Nutritional morbidity in survivors of congenital diaphragmatic hernia.

PURPOSE: The purpose of this report is to detail the nutritional sequelae seen in survivors of congenital diaphragmatic hernia (CDH) followed in a multidisciplinary clinic. METHODS: Data on 121 surviving CDH patients seen between 1990 and 2000 were collected. Regression analysis was used to determine the impact of factors such as Apgar score, birth weight, extracorporeal membrane oxygenation (ECMO), and patch repair on outcomes associated with nutritional morbidity. RESULTS: There were 100 left and 21 right CDH defects. Mean birth weight and 5-minute Apgar score were 3.1 kg (+/-0.8) and 6.8(+/-2), respectively. Extracorporeal membrane oxygenation was required in 43 (36%) patients and patch repair in 39 (32%). A gastrostomy was required in 39 (32%) patients and a fundoplication in 23 (19%) patients. The side of the defect did not affect the frequency of these procedures. Fifty-six percent of patients were below the 25th percentile for weight during most of their first year. Regression analysis found that duration of ventilation (P <.001) and the presence of a patch repair (P =.03) were independent variables predictive of failure to thrive thereby requiring a gastrostomy tube. Patch repair also was predictive of need for subsequent fundoplication caused by gastroesophageal reflux (P <.001). Twenty-nine patients (24%) had severe oral aversion. Risk factors were prolonged ventilation (P =.001) and oxygen requirement at discharge (P =.015). Two thirds of these patients subsequently improved. CONCLUSIONS: Nutritional problems continue to be a source of morbidity for survivors of CDH, particularly in the first year of life. Not surprisingly, patients who had prolonged intubation and prosthetic material at the gastroesophageal junction fared worse. Despite aggressive nutritional management, 56% of the population remained below the twenty-fifth percentile for weight. These data show the need for careful nutritional assessment in all CDH patients, especially those at high risk for malnutrition.

Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic.

BACKGROUND/PURPOSE: In 1990, the authors began a multidisciplinary follow-up clinic for congenital diaphragmatic hernia (CDH) patients. Although the nonpulmonary complications associated with CDH have been reported previously from this clinic, the purpose of this report is to detail the pulmonary outcome in survivors of CDH with severe pulmonary hypoplasia. METHODS: Between 1990 and 1999, one hundred patients were seen in the clinic. Before hospital discharge, all patients had baseline tests performed, which were repeated per protocol at clinic during follow-up. The data were analyzed by regression analysis to identify and determine the impact of factors on outcomes associated with the long-term pulmonary morbidity. RESULTS: The average birth weight was 3.16 kg (+/-0.7) with a mean Apgar score of 7 (+/- 2) at 5 minutes. Forty-one patients had an antenatal diagnosis performed. Extracorporeal membrane oxygenation (ECMO) was utilized in 29 patients, and a patch repair was required in 32, whereas 16 patients received both. Average time to extubation was 20.7 (+/- 20) days and mean time to discharge was 59.7 (+/- 61) days. Regression analysis showed that both the need for ECMO and a patch repair were independent predictors of delay in extubation (P <. 001, R(2) = 36%), and delay in discharge from the hospital (P =.001, R(2) = 29%). ECMO also was significantly correlated with the need for diuretics at discharge (P <.001, R(2) = 18%), and with the presence of left-right mismatch (P =.009, R(2) = 9%) and V/Q mismatch (P =.005, R(2) = 11%) on subsequent pulmonary ventilation-perfusion examinations. Sixteen patients required O(2) at discharge, and diuretics were necessary in 43 patients. Seventeen patients at discharge required bronchodilators, and during the first year an additional 36 required at least transient therapy. Similarly, 6 patients at discharge required steroids, and an additional 35 patients required at least transient therapy during the first year. Chest x-rays, although frequently abnormal, had little correlation with clinical outcome, but did influence medical therapy. V/Q scans had limited utility in patient management, and the presence of V/Q mismatch was not highly specific for future obstructive airway disease. Nevertheless, V/Q mismatch was sensitive for obstructive airway disease assessed by spirometry. Twenty-five patients over 5 years of age performed pulmonary function tests (PFTs), which showed 72% normal PFT results and 28% with evidence of obstructive airway disease. Before January 1997, 2 of 8 patients who required urgent treatment in the emergency department (ED) were admitted to the intensive care unit (ICU) secondary to acute respiratory distress. After the implementation of respiratory syncytial viral prophylaxis in January 1997, 8 patients were treated in the ED for acute respiratory distress, but none required admission to the ICU. CONCLUSIONS: Pulmonary problems continue to be a source of morbidity for survivors of CDH long after discharge. The need for ECMO and the presence of a patch repair are both predictive of more significant morbidity, but the data clearly show that non-ECMO CDH survivors also require frequent attention to pulmonary issues beyond the neonatal period. These data show the need for long-term follow-up of CDH patients preferably with a multidisciplinary team approach.

