Congenital Diaphragmatic Hernia

Over the last two decades there has been a constant improvement in the understanding of the pathophysiology of Congenital Diaphragmatic Hernia (CDH) and its management. However, the ideal treatment remains elusive. The earlier management strategy of immediate surgery is replaced by the principle of physiological stabilisation and delayed surgery. Conventional mechanical ventilatory techniques, with high pressures and hyperventilation to reverse ductal shunting and cause alkalinization, are being questioned because of the risks of barotrauma and consequent broncho-pulmonary dysplasia. It has also been shown that paralysis with pancuronium bromide for patients on conventional mechanical ventilation results in increased incidence of sensorineural hearing loss in childhood survivors of CDH. With the introduction of the concept of permissive hypercapnia and high frequency oscillation ventilation, the complications of pulmonary barotrauma are circumvented. Although ECMO therapy is invasive, yet has improved survival by about 15% independently, especially in critically ill infants who have the predictive mortality rate of more than 80%. Further insights into the pathophysiology of CDH and the introduction of less invasive therapeutic techniques in the form of high frequency oscillation ventilation, inhalation nitric oxide, surfactant, and perfluorocarbon liquid ventilation may even make the need for ECMO redundant.     

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. This study was presented at the College of American Pathologists Meeting, San Diego, California, USA, 10–14 September 2003.     

Congenital Diaphragmatic Hernia: Experimental Approach

Congenital diaphragmatic hernia is the only relatively common congenital malformation which requires operative treatment during the neonatal period, and the incidence is reported to be one in 2,000–5,000 births. Although a diaphragmatic defect can be easily corrected by pulling out the herniated viscera of the chest and closing the diaphragma, the mortality rate of infants with congenital diaphragmatic hernia is high despite improvements in neonatal intensive care, because the hypoplastic lungs on the affected side can not provide life support after birth. The severity of associated pulmonary hypoplasia is the most important factor determining survival in an infant with congenital diaphragmatic hernia. From experimental study, it should be emphasized that retardation in the lung growth, regardless of its potential for further growth, just at the time of pleuroperitoneal canal closure, may result in congenital diaphragmatic hernia; the hypoplastic lung on the side of herniation would not result from the compression of the lung by the herniated organs, but it may be induced by the limited space for further growth.     

先天性膈疝患儿围手术期处理

目的探讨先天性膈疝(CDH)围手术期处理,以期提高CDH患儿生存率。方法回顾性分析2004年5月-2008年12月本院收治的确诊CDH的17例病例。比较其中新生儿与非新生儿患儿电解质平衡、酸碱平衡紊乱的发生率,取二组手术病例对比手术后呼吸支持需要率以及呼吸支持时间。应用SPSS10.0软件进行统计学分析。结果新生儿组酸碱平衡紊乱的发生率明显高于非新生儿组(100.0%vs37.5%,χ2=6.561,P<0.05)。术后,新生儿组呼吸支持需要率明显高于非新生儿组(100.0%vs28.6%,χ2=5.238,P<0.05),新生儿组呼吸支持时间(222.75h)较非新生儿组(8.50h)明显延长。结论新生儿与非新生儿相比,手术前酸碱平衡紊乱较明显,术后可能更加需要呼吸支持。细致的围手术期处理有助于提高治疗效果。     

Postmortem Findings and Clinicopathological Correlation in Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a severe life-threatening disease, with an incidence of 3 per 10,000 births, that can occur as an isolated defect or in combination with other congenital anomalies. We reviewed the clinical and autopsy reports of 39 subjects with CDH that were autopsied between 1988 and 2001 to determine whether autopsy had an additional value in the detection of malformations in patients with CDH. We compared the clinical data (including echographic results in some patients) concerning congenital anomalies with the autopsy results. Before autopsy, 6 structural cardiac defects, 3 anomalies of the urogenital system, and 3 anomalies of the digestive tract were observed in 10 patients (clinical and echographic results). However, with postmortem examination, only 4 structural cardiac defects were confirmed, 2 cases showed another cardiac anomaly, and 7 new cardiac defects were found. In the urogenital system, 1 anomaly was confirmed, 1 was not confirmed, and 1 showed another malformation. In addition, in 7 patients new urogenital malformations were found after autopsy. In the digestive tract, all 3 malformations were confirmed, but we found 3 new malformations after postmortem examination. All clinically established dysmorphic features and anomalies of the skeletal system and central nervous system were confirmed by autopsy, and no additional malformations were found. We concluded that postmortem examination has an important additional role in the detection of structural cardiac defects and malformations of the urogenital system and digestive tract in children with CDH.Marieke F. van Dooren and Natascha N.T. Goemaere both contributed equally to this article.     

