Recurrence after CDH-repair – The Impact of surgical Techniques
K. Zahn, K. Reinshagen, L.M. Wessel
*Dept. of Pediatric Surgery, University-hospital of Mannheim, Germany
Abstract
Patients with congenital diaphragmatic hernia present complex hemodynamic, respiratory and reconstructive challenges. Recurrence is one of the most severe surgical complications after surgical repair of the diaphragmatic defect. In literature the incidence varies depending on operative technique and patient selection between 3.57% and 80%. The purpose of this study was to evaluate the impact of surgical techniques on the rate of recurrence.
We analyzed our patients’ data that are enclosed in a distinct follow-up-program since 1998 regarding incidence and time of recurrence depending on different operative procedures. Four different operative techniques have been used during this period of time: primary closure (100 patients), simple patch (21 patients), ‘oversize patch’ (12 patients) and ‘conical patch’ (169 patients).
We observed 4 cases of recurrence after primary closure (4%), 9 with simple patch (43%), 4 with ‘oversize patch’ (33%) and 15 recurrences after repair with a ‘conical patch’ (8.9%). Recurrence after CDH-repair was observed within 12 months after surgery in 2/3 of the patients, and in 90% within 24 months postoperatively.
After repair with a simple patch the recurrence rate was 45%, which matches reports in literature. By using a ‘conical patch’ the recurrence rate could be lowered significantly by approximately 35%.
pericardial cavity. Closure of the diaphragm takes place in week 8. In one specimen, the rest of the pleuroperitoneal canal (PPC) is preserved as a tiny hole.
The use of array CGH for the detection of genomic imbalances in patients with CDH
Paul D Brady, Jan Deprest, JP Fryns, Joris R Vermeesch.
Centre for Human Genetics, KU Leuven, Belgium
We have been undertaking array CGH using a 1 Mb BAC array for the past five years for postnatal referrals for MR/MCA, and for prenatal referrals on a case-by-case basis. A number of syndromic MR/MCA patients with diaphragmatic hernia included in the observed phenotype, both pre- and post-natally, have been analysed. Since array CGH detects genomic imbalances below the level of resolution of conventional karyotyping, we hypothesise that the association of such imbalances with CDH may assist in the identification of genes, or regions, involved in the development of CDH. We present a summary of the 5 cases in which genomic imbalances were detected by array CGH. These regions include del 2q21.1-2q22.3, del 4p16.3pter (WHS region), dup 7q21.13, del 8p23.3-p22 (8p23.1 deletion region), del 15q26.1qter (15q26 critical region). Deletions of the 15q26.1 region are strongly associated with CDH, with NR2F2 being a strong candidate gene in this region. The 8p23.1 microdeletion is also associated with CDH, as is the Wolf-Hirschhorn Syndrome region on 4p16.3. These findings reinforce the notion that genes involved in the etiology of CDH are located within these regions. However, imbalances of 2q21-q22, and 7q21.13, are not associated with the development of CDH and may also prove to contain dosage sensitive genes involved in the formation of diaphragmatic hernia. The collection of more pathogenic CNVs associated with CDH may help to unravel the genetic networks underlying the cause of this disorder, and provide further insight into the genes involved in development of the diaphragm and lungs.
Abstract
The embryology of lung, pleural cavities and the diaphragm. SEM study in human embryos.
D. Kluth(1) , H. Sydow(2) and G. Steding(2)
(1) Department of Pediatric Surgery , University Hospital Leipzig, Germany
(2) Department of Embryology, Anatomisches Institut der Universität Göttingen, Germany
Detailed knowledge of diaphragmatic development is still controversial. The main source of information are 1) serial sections of human emryos 2) 3D reconstructions based on serial sections 3) Serial sections, 3D reconstructions of serial sections and Scanning electron microscopy (SEM) analysis of 3D preparations of appropriate animal models. In this paper, SEM pictures of human specimen collected in the Department of Anatomy (G.S) are presented.
Material and Methods:
From the above mentioned collection, human embryos were micro dissected (G.S.) and processed for SEM analysis. Embros were between 5 and 8 weeks old. Development of the pleural cavities, the lungs and the diaphragm is depicted.
Results:
The pleural cavity is initially part of the pericardial-peritoneal canal. The lung primordium arouses from the floor of the foregut directly dorsal to the heart. During the formation of the pleural cavities, the lungs are transposed into a lateral and caudal position. At week 6 the pleural cavity is separated from the pericardial cavity. Closure of the diaphragm takes place in week 8. In one specimen, the rest of the pleuroperitoneal canal (PPC) is preserved as a tiny hole.
Discussion:
In this series of human embryos, a detailed description of the development of the pleural cavities, the early lung and the diaphragm is presented. Comparing their development with SEM studies in rat embryos (D.K.) morphological similarities are striking. Due to the lack of human embryos, certain developmental processes as detailed studies of PPC closure are not possible. In this case, complimentary studies in animal models are useful.
Presenting Author:
Dietrich Kluth, MD, PhD
Department of Pediatric Surgery, University Hospital Leipzig,
Liebigstraße 20a, 04103 Leipzig
e-mail: dietrich.kluth@medizin.uni-leipzig.de
Associated Anomalies in Congenital Diaphragmatic Hernia
Katharina Link, Sven Kehl, Thomas Schaible, Wolfgang Neff, Marc Sütterlin, Jörn Siemer
Perinatal-Center Mannheim, Germany
Objective: To evaluate the frequency and impact of associated malformations in fetuses and newborns with congenital diaphragmatic hernia (CDH).
Methods: Between 2001 and 2008, 362 cases of CDH were treated at the Mannheim Perinatal Center. All prenatally and postnatally detected anomalies were considered. Neonatal survival was evaluated with regard to observed malformations.
Results: In 143 of the 362 cases with CDH at least one additional anomaly was found. All together, 272 malformations, besides the CDH, were detected (25% of them prenatally by ultrasound). 62 newborns were compromised by major anomalies. Over all, observed anomalies were heterogenic, and cardiovascular malformations were found most. Newborns with major anomalies showed significant lower survival rates than newborns with CDH and no additional malformations.
Conclusion: Associated anomalies are frequent in newborns with CDH. Especially cardiovascular abnormalities need to be considered. Additional major malformations impair neonatal outcome.
PERINATAL RISK FACTORS AND MORTALITY IN CONGENITAL DIAPHRAGMATIC HERNIA (CDH) INFANTS.
Andrea Conforti, Irma Capolupo, Maria Paola Ronchetti, Francesco Morini, Laura Valfrè, Lorna Spagnol, Carlo Corchia, Pietro Bagolan
Background: since the introduction of new therapeutic approaches, the survival rate in CDH infants has dramatically increased. Nonetheless, mortality is still reported up to 40%. Aim of the study was to evaluate the role of different perinatal risk factors, possibly related to higher mortality rate.
Patients and methods: all patients treated for high risk left CDH between 2000 and 2007 were included. High risk was defined CDH with prenatal diagnosis and/or respiratory symptoms within 6 hours of life.
Risk factors evaluated were gestational age (<37 vs. ≥37 wks), birth weight (<2500 vs. ≥2500 gr), associated cardiac abnormalities, liver in the chest, pulmonary hypertension and the diaphragmatic defect size (patch repair needed). Statistical analysis was performed Fisher exact test and calculation of relative risk (RR).
Results: in the study period, 143 high risk left CDH infants were observed. Overall mortality rate was 35%, 38 newborns died before and 12 after surgery. Results are summarized below.
