Intestinal rotation in experimental congenital diaphragmatic hernia

This study examines whether experimental congenital diaphragmatic hernia (CDH) induced by nitrofen in rats is accompanied by intestinal malrotation similar to that observed in the human condition. Time-dated pregnant rats were fed 100 mg of nitrofen on day 9.5 gestation, and fetuses were examined on days 17, 19, and 21. Body weight, lung weight, grade of bowel herniation into the umbilical cord and grade of intestinal malrotation were compared with those of age-matched controls. Body and lung weights were significantly lower in nitrofen-exposed on days 17, 19, and 21. The umbilical hernia persisted on day 17 in 100% of experimental animals and 66% of controls (P < .01). Intestinal malrotation was more severe in experimental rats than in controls on days 19 (63% v 17% grade 2; P < .01) and 21 (27% v 0% grade 1; P < .01). Finally, 52% of nitrofen-fed fetuses with CDH had malrotation at term, whereas only 18.2% of those without it did (P < .05). There was a significant (P < .001) negative correlation between the lung weight/body weight ratio and the degree of malrotation in nitrofen-treated fetuses. In conclusion, maternal nitrofen exposure on gestational day 9.5 induces intestinal malrotation in fetal rats by (1) delaying fetal growth and maturation; (2) causing CDH, which permits displacement of the liver and the gut into the thorax during the critical period of reintegration and fixation; and (3) inducing lung hypoplasia and reducing thoracic volume during this period.