Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1437-1443

Lung Morphometry after Repetitive Antenatal Glucocorticoid Treatment in Preterm Sheep

KAREN E. WILLET, ALAN H. JOBE, MACHIKO IKEGAMI, JANA KOVAR, and PETER D. SLY

Division of Clinical Sciences, Telethon Institute for Child Health Research, Department of Anatomy & Human Biology and Department of Pediatrics, University of Western Australia, Perth, Australia; and Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio

Antenatal glucocorticoids are thought to be less effective when delivery occurs more than 7 d after initiation of treatment; therefore, repeat courses are often administered. We examined lung structure after single or repetitive antenatal glucocorticoid injections in fetal sheep. Pregnant ewes received single or repetitive doses of 0.5 mg/kg betamethasone at 7-d intervals by maternal or fetal injection, beginning at D104 or D114 with delivery at D125, D135, or D146 gestation (term = 150 d). Changes in lung structure were more pronounced after repetitive versus single injections. Repetitive fetal or maternal injections beginning at D104 (delivery at D125) resulted in comparable structural changes: alveolar volume increased by 50 to 80%, alveolar numerical density decreased by 30 to 40%, and pleural and interlobular septal volumes decreased by as much as 70%. Similar changes were seen in animals delivered at D135 after repetitive maternal injections beginning at D114. There were no structural differences between control and repetitive betamethasone animals when delivery was delayed until D146, indicating that betamethasone induced structural changes were reversible.

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