Died 50 pts | Alive 93 pts | p | RR | CI 95% | |
Gestational age (<37 vs. ≥37 wks) | 15/35 | 11/82 | 0.01 | 1.93 | 1.25 – 2.97 |
Birth weight (<2500 vs. ≥2500 gr) | 15/35 | 12/81 | 0.02 | 1.84 | 1.19 – 2.85 |
Cardiac abnormalities | 11/39 | 2/91 | 0.0002 | 2.91 | 2.07 – 4.10 |
Liver in the chest | 43/7 | 36/35 | 0.0001 | 4.98 | 2.20 – 10.30 |
Pulmonary hypertension | 40/10 | 22/71 | 0.0001 | 5.81 | 3.05 – 11.05 |
Defect size | 10/2 | 21/72 | 0.0001 | 11.94 | 2.77 – 51.35 |
Conclusion: all risk factors considered were significantly associated with a higher mortality. The need of patch repair was the main mortality predictive factor in operated patients. Risk factors highly related to mortality rate might be counseled at birth or aa soon as become evident.
Experience with isolated diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO) by the FETO consortium
UZ Leuven, Leuven, Belgium: Elise Done’, Tim Van Mieghem, Leonardo Gucciardo, Roland Devlieger, Jan Deprest
King’s College Hospital, London, UK: Jacques Jani, Catalina Valencia, Kypros Nicolaides
Hospital Clinic, Barcelona, Spain: Josep-Maria Martinez, Rogelio Cruz, Eduardo Gratacos.
Contact: jan.deprest@uzleuven.be
Objective: To examine operative and perinatal aspects of current experience with fetoscopic endoluminal occlusion of the trachea (FETO) in congenital diaphragmatic hernia (CDH).
Methods: Multicenter study in singleton pregnancies with CDH treated by FETO. The entry criteria for FETO were severe CDH on the basis of sonographic evidence of intrathoracic herniation of the liver and low lung area to head circumference ratio (LHR) defined as the observed to the expected normal mean for gestation (o/e LHR) equivalent to an LHR of 1 or less at mid-gestation.
Results: FETO was carried out in 210 cases, including 175 cases with left-sided, 34 right-sided and one with bilateral CDH. FETO was performed at a median gestation of 27.1 (range 23.0-33.3) weeks. The median duration of FETO was 10 (range 3-93) minutes. Spontaneous preterm prelabor rupture of membranes (PPROM) occurred in 99 (47.1%) cases at 3-83 (median 30) days after FETO and it was within 3 weeks of the procedure in 35 (16.7%) cases. Removal of the balloon was prenatal either by fetoscopy or ultrasound-guided puncture, intrapartum by EXIT or postnatal either by tracheoscopy or percutaneous puncture. Delivery was at 25.7-41.0 (median 35.3) weeks and it was before 34 weeks in 65 (30.9%) cases. In 204 (97.1%) cases the babies were live born and 98 (48.0%) were discharged from the hospital alive. On the basis of the relation between survival and o/e LHR in expectantly managed fetuses with CDH, as reported in the antenatal CDH registry, we estimated that in fetuses with left CDH treated with FETO the survival rate increased from 24.1% to 49.1% and in right CDH survival increased from 0% to 35.3% (p<0.001).
Conclusions: FETO in severe CDH is associated with a high incidence of PPROM and preterm delivery but a substantial improvement in survival compared to earlier data from the antenatal CDH registry
Repetitive MRI measurements of lung volume in fetuses with CDH to investigate the serial time course of pulmonary hypoplasia during gestation
A.K. Kilian, K.A. Büsing, A. Bauer, T. Schaible, S.O. Schönberg, K.W. Neff / Mannheim
Purpose
The individual development of lung volumes in fetuses with congenital diaphragmatic hernia (CDH) in serial time course of pregnancy is unknown. The purpose of the presented study was to investigate the degree of impairment of pulmonary development with fetal lung hypoplasia using serial MRI to evaluate fetal lung volume (FLV) during gestation.
Materials and Methods
43 fetuses with CDH with a gestational age of 23-38 (mean 29.7) weeks were examined with MRI to measure the FLV. FLV was calculated absolutely and additionally was expressed as a proportion of the age-related predicted data (observed/expected FLV=relative FLV, rFLV). All 43 fetuses received a minimum of two MRI examinations during pregnancy with at least 4 weeks between the examinations.
Results
In all 43 fetuses with CDH there was an increase of 9% (range 1.5-24.3%) of the absolute FLV. 28/43 fetuses showed a decrease of the mean relative FLV from 32.7 to 24.6% (difference 8.1%, range 1.1-13.7%). 12 fetuses showed increasing mean rFLV from 27.1 to 31.9% (difference 4.8%, range 1.7-10.4%) and 3 revealed stable values in rFLV. Overall there was a difference in individual values of rFLV up to 75%.
Conclusion
There is a wide variation in fetal lung volume development in children with CDH in serial time course during pregnancy. In our cohort there are decreasing, stable and increasing rFLVs up to an individual difference of 75%. All fetuses showed an increase of the absolute FLV, but 2/3 of the fetuses had decreasing relative FLVs, which has to be considered in therapeutic options.
A der (5) t(5;12) mosaicism in a prenatal Congenital Diaphragmatic Hernia-case: The usefulness of high-resolution SNP-arrays
D.Veenma1,2, L.W.J.E.Beurskens2, H.Douben1, B.Eussen1 , L.Govaerts1, M.H.Lequin3, A.R.M. van Opstal1. D.Tibboel2 and A. de Klein1
Department of Clinical Genetics1, Pediatric Surgery2 and Radiology3, Erasmus MC, Rotterdam
Up until now, the multifactorial aetiology of CDH is still poorly understood, although strong evidence for a genetic component is suggested. Using classic cytogenetic techniques such as G-band karyotyping and targeted FISH, chromosomal abnormalities are detected in 10-20% of (complex) CDH cases. However due to the advancement in molecular techniques such as SNP-arrays, also the smaller and more cryptic aberrations can be identified nowadays.
A special form of a genetic aberration is mosaicism which is defined as the presence of more than one genetically distinct population of somatic cells in a single organism .CDH caused by mosaicism, specifically of tetrasomy 12p, is rather common within the Pallister-Killian syndrome. However, only a few other mosaic chromosomal abnormalities have been described in relation to CDH and never a mosaic chromosomal translocation (der(5)t(5;12). Difficulties in detecting low-level mosaicism (for clinically significant chromosome abnormalities) could partly account for these low-incidences. Also, performance of thorough postmortem follow-up of the mosaic genetic aberration in multiple tissues is performed rarely.
Here we report the detailed clinical, cytogenetic and molecular analysis (FISH, SNP array) of a prenatally detected complex-CDH case with a low-mosaic loss of most of the 5p chromosome (der (5) t(5;12)(p13.2;p13)). High resolution SNP array was sensitive enough to detect this low-mosaic (20%) in blood. Since this case concerned a post-zygotic mutation, we investigated the mosaic rate in the phenotypically affected tissues such as lung and diaphragm. Unexpectedly, we found a similar percentage of loss of chromosome 5p between normal and affected tissues. Therefore, an expected linear correlation between phenotypically abnormal tissues and chromosomal mutation rates were not found in this case-report.
Prenatal prediction of chronic lung disease based on fetal MR lung volumetry in survivors with congenital diaphragmatic hernia
A. Debus, C. Hagelstein, A.K. Kilian, K.A. Büsing, T. Schaible, S.O. Schoenberg, K.W. Neff, Mannheim
Purpose
To predict chronic lung disease (CLD) in survivors with congenital diaphragmatic hernia (CDH) based on the results of antenatal observed to expected MR fetal lung volume measurements (o/e MR FLV).
Materials and methods
Absolute and o/e MR FLV were calculated in 172 fetuses with CDH between 23 and 39 weeks gestation (33.5 ± 2.6 weeks) using multiplanar T2-weighted half-fourier acquired single-shot turbo spin echo (HASTE) imaging. A three-fold grading (mild, moderate and severe) of chronic lung disease was performed based on the need for supplemental oxygen at days 28 and 56 after delivery.