Stretch-induced upregulation of VEGF gene expression in murine pulmonary culture: a role for angiogenesis in lung development.

BACKGROUND/PURPOSE: The authors' have shown pulmonary alveolarization (capillary and alveolar growth) both after fetal tracheal occlusion and postnatal pulmonary distension. The trophic and developmental mechanisms responsible for this growth remain largely unknown; however, experimental systems have defined an enhanced expression of angiogenic proteins in response to tissue stretch. The authors hypothesize that the stimulation of pulmonary alveolarization after stretch is secondary to upregulation of the potent endothelial cell mitogen vascular endothelial growth factor (VEGF) and that the endothelial cell represents the central stimulus of parenchymal growth. METHODS: A mixed primary pulmonary cell culture obtained by enzymatic digestion of fetal, neonatal, and adult mouse lung was plated on Bioflex elastomer bottom plates, grown to confluence, rendered quiescent, and subjected to continuous cycles of stretch-relaxation with nonstretched cells as controls. Cells were harvested at time-points 0, 30 minutes, 2 hours, 4 hours, 8 hours, and 24 hours. RNA was extracted and VEGF gene expression analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Similar cell groups were harvested, processed, and analyzed utilizing Western Blot techniques. VEGF PCR of mRNA isolated from fetal sheep subjected to surgical creation of diaphragmatic hernia both with (DH-TL) and without (DH) tracheal ligation also was analyzed. RESULTS: VEGF mRNA isoforms 120, 164, and 188 showed increased expression in all stretched groups, which was noted by 30 minutes with maximal expression seen at 2 to 4 hours and a return to baseline expression by 24 hours. VEGF protein was similarly elevated in all stretched cell groups. In preliminary studies, DH/TL sheep showed upregulation of VEGF compared with DH sheep alone. CONCLUSIONS: These data show in an in vitro system that "pulmonary stretch" upregulates VEGF mRNA and protein expression supporting the role of angiogenesis in the stretch-induced pulmonary alveolarization. The authors speculate that such angiogenic activity is a rate-limiting factor in stimulating alveolar epithelial development, and as a treatment modality, therapeutic angiogenesis may provide a noninvasive method with which to treat pulmonary hypoplasia.

Congenital diaphragmatic hernia: where are we and where do we go from here?

The infant born with congenital diphragmatic hernia (CDH) remains one of the most complex patients to manage. Pulmonary hypoplasia and immaturity of the CDH lung are well recognized as the definitive limitation leading to the high mortality rates. Based on the knowledge that CDH is more a physiological disease than a surgical disease, we have shifted our management strategy from immediate repair to delayed repair and stabilization. The associated pulmonary hypertension and right-to-left shunt are common and rarely the cause of death and as such may be largely ignored. Extracorporeal membrane oxygen has been shown to salvage some of the most severely affected neonates. Other advanced and experimental respiratory therapies merit investigation in properly conducted prospective randomized multi-center trials. Survivors of CDH have predictable pulmonary, gastrointestinal and nutritional problems which, when identified and treated early, are correctable. CDH survival is close to 90% at most advanced centers. Uniform standards for CDH management do not exist however. Therefore a minimal set of practice standards should be developed from evidenced-based scientific review.