Repeated use of betamethasone in rabbits: effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome.

Abstract

The aim of the study was to determine whether reduced birth weight, adrenal suppression, and lung maturation occur in parallel and are cumulative with increasing courses of betamethasone. Time-bred rabbits were assigned to a control group or to receive saline solution or 1, 2, or 3 courses of betamethasone (early treatment, beginning day 19). Two additional groups (n = 5 per group) were given 1 or 2 late courses (late treatment). Birth weight, serum cortisol, adrenal 17alpha-hydroxylase (P450c17) messenger ribonucleic acid and fetal lung surfactant proteins A and B were quantified on day 27. Fetal weight was inversely proportional to the number of courses, with late treatment having a greater effect. Maternal cortisol and P450c17 levels were progressively suppressed with each early course, but fetal cortisol and P450c17 levels were only suppressed after 3 courses. A single late treatment profoundly suppressed both maternal and fetal cortisol and P450c17 messenger ribonucleic acid levels. In contrast, fetal lung surfactant proteins A and B increased progressively with betamethasone courses, regardless of timing. Time from last injection to delivery determined adrenal suppression, whereas total betamethasone courses determined surfactant protein production. Lower birth weight was dependent on the number of courses and was greater with late treatment.