Results
Survival at discharge was 86.0 % (148/172 patients). 82/148 survivors (55.4 %) developed CLD. Mean o/e MR FLV of patients with CLD was significantly smaller (24.1 ± 7.5 %) compared to the mean o/e MR FLV of 66 patients who did not develop CLD (38.8 ± 12.4 %, p < 0.05). Grading of CLD revealed significant differences (p < 0.05) of the o/e MR FLV between 46 patients with mild CLD (26.3 ± 7.8 %) compared to 23 patients who developed moderate CLD (21.7 ± 6.3 %) and 13 patients with severe CLD (20.2 ± 5.0 %). No statistically significant differences in FLV could be demonstrated between the moderate and severe stages of CLD.
Conclusion
The prenatally assessed o/e MR FLV is a reliable and significant predictor of an impaired lung development with CLD in survivors with CDH. Parental counseling and early neonatal therapeutic decisions can additionally be based on the prenatally determined FLV.
Correlation between the observed to expected ratio of the sonographic LHR and the MRI total fetal lung volume in isolated congenital diaphragmatic hernia.
I.SANDAITE*, F.CLAUS†, T.VAN MIEGHEM*, L .GUCCIARDO*, E.DONE*, B.DE DOBBELAER† and J.A.DEPREST*
*Unit of Prenatal and Gynecological Ultrasound and Fetal Therapy, Department of Obstetrics and Gynecology, † Department of Radiology - University Hospitals Gasthuisberg, Leuven, Belgium
PURPOSE:
Sonographic measurement of the fetal lung area to head circumference ratio (LHR) and the position of the liver is the most widely used method to predict the prognosis of congenital diaphragmatic hernia (CDH). Magnetic resonance imaging (MRI) allows accurate volumetry of the total fetal lung volume (TFLV). The objective of this study is to correlate the observed to expected ratio (O/E) of the LHR and the TFLV in a consecutive series of 158 patients.
METHODS:
Kehl S, Hart N, Schaible T, Neff W, Sütterlin M, Siemer J
Lung volume assessment by 3D ultrasound in congenital diaphragmatic hernia
Introduction:
The congenital diaphragmatic hernia has got an incidence of 1:2500. The defect of the diaphragm leads to an herniation of abdominal organs. This causes serious impairment of lung development, affecting the ipsilateral lung more than the contralateral one. This is associated with a high postnatal mortality due to pulmonary hypoplasia. The assessment of the lung by magnetic resonance imaging has been established as golden standard. A reliable measurement is important for the prediction of postnatal outcome. The aim of our study was to prospectively assess the fetal lung volume by 3D ultrasound and to verify the reliability of this method by comparing with the volume measured by magnetic resonance imaging.
Material and methods:
The contralateral fetal lung volume was measured by 3D ultrasound in more than 60 examinations. This lung volume assessment was compared with the magnetic resonance imaging measurement from the some day. For the 3D ultrasound the Voluson 730 Expert was used. The 4D View Software with the virtual organ computer-aided analysis (VOCAL) method was used to measure lung volume. For the magnetic resonance imaging calculation multiplanar T2 HASTE and true-FISP sequences were performed by a body-phased-array coil.
Results:
The assessment of the contralateral lung volume by 3D ultrasound achieved similar lung volumes compared to the magnetic resonance imaging.
Conclusions:
After an initial learning curve the contralateral lung volume assessment by 3d ultrasound in congenital diaphragmatic hernia provide reliable measurement. Further studies have to show their prediction of postnatal outcome.
Maternal hyperoxygenation test in fetuses with congenital diaphragmatic hernia as a predictor of neonatal outcome.
Elisa Done’, Leonardo Gucciardo, Tim van Mieghem, Karel Allegaert, Anne Debeer, Gunnar Naulaers, Dominique van Schoubroeck, Roland Devlieger, Jan Deprest
University Hospitals Leuven, Belgium
Objective: To predict neonatal pulmonary outcome in fetuses with severe congenital diaphragmatic hernia (CDH), using changes in fetal pulmonary artery reactivity to maternal hyperoxygenation. We have earlier shown that this test predicts better after balloon removal (around 34 weeks), and is independently predictive as compared to lung-to-head ratio.
Methods: 59 fetuses with CDH were assessed after 30 wks gestational age (GA). Fetuses were either expectantly managed (n=27) or underwent tracheal occlusion (n=32, test was performed after balloon removal). Doppler measurements of pulsatility index (PI) in the 1st branch of the contralateral pulmonary artery were performed before and after maternal administration of 60%O2 by mask. Outcome measures included % of PI decrease after O2 exposure (delta PI), expected lung-to-head-ratio (O/E LHR), neonatal survival (at discharge) and occurrence of severe pulmonary hypertension (PHT), defined as the presence of a pre- /postductal O2 saturation gradient of >20mmHg not responding to NO therapy.
Results: The oxygenation test was performed at a median GA 33.6 (+SD) wks and median GA at delivery was 37.1 (+SD) wks. 36 fetuses (61%) survived until discharge and had a significantly higher O/E LHR and deltaPI values compare to the ones who died (n=23,39%). Only one of the survivors(2%) and 20/23 fetuses (87%) out of those who died after birth, had severe PHT, with lower O/ELHR and delta PI values compared to the 23 cases who did not have PHT or those who responded to NO therapy. In 15/59 fetuses (25%) it no echocardiographic data were available.
Data (mean ± SD) and significance levels are displayed in table 1 and figures 1a-b-c-d. Discriminant analysis confirmed both the O/E LHR and delta PI as being independent predictors of outcome.
Conclusion:
Third trimester O/E LHR and Delta PI are both predictive parameters for neonatal outcome in fetuses affected by isolated CDH.
| Survivors | Not survivors |
| n=36 (61%) | n=23 (39%) |
O/E LHR | 43% 0.15 | 27% 0.10 |
Delta PI | 24% 0.11 | 13% 0.11 |
| Not severe PHT | Severe PHT |
| n=23 (52%) | n=21 (58%) |
O/E LHR | 42% 0.13 | 42% 0.13 |
Delta PI | 24% 0.10 | 24% 0.10 |
Table 1: O/E LHR and PI values (mean-SD) in patients, according to outcome.
a b c d
Figure 1(a-b): Oneway ANOVA analysis of the correlations between delta PI and neonatal outcome-occurrence of severe PHT (p 0.0008- p < 0.0013); 1(c-d): Idem for O/E LHR (p < 0.0001- p 0.0012).
Minimally invasive CDH repair – Focus on perioperative
management as a new aspect ???
C. Gernoth, E. Thil
Clinic of Anaesthesiology and Intensive Care Medicine
University Hospital Mannheim, Germany
Background and goals of perioperative care
Minimally invasive surgery (MIS) for latepresenting congenital diaphragmatic
hernia (CDH) has been implemented previously, but few neonatal cases have
been reported. Criteria for the decision open vs. endoscopic repair remain
uncertain, no data exists about optimized perioperative anaesthetic
management.
Main goals are to minimise harm caused by carbon dioxide insufflation and to
improve surgical conditions for hernia reduction.
Pathophysiologic aspects under review of current literature
Currently the use of MIS in newborns remains controversial. The insufflation
of carbon dioxide can rapidly impair hemodynamic and respiratory conditions
in this fragile patient collective. Besides local effects of increased
intrathoracic and intraabdominal pressure, increasing partial pressure of CO
levels causing respiratory acidosis, increasing systolic pulmonary artery
pressure (PAP), aggravating right-to-left-shunting and finally hypoxemia are
the effects that have to be avoided. Starting surgery at a stabilised point of
time helps to reduce negative outcomes, also standardized preoperative
ventilation strategies are important to minimise ventilator induced lung injury
(VILI)[1,2].
