Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model

To evaluate effects of in-utero endoluminal balloon tracheal occlusion (TO) as suggested for the treatment of Congenital Diaphragmatic Hernia (CDH) on the higher airways of a fetal lamb model.

Fetuses from time-dated pregnant ewes underwent at 94 days (term=145 days) in-utero tracheal occlusion. In study animals an endoluminal, detachable balloon was placed by tracheoscopy. For that purpose a 1.2mm fibre-optic, semi-rigid endoscope and a medically graded latex balloon were used. In group I (n=9) lambs were delivered after 2 weeks. In group II (n=8) the tracheal occlusion was released after 2 weeks, to allow in-utero recovery until term. In positive control animals (group III; n=5) the trachea was clipped at 98 days and fetuses were harvested near term by cesarean section. A total of 17 contralateral littermates in multiple pregnancies served as negative controls. After macroscopic inspection of the trachea, sections were evaluated by light microscopy. Alterations were scored with an empirical interval score for each of the different anatomical elements in the fetal trachea (epithelium, submucosa, cartilage, pars membranacea).

For the animal experiments in group I, all balloons were found in place and according to the pulmonary response they were obstructive. Tracheas were macroscopically dilated by the plug mainly due to elongation of the pars membranacea. The total histologic score was correlated to the increase in circumference (mean increase: 3.0mm). In nearly all cases, the tracheal epithelium at the level of the plug had lost its typical folding pattern. In 44% of cases, local epithelial defects were observed and in 33% of cases there was squamous metaplasia. A chronic inflammatory response was present in over half of the cases, sometimes with giant cell reaction. In group II (the in-utero recovery group) the total score was significantly lower than in group I, with much less prominent unfolding and absence of epithelial defects. Squamous metaplastia was still present in half of the cases; whereas inflammatory responses were less frequent. In group III the trachea expanded normally after removal of the clip. The epithelium had compacted folds, and cilia were well preserved. In two animals however, intraluminal synechia were observed. Below the level of occlusion animals of groups I and II all showed areas of unfolding, but without metaplasia or epithelial defects.

Tracheal obstruction by means of endoluminal plugging has been suggested as an alternative in-utero treatment for congenital diagphragmatic hernia. The balloon causes mild epithelial changes, such as unfolding, limited epithelial defects (<25% of the exposure surface) and local inflammatory changes. These changes disappear nearly completely following in-utero unplugging during the rest of gestation. Unfolding of the epithelium is also seen in the trachea under the plug.