Congenital Diaphragmatic Hernia Induced by Nitrofen in Mice and Rats: Characteristics as Animal Model and Pathogenetic Relationship between Diaphragmatic Hernia and Lung Hypoplasia

Abstract Congenital diaphragmatic hernia (CDH) and lung hypoplasia were induced in high frequency and dose-dependently in the offspring from dams, treated orally with 2,4-dichlorophenyl- p -nitrophenyl ether (nitrofen) during pregnancy in CD-I mice and CD rats. Both in mice and rats, CDH found in the fetal and neonatal periods was a posterolateral type of diaphragmatic hernia (DH) showing a distinct side-preponderance: the left-side preponderance in mice and right-side preponderance in rats. CDH in the offspring, surviving after weaning, was mostly of retrosternal type in mice and of pericardial type in rats. CDH induced experimentally in the present study can be regarded as an excellent animal model for human CDH in terms of both anatomical features and the time of appearance of different types of CDH as well as clinical symptoms.
Lung hypoplasia was observed in the offspring with and without CDH; though its severity was greater in those with CDH. The offspring with severe lung hypoplasia died of respiratory insufficiency during the neonatal period, regardless of the presence or absence of CDH. These findings suggest that lung hypoplasia is not a consequence of CDH, but that a common pathogenetic process in the early embryonic stage might involve both lung hypoplasia and CDH.     

Morphometric Analysis of Preterm Fetal Pulmonary Development in the Sheep Model of Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) in humans carries high mortality/morbidity attributed to associated pulmonary hypoplasia. An understanding of the effects of CDH on fetal lung growth is important for development of successful treatments. This study aimed to quantitate structural differences between normal and CDH-affected preterm lamb lungs. We hypothesized that (a) pulmonary hypoplasia is present in preterm CDH-affected lungs; (b) the relative degree of pulmonary hypoplasia increases with gestation; and (c) the left upper lobe (LUL) is affected most. Fetal lambs were allocated to two groups. One group underwent surgery (72–74 days gestation) inducing CDH. Both groups (n = 7, n = 7) were delivered by cesarean section at 129 days (term: 145–149). Lungs were obtained at autopsy, were inflation-fixed, processed for histology, and morphometry was performed. Preterm lungs of CDH-affected lambs in comparison to those of normal lambs demonstrated a reduction in the following: lung weight (37.7 g vs. 116.3 g); lung weight:body weight (0.012 vs. 0.040); fixed lung volume (33.6 ml vs. 96.9 ml); gas-exchange surface area (4.56 m² vs. 13.70 m²); parenchyma:nonparenchyma (59:41 vs. 72:28); and parenchymal airspace:tissue (16:84 vs. 35:65). Non-parenchyma connective tissue was increased (58%), airspaces were more numerous (1077/mm²) and smaller (perimeter 76.6 μm), gas-exchange surface density (2394 cm⁻¹) was greater and capillary loading (0.04 ml/m²) was reduced compared to preterm normal lung (49%; 778/mm²; 108.7 μm; 2003 cm⁻¹, 0.11 ml/m², respectively). The LUL was affected most. These data quantitate pulmonary hypoplasia in preterm CDH-affected lambs. Comparisons with published data indicate increasing relative hypoplasia as gestation proceeds. Fetal interventions will affect lung development, depending on timing, with intervention still likely to be worthwhile during late gestation. Received October 6, 1998; accepted March 17, 1999.     

