Current Concepts in the Management of Congenital Diaphragmatic Hernia in Infants

The therapeutic approach to congenital diaphragmatic hernia (CDH) has shifted from one of immediate repair to management of pulmonary hypertension, physiologic stabilization, and delayed surgical repair. Lung hypoplasia, remodeled pulmonary vasculature, and ventricular dysfunction all contribute to the high morbidity and mortality associated with CDH. In addition, genetic syndromes associated with CDH can increase the incidence of serious anomalies and hence impact survival. Prenatal and postnatal management of infants with CDH is challenging in the best of circumstances and need multidisciplinary teams for optimal outcomes. However, advances using ultrasound and fetal MRI can predict prognosis and survival and plan for postnatal management. Survival rates for patients with CDH have increased for the past decade with better management at resuscitation; implementation of gentle ventilation strategies; and medical management of pulmonary hypertension, physiologic stabilization, and extracorporeal membrane oxygenation. However, follow-up of these infants for long-term morbidities is essential for optimal outcomes after discharge.     

Current and future strategy in the treatment of congenital diaphragmatic hernia

The severity of congenital diaphragmatic hernia (CDH) depends on the degree of lung hypoplasia. It is still difficult to rescue the most severely affected infants with cardiopulmonary insufficiency immediately after birth. However, the recent treatment strategy has improved the outcome of CDH. High-frequency ventilation (HFV) and gentle ventilation have been reported to be effective in the treatment of CDH by minimizing the barotrauma of the hypoplastic lung. Various vasodilators such as nitric oxide and prostaglandin-E1 have been found to be improve the pulmonary hypertension due to hypoplastic lung. On the other hand, the indications for extracorporeal membrane oxygenation (ECMO), which used to be the most powerful life support for severe CDH, have become limited. In our institute, antenatally diagnosed CDH infants with inadequate oxygenation despite maximum respiratory support immediately after birth are excluded from ECMO candidates because of fatal lung hypoplasia. Recently, it has been reported that temporary tracheal occlusion can accelerate fetal lung growth and improve the outcome of severe CDH. Percutaneous fetal endoluminal tracheal occlusion is expected to become an effective and minimally invasive treatment for fatal lung hypoplasia due to CDH.     

Neonatal thoracoscopic repair of congenital diaphragmatic hernia: selection criteria for successful outcome

Background/Purpose

Complications of open conversion, hypercarbia, and intestinal injury have plagued minimally invasive approaches to congenital diaphragmatic hernia (CDH) repair in neonates. To safely begin using minimally invasive techniques for neonatal CDH repair, we formulated preoperative selection criteria and operative techniques that would enhance chances for successful thoracoscopic primary diaphragm repair and uncomplicated outcome.

Methods

During the period from January 2003 to October 2004, neonates were selected for thoracoscopic CDH repair using anatomic and physiologic criteria. Anatomically, all patients were required to have stomach in the abdomen by radiography. Physiologically, all patients were required to be on minimal ventilator support with preoperative ventilator peak inspiratory pressures in the low 20s mm Hg. No patient could have clinical evidence of pulmonary hypertension at the time of surgery. Thoracoscopic CDH repair was performed using 3 trocars (3 and 5 mm). The hernia contents were reduced into the abdomen using 5-mm Hg insufflation, and the diaphragms were repaired primarily using interrupted 3-0 Ethibond simple sutures (Ethicon, Inc, Piscataway, NJ). Posterolateral diaphragm stitches were passed around the posterolateral ribs and tied extracorporeally.

Results

Thirty neonates with CDH were admitted to Children's Hospital Boston and Vanderbilt Children's Hospital during the study period. Eight patients (27%) met selection criteria and 7 underwent thoracoscopic CDH repair. Primary diaphragmatic repair was successfully accomplished thoracoscopically in all neonates without perioperative complication. Preoperative anatomic criteria correlated accurately with intact esophageal hiatus and primary diaphragm repair. Physiologically, each patient tolerated intrathoracic insufflation and CDH repair without clinical pulmonary hypertension or blood pressure lability. Three patients had intraoperative respiratory acidosis that was reversed with ventilator changes. Operative times averaged 152 minutes and ranged from 212 to 106 minutes. Postoperative mechanical ventilation ranged from 0 to 7 days, and the length of hospitalization ranged from 5 to 32 days. Longest follow-up has been 17 months. One patient required reoperation for recurrent CDH at 10 months after repair, but there have been no other long-term complications.

Conclusions

Neonatal thoracoscopic CDH repair is safe in selected patients who have good preoperative pulmonary function and anatomy amenable to primary diaphragmatic repair. A wider range of neonates may be acceptable for thoracoscopic CDH repair with increasing surgical experience.     

Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH.

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.     

Congenital diaphragmatic hernia: searching for answers

BACKGROUND: Pulmonary hypoplasia and hypertension are the primary causes of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). At present, the origin of CDH and the causes of pulmonary hypoplasia and hypertension are unknown. DATA SOURCES: This article reviews the available published data regarding the origin of CDH and the pathogenesis of the associated pulmonary hypertension and hypoplasia. These investigations have employed human tissues as well as two types of CDH animal models. CONCLUSIONS: Investigations performed to date have not yet provided definitive answers regarding the pathogenesis of CDH. However, they have yielded many new and exciting discoveries and several opportunities for intervention. Ongoing research should open new possibilities to improve the outcome for these unfortunate babies with CDH.     

Postnatal pulmonary hypertension after repair of congenital diaphragmatic hernia: predicting risk and outcome

BACKGROUND: Pulmonary hypertension (PH) after congenital diaphragmatic hernia (CDH) repair remains a significant cause of morbidity and mortality. Although treatment advances have improved overall survival, a new cohort of patients is surviving with PH beyond the postnatal period. Because the clinical entity of postnatal persistent pulmonary hypertension (PPHTN) in CDH patients has not been published, the authors undertook a retrospective study of our neonatal CDH experience to characterize this group of infants. METHODS: Charts of all infants with CDH treated at this institution from January 1991 to June 1997 were reviewed (n = 51). Persistent pulmonary hypertension by echocardiographic (Echo) measurements at the time of discharge identified PPHTN patients. Control survivors had normal pulmonary artery pressures at discharge. Physiological parameters and the results of therapeutic interventions were analyzed to predict PPHTN. RESULTS: Seven infants (four boys, three girls) had PPHTN at discharge. Significant differences with the control group were noted in length of stay, duration of intubation, and duration of nitric oxide therapy. Extracorporeal membrane oxygenation (ECMO) duration was not significantly different between the groups. By 12 months of age, PPHTN resolved in six patients (87%), and one died at 13 months. Regardless of therapy, two parameters showed 100% positive predictive value for identifying patients with PPHTN (P < .001): an Echo demonstrating PH at 2 months of age or continued oxygen requirement at 3 months. Oxygen requirement at 2 months had a 67% predictive value of PPHTN. CONCLUSIONS: With current treatment strategies for CDH, infants can survive with persistent pulmonary hypertension beyond the newborn period. The long-term survival rate is excellent, and normalization of pulmonary artery pressures can be expected. PPHTN can be predicted in those infants with Echo-defined pulmonary hypertension at 2 months.     

Correlation of fetal posture and congenital dislocation of the hip

A statistical study was carried out on the incidence of CDH associated with mechanical factors in the uterus, including congenital genu recurvatum. There were 72 cases of CDH among 6559 infants (1.1 per cent). The incidence of CDH was 0.7 per cent in cephalic presentation, 2 per cent in footling presentation and 20 per cent in single-breech presentation. In another series, CDH was found in six of seven infants with congenital genu recurvatum. These findings suggest that a fetal posture with the hip flexed and the knee extended predisposes to the development of CDH.     

Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia

Background/Purpose

Advances in management of patients with congenital diaphragmatic hernia (CDH) have improved mortality rates but with a risk of increased pulmonary morbidity. The prognosis for CDH survivors remains difficult to predict owing to the lack of adequate methods. We used single photon emission computed tomography (SPECT) to measure the regional distribution of ventilation and perfusion in CDH infants to quantify the degree of lung function impairment and relate it to neonatal clinical disease severity.

Methods

Single photon emission computed tomography was performed in 12 CDH infants at the mean age of six months. Ventilation and perfusion were traced with 5 MBq Technegas and technetium-labelled albumin macro-aggregates, respectively. Neonatal clinical data collected during the patient's stay in the pediatric intensive care unit was correlated with the SPECT data.

Results

Single photon emission computed tomography revealed varying degrees of ventilation-perfusion abnormalities which correlated with the presence of pulmonary artery hypertension, days on ventilator and days on extracorporeal membrane oxygenation.

Conclusions

The grade of clinical disease severity in infants following CDH repair is closely related to the ventilation-perfusion abnormality as seen using SPECT. The persistence of pulmonary artery hypertension into the postoperative neonatal period appears to be an important pathophysiological factor related to ventilation-perfusion abnormalities. Single photon emission computed tomography provides valuable clinical information for patient follow-up.     

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of 200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.     

Current progress in neonatal surgery

Neonatal surgery is the most specialized and sophisticated field of pediatric surgery. I herein review esophageal atresia, abdominal wall defects, gastrointestinal perforation, and congenital diaphragmatic hernia (CDH) as representative types of neonatal surgery. The clinical results of esophageal atresia have been considered to reflect the level of medicine of an individual country. Owing to an early diagnosis, improved operative techniques, and better perioperative management, the mortality rate has now become almost 0%. In addition, a minimally invasive thoracotomy is considered to improve long-term quality of life. The overall mortality rate of neonatal surgical disease has markedly decreased and is now less than 10%. However, abdominal wall defects, gastrointestinal perforation, and CDH still show a high mortality rate. A high incidence of chromosomal anomalies results in a poor outcome for abdominal wall defect. A gastrointestinal perforation in an infant complicated with an extremely how birth weight shows a high mortality rate. In CDH, pulmonary hypoplasia as well as pulmonary hypertension often causes an acute respiratory and circulatory deterioration after birth. Neither intensive care for pulmonary hypertension, including ECMO, nor fetal intervention has yet achieved a satisfactory outcome. Permissive hypercapnea and a delayed operation aiming at circulatory stabilization have resulted in a good survival rate. However, CDH survivors may be at risk for long-term morbidities. The method to induce pulmonary development is considered to be mandatory to achieve a good quality of life for severe CDH.     

Clinical and research developments in congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a lethal human birth defect occuring in 1 : 2 500 births. An infant with CDH is born every 24–36 hours in the UK. Hypoplastic lung development is the leading contributor to the 40–50% mortality of CDH ( 1 ). Efforts to improve survival have focused on fetal intervention, advances in intensive care, in utero diagnosis and delivery at specialist centres 1 - 3 ). High frequency oscillatory ventilation, permissive hypercapnia, inhaled nitric oxide and ECMO have been employed with variable outcome 4 - 6 ). Preoperative stabilisation and delayed surgical repair is currently performed at most centres ( 7 , 8 ). The impact of abnormal lung development on affected infants has stimulated research on the developmental biology of CDH. Traditionally lung hypoplasia has been viewed as a consequence of in utero compression of the fetal lungs by herniated viscera prolapsing through a defect in the diaphragm. Based on this ‘compression theory’ fetal surgery was pioneered to repair CDH and rescue lung growth in ‘high risk’ cases. It has shown no survival benefits. New insights into mechanisms regulating fetal lung growth and maturation are providing alternative less invasive antenatal strategies. Prompted by the observation that humans with congenital larnygeal atresia have enlarged hyperplastic lungs fetoscopic tracheal occlusion (FETENDO‐PLUG) is being evaluated in human trials for the ‘high risk’ CDH fetus With liver herniation ( 3 ). Pharmacological strategies to ameliorate pulmonary hypoplasia in CDH are under investigation. Human studies have shown that the lungs of babies with severe CDH resemble the immature lungs of premature newborns with respiratory distress syndrome (RDS). Prenatal hormonal therapy regimens adapted from RDS protocols have demonstrated striking improvements in lung maturation in experimental CDH models. An international multicentre trial of corticosteroid therapy is now underway in prenatally diagnosed CDH patients ( 9 ). Closure of the human diaphragm at 8 weeks gestation limits detailed embryological investigation of CDH to teratogenic models. The ‘compression theory’ of pulmonary hypoplasia has been challenged by studies of primordial lung development prior to diaphragmatic hernia ( 10 ). Disruption of stereotyped airway branching correlates with and precedes CDH indicating an intrinsic defect of lung development in CDH. Organotypic culture sytems are providing invaluable research tools to manipulate lung hypoplasia and investigate the role of growth factors and cell signalling pathways. Genetic studies in murine models and the fruitfly Drosophila melanogaster have elucidated the molecular control of respiratory organogenesis. Testing fibroblast growth factors (FGFs), epidermal growth factor (EGF) and heparin on normal and hypoplastic lung primordia has demonstrated profound differences in embryonic growth and pulmonary morphogenesis that indicate intrinsic defects in mitagenic regulatory pathways fundamental to CDH 11 - 13 ). What are the future therapeutic implications for clinicians treating CDH? Selection of patients for fetal surgery will require more accurate prognostic indicators of poor perinatal outcome. Fetal surgery at present may be ‘too little too late’ to correct an established embryopathy in pulmonary development. Antenatal corticosteroid therapy is the subject of a multicentre trial. Fetoscopic delivery of targeted growth factors to enhance airway development in CDH will require careful appraisal. The concept of a pharmacological agent or medical ‘PLUG’ to reverse pulmonary hypoplasia is a goal for the future. Postnatal therapies to reduce barotrauma will salvage those newborns with the less severe degrees of pulmonary hypoplasia. Finally prevention of the birth defect by preconceptual prophylaxis (as in the case of neural tube defects) may represent the ultimate solution for this highly lethal human anomaly ( 14 ).     

Oxygen-induced vasodilation is blunted in pulmonary arterioles from fetal rats with nitrofen-induced congenital diaphragmatic hernia

BACKGROUND/PURPOSE: Persistent pulmonary hypertension contributes to the high mortality rate associated with congenital diaphragmatic hernia (CDH). Oxygen is an important stimulus for pulmonary vasodilation in the perinatal period. The authors have investigated the responses of isolated pulmonary arterioles from fetal rats with and without CDH to an increase in oxygen tension. METHODS: CDHs were induced in fetal rats by feeding nitrofen to timed-pregnant rats at midgestation. A third-generation pulmonary arteriole was isolated from the right lung at term. Isolated arterioles were pressurized at their "optimal distending pressure." Diameter changes in response to an increase in oxygen tension from 25 to 40 mm Hg ("hypoxic" conditions) to 90 to 150 mm Hg ("normoxic" conditions) were recorded for K(+) preconstricted arterioles from control rats, from rats with nitrofen-induced CDH, and from rats that were nitrofen exposed but did not have a CDH. RESULTS: "Normoxic" exposure reversed the K(+) preconstriction in control arterioles by 124 +/- 26%. In contrast, arterioles from rats with nitrofen-induced CDH dilated significantly less than controls (20 +/- 15% of the K(+) preconstriction). The responses of arterioles from rats that were nitrofen exposed but did not get a CDH were not different (P >.05) from controls. CONCLUSIONS: Oxygen-induced vasodilation is blunted in pulmonary arterioles from rats with nitrofen-induced CDH. Blunted oxygen-induced vasodilation may contribute to persistent pulmonary hypertension in CDH. J Pediatr Surg 36:593-597.     

The surgical management of total atrioventricular canal lesions.

Between 1969 and 1976 sixteen children have had surgery for total atrioventricular canal lesions at the Royal Children's Hospital, Melbourne. Twelve infants had palliative banding of the main pulmonary artery to control heart failure and prevent the development of pulmonary hypertension, with two hospital deaths (17%) and one late death. One other patient has been lost to follow-up and may also have died. Nine patients have undergone complete repair, with three hospital deaths (33%), and one later death at reoperation for residual mitral incompetence. Five of these had previously had banding of the main pulmonary artery, and the mortality has occurred exclusively in this group. The techniques of repair are discussed, and reasons advanced in favour of early primary repair of the defect in preference to palliative banding and later secondary repair.     

Fetal stabilization for antenatally diagnosed diaphragmatic hernia

BACKGROUND/PURPOSE: Infants with congenital diaphragmatic hernia have pulmonary hypoplasia resulting in persistent pulmonary hypertension of neonates (PPHN), which is the main contributor to both high mortality and morbidity. The pulmonary artery bed in patients with congenital diaphragmatic hernia (CDH) is underdeveloped and is very sensitive to slight stimuli. It is, therefore, vital to avoid any factors that might increase pulmonary vascular resistance during the perinatal treatment of these patients. Recently, fetal anesthesia for perinatal stabilization in patients with CDH has been reported. However, the efficacy of this method remains controversial. The aim of this study is to analyze the benefits of fetal stabilization using fetal anesthesia in patients with CDH. METHODS: The authors have seen 9 cases of antenatally diagnosed CDH and attempted fetal stabilization. The indication for fetal stabilization was a lung thoracic ratio of less than 0.2, without any severe associated anomalies. The protocol for fetal stabilization was (1) monitoring the fetal respiratory movement and heart beat by ultrasonography, (2) the administration of morphine (20 to 30 mg) and diazepam (5 mg) to the mother, (3) the confirmation of any interruptions in fetal movement followed by a cesarean section, (4) pancuronimum (0.5 mg) was given through the umbilical vessels, (5) intubation before clamping of the umbilical cord, and (6) high-frequency oscillatory ventilation (HFO) without bagging. RESULTS: The lung-thratic ratio (LTR) was between 0.06 to 0.17 (average, 0.10+/-0.04). Operation was performed in 7 of 9 patients at between 2.5 and 27 hours after birth. The overall survival rate was 66.7% (6 of 9). All of the patients who underwent operation within 5 hours after birth survived. CONCLUSIONS: Perinatal stabilization using fetal anesthesia was found to be effective in preventing PPHN and shortening the period of preoperative stabilization. It also improved the survival rate of patients with severe CDH.     

Congenital Diaphragmatic Hernia: Advances in Prenatal Therapy

Congenital diaphragmatic hernia (CDH) is one of the most common causes of neonatal morbidity and mortality. The clinical spectrum of CDH ranges from minimally affected infants who do well with modern neonatal care to severely affected infants who die despite all interventions. Two decades of research have led to advances in the prenatal diagnosis of CDH and have better defined the natural history of CDH. Fetuses with CDH now can be stratified into "low" and "high" risk groups based on sonographic parameters. "Low risk" fetuses have an excellent chance of survival with postnatal therapy. Prenatal intervention is reserved for "high risk" fetuses. Ongoing research is focused on improving both prenatal and postnatal treatment of these severely affected infants.     

Small lungs and suspect smooth muscle: congenital diaphragmatic hernia and the smooth muscle hypothesis

Lung hypoplasia and congenital diaphragmatic hernia (CDH) represent an unsolved clinical and scientific problem. Early lung morphogenesis is coupled to development and function of pulmonary smooth muscle. Activity of the latter is abnormal from the earliest stages of hypoplastic lung development and before supervening CDH. A “smooth muscle hypothesis” is advanced to help explain embryonic lung malformations, fetal failure of lung growth, and postnatal susceptibility to barotrauma, airway hyperreactivity, and pulmonary hypertension in CDH. Exploring the interaction of smooth muscle function and airway pressures may help optimise tracheal occlusion and provide support for both an adequately powered trial of glucocorticoids and also for experimental “preventilation” strategies in fetal CDH.     

The effect of extracorporeal membrane oxygenation on the survival of neonates with high-risk congenital diaphragmatic hernia: 45 cases from a single institution

At The Children's Hospital, Boston (TCH), in the 3 years before extracorporeal membrane oxygenation (ECMO) was available, infants with high-risk congenital diaphragmatic hernia (CDH) had a 47% survival rate. In February 1984, ECMO was introduced and offered to all high-risk CDH infants with a 100% predicted mortality. Since February 1984, 45 infants with high-risk CDH presented to TCH. Twenty-six (58%) were supported with ECMO; 19 (42%) never met the criteria for 100% predicted mortality and were supported with conventional mechanical ventilation (CMV). Overall survival was 49%. Nine (35%) of the 26 ECMO patients survived. Thirteen (68%) of the 19 CMV patients survived. Although there was no change in survival, there was a change in the cause of death. Deaths in the ECMO group were either early (n = 8, secondary to a complication of ECMO or lack of pulmonary improvement) or late (n = 9). The late deaths were infants who were successfully weaned from ECMO, never weaned from CMV, and who died secondary to complications of chronic lung disease.     

Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.     

Congenital diaphragmatic hernia, extracorporeal membrane oxygenation, and death: a spectrum of etiologies

Extracorporeal Life Support Organization (ELSO) registry data show increased mortality in congenital diaphragmatic hernia (CDH) infants compared with other extracorporeal membrane oxygenation (ECMO) indications. To test the hypothesis that death might be related to various clinical parameters, retrospective data collection was solicited on 175 ECMO-related CDH deaths from 41 American ECMO centers (ELSO Registry 1980 through 1989). Data capture forms were received on 100 of 175 infants representing 29 of 41 centers. After review of all available material, a predominant cause of death was assigned. Other diagnoses were given secondary status. We analyzed arterial blood gas values at 6, 3, and 1 hour pre-ECMO, as well as at the time of highest recorded PO2 (preductal and postductal) and lowest recorded PCO2, and correlated these findings with predominant cause of death. The relationship between individual variables and cause of death was assessed by t test. Multivariate analysis was performed by using a stepwise discriminate procedure. The most common predominant causes of death were brain death (29%), pulmonary hypertension (25%), and pulmonary hypoplasia (17%). Correlation of arterial blood gas values at 6, 3, and 1 hour pre-ECMO with predominant causes of death established the following statistically significant associations (P less than .05): (1) pulmonary hypoplasia and low PO2 at 6 hours pre-ECMO; (2) brain death and low pH at 1 hour pre-ECMO; and (3) pulmonary hypertension and high HCO3- at 1 hour pre-ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular malformations in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Newborns with congenital diaphragmatic hernia (CDH) frequently have associated anomalies that have a major impact on survival rate independent of pulmonary hypoplasia and pulmonary hypertension. Cardiovascular malformations (CVM) represent a major group of lethal extrapulmonary abnormalities that often assume greatest prognostic significance in most CDH studies. Animal models resembling human CDH may aid knowledge of the basic embryology that leads to the coexpression of CDH and CVM. This study, therefore, analyzed the incidence and spectrum of CVM in fetal rats with CDH. METHODS: Left-sided CDH (LCDH) was induced in fetal rats by the maternal administration of 100 mg of nitrofen by gavage on day 9.5 gestation (term, day 22). Control animals received olive oil (OO) and were used for comparative analysis. Fetal rats were harvested by cesarean section on day 21.5 or day 22, histologically processed and examined for CVM. RESULTS: A significant number of CVM were observed in 15 of 60 (25%) LCDH rats compared with 4 of 60 (6.7%) nitrofen non-CDH rats (P = .01). The spectrum of abnormalities in CDH included ventricular septal (VSD) defects (n = 6), vascular rings (n = 4), anomalous subclavian arteries (n = 3), atrioventricular septal defects (n = 1) and Fallot's tetralogy (n = 1). A VSD (n = 1), double-outlet right ventricle VSD (n = 1) and Fallot's tetralogy (n = 2) were noted in nitrofen non-CDH rats. Control (OO) fetal rats (n = 60) displayed no malformations. CONCLUSIONS: These results confirm a significant incidence and spectrum of CVM in a teratogenic CDH model similar to that seen in humans with CDH. The findings of this study reinforce the validity of the nitrofen model as a research tool to uncover the genetic and molecular mechanisms responsible for the genesis of CDH and allied malformations.