Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respir atory failure in the newborn. Pulmonary hypoplasia often limits survival. V itamin A (Vit A) is an important signal for lung growth. We hypothesized th at antenatal treatment with VitA would stimulate lung growth and decrease m ortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether). Nitrofen was administere d to pregnant rats on day 12 of gestation (term 22 days). Rats were assigne d to five groups: three groups received one dose of oral antenatal Vit A (1 5,000 IU) before (day 10), concomitant with (day 12), or after (day 14) nit rofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in a ll groups receiving VitA(day 10, 44%; day 12, 20%; and day 14, 40%) compare d with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was hi gher in all 3 Vit A-treated groups (day 10, 40%; day 12, 58%; and day 14, 7 0%) compared with the nitrofen-treated group (16%; P < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vt A lowers the incidence and severity of exper imental CDH and increases lung growth and maturation.