Cases Of Congenital Diaphragmatic Hernia Research Articles

Prevention of heart failure in the management of congenital diaphragmatic hernia by maintaining ductal patency. A case report

Congenital diaphragmatic hernia is a rare entity in childhood carrying a high mortality rate of 30% to 50%. Ipsilateral pulmonary hypoplasia, increased pulmonary vascular resistance, and potential cardiac failure complicate early postnatal life. Surgical correction can either be performed on the first day of life or be deferred to a time after stabilization of the infant. Our patient presented with a left-sided Bochdalek's hernia containing large and small bowel. She required intubation and resuscitation on day 1 of life, and surgical repair had to be postponed. Further respiratory deterioration required commencement of inhaled nitric oxide and high-frequency ventilation. Pulmonary artery pressure rose to suprasystemic level. Closure of the ductus arteriosus on day 8 resulted in imminent right-sided heart failure. Commencement of alprostadil (prostaglandin E 1) reopened the ductus and stabilized the patient. Surgical repair was successful 3 days later. Alprostadil should be considered as an important component of therapy in severe cases of congenital diaphragmatic hernia, where deterioration of right-sided heart function occurs.

Epidemiologic characteristics of congenital diaphragmatic hernia among 2.5 million california births, 1989–1997

Congenital diaphragmatic hernia (CDH) is a severe birth defect of unknown etiology. The aims of the current report were to extend the literature on the descriptive epidemiology of CDH and to determine whether its mortality rate decreased in California during the study period. Using data from a large population-based registry, we ascertained 631 CDH cases from 1989 to 1997. We also classified cases as isolated or nonisolated based on the presence and type of major accompanying malformations. Approximately 2.5 million live and stillbirths occurred during the ascertainment period. Multivariate Poisson regression analysis was applied to examine the time trend and risk factors. The overall prevalence of CDH was 2.49 per 10,000 live and stillbirths and did not vary over the study period. Isolated cases, which accounted for 58% of cases, revealed a prevalence of 1.45 per 10,000. Heart malformations were the most frequent major anomalies accompanying CDH. We observed a lower risk of isolated CDH among blacks. Advanced maternal age groups had a higher risk for nonisolated CDH. Multiparous women tended to have a lower risk for nonisolated CDH. Male infants and multiple births had an increased risk for isolated and nonisolated CDH. Infant mortality was slightly decreased over the study period. CDH cases with additional anomalies had higher mortality rates than isolated cases. Our observations add to the relatively few population-based descriptive epidemiologic studies of the prevalence and mortality, and maternal and infant characteristics of CDH.

Distal 4p microdeletion in a case of Wolf‐Hirschhorn syndrome with congenital diaphragmatic hernia

Wolf-Hirschhorn syndrome (WHS) is a well-known genetic condition characterized by typical facial anomalies, midline defects, skeletal anomalies, prenatal and postnatal growth retardation, hypotonia, mental retardation, and seizures. Affected patients with a microdeletion on distal 4p present a milder phenotype that lacks congenital malformations. WHS is rarely associated with congenital diaphragmatic hernia (CDH), and only 8 cases are reported in the literature. In almost all cases of CDH and WHS a large deletion of the short arm of chromosome 4 is present. A microdeletion of 2.6 Mb on distal 4p associated with CDH and multiple congenital malformations (i.e., cleft palate) is reported for the first time. Such a microdeletion should prompt a molecular study for WHS when in a fetus/newborn with CDH the association with cleft lip/palate and typical facial appearance (flat facial profile, hypertelorism) is found.