Own Experiences in context and recommandations
But nevertheless intraoperative standardized ventilation strategies
(compliance adapted peep concept), the use of volatile anesthetics to reduce
vascular resistance and optimized fluid management (echocardiographic
supplemented ) can be essential during this two hour lasting procedure to
improve outcome in this fragile patients. What intraabdominal pressure can
be tolerated, is muscle relaxation everything or do we gain lower rates for
abdominal patches at the price of increasing rates of recurrent diaphragmatic
hernia cases, renal impairment or bowel complications ?
In consideration of the mentioned aspects of pre- and postoperative care our
expanded intraoperative care protocol is presented focussing on improved
outcome for this particular group of critically ill neonates.
[1]
aspects under review of current literature
Own Experiences in context and recommendations
References
Gomes Ferreira C, Reinberg O, Becmeur F, Allal H, De Lagausie P, Lardy H, Philippe P, Lopez M, Varlet F, Podevin G, Schleef J, Schlobach M.
Surg Endosc. 2009 Jul;23(7):1650-9. Epub 2009 Mar 5.
[2]
Guner YS, Chokshi N, Aranda A, Ochoa C, Qureshi FG, Nguyen NX, Grikscheit T, Ford HR, Stein JE, Shin CE.
J Laparoendosc Adv Surg Tech A. 2008 Dec;18(6):875-80.
[3]
Bagolan P et al.
J Pediatr Surg. 2004 Mar;39(3):313-8; discussion 313-8. Links
Contact:
christian.gernoth@umm.de
christian.gernoth@neckar-odenwald-kliniken.de
Elke.thil@
________________________________________________________
Measurement of functional residual capacity and lung compliance prior and after surgical repair of congenital diaphragmatic hernia might help improve outcome: observations in 10 patients
Kathrin Stadler[1], Jürgen Dinger1, Dietmar Roesner[2]
Background/Purpose: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival. The knowledge on lung mechanics and lung volumes in these patients with hypoplastic lungs is still limited. Therefore, we performed measurements of functional residual capacity (FRC), compliance of the respiratory system (CRS), and tidal volume in 10 infants (gestational age, 33 to 41 weeks; birth weight, 2.040 to 3.875g) before and after surgical repair of neonatal CDH.
Methods: We studied the influence of different levels of positive end-expiratory pressure (PEEP) and suction via inserted ipsilateral chest tube connected to a water seal on lung volume and lung mechanics. A computerized tracer gas (SF6) washout method was used for serial measurements of FRC. Compliance of the respiratory system was determined according to insufflatory method.
Results: We found a preoperative compliance between 1.4 and 3.9 mL/kPa/kg and a preoperative FRC between 8.7 and 14.1 mL/kg, indicating severe hypoplasia of the lungs in all patients. Immediately after surgical repair of CDH - under mechanical ventilation at 4 cm of water of PEEP and at -10 cm of water of suction via chest drain with the need of high fraction of inspired oxygen - compliance decreased to 85% (78% to 97 %) of preoperative value, and FRC increased to 132% (107% to 154%) of preoperative value. After reduction of PEEP from 4 to 2 or 1 cm of water and lowering suction from -10 cm of water to 0 cm of water, FRC decreased to 103% (80% to 125%) of preoperative value and compliance, and tidal volume improved to 130% (110% to 147%) of preoperative value. These changes yielded in increased alveolar ventilation, correction of acidosis and improvement in oxygenation. During the first days after surgery inadequate high PEEP or strong suction via chest tube drainage resulted in increase in FRC paralleled by decrease in compliance indicating overdistension of these hypoplastic lungs.
Conclusions: The data show that overdistension of hypoplastic lungs in infants with CDH can be detected and excluded by repeated measurements of FRC and compliance in these critical ill infants. These data might help setting appropriate ventilator parameters for gentle ventilation and thereby improve gas exchange and outcome.
1Clinic of Paediatrics, 2 Clinic of Paediatric Surgery,
Medical Faculty “Carl Gustav Carus”,Technical University of Dresden,
Fetscherstr. 74, 01307 Dresden, Germany
_______________________________________________________________
Title: Risk factors for chronic lung disease and early mortality in infants with congenital diaphragmatic hernia
Author: CDH Euro Consortium
Background: Congenital diaphragmatic hernia (CDH) is associated with a mortality of 10-35% in live-born patients. CDH survivors are at risk of developing long-term pulmonary sequelae, such as chronic lung disease (CLD), asthmatic symptoms, and recurrent respiratory tract infections.
Objective: to describe the incidence and risk factors for CLD and death at or before 28 days of life in infants with CDH.
Design/Methods: Newborns with unilateral CDH born between 2005 and 2007 at the participating centres of the CDH Euro Consortium were eligible for inclusion. Data on survival, pulmonary status at day 28, ventilation treatment, and basic patient characteristics were collected. CLD and death at or before day 28 were the primary endpoints. CLD was defined as oxygen dependency at day 28. The severity of CLD was graduated at day 56 according to the definition of Bancalari. Univariate analyses were performed, using Chi-square test and Mann-Whitney tests. Logistic regression analysis was performed for baseline variables which were significant in univariate analysis.
Results: In total,>369 patients were included in the analysis. At day 28, 29% of the patients had CLD and 30% of the patients had died. Of the patients with chronic lung disease, 44% had mild, 19% had moderate and 29% had severe CLD. An ECMO procedure was performed in 22% of the infants. Risk factors for mortality at or before day 28 were HFO as initial ventilation mode (OR 8.2, 95%CI 4.3-15.8), an intrathoracal position of the liver (OR 4.9, 95% CI 2.3-10.4) and being inborn (OR 4.2, 95%CI 1.4-12.6). Risk factors for chronic lung disease were an intrathoracal position of the liver (OR 5.9, 95% CI 3.2-10.8) and a higher gestational age at birth (OR 0.8, 95% CI 0.7-0.9).
Conclusion: This study shows important risk factors for CLD and mortality. Unexpectedly, high frequency oscillatory ventilation as an initial ventilation mode was an important risk factor for death at or before day 28. Multicenter randomized clinical trials are urgently needed to study this prospectively. In future, this may lead to standardized treatment protocols and a reduction of pulmonary morbidity in CDH survivors.
SURGICAL ASPECTS IN CONGENITAL DIAPHRAGMATIC HERNIA
Pietro Bagolan
Department of Medical and Surgical Neonatology
Bambino Gesù Children’s Research Hospital
Newborn Surgery Unit
Rome- Italy
Advances in neonatal intensive care and ventilation have greatly improved the outlook for live-born infants with congenital diaphragmatic hernia (CDH). Current management strategy of CDH still remains challenging but also lacking in evidence based practice either for surgeon or for neonatologist.
Operative timing is currently managed with cardiopulmonary stabilization (average time 6.3 days in 4204 operated patients from CDH study group) in spite of two randomized trials concluded that there is no difference in survival and ECMO use, irrespective of surgical timing. Indication to surgical repair is also controversial as suggested by the more than 30 different ways to give it. Surgical repair is performed in operating theatre but sometimes the patient is better managed in neonatal intensive care unit (NICU) to avoid any harmful transport and allow high frequency oxillatory ventilation HFOV during operation. The use and indication criteria of ECMO are also debated. When indicated it is recently more frequently used during preoperative stabilization (85% of those requiring ECMO) and more than 50% of them undergo repair while on ECMO. The risk of hemorrhage in this group of patients gave rise to a few strategies to decrease bleeding but a prospective randomized trial found that there were no difference in hemorrhagic complications (including intraventricular hemorrhage) between the placebo and the aminocraproic acid treated groups. However the use of aminocaproic acid has become a standard procedure when surgical repair has to be performed on ECMO due to the significant lower rate of surgical site bleeding in treated patients. The subcostal incision on the ipsilateral side of the defect is the approach used by 90% of surgeons with two main operative strategies: primary closure of the defect with nonabsorbable suture or prosthetic patch (of different materials) tailored to restore a more natural, tension free diaphragm shape (2016, 50% of operated patient from CDH study group). Recent effort has also focused on the use of bio-prostheses aimed to provide a “substitute” that grows with the patient. Muscle flaps are sometimes performed for very large defects or agenesis and abdominal fascia occasionally not closed to avoid respiratory compromise due to excessive abdominal pressure increase. Primary tube thoracostomy is infrequently indicated when intraoperative complications, such as hemorrhage or uncontrolled air leak, are absent. Minamilly invasive surgery (more often thoracoscopic than laparoscopic) has also been used in children with CDH even though its application in high risk infant must be interpreted with caution.
