L. Pratt et al., Repeated use of betamethasone in rabbits: Effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome, AM J OBST G, 180(4), 1999, pp. 995-1005
OBJECTIVE: The aim of the study was to determine whether reduced birth weig
ht, adrenal suppression, and lung maturation occur in parallel and are cumu
lative with increasing courses of betamethasone.
STUDY DESIGN: Time-bred rabbits were assigned to a control group or to rece
ive 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 o
r 2 late courses (late treatment). Birth weight, serum cortisol, adrenal 17
alpha-hydroxylase (P450c17) messenger ribonucleic acid and fetal lung surf
actant proteins A and B were quantified on day 27.
RESULTS: 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 cort
isol and P450c17 levels were only suppressed after 3 courses. A single late
treatment profoundly suppressed both maternal and fetal cortisol and P450c
17 messenger ribonucleic acid levels. In contrast, fetal lung surfactant pr
oteins A and B increased progressively with betamethasone courses, regardle
ss of timing.
CONCLUSIONS: Time from last injection to delivery determined adrenal suppre
ssion, whereas total betamethasone courses determined surfactant protein pr
oduction. Lower birth weight was dependent on the number of courses and was
greater with late treatment.