This study examines whether experimental congenital diaphragmatic hern
ia (CDH) induced by nitrofen in rats is accompanied by intestinal malr
otation similar to that observed in the human condition. Time-dated pr
egnant rats were fed 100 mg of nitrofen on day 9.5 of gestation, and f
etuses were examined on days 17, 19, and 21. Body weight, lung weight,
grade of bowel herniation into the umbilical cord and grade of intest
inal malrotation were compared with those of age-matched controls. Bod
y and lung weights were significantly lower in nitrofen-exposed rats o
n days 17, 19, and 21. The umbilical hernia persisted on day 17 in 100
% of experimental animals and 66% of controls (P < .01). Intestinal ma
lrotation was more severe in experimental rats than in controls on day
s 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 sig
nificant (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 ind
uces intestinal malrotation in fetal rats by (1) delaying fetal growth
and maturation; (2) causing CDH, which permits displacement of the li
ver and the gut into the thorax during the critical period of reintegr
ation and fixation; and (3) inducing lung hypoplasia and reducing thor
acic volume during this period. Copyright (C) 1995 by W.B. Saunders Co
mpany.