Recurrence of diaphragmatic hernia, ranging from 14% to 22% with a reported average latency between 4 and 8 moths, could be prevented if reconstructed diaphragm grows with patients. Prompt or delayed repair with close clinical and radiological monitoring of the recurrence (and sometimes re-recurrence) is debated as well as its surgical approach (thoracic or abdominal).
Timing, stabilization, site of operation, use-timing-associated therapy of ECMO, patch type and indication, thoracic tube, minimal invasive surgery are all controversial issues for surgeon. Some of these, such as delayed surgery and ECMO, are considered a cornerstone and a key component of stabilization. Other choices of the interventional treatment are still largely based on the belief of individual team leaders.
PIETRO BAGOLAN: CDH PUBLICATIONS
1 Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time.
Morini F, Capolupo I, Masi R, Ronchetti MP, Locatelli M, Corchia C, Bagolan P.
J Pediatr Surg. 2008 Feb;43(2):380-4.
2 Predictors and statistical models in congenital diaphragmatic hernia.
Casaccia G, Ravà L, Bagolan P, di Ciommo VM.
Pediatr Surg Int. 2008 Apr;24(4):411-4. Epub 2008 Feb 16.
3 Neonatal-onset nemaline myopathy mimicking congenital diaphragmatic hernia.
Danhaive O, Lozzi S, D'amico A, Devito R, Boldrini R, Corchia C, Bagolan P, Bertini E.
J Pediatr Surg. 2007 Jul;42(7):E19-22.
4 Congenital diaphragmatic hernia in CHARGE syndrome.
Casaccia G, Digilio MC, Seymandi PL, Bagolan P.
Pediatr Surg Int. 2008 Mar;24(3):375-8. Epub 2007 Jun 19
05 Lung volumes and distribution of ventilation in survivors to congenital diaphragmatic hernia (CDH) during infancy.
Dotta A, Palamides S, Braguglia A, Crescenzi F, Ronchetti MP, Calzolari F, Iacobelli BD, Bagolan P, Corchia C, Orzalesi M.
Pediatr Pulmonol. 2007 Jul;42(7):600-4.
06 Long-term follow up of infants with congenital diaphragmatic hernia.
Bagolan P, Morini F.
Semin Pediatr Surg. 2007 May;16(2):134-44. Review.
07 Pleural effusion requiring drainage in congenital diaphragmatic hernia: incidence, aetiology and treatment.
Casaccia G, Crescenzi F, Palamides S, Catalano OA, Bagolan P.
Pediatr Surg Int. 2006 Jul;22(7):585-8. Epub 2006 Jun 13.
08 Corticosteroids for fetuses with congenital diaphragmatic hernia: can we show benefit?
Lally KP, Bagolan P, Hosie S, Lally PA, Stewart M, Cotten CM, Van Meurs KP, Alexander G; Congenital Diaphragmatic Hernia Study Group.
J Pediatr Surg. 2006 Apr;41(4):668-74; discussion 668-74.
09 Mothers' adaptation to antenatal diagnosis of surgically correctable anomalies.
Aite L, Zaccara A, Nahom A, Trucchi A, Iacobelli B, Bagolan P.
Early Hum Dev. 2006 Oct;82(10):649-53. Epub 2006 Feb 28
10 Distal 4p microdeletion in a case of Wolf-Hirschhorn syndrome with congenital diaphragmatic hernia.
Casaccia G, Mobili L, Braguglia A, Santoro F, Bagolan P.
Birth Defects Res A Clin Mol Teratol. 2006 Mar;76(3):210-3
11 Parents' informational needs at the birth of a baby with a surgically correctable anomaly.
Aite L, Zaccara A, Trucchi A, Nahom A, Iacobelli B, Bagolan P.
Pediatr Surg Int. 2006 Mar;22(3):267-70. Epub 2006 Jan 21.
12 Birth weight and McGoon Index predict mortality in newborn infants with congenital diaphragmatic hernia.
Casaccia G, Crescenzi F, Dotta A, Capolupo I, Braguglia A, Danhaive O, Pasquini L, Bevilacqua M, Bagolan P, Corchia C, Orzalesi M.
J Pediatr Surg. 2006 Jan;41(1):25-8; discussion 25-8.
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13 Effects of surgical repair of congenital diaphragmatic hernia on cerebral hemodynamics evaluated by near-infrared spectroscopy.
Dotta A, Rechichi J, Campi F, Braguglia A, Palamides S, Capolupo I, Lozzi S, Trucchi A, Corchia C, Bagolan P, Orzalesi M.
J Pediatr Surg. 2005 Nov;40(11):1748-52.
14 Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia.
Bagolan P, Casaccia G, Crescenzi F, Nahom A, Trucchi A, Giorlandino C.
J Pediatr Surg. 2004 Mar;39(3):313-8; discussion 313-
15 Antenatal diagnosis of diaphragmatic hernia: parents' emotional and cognitive reactions.
Aite L, Trucchi A, Nahom A, Casaccia G, Zaccara A, Giorlandino C, Bagolan P.
J Pediatr Surg. 2004 Feb;39(2):174-8; discussion 174-8.
16 Antenatal diagnosis of surgically correctable anomalies: effects of repeated consultations on parental anxiety.
Aite L, Trucchi A, Nahom A, Zaccara A, La Sala E, Bagolan P.
J Perinatol. 2003 Dec;23(8):652-4.
17 Severe congenital diaphragmatic hernia (CDH): a critical analysis of eight years' experience.
Bagolan P, Casaccia G, Nahom A, Trucchi A, Zangari A, Laviani R, Pirozzi N, Di Liso G, Orzalesi M.
Eur J Pediatr Surg. 2002 Apr;12(2):95-100
18 Multidisciplinary management of fetal surgical anomalies: the impact on maternal anxiety.
Aite L, Trucchi A, Nahom A, Spina V, Bilancioni E, Bagolan P.
Eur J Pediatr Surg. 2002 Apr;12(2):90-4.
19 Maximal oxygen consumption and stress performance in children operated on for congenital diaphragmatic hernia.
Zaccara A, Turchetta A, Calzolari A, Iacobelli B, Nahom A, Lucchetti MC, Bagolan P, Rivosecchi M, Coran AG.
J Pediatr Surg. 1996 Aug;31(8):1092-4; discussion 1095
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STUDY OF GASTROESOPHAGEAL AND INTESTINAL INNERVATION AND MOTILITY IN RATS AND BABIES WITH CONGENITAL DIAPHRAGMATIC HERNIA
Pederiva F, Aras Lopez R, Martinez L, Tovar JA
Department of Pediatric Surgery and Research Laboratory, Hospital Universitario La Paz, Madrid, Spain
BACKGROUND: Gastroesophageal reflux, late intestinal obstruction, distension and constipation have been described in survivors of congenital diaphragmatic hernia (CDH), likely related to motor disfunction. Gastroesophageal and intestinal neural cells come from vagus nerve and belong to the enteric nervous system. The present study tested the hypothesis that the enteric nervous system might be abnormal in babies and rat fetuses with experimental CDH.