Pathogenesis of Congenital Diaphragmatic Hernia Induced by Transplacental Infusion of Bisdiamine into Rats

Abstract: We studied the pathogenesis of congenital posterolateral diaphragmatic hernia induced by bisdiamine in rats. The frequency of live fetuses with left congenital diaphragmatic hemia (which resembles a hernia through the foramen of Bochdalek in man) was high (78.4%) when pregnant rats were administered bisdiamine by gavage once at a dose of 400 mg/kg on day 9 of pregnancy. Then the bisdiamine-treated rat fetuses were examined at successive developmental stages. Histopathological observation revealed that l) in the control fetus on day 14 of pregnancy, the mesothelial cells lining the pleural aspect of the pleuroperitoneal fold were eventually clustered close to the pleuroperitoneal opening, giving the appearance of a high wave lapping the shore; 2) in the affected fetus on day 14 of pregnancy, the mesothelial cells of the pleural aspect of the fold were scarce; 3) in the affected fetuses during days 14–16 of pregnancy, primary lung hypoplasia was seen. On day 19 of pregnancy, no remarkable differences in the gross appearance of the right lung were found between the affected and control fetuses. Each lung (right and left) of the affected embryos may be considered to have the potential for further growth and development. The development of the mesothelium of the pleura may be greatly influenced by the growth and enlargement of the thorax (mainly the lung), and a retardation of lung growth near the time of pleuroperitoneal canal closure may induce the hernia in diaphragm.     

Congenital diaphragmatic hernia and chromosomal abnormalities: report of a lethal association

Congenital diaphragmatic hernia carries a high mortality which is often the consequence of associated anomalies. A chromosomal abnormality of the long arm of chromosome 8 resulted in a fatal combination of anomalies associated with CDH.     

Diaphragmatic Hernia Induced in Rat Fetuses by Administration of Bisdiamine

Administration of N, N'-bis (dichloroacetyl)-l,8-octamethylenediamine, bisdiamine, to pregnant Donryu rats on a single day of gestation induced unilateral and bilateral diaphragmatic hernias in fetuses with high incidence. The protruded liver was not covered with a serous membrane or a muscular layer. Incidence of unilateral diaphragmatic hernia on the left side was high when bisdiamine was administered on day 9 or 13 of gestation, and that on the right side was high when administered on day 12 of gestation. Incidence of bilateral diaphragmatic hernia was high when bisdiamine was administered on day 12 of gestation. Differences in sensitivity to hernia formation according to day of bisdiamine administration between right and left sides may reflect differences in developmental chronology between the two sides. Two distinct times for induction of left diaphragmatic hernia might be attributed to at least two different mechanisms. The present model is expected to help analyzing not only anatomical characteristics of congenital diaphragmatic hernia but also possible mechanisms responsible for their development.     

Congenital diaphragmatic hernia in CHARGE syndrome

Congenital diaphragmatic hernia (CDH) has been rarely described in CHARGE syndrome. We report a patient affected by CHARGE syndrome presenting with a right-sided Bochdalek-type diaphragmatic hernia, and collect the pertinent literature. Furthermore, we review the embryogenesis of the diaphragm and the pathogenesis of CDH to highlight if this malformation could be explained by a developmental anomaly of CHARGE. On the basis of our study, we suggest that patients affected by CDH, facial asymmetry and cardiovascular or urogenital malformations, should be actively screened for CHARGE syndrome findings.     

Congenital diaphragmatic hernia presenting after the newborn period

Late-presenting congenital diaphragmatic hernia (CDH) is often difficult to diagnose and delay in treatment is common. Seven patients were operated beyond the newborn period for left-sided Bochdaleck hernia. Their age ranged from 1 month to 9 years. Six of them became symptomatic within the 1st year of life (1 week to 9 months of age). Either feeding difficulties or recurrent respiratory infections were initially present. In all of them chest X-rays were performed but delay in diagnosis ranged from 1 week to 5 years. All diaphragmatic defects could be closed by an abdominal approach without postoperative complications. Clinical symptoms disappeared postoperatively. In children with respiratory complaints or feeding difficulties one should be aware of late presenting CDH. A careful analysis of chest films and searching for connecting bowel segments passing through the diaphragmatic defect may help to avoid incorrect diagnosis and undesirable delay in treatment. Confusion with pneumonia or pneumothorax can be diminished by placing a feeding tube and instillation of contrast material. Ultrasound should be used supportively in all suspected diseases of the diaphragm.     

Congenital diaphragmatic hernia and retinoids: searching for an etiology

Congenital diaphragmatic hernia (CDH) is a major life-threatening cause of respiratory failure in the newborn. Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the epidemiology and pathophysiology of human CDH, the metabolism of retinoids and the implications of retinoids in the development of the diaphragm and lung. Finally, we describe the existing evidence of a disruption of the retinoid-signaling pathway in CDH.