Higher observed-to-expected lung-to-head ratios were independently associated with a lower risk for mortality by day 28 (OR 0.97, 95% CI 0.95-0.99), BPD (OR 0.97, 95% CI 0.94-0.98) and need for ECMO (OR 0.98, 95% CI 0.96-0.99). An intrathoracic position of the liver was independently associated with an increased risk for BPD (OR 3.12, 95% CI 1.41-6.90) and need for ECMO therapy (OR 3.25, 95% CI 1.54-6.88). Conclusion: Survival rates in patients with CDH increased significantly after the implementation of a standardized treatment protocol. Copyright http://repub.eur.nl/res/pub/21581/ 2010-11-01T00:00:00Z http://repub.eur.nl/res/pub/28622/ 2010-11-01T00:00:00Z Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research. http://repub.eur.nl/res/pub/30304/ 2008-07-14T00:00:00Z Background: Several concepts of treatment in neonatal ARDS have been proposed in the last years. The present study compared the effects of open lung concept positive pressure ventilation (PPVOLC) with a conventional ventilation strategy combined with administration of two different surfactant preparations on lung function and surfactant homoeostasis. Methods: After repeated whole-lung saline lavage, 16 newborn piglets were assigned to either PPVOLC(n = 5) or surfactant treatment under conventional PPV using a natural bovine (n = 5) or a monomeric protein B based surfactant (n = 6). Results: Comprehensive monitoring showed each treatment strategy to improve gas exchange and lung function, although the effect on PaO2and pulmonary compliance declined over the study period in the surfactant groups. The overall improvement of the ventilation efficiency index (VEI) was significantly greater in the PPVOLCgroup. Phospholipid and protein analyses of the bronchoalveolar lavage fluid showed significant alterations to surfactant homoeostasis in the PPVOLCgroup, whereas IL-10 and SP-C mRNA expression was tendentially increased in the surfactant groups. Conclusion: The different treatment strategies applied could be shown to improve gas exchange and lung function in neonatal ARDS. To which extent differences in maintenance of lung function and surfactant homeostasis may lead to long-term consequences needs to be studied further.