Effect of in Utero Vesicostomy on Pulmonary Hypoplasia in the Fetal Lamb with Bladder Outlet Obstruction and Oligohydramnios: A Morphometric Analysis

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Abstract
A model of early gestation bladder outlet obstruction and oligohydramnios in the fetal lamb is characterized by small, immature lungs (pulmonary hypoplasia). The current study examines how in utero relief of urinary tract obstruction produced early in gestation modifies pulmonary hypoplasia. Bladder obstruction was created at 60 days gestation in fetal sheep (term = 140 days); 11 fetuses then underwent in utero decompression at 95 to 100 days; six were left obstructed. Five normal fetuses served as controls and two underwent sham obstruction and vesicostomy. All were delivered and sacrificed near term (135 days), the right lung was inflation-fixed and its volume determined. Relative volumes of alveoli, alveolar ducts, and tissue, alveolar surface area, and alveolar numerical density were estimated morphometrically. Kidneys were examined histologically. In all animals persistent bladder obstruction produced oligohydramnios. Bladder obstruction to term produced pulmonary hypoplasia with a mean right lung volume-to-body weight ratio (LV:BW) of 14.3 cc./kg. (normal = 36.4, p less than 0.001). Structural immaturity was evidenced by an airspace fraction of only 57% (normal = 68%, p less than 0.05). Kidneys in these animals were not dysplastic; there was hydronephrosis or evidence of spontaneous urinary decompression. In eight of the 11 animals, decompression improved the LV:BW ratio to 28.4 cc./kg. (vs. obstructed, p less than 0.001; vs normal, p less than 0.05) and normalized maturity. All had increased amniotic fluid at delivery; kidneys in 7/8 animals were normal, and the other had moderate hydronephrosis. One of the 11 animals had normal kidneys, oligohydramnios, immature lungs, but with normal volume. Oligohydramnios was present in the other two of 11 fetuses despite successful decompression and they had markedly dysmorphic kidneys and profoundly hypoplastic and immature lungs (LV:BW 5.1 cc./kg.). Even after 35 days (25% gestation) of obstruction, in utero urinary tract decompression permits better lung growth and maturation than in persistently obstructed animals. The degree of renal damage from obstruction appears to be a critical determinant in the correction of pulmonary hypoplasia.