Betamethasone and the Rhesus Fetus: Effect on Lung Morphometry and Connective Tissue

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Abstract
Summary: Pregnant rhesus monkeys (Macaca mulatta) at 67 to 85% of term pregnancy were treated with betamethasone for 3 days and then delivered by cesarean section. These treated fetuses had larger lung volumes (32.6 × 1.8 ml/kg of body weight) compared to gestational age-matched controls (22.9 × 3.2 ml/kg of body weight; P < 0.025) but no alterations in surfactant properties as measured by amniotic fluid L/S ratios, alveolar deflation stability, or lung phosphatidylcholine. These findings suggest that betamethasone effects an increase in fetal lung volume by some method other than alteration in alveolar surfactant concentrations. Results also demonstrated an 11% increase in the collagen to elastin concentration in the treated fetuses as compared to the control animals (P < 0.01), suggesting alterations in lung connective tissue. Morphometric studies done on the air-fixed inflated lung demonstrated a decrease in the number of alveoli per unit volume of lung among the treated animals (0.95 × 0.07 × 106) compared to the control animals (1.19 × 0.08 × 106; P < 0.025) and a reduction in the mean surface area of the lungs of the treated animals (506 × 10 cm2 per cm3) compared to the control animals (561 × 9 cm2 per cm3; P < 0.005). These findings suggest that at least part of the increased maximal lung volumes is related to increased alveolar distensibility. Together, these pressure volume findings, biochemical studies, and morphometric analyses indicate that a major effect of betamethasone on the rhesus fetal lung is to alter lung connective tissue characteristics. Alterations in lung surfactant appear to be of less functional significance in this rhesus fetal model. The disparity between these findings and other animal studies might be due to differences in species, the preparation, or the method of glucocorticoid administration. Speculation: Maternal betamethasone treatment produces alterations in the connective tissue properties of the developing fetal lung, which could have long-lasting effects on lung mechanical properties.