MATERIAL AND METHODS: Sections of small and large intestine from 6 newborns dead of CDH and 6 controls were stained with anti-neurofilament antibody and the amount of neural tissue over the muscle surface was measured. Pregnant rats received either nitrofen or vehicle on E9.5. Embryos were recovered on E15, E18 and E21 and sections of the control and CDH esophagus, small bowel and large intestine were stained for anti-PGP 9.5 marker, NADPH-diaphorase (NADPHd) and acetylcholinesterase (AChE). The proportion of neural tissue over the muscle surface was measured and the NADPHd- and AChE-positive motor endplates (MEPs) per section were counted. Whole mount preparations of E18 and E21 stomachs were stained for AChE and the intramural ganglia were counted and measured. The frequency of rat esophagus and small bowel contractions was recorded under inverted microscope for 5-min periods. Comparison between groups was made with non-parametric tests.
RESULTS: No differences were found in the percentage of neural tissue in the small and large bowel in babies. The relative neural/muscle surface and the number of NADPHd- and AChE-positive MEPs were decreased on E15 and E18 in the esophagus, small and large intestine of embryos with CDH, but they tended to improve on E21 in the esophagus and small bowel, following the human pattern; whereas they remained decreased in the colon. The number and the mean surface of stomach ganglia were significantly smaller in E18 and E21 fetuses with CDH. The number of contractions per minute was decreased in esophagus and small bowel of animals with CDH at all endpoints.
CONCLUSIONS: The intrinsic innervation of the esophagus and intestine and their development are abnormal in rat fetuses with CDH. Although the neural network tends to normalize near term both in rats and in babies, the contractility is still decreased. These anomalies could contribute to explain the long-term gastrointestinal morbidity in this condition.
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TOTAL Trials for moderate and severe pulmonary hypoplasia as a consequence of isolated congenital diaphragmatic hernia – 9 months after kick off.
Jan Deprest, Kypros Nicolaides, Yves Ville, Dick Tibboel, Marian Verkerk, Catarina Rodriques, Eduardo Gratacos.
University Hospitals Leuven (Belgium), King’s College London(United Kingdom), Necker Paris(France), Erasmus Rotterdam (Holland), UMC Groningen (Holland) and Hospital Clinic Barcelona (Spain).
Background: The diagnosis of isolated Congenital Diaphragmatic Hernia (iCDH) can be made in the prenatal period. Its outcome can be predicted in the prenatal period by determination of liver position and measurement of the observed/expected lung area to head circumference ratio (O/E LHR) which is a measure of pulmonary hypoplasia [1] [2]. The proposers have extensive experience with prenatal intervention, consisting of percutaneous fetoscopic endoluminal tracheal occlusion (FETO) with subsequent removal of the balloon [3]. When offered to fetuses with a LHR<1.0 and liver up (severe pulmonary hypoplasia), survival seems to be improved and the occurrence of broncho-pulmonary dysplasia decreases by 30% as compared to same severity cases. Outcome is dependent on O/E LHR prior to occlusion and gestational age at birth [4]. In other words, a firmer lung response can be expected in fetuses with larger lung size [5]. However clinical experience remains unsubstantiated by an appropriately designed trial.
Methods:We hypothesize that fetuses with moderate iCDH (=O/E LHR 25-34.9%, irrespective of liver position or O/E LHR 35-44.9% with liver up) may have less BPD following FETO, as compared to fetuses expectantly managed during pregnancy. To avoid the consequences of postprocedural membrane rupture, the balloon will be placed between 30-32+6 wks and removed between 34-35+6 wks. In case of a 20% decrease, and with a sequential analysis (first look n=42, in total 53 patients in each arm [alpha=0.05; beta=0.8]). Postnatal management will be according to the standardized protocol drafted by an external committee. This multicenter trial is up and running and 17 patients are enrolled. Practical issues on trial participatin will be discussed.
Several issues precluded so far the establishment of a trial in the group with severe pulmonary hypoplasia (O/E LHR<25%). At this moment, the E.C. of the KU Leuven is looking at a new proposal for a trial in severe CDH that would meet earlier objections. An ethical framework for this has been proposed for that purpose. The endpoint of this second trial is survival, and the hypothesis is that FETO would nearly double survival from an expected survival rate of under 20%..
For both trials, patients are managed in the postnatal period by referring centers. Fetal evaluation, randomization and fetal intervention are done at one of the feto centers.
Contact: eurofoetus@eurofoetus.org
[1] Jani J, Nicolaides K H, Keller R L, et al. 2007. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol 30(1):67-71.
[2] Jani J, Benachi A, Nicolaides KH, Allegaert K, Gratacós E, Mazkereth R, Matis J, Tibboel D, van Heijst A, Storme L, Rousseau V, Greenough A, Deprest JA . Prenatal prediction of neonatal morbidity in congenital diaphragmatic hernia: a multicenter study. Ultrasound Obstet Gynaecol 2008 (in press).
[3] Deprest J, Gratacos E, and Nicolaides K H. 2004. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol 24(2):121-6.
[4] Jani J, Nicolaides K, Gratacos E, et al. 2007. Short term neonatal morbidity in severe left-sided congenital diaphragmatic hernia treated by tracheal occlusion before 30 weeks. Am J Obstet Gynecol 197(6):S162. (currently in press Ultrasound Obstet Gynecol 2008)
[5] Jani J C, Nicolaides K H, Gratacos E, Vandecruys H, and Deprest J A. 2006. Fetal lung-to-head ratio in the prediction of survival in severe left-sided diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO). Am J Obstet Gynecol 195(6):1646-50.
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Beck V, Mayer S, Klaritsch P, Roubliova X, Petersen S, Deprest J
Tracheal occlusion early in gestation leads to greater lung growth and improved remodeling of pulmonary arteries. A nitrofen rat model for congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and abnormal airway and pulmonary artery development. Prenatal tracheal occlusion (TO) promotes lung growth and partial reversal of structural anomalies in animal models. Limited data exists regarding TO effects at different phases of lung development. This study evaluates the impact of early (d19, pseudoglandular phase) versus late TO (d20, cannalicular phase) in a nitrofen rat model.
Wistar rats were mated within a 1-hour interval. Nitrofen was gavage fed on d9 of gestation. On d19 and d20 fetal TO was performed, respectively. Sham-operated and untouched littermates served as controls. On d21 fetuses were harvested. Only fetuses with left-sided CDH were included in further analyses with a minimum of 6 fetuses per group. Unpaired t-test with Bonferroni correction was used for statistical analysis.
Lung-body-weight ratio was significantly increased in both TO groups compared to controls with significantly higher values after early versus late TO. Ki-67 RT-qPCR confirmed significantly increased proliferation in the early TO group compared to late TO and control groups. Media and adventitia thickness (%MT, %AT) were consistently reduced in the early TO group versus controls. In the late TO group an effect was only seen in small and medium-size arteries. %MT was significantly smaller in arteries of all sizes in the d19 versus the d20 TO group. There was a similar impact on airway morphology in both TO groups compared to controls.
Our study confirms enhanced lung growth and reversal of structural abnormalities as a result of fetal TO in a nitrofen rat model. Effects in this model are more evident after early TO (d19) than late TO (d20).
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TRACHEAL OCCLUSION IN EXPERIMENTAL DIAPHRAGMATIC HERNIA: CORRELATION BETWEEN LUNG MORPHOMETRY AND HAEMODYNAMICS
J Prat, R Cruz, L Krauel, X Tarrado, V Fusté, O Moreno, M Castañón, A Nadal, A Albert.
Objective: To analyze the effect of fetal tracheal occlusion (TO) on pulmonary blood perfusion and morphometry in a rabbit model of diaphragmatic hernia (DH).
Methods: This project was approved by the Ethical Committee for Animal Experimentation. Fetal rabbits had a surgically created left DH on gestational day (GD) 23. On GD 28, TO was randomly done to roughly 50% of DH surviving fetuses. During C-section on GD 30 (term=GD31) ultrasound measurements of the right lung were performed in utero: Fractional Moving Blood Volume (FMBV) estimating lung perfusion and pulmonary artery Pulsatility Index (PI) for vascular resistance. The surviving fetuses were then harvested, together with non-operated littermates serving as controls. After spontaneous breathing, the newborns were weighed, sacrificed, autopsied and their lungs weighed and prepared for H/E morphometry. Radial alveolar count (RAC) and lung to body weight ratio (LBWR) were measured to assess pulmonary hypoplasia.
