Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH

Reply: "Prenatal Prediction of Pulmonary Hypoplasia: US and MR Imaging Working Together"

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Evidence and patterns in lung response after fetal tracheal occlusion: Clinical controlled study

Purpose: To prospectively assess changes in lung volume in fetuses with isolated severe congenital diaphragmatic hernia (CDH) after fetoscopic endoluminal tracheal occlusion (FETO) compared with those in fetuses with CDH of variable severity who were expectantly managed. Materials and Methods: Informed consent was obtained for this ethics committee-approved study. Forty fetuses with severe CDH (lung-to-head ratio < 1 and intrathoracic liver) who underwent FETO and 18 fetuses with CDH of variable severity who were expectantly managed were longitudinally followed up by using magnetic resonance (MR) imaging volume measurements. Fetuses born prior to 32 weeks were excluded from the study. For those undergoing FETO, lung volume responsiveness was defined as the proportionate increase in observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) at 2-5 weeks after FETO compared with the pre-FETO value. Changes in lung volume were compared by using the Mann-Whitney U test. Regression analysis was used to investigate the effect of pre-FETO O/E ratio of TFLV, gestational age at FETO and at delivery, lung volume responsiveness, occlusion period, side of CDH, and balloon removal prior to delivery on survival. Correlation between post-FETO lung volume responsiveness and gestational age at FETO was performed by using linear regression analysis. Results: A total of 260 MR imaging examinations were performed. For expectantly managed fetuses, O/E ratio of TFLV remained unchanged during gestation, whereas it significantly increased after FETO. Regression analysis demonstrated that pre-FETO O/E ratio of TFLV and lung volume responsiveness at 3.3 weeks after FETO provided significant independent prediction of postnatal survival. There was a significant negative association between lung volume responsiveness and gestational age at FETO. Conclusion: In fetuses with CDH, pre-FETO O/E ratio of TFLV and lung volume at 3.3 weeks after FETO provide independent prediction of postnatal survival. © RSNA, 2009.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Fetal Body Volume at MR Imaging to Quantify Total Fetal Lung Volume - Normal Ranges

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Lung volumes in fetuses with diaphragmatic hernia: comparison of 3D US and MR imaging assessments

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Prenatal prediction of survival in isolated diaphragmatic hernia using observed to expected total fetal lung volume determined by magnetic resonance imaging based on either gestational age or fetal body volume

Objectives: To compare the predictive value of the prenatal observed to expected (o/e) lung volume as measured by fetal magnetic resonance imaging (MRI), based on an algorithm using either the gestational age or fetal body volume (FBV), for neonatal survival of fetuses with isolated congenital diaphragmatic hernia (CDH). Methods: We included 53 fetuses with a prenatal diagnosis of isolated CDH, 26 without and 27 with prenatal tracheal occlusion, who were assessed by fetal MRI, liveborn after 32 weeks, and in whom follow-up until discharge from the neonatal care unit was available. Measurements of lung volumes were expressed as a percentage of the appropriate mean (o/e total fetal lung volume (TFLV) x 100) either for gestational age or for FBV. Measurements of FBV were expressed as a percentage of the appropriate mean (o/e FBV x 100) for gestation. Fetuses with prenatal intervention were all assessed ≥24 h after balloon removal. Regression analysis was used to examine the effect on postnatal survival of either o/e TFLV based on gestational age or based on FBV, gestation at delivery, side of CDH, intrathoracic position of the liver and prenatal intervention. Receiver-operating characteristics (ROC) curves were constructed for the prediction of survival by o/e TFLV based on gestational age and o/e TFLV based on FBV, for all fetuses, as well as for those with o/e FBV between 90 and 110% and those with values beyond that range. A power calculation for the number of fetuses needed to show a difference between the ROC curves was performed. Results: Regression analysis demonstrated that o/e TFLV based on gestational age and on FBV were the only independent predictors of postnatal survival. The area under the ROC curve for prediction of postnatal survival from the o/e TFLV based on gestational age was 0.811, and for that based on FBV it was 0.868 (P 110%, the area for measurements based on gestational age was 0.895 and 0.733, respectively; when based on FBV it was 0.906 and 0.833 (P < 0.01 for all). A minimum of 273 patients would be needed to provide a probability of 90% of detecting a difference between the areas under both ROC curves. Conclusions: In fetuses with isolated CDH, lung volume as measured by fetal MRI was significantly correlated with survival. Prediction tended to be better by o/e TFLV based on FBV rather than gestational age. The difference in the prediction of survival between o/e TFLV based on FBV or gestational age was dependent on fetal biometry. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Quantification of intrathoracic liver herniation by magnetic resonance imaging and prediction of postnatal survival in fetuses with congenital diaphragmatic hernia