PRENATAL DIAGNOSIS AND PERINATAL OUTCOME OF 38 CASES WITH CONGENITAL DIAPHRAGMATIC HERNIA: 8-YEAR EXPERIENCE OF A TERTIARY BRAZILIAN CENTER

To evaluate the perinatal results for neonates with congenital diaphragmatic hernia diagnosed prenatally. We reviewed data from 38 cases of congenital diaphragmatic hernia diagnosed prenatally from January 1995 to December 2003 in the Fetal Medicine Unit of the Department of Obstetrics and Gynecology, São Paulo University Medical School. The main data analyzed were gestational age at diagnosis, fetal karyotyping, side of diaphragmatic defect, presence of associated structural malformations, hepatic herniation, and severe mediastinal shift. Perinatal outcomes were obtained by reviewing hospital documents or by directly calling the patients' immediate relatives. Mean gestational age at diagnosis was 29 weeks (range, 16-37 weeks). Thirty (79%) cases had a left diaphragmatic defect and 8 (21%) had a right lesion. Associated structural malformations were observed in 21 (55%) cases, in which 12 fetuses had a normal karyotype and 9 had chromosomal abnormalities. Isolated congenital diaphragmatic hernia was confirmed in 17 (45%) cases. The overall perinatal mortality rate was 92%. Rates of fetal deaths, early neonatal deaths, late neonatal deaths, and survival were 42%, 50%, 0%, and 8%, respectively, in cases with associated structural malformations but normal karyotyping; 56%, 44%, 0%, and 0% for cases with chromosomal abnormalities; and, 0%, 76%, 12%, and 12% in cases with isolated congenital diaphragmatic hernia. The neonatal mortality rate was 89% in cases with isolated congenital diaphragmatic hernia. Perinatal mortality was very high in prenatally diagnosed cases of congenital diaphragmatic hernia. Earlier perinatal deaths are associated with the presence of other structural defects or chromosomal abnormalities. In cases of isolated congenital diaphragmatic hernia, mortality is related to the presence of herniated liver, right-sided lesion, and major mediastinal shift.

Pulmonary Hypertension in Human Newborns With Congenital Diaphragmatic Hernia Is Associated With Decreased Vascular Expression of Nitric-Oxide Synthase

The molecular basis of the pathogenesis of pulmonary hypertension (PH) associated with congenital diaphragmatic hernia (CDH) is poorly understood. Variation in responses to therapeutic strategies such as nitric oxide (NO) inhalation and extracorporeal membrane oxygenation (ECMO) in patients with CDH remains a major problem in pediatric critical care. We investigated the expression pattern of NO-generating enzyme nitric-oxide synthase (NOS) (both endothelial [eNOS] and inducible [iNOS] isoforms) in the lungs of CDH patients with PH and evaluated the influence of ECMO on the expression levels of these genes in an attempt to understand the underlying molecular mechanisms. Lung autopsy specimens from 23 cases of CDH not treated by ECMO and 10 ECMO-treated CDH cases were studied and compared with 11 age-matched controls. Expression of iNOS and eNOS was assessed by immunohistochemistry and video-image analysis. Expression of iNOS in the endothelium of small pulmonary arteries (external diameter < or =200 Mum) was significantly lower in CDH cases that had not received ECMO treatment (p = 0.04). ECMO-treated CDH cases did not differ from controls in iNOS expression. Alveolar macrophages (CD68+ cells), of which the number also was increased, showed significantly enhanced staining for iNOS in CDH cases (p = 0.03) compared with controls. The observed decrease in pulmonary expression of iNOS in patients with CDH suggests a potential role in the pathogenesis of pulmonary hypertension in newborns with CDH. ECMO treatment was correlated with induction of this enzyme, which may result in NO-mediated vasodilatation and thereby transiently reduce the pulmonary hypertension in CDH.

Lung hypoplasia in congenital diaphragmatic hernia. A quantitative study of airway, artery, and alveolar development.

Abstract From a case of congenital diaphragmatic hernia the pattern of growth of the airways, alveoli, and pulmonary arteries of both lungs, each hypoplastic, has been analysed quantitatively. The impairment of growth for each type of structure is not necessarily the same and differs in each lung. Airway and alveolar numbers are both greatly reduced, although the latter are more nearly normal when related to the number of terminal bronchioli in the lung. In each lung the size of the pulmonary artery at the hilum is appropriate to the lung volume but small for the age of the child. Muscle is found in much smaller arteries than is normal but not to a more peripheral level. The way the lungs in a case of congenital diaphragmatic hernia might grow after surgical correction of the hernia is discussed and a plea made for respiratory physiological studies in such cases.