Results: Five DH fetuses, 10 DH+TO fetuses and 14 controls were suitable for study. Both operated groups showed significant lower LBWR (p<0,007) than controls (DH 1.47±0.31 and DH+TO 1.53±0.39 vs control 2.32±0.42). Control and DH+TO showed no significant difference in RAC (control 5.54±1.23 vs DH+TO 4.18±0.24), FMBV (control 24.1±2.8 vs DH+TO 28±6.8) and PI (control 5.22±1.1 vs DH+TO 5.8±2.2). DH fetuses had a significantly lower RAC (3.14±0.36), lower FMBV (14.7±4.7) and higher PI (8.1±2.9) than control and DH+TO groups. There is a significant negative correlation between FMVB and PI (r=-0.34; p=0.02). RAC is clearly correlated with PI values (R=0.68; p=0.014); however, correlation between RAC and FMVB is weak and not significant.
Conclusion: Late gestational tracheal occlusion can revert the hipoplastic pattern of the lungs in fetuses with DH. Improvement is not only histological, a parallel haemodynamic response decreases pulmonary vascular resistances, enhancing lung circulation.
Health related quality of life in children with congenital diaphragmatic hernia at ECMO-Center Mannheim
The treatment of neonates with congenital diaphragmatic hernia (CDH) underlies ongoing improvement. The use of inhalative NO, high frequency oscillation and extracorporal membrane oxygenation (ECMO) seems to show benefits on survival rates of these patients. Hereby children with a very serious prognosis may survive afterall. Yet we know, that follow up studies of CDH patients show, that there appear new comorbidities after the neonatal period, such as lung problems, gastrointestinal dysfunction, growth retardation, and neurological deficits. These follow up studies only very seldomly take the health-related quality of life in CDH patients into account. The few data on health related quality of life in CDH patients covers only a small number of patients that recieved ECMO-therapy.
At our center about a third of all CDH patients undergo ECMO-therapy. Due to this, a retrospective analysis was performed to show a possible effect of ECMO-therapy on the health related quality of life in CDH patients. Therefore, a standardised questionnaire on health related quality of life of preschool children (TAPQOL) was sent to CDH patients and their parents. The questionnaire consists of 43 items of 12 scales (lung problems, skin problems, stomach problems, appetite, sleeping problems, problem behavior, anxiety, positive mood, social functioning, motor functioning, communication and liveliness). A higher score implies a higher quality of life.
The TAPQOL questionnaire was sent to 160 CDH patients born in 2002 to 2006. 101 of the questionnaires were returned, from which 38 children had recieved ECMO-therapy. The data of the CDH patients was compared to a control group of 229 healthy children of the same age. Furthermore, the scores of the CDH patients that underwent ECMO-therapy were compared with the scores of the CDH patients without ECMO-therapy. The statistical analysis were performed in SPSS.
Our data showed, that compared to the control group, the CDH patiens had a significant lower quality of life in the following scales: stomach problems, lung problems, liveliness and motor functioning. These results reflect the data of earlier follow up studies.
The comparison within our group of CDH patients surprisingly showed only a significant lower score in the scale “lung problems” for the CDH patients that recieved
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Right versus left-sided congenital diaphragmatic hernia -
postnatal outcome at a specialized tertiary care center
Thomas Schaible, MD, Thomas Kohl*, MD, Joachim Brade**, PhD, Lucas M Wessel§, MD, K Wolfgang Neff§§, MD, Stefan O Schönberg§§, MD, Karen A Büsing§§, MD
Department of Pediatrics, Department of Medical Statistics**, Department of Pediatic Surgery§ and Department of Clinical Radiology and Nuclear Medicine§§, University Hospital Mannheim, and Department of Obstetrics and Prenatal Medicine, German Center for Fetal Surgery & Minimally Invasive Therapy, University Hospital Bonn*
Corresponding Author:
Thomas Schaible, MD
Department of Pediatrics
University Medical Centre Mannheim
Medical Faculty Mannheim, University Heidelberg
Theodor Kutzer Ufer 1-3
68167 Mannheim
Germany
phone 0049 621-383-2248
fax 0049 621-383-3818
Email: thomas.schaible@umm.de
Key words: right congenital diaphragmatic hernia, outcome, chronic lung disease
Purpose
In congenital diaphragmatic hernia (CDH), the impact of the location of the defect on neonatal outcome is still uncertain. We therefore performed a matched pair analysis to systematically compare survival, extracorporeal membrane oxygenation (ECMO) requirement, and the development of chronic lung disease (CLD) in infants with right versus left-sided CDH.
Methods
We assessed 106 neonates with CDH. For 17 of 18 infants with right-sided CDH (r-CDH) we were able to allocate infants with left CDH (l-CDH) with no relevant difference in previously described prognostic factors such as pulmonary hypoplasia, birth weight, and prematurity.
Results
There was a strong trend toward better survival in infants with r-CDH than in l-CDH (94% versus 70%; p = 0.07). In l-CDH more neonates died of severe pulmonary hypertension despite ECMO therapy. In r-CDH, less neonates died yet higher degrees of pulmonary hypoplasia and oxygen requirement were observed despite ECMO therapy. Overall, CLD was associated with a higher degree of pulmonary hypoplasia and oxygen requirement (p = 0.016).
Conclusions
In CDH, the location of the defect may have a substantial impact on postnatal survival and the development of CLD. In l-CDH, dextrocardia probably interferes with prenatal pulmonary perfusion inducing pulmonary hypertension resistant to therapeutic management including ECMO. R-CDH infants have an increased benefit from ECMO but the better survival entails a higher pulmonary morbidity.
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MORBIDITY IN INFANTS AFFECTED BY CONGENITAL DIAPHRAGMATIC HERNIA.
L. Valfrè, A. Braguglia, F. Morini, A. Conforti, N. Chuklantseva, A. Dotta, C. Corchia, P. Bagolan.
AIM: New treatments seem to improve survival rate in CDH infants in comparison with past decades. However this better survival has raised concern about the medium and long term morbidity, even in the first few years of life. Aim of our study is to evaluate the role of a multidisciplinary approach to high risk CDH survivors at follow-up.
METHODS: All high risk (prenatal diagnosis and/or respiratory symptoms within 6 hours of life) CDH survivors treated in a 3rd level intensive care and surgical neonatal centre between 2004 to 2008 were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Prevalence of late morbidity was prospectively evaluated at follow up 6,12 and 24 months of age. Evaluation included gastro-esophageal, pulmonary, cardiac and orthopedic assessment. Results are expressed as prevalence. Fisher exact test was used as appropriate.
MAIN RESULTS: 58 infants were enrolled into follow-up program , 41 infants were prospectively evaluated for at least 2-years of age. Main results are summarized in the table.
CONCLUSION: At 2 years follow-up, high risk CDH survivors still present high rate of morbidity. Gastrointestinal sequelae and alterated respiratory functional test significantly decrease whereas skeletal and respiratory infections increase two years after discharge in high risk CDH survivors. Better gastrointestinal outcomes are probably due to the strict follow-up program. The time-linked discover of skeletal disorders is consistent with international literature and represent the classical long term sequelae of CDH survivors. These results highlight the importance of a multidisciplinary long term follow up to prevent when possible long term sequelae and complications. More studies are needed to better understand the role of new treatments on the development of late morbidity in CDH survivors. The longer the follow-up, the better for patients!
