PRENATAL GLUCOCORTICOIDS IMPROVE PULMONARY MORPHOMETRICS IN FETAL SHEEP WITH CONGENITAL DIAPHRAGMATIC-HERNIA

Purpose: Prenatal glucocorticoids reverse pulmonary immaturity in rode nts with pharmacologically induced congenital diaphragmatic hernia (CD H). The authors applied quantitative stereologic morphometric techniqu es to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH. Methods: Diaphragmatic hernias we re created surgically in fetal lambs at gestational day 80. The fetuse s were treated with intravenous cortisol (n = 6) or normal saline cont rol (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure fr om each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400x using a 42-point equidistan t counting grid, Ten morpho metric parameters (Mean +/- SEM) were meas ured by point-counting 60 fields/lung, and analysis of variance was pe rformed. Results: The CDH-cortisol-treated lungs showed striking signi ficant maturational improvements when compared with lungs of CDH-norma l saline controls by seven of ten morphometric parameters, Conclusions : (1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The obser vation that prenatal glucocorticoid therapy improves measures of matur ity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH. Copyright (C ) 1997 by W.B. Saunders Company.