Real and apparent mortality from congenital diaphragmatic hernia.

Some 50 cases of congenital diaphragmatic hernia (CDH) born in the authors' regional referral area over the 14 years from 1980 to 1993 were reviewed, contrasting 7 years when management included preoperative ventilatory stabilization with the preceding 7 when urgent surgery was performed. Six children experienced no respiratory distress and suffered no mortality. For infants with respiratory distress in the first 6 h of life, ventilatory stabilization improved survival rates of those who reached the surgical centre from 45 per cent between 1980 and 1986 to 59 per cent between 1987 and 1993. A larger proportion of the total number of patients, however, continued to die without reaching the surgical centre. The improvement in survival rate based on the true incidence of CDH was from 28 per cent in the first period to 38 per cent in the second. The apparent poor survival rate of patients born in central obstetric units compared with those born in peripheral units (37 versus 75 per cent) can be attributed to patient selection; a larger number of children born in central units were transferred for surgery (70 versus 57 per cent). There is no evidence that paediatricians have altered their referral practice to include prolonged ventilation outside the surgical unit since delayed surgery was advocated. Assessment of the impact of altering the management of CDH cannot be made without knowing the number of patients who die before transfer to a neonatal surgical unit. Any serious attempt to reduce the mortality rate of CDH must be directed to neonates who are not presently referred to the surgical service.

Accuracy of fetal lung volume assessed by three‐dimensional sonography

To determine the accuracy and precision of prenatal three-dimensional (3D) ultrasound in estimating fetal lung volume using the rotational multiplanar technique (VOCAL) by comparing it to postmortem volume measurements. Fetal lung volume was measured during 3D ultrasound examination using a rotational multiplanar technique in eight cases of congenital diaphragmatic hernia (CDH) (six left and two right-sided) and in 25 controls without pulmonary malformation, immediately before termination. Prenatal 3D sonographic estimates of fetal lung volume were compared with postmortem measurement of fetal lung volume achieved by water displacement. The intraclass correlation coefficient of fetal lung volume estimated by 3D ultrasound and measured at postmortem examination was 0.95 in CDH cases and 0.99 in controls. Based on Bland-Altman analysis, the bias, precision and limits of agreement were, respectively, 0.35 cm(3), 1.46 cm(3) and between -2.51 and + 3.21 cm(3) in cases with CDH and 0.08 cm(3), 2.80 cm(3) and between -5.41 and + 5.57 cm(3) in controls. The mean relative error of 3D ultrasound fetal lung volume measurement was -7.19% (from -42.70% to + 18.11%) in CDH cases and -0.72% (from -30.25% to + 19.22%) in controls, while the mean absolute error of 3D ultrasound fetal lung volume measurement was 1.40 (range, 0.71-2.52) cm(3) and 2.12 (range, 0.05-4.98) cm(3), respectively. Accuracy of 3D ultrasound for measuring fetal lung volumes was 84.86 (range, 57.30-99.48)% in cases with CDH and 91.38 (range, 69.75-99.45)% in controls. The mean intraobserver variability for lung volume estimated by 3D ultrasound was 0.28 cm(3) in controls and 0.17 cm(3) in CDH cases. Prenatal 3D ultrasound can estimate accurately fetal lung volume using the rotational multiplanar technique for volume measurements (VOCAL), even in fetuses with very small lungs, such as cases with isolated CDH.

Congenital Diaphragmatic Hernia with Familial Occurrence in a Taiwanese Pedigree

Congenital diaphragmatic hernia (CDH) is a developmental defect that accounts for 8% of all major congenital anomalies and is associated with a high mortality rate despite optimal postnatal treatment. Its etiology is uncertain. We report a case of familial CDH in a Taiwanese family. We believe autosomal recessive inheritance is the possible genetic etiology of CDH in this family.