Objective: To quantify the degree of intrathoracic liver herniation by magnetic resonance imaging (MRI) and evaluate its effect on postnatal survival in fetuses with isolated congenital diaphragmatic hernia (CDH). Methods: Forty fetuses that were expectantly managed and that were delivered after 32 weeks' gestation were included in this study. On axial T2 weighted MR images the degree of intrathoracic liver herniation was measured by volumetry, using the xyphoid process and thoracic apex as landmarks. The ratio of the volume of the liver that was herniated into the thoracic cavity to the volume of the thoracic cavity was calculated (LiTR). All the fetuses also underwent lung volumetry, and the ratio of the observed/expected total fetal lung volume (o/e TFLV) was calculated. Regression analysis was used to investigate the effect on survival of side of occurrence of CDH, o/e TFLV, LiTR and gestational age at delivery. Receiver-operating characteristics (ROC) curves were constructed to examine the prediction of survival by o/e TFLV or LiTR alone and o/e TFLV and LiTR together. Results: Univariate regression analysis demonstrated that significant predictors of survival were o/e TFLV and LiTR. Multiple regression analysis demonstrated that o/e TFLV and LiTR provided independent prediction of survival. The area under the ROC curve (AUC) for the prediction of postnatal survival from o/e TFLV alone was 0.846 (P < 0.001; SE = 0.062) and the AUC from LiTR alone was 0.875 (P = 0.001; SE = 0.072). The AUC for the prediction of postnatal survival from o/e TFLV and LiTR combined was 0.912 (P < 0.001; SE = 0.045), however it was not statistically significantly different from that of o/e TFLV alone. Conclusion: In expectantly managed CDH fetuses, assessment of LiTR using MRI provided prediction of postnatal survival independently from o/e TFLV. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Fetal Body Volume: use at MR imaging to quantify relative lung volume in fetuses suspected of having pulmonary hypoplasia

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Safe and effective cryopreservation methods for long-term storage of human-amniotic-fluid-derived stem cells

What's already known about this topic? Stem cells can be isolated from amniotic fluid and may be used for cell therapy and tissue engineering applications in perinatal medicine. Clinical implementation requires development of an adapted cell banking system including optimal processing and cryopreservation of amniotic fluid samples, with maintenance of cell viability and characteristics after thawing. What does this study add? We identified three suitable cryopreservation protocols of fresh amniotic fluid samples with high cell recovery rate and unchanged stem cell characteristics post-thawing. One of these is compatible with current good manufacturing practice legislation and can be performed in fetal medicine units without stem cell culture expertise. Objectives: Stem cells (SCs) can be isolated from amniotic fluid (AF) for a variety of perinatal applications. In view of this, we compared different cryopreservation protocols for these AFSCs. Methods: We screened seven freezing and thawing protocols using two well-established human AFSC lines: freezing protocol 1 (FP1), 10% dimethyl sulfoxide (DMSO); FP2, 2.5% DMSO, caspase inhibitor, and catalase; FP3, 5% glycerol, caspase inhibitor, and catalase; FP4, sperm freezing medium; FP5, slow-freezing solution; FP6, ethylene glycol, sucrose, and Ficoll 70; and FP7, vitrification solution. Outcome measures were post-thawing cell viability, recovery, doubling time and mesenchymal SC markers. The three best performing protocols were subsequently tested on cells isolated from clinical consecutive freshly harvested AF samples from two fetal medicine units. Results: Protocols 1, 5, and 6 performed significantly better on well-characterized cell lines. They performed equally well on cell pellets from freshly harvested AF (n=28). Conclusions: We identified three suitable cryopreservation protocols because of high cell recovery and unchanged SC characteristics. Given one of these, the slow-freezing solution, is compatible with current good manufacturing practice legislation, it may be ultimately clinically used.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe