Late administration of antenatal vitamin A promotes pulmonary structural maturation and improves ventilation in the lamb model of congenital diaphragmatic hernia.

PURPOSE: The lungs in congenital diaphragmatic hernia (CDH) are hypoplastic and immature making respiratory support one of the most challenging aspects of caring for these neonates. Vitamin A is essential for normal lung growth and development. It also promotes alveolarization. The aim of this study is to investigate the effects of antenatal vitamin A on lung growth and alveolarization and ventilation in the lamb model of CDH. METHODS: This study was approved by the Animal Care Committee of the State University of New York at Buffalo, and conforms to the National Institute of Health guidelines. Diaphragmatic defects were created at 79-81 days gestation. Group 1 lambs (CDH, n = 5) were untreated. In group 2 (CDH + vitamin A, n = 6) and group 3 lambs (control + vitamin A, n = 3) right jugular venous catheters were inserted at 118-120 days and retinyl palmitate (vitamin A) was administered until 135 days. The control group (n = 5) consisted of twin littermates. Lambs were delivered at 136-139 days and ventilated for 2 h according to a set protocol. The left lungs were harvested and fixed for histology. RESULTS: Lung compliance was significantly higher in CDH + vitamin A (median 0.27, range 0.1-0.48 ml/cmH(2)O/kg) versus CDH lambs (median 0.07, range 0.07-0.18 ml/cmH(2)O/kg), P < 0.05. At 1 h CDH + vitamin A lambs experienced significantly lower PaCO(2) (median 115, range 35-194 mmHg vs. median 192, range 168-234 mmHg) and higher arterial pH (median 7.0, range 6.74-7.35 vs. median 6.73, range 6.5-6.81) than CDH lambs, P < 0.05. The lung weight to body weight ratio of CDH + vitamin A lambs was significantly less than that of CDH lambs (P < 0.05). Histology showed small thick walled air-spaces and no true alveoli in CDH lambs. In contrast, true alveoli and thinning of the inter-alveolar septums were seen in CDH + vitamin A lambs. CONCLUSION: This is the first study to demonstrate an improvement in lung function and structural maturation when antenatal vitamin A is given in a surgical model of CDH.

Antenatal vitamin A decreases ventilation-induced lung injury in the lamb model of congenital diaphragmatic hernia.

OBJECTIVE: Infants with congenital diaphragmatic hernia (CDH) are susceptible to ventilation-induced lung injury. Vitamin A may protect the lung from injury during ventilation. The authors investigated the effects of antenatal vitamin A on ventilation-induced lung injury in CDH lambs using lung myeloperoxidase (MPO) activity as an indicator of lung injury. METHODS: Left-sided diaphragmatic defects were created in 10 lambs at 79-81 days' gestation. Six CDH lambs had right jugular venous catheters inserted at 120 days' gestation and were given vitamin A until 135 days' gestation. Four CDH lambs were not treated. Twin littermates (n = 3) served as controls. All lambs were delivered at 136-139 days of gestation and ventilated for 2 hours. Lambs were sacrificed following ventilation and samples of left lung were snap frozen. MPO was extracted from lung tissue and MPO activity was assayed. RESULTS: CDH lambs treated with antenatal vitamin A demonstrated significantly lower MPO activity than untreated CDH lambs (0.0477 +/- 0.0150 vs. 0.1106 +/- 0.0230 units/mg protein, p < 0.05). CONCLUSION: This is the first study to look at the effect of vitamin A on lung injury in CDH. In the lamb model of CDH, antenatal vitamin A decreases ventilation-induced lung injury.

Diagnosing Hirschsprung's disease: increasing the odds of a positive rectal biopsy result.

BACKGROUND/PURPOSE: Rectal biopsies are performed as a definitive means of diagnosing Hirschsprung's Disease (HD) in children presenting with constipation. The authors hypothesized that key features in the history, physical examination, and radiographic evaluation would allow us to avoid unnecessary rectal biopsies. METHODS: A retrospective analysis was conducted on patients undergoing rectal biopsy between 1995 and 2001. Patients with HD were identified (n = 50), and a concurrent cohort of patients with idiopathic constipation (IC; n = 50) was selected. Pertinent features in patients with HD versus those with IC were cross tabulated using Pearson Chi2 testing (significance was P <.05). RESULTS: Sixty percent of patients with HD and 15% of patients with IC experienced onset of symptoms in the first week of life. HD patients more frequently experienced delayed passage of meconium (P <.05), abdominal distension (P <.05), vomiting (P <.05), and transition zone on contrast enema (P <.05). All patients with HD had one or more of these significant features. In contrast, only 64% of patients with IC had one or more of these features. The classic triad of symptoms (ie, delayed passage of meconium, vomiting, and abdominal distension) was present in 18%, and one or more of these symptoms was present in 98% of HD patients. In contrast, only 60% of patients with IC had a history of delayed passage of meconium, vomiting, or abdominal distension. CONCLUSIONS: A history of delayed passage of meconium, abdominal distension, vomiting or the results of a contrast enema identified all patients with HD and excluded HD in approximately 36% of patients with idiopathic constipation. The authors have shown that key features in a patient's history, physical examination, and radiologic evaluation can differentiate between HD and IC. In a child presenting with constipation and none of the above features, it is not necessary to perform a rectal biopsy to exclude HD.