Outcomes of Congenital Diaphragmatic Hernia: A Population-Based Study in Western Australia

Outcomes of Congenital Diaphragmatic Hernia: A Population-Based Study in Western Australia

Antenatal detection and impact on outcome of congenital diaphragmatic hernia: A 12-year experience in Auvergne (France)

Objective To evaluate the detection rate of prenatal diagnosis and its impact on outcome in congenital diaphragmatic hernia (CDH). Study design We retrospectively studied 51 cases of CDH registered in the Auvergne area from January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut Européen des Génomutations). Our main outcome measurements were the detection rate of prenatal diagnosis, the incidence and types of associated anomalies and outcome (termination of pregnancy, in utero fetal demise, neonatal death, survival at the time of registration). Results Twenty-nine cases of isolated CDH were identified of which 13 were detected prenatally (45%) at a mean gestational age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal diagnosis of CDH or any associated anomaly in 16 (73%; p = 0.03) at a mean gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP) and 11 (38%) live births with early neonatal death in 7 (24%) cases despite delivery in a tertiary care centre in 10/11 cases (four survivors = 14%). Most of the undetected cases were isolated CDH (16/22 = 73%) of which 1 (5%) was a stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%) were not born at the tertiary care centre ( p = 0.001). The overall survival rate was 41% with a large variability depending on associated anomalies and prenatal diagnosis ( p < 0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16 (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH and 4/6 (67%) CDH with associated anomalies). Conclusion Prenatal diagnosis of CDH leads to the delivery of affected babies in tertiary care centres but it remains a challenge in particular for isolated CDH cases and it is associated with a lower survival rate. Associated anomalies contribute to prenatal detection, are related to a higher TOP rate but do not facilitate the detection of diaphragmatic defect per se.

Infants with Bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital‐based malformation surveillance program

Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect. In order to learn more about possible genetic causes, we reviewed and classified 203 cases of the Bochdalek hernia type identified through the Brigham and Women's Hospital (BWH) Active Malformation Surveillance Program over a 28-year period. Phenotypically, 55% of the cases had isolated CDH, and 45% had complex CDH defined as CDH in association with additional major malformations or as part of a syndrome. When classified according to likely etiology, 17% had a Recognized Genetic etiology for their CDH, while the remaining 83% had No Apparent Genetic etiology. Detailed analysis using this largest cohort of consecutively collected cases of CDH showed low precurrence among siblings. Additionally, there was no concordance for CDH among five monozygotic twin pairs. These findings, in conjunction with previous reports of de novo dominant mutations in patients with CDH, suggest that new mutations may be an important mechanism responsible for CDH. The twin data also raise the possibility that epigenetic abnormalities contribute to the development of CDH.

Foetal surgery and cleft lip and palate: current status and new perspectives

Now-a-days, high-resolution ultrasound allows an accurate and relatively early diagnosis of congenital malformations. In a limited number of such conditions foetal surgery may be lifesaving. However, premature labour has been the major drawback for open foetal surgery. Recently, improvement of video-endoscopic technology has boosted the development of operative techniques for feto-endoscopic surgery, which has been demonstrated to be less invasive than the open approach. Main clinical application of fetoscopic procedures today is the treatment of feto-foetal transfusion syndrome. Although still in development, feto-endoscopic surgery seems to offer new hope for surgical foetal therapy not only in cases of life threatening conditions. Experimental intrauterine correction of cleft lip and palate (CLP) has been lately performed using the feto-endoscopic approach. This procedure offers two major advantages: first, scarless foetal wound healing and bone healing without callus formation, which would also allow a better/normal maxillary growth, and second, significant decrease of foetal and maternal morbidity. Herein, we report the current status of experimental and clinical foetal surgery and propose possible directions for continuing research to make intrauterine procedures safer. Furthermore, we discuss current knowledge and new perspectives of experimental foetal cleft lip and palate repair, which in the future may lead to such excellent results in the operative treatment of clefts, that less or no secondary corrections and therapies, such as orthodontic, dental, logopedic, etc. would be needed. Only if these conditions can be fulfilled, will we be able to improve substantially our therapy for the human foetus with a cleft lip and palate. In spite of all efforts, however, it must be considered that it may not ever be possible to find the optimal treatment method for this or other craniofacial malformations.

Bilateral congenital diaphragmatic hernia

Bilateral congenital diaphragmatic hernia (CDH) is a rare condition, with the literature suggesting a bleak prognosis. We describe a case of bilateral CDH that, despite confirming the challenges of diagnosis, demonstrates that the condition can have a favourable outcome.

Congenital Diaphragmatic Hernia and Chromosome 15q26: Determination of a Candidate Region by Use of Fluorescent In Situ Hybridization and Array-Based Comparative Genomic Hybridization

Congenital diaphragmatic hernia (CDH) has an incidence of 1 in 3,000 births and a high mortality rate (33%-58%). Multifactorial inheritance, teratogenic agents, and genetic abnormalities have all been suggested as possible etiologic factors. To define candidate regions for CDH, we analyzed cytogenetic data collected on 200 CDH cases, of which 7% and 5% showed numerical and structural abnormalities, respectively. This study focused on the most frequent structural anomaly found: a deletion on chromosome 15q. We analyzed material from three of our patients and from four previously published patients with CDH and a 15q deletion. By using array-based comparative genomic hybridization and fluorescent in situ hybridization to determine the boundaries of the deletions and by including data from two individuals with terminal 15q deletions but without CDH, we were able to exclude a substantial portion of the telomeric region from the genetic etiology of this disorder. Moreover, one patient with CDH harbored a small interstitial deletion. Together, these findings allowed us to define a minimal deletion region of approximately 5 Mb at chromosome 15q26.1-26.2. The region contains four known genes, of which two--NR2F2 and CHD2--are particularly intriguing gene candidates for CDH.

The SIS extracellular matrix scaffold?preliminary results of use in congenital diaphragmatic hernia (CDH) repair

There is no ideal bio-tensile material for tissue replacement in paediatric surgical conditions. A variety of materials have been described to replace or reinforce tissue deficits in congenital diaphragmatic hernia (CDH). The problems with these materials range from extensive surgery to body wall deformity and hernia recurrence. The ideal graft would be safe, strong, have the potential to grow and not require replacement, not affect chest wall development or produce deformity, and have minimal risk of recurrence. Surgisis is a biomaterial composed of porcine intestinal submucosa that provides inherent tensile strength as a collagen lattice and is ultimately replaced by native collagen tissue. Our objective was to prospectively assess the utility of Surgisis as a replacement graft in a cohort of 10 children undergoing primary or recurrent CDH repair. The graft was well tolerated, and there was no recurrence of herniation. We conclude that Surgisis collagen mesh may be a useful alternative for tissue replacement or reinforcement in difficult cases of CDH and diaphragmatic agenesis. The biological framework of Surgisis may also prove useful in other situations of complex tissue loss in children.

Survival rate in congenital diaphragmatic hernia: the experience of the canadian neonatal network

Background/purpose The Canadian Neonatal Network prospectively collects data from 17 pediatric hospitals accounting for 75% of all neonatal intensive care unit beds nationwide. The purpose of this study was to (1) analyze the database to compare actual survival rates of neonates with congenital diaphragmatic hernia (CDH) to predicted outcomes and (2) assess whether institutional CDH volume was associated with improved survival rate. Methods Actual survival rates for CDH patients born during a 22-month period were determined from the registry. Predicted survival rates were calculated using the CDH Study Group logistical regression equation. Actual survival rate was compared with predicted using χ 2 analysis. Survival rates were stratified by institutional CDH volume and compared using binomial analysis. P value of less than .05 was deemed statistically significant. Results Of approximately 20,500 neonatal admissions, 88 cases of CDH were recorded. Seventy-three of 88 (83%) neonates with CDH survived to discharge, whereas the predicted survival rate was 62% ( P < .001). Three centers were considered “high-volume” centers with at least 12 CDH diagnoses, and 11 were considered “low-volume” centers. Actual CDH survival was significantly greater at high-versus low-volume centers (90% v 77%; P < .01). Conclusions From these prospective data, survival rates of Canadian neonates with CDH are significantly better than predicted by the CDH Study Group equation. Further, high-volume centers in Canada have a significantly higher CDH survival rate than low-volume centers.

Fetal Lung Volume Estimated by 3‐Dimensional Ultrasonography and Magnetic Resonance Imaging in Cases With Isolated Congenital Diaphragmatic Hernia

To assess the agreement of 3-dimensional ultrasonography and magnetic resonance imaging in estimating fetal lung volume in cases with isolated congenital diaphragmatic hernia. Fetal lung volume was measured in 11 cases of congenital diaphragmatic hernia (10 left and 1 right) by 3-dimensional ultrasonography and magnetic resonance imaging. These examinations were performed during the same week. The operators were blinded to each other's results. Intraclass correlation was used to evaluate the agreement between 3-dimensional ultrasonography and magnetic resonance imaging estimations of the ipsilateral, contralateral, and total fetal lung volume. A Bland-Altman graph was plotted to detect possible discordant observations. The global intraclass correlation coefficient between magnetic resonance imaging and 3-dimensional ultrasonographic measurement of fetal lung volume was 0.94 (95% confidence interval, 0.78-0.98) with no outliers observed on the Bland-Altman plot. There is a good agreement between 3-dimensional ultrasonography and magnetic resonance imaging for fetal lung volume estimation in cases with congenital diaphragmatic hernia.

Right congenital diaphragmatic hernia: prenatal assessment and outcome

Purpose To understand the natural history of right congenital diaphragmatic hernia (CDH), the authors retrospectively reviewed 27 cases of right CDH that presented for prenatal evaluation or postnatal treatment. Methods Between 1995 and September 2002, a total of 194 cases of fetal CDH were evaluated and included 22 right-sided defects. The authors reviewed prenatal diagnostic studies (ultrasound scan, magnetic resonance imaging [MRI] echocardiography) and pre- and postnatal outcomes in these 22 cases of right CDH. Five additional cases of right CDH without a prenatal diagnosis were reviewed. Results The mean gestational age at evaluation was 26.1 weeks. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5. In all cases, the fetal liver was herniated into the right chest. Associated anomalies were common. There were no karyotype abnormalities (17 of 22 tested). There were 4 terminations. Nine of the 18 (50%) continuing pregnancies had polyhydramnios, premature rupture of membranes, or preterm labor. The mean gestational age at birth was 36.8 weeks. One patient underwent tracheal occlusion at 27 weeks, and 2 patients died before postnatal repair. Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate was 19 of 23 (83%). A Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) patch was utilized in 14 of 21 neonates undergoing surgery. Twelve of 23 (52%) required extracorporeal membrane oxygenation (ECMO) with a 75% survival rate. Significant morbidity occurred in 10 of 19 survivors and included neurologic sequelae in 6 of 19 (32%). Conclusions MRI was helpful in the determination of liver position and confirmation of diagnosis. The high incidence of preterm complications, frequent need for ECMO, and high prevalence of comorbidities are indicative of the severity of this CDH population and warrant close prenatal surveillance and delivery at a tertiary care center with ECMO capability.

Congenital diaphragmatic hernia and chromosomal anomalies: autopsy study.

In a 10-year review of autopsy records from Lutheran General Hospital (1992-2002), 13 cases of congenital diaphragmatic hernia (CDH) were found. The fetuses ranged between 21 and 35 wk of gestation. Four were born alive and five were diagnosed prenatally. The defect was left-sided in 11 cases. Cytogenetic study revealed five cases with normal karyotype and three cases with complex karyotypes. In five cases, no karyotype was performed. The three complex karyotypes were: 46,XX,del(8)(p23.1), 47,XX, +i(12)(p10)[6]/46XX[14] (Pallister-Killian syndrome), and 47,XY,+der(22)t(11:22) (q23.3:q11.2). The unbalanced translocation of chromosomes 11 and 22 in congenital diaphragmatic hernia has not been previously described. Three fetuses had heart abnormalities, including one which was associated with the 8p deletion. The other two had no karyotype study. Neither in this study, nor in the literature, is there a consistent or prevailing association between a specific chromosomal anomaly and CDH. The embryologic closure of the diaphragmatic leaflets may be mediated by a nonstructural chromosomal defect, more than one gene, and/or may be related to abnormalities not currently detectable.