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SENSORINEURAL HEARING LOSS AND SEVERE NEONATAL RESPIRATORY FAILURE
*P.Midrio, **C.Morando, **E.Orzan, °M.Filippone, *A.Sgrò, *PG.Gamba
* Division of Pediatric Surgery, University of Padova, Italy
**Department of Pediatrics, University of Padova, Italy
° Neonatal Intensive Care Unit, Department of Pediatrics, University of Padova, Italy
Background: Congenital diaphragmatic hernia (CDH) survivors have increased morbidity, including sensorineural hearing loss (SNHL). The relationship between CDH and SNHL has not been explained. Many studies analyzing patients treated for severe neonatal respiratory failure, reported a higher incidence of SNHL in CDH patients than in non-CDH peers.
Objectives: To report and compare prevalence and severity of SNHL and presence of conductive hearing loss (CHL) in two populations of neonates with severe neonatal respiratory failure exposed to NICU risk factors.
Methods: Patients born between 1989 and 2008 were divided into two groups: CDH and neonatal primary pulmonary hypertension (PPHN). A retrospective chart review was performed to identify audiologic risk factors (mechanical ventilation, high frequency oscillatory ventilation, gentamycin and neuromuscular blocking agents) and audiometric evaluation (speech audiometry, otoacoustic emission, immitance measures) in survivors from both groups.
Results: Among 57 CDH-children 3 had permanent severe SNHL (5.2%), one of whom with Turner syndrome. None of the 15 PPHN-children had SNHL. Prevalence of CHL was almost the same in both populations.
Conclusions: In our study CDH survivors have lower prevalence of SNHL than previously reported. SNHL does not appear related to this specific malformation. Case-control study with larger populations is needed to better understand the role of NICU risk factors in the development of SNHL in children affected by severe neonatal respiratory failure.
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Mortality in congenital diaphragmatic hernia: euphoria, depression, and the impact of “patient’s selection”
Aim of the study: To evaluate the changes of mortality rate in patients with congenital diaphragmatic hernia (CDH) in a third level referral centre and to define the impact of “patient’s selection” on mortality rate.
Methods: Retrospective review of the case notes of all patients with high risk CDH (prenatal diagnosis and/or symptoms within 6 hours of life) consecutively treated between January 2000 and December 2008 with a defined protocol. Mortality rate (before discharge) was recorded for each year. Prevalence of prenatal diagnosis, major cardiac associated anomalies, liver in the chest, persistent pulmonary hypertension, and patch repair, and mean length of mechanical ventilation were extracted for every year and used to derive the changes in severity of CDH population. Changes of mortality rate over time were analyzed by X2 test. The correlation between the changes of mortality rate and the indices was analyzed by Pearson’s test, one-tail p value < 0.05 was considered statistically significant.
Main Results: In the study period we treated 158 patients with high risk CDH. Overall mortality rate was 36.1%, significantly changing over time from 6.7% in 2000 to 43.7% in 2008 (p<0.02). Over the study period, we found a significant correlation between fluctuations of mortality rate and the following variables: prevalence of prenatal diagnosis (r=0.85, p<0.002), major cardiac associated anomalies (r=0.81; p<0.004), and persistent pulmonary hypertension (r=0.91; p<0.001).
Conclusions: In our Institution, postnatal mortality significantly changed over time, despite no changes in the treatment team and protocol. Changes in mortality rate were significantly correlated with changes in prevalence of prenatal diagnosis, major cardiac anomalies and persistent pulmonary hypertension. These findings suggest that in CDH, “patient’s selection” may influence mortality rate, whose changes may reflect physiological “floating” in acuteness of CDH patients.
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Mortality in congenital diaphragmatic hernia: euphoria, depression, and the impact of “patient’s selection”
Francesco Morini, Irma Capolupo, Maria Paola Ronchetti, Annabella Braguglia, Carlo Corchia, Pietro Bagolan
Department of Medical and Surgical Neonatology, “Bambino Gesù” Children’s Research Hospital, Rome, Italy
Aim of the study: To evaluate the changes of mortality rate in patients with congenital diaphragmatic hernia (CDH) in a third level referral centre and to define the impact of “patient’s selection” on mortality rate.
Methods: Retrospective review of the case notes of all patients with high risk CDH (prenatal diagnosis and/or symptoms within 6 hours of life) consecutively treated between January 2000 and December 2008 with a defined protocol. Mortality rate (before discharge) was recorded for each year. Prevalence of prenatal diagnosis, major cardiac associated anomalies, liver in the chest, persistent pulmonary hypertension, and patch repair, and mean length of mechanical ventilation were extracted for every year and used to derive the changes in severity of CDH population. Changes of mortality rate over time were analyzed by X2 test. The correlation between the changes of mortality rate and the indices was analyzed by Pearson’s test, one-tail p value < 0.05 was considered statistically significant.
Main Results: In the study period we treated 158 patients with high risk CDH. Overall mortality rate was 36.1%, significantly changing over time from 6.7% in 2000 to 43.7% in 2008 (p<0.02). Over the study period, we found a significant correlation between fluctuations of mortality rate and the following variables: prevalence of prenatal diagnosis (r=0.85, p<0.002), major cardiac associated anomalies (r=0.81; p<0.004), and persistent pulmonary hypertension (r=0.91; p<0.001).
Conclusions: In our Institution, postnatal mortality significantly changed over time, despite no changes in the treatment team and protocol. Changes in mortality rate were significantly correlated with changes in prevalence of prenatal diagnosis, major cardiac anomalies and persistent pulmonary hypertension. These findings suggest that in CDH, “patient’s selection” may influence mortality rate, whose changes may reflect physiological “floating” in acuteness of CDH patients.
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Survival rates of infants with congenital diaphragmatic over a 12 year period before and after changes in medical management.
Department of Neonatology etc
PML, DT, ER, PMD, MJS
Aim: To describe the survival rates for infants with congenital diaphragmatic hernia (CDH), over two time periods before and after abrupt changes were made in the management of this condition.
Setting: RCH Melbourne is a tertiary referral paediatric hospital which admits only outborn infants to the Neonatal Unit.
Patients and methods: 147 patients with CDH admitted to the neonatal unit over a 12 year period, 1998 to 2009, were identified from hospital databases. The 2 epochs were:
Era 1 from Jan1998 to Apr 2003; Era 2 from May 2003 to Jun 2009.
A retrospective review of patient records was performed to collect demographic and other data. Ventilation data and other aspects of management were collected prospectively.
Results:
Table 1
Era 1 | Era 2 | Comment | |
Total number | 61 | 86 | |
Left / Right | 50 / 6 | 64 / 12 | |
Male / Female | 38 / 18 | 47 / 29 | |
Admitted < 24 hours (HR) | 56 (92) | 76 (88) | |
Lived / Died | 38 / 18 | 63 / 13 | |
Antenatal diagnosis made | 37 (61) | 41 (48) | |
Patch repair | 21 (38) | 27 (36) | |
Day surgery performed | 4.1 ± 3.9 | 5.6 ± 2.8 | NS * |
Total days HFOV | 289 | 648 | |
Total days jet ventilation | 124 | 468 | |
Total days nitric oxide | 392 | 1055 | |
ECMO (survived) | 5 (1) | 1 (1) | |
Prostaglandin E1 | 0 | 56 | |
Where surgery performed Theatre NNU | N/A N/A | 32 48 | |
Length of stay (days) | 37.3 ± 38.0 | 37.3 ± 29.8 | NS * |
Survival (all patients, %) | 70.5 | 84.9 | P=0.035 # |
Survival (HR patients, %) | 67.9 | 82.9 | P=0.044 # |
HR = High risk HFOV = high frequency oscillatory ventilation
* = t-test # = chi squared N/A = not available
Discussion:
Inhaltlich verantwortlich gemäß § 6 MDStV ist der/die jeweilige Direktor/in bzw. Leiter/in der Einrichtung.
Universitätsmedizin Mannheim
Klinikum Mannheim GmbH
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68167 Mannheim
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program 2009