Exposure to synthetic
glucocorticoids in utero markedly improves survival after
preterm birth, but repeated exposures impair fetal and postnatal growth and are associated with evidence of
insulin resistance in later life. The
insulin-like growth factor (IGF) axis is an important regulator of growth and metabolism before and after birth. We have therefore investigated the effects of repeated maternal
betamethasone injections on plasma
IGF-I,
IGF-II, and
IGF-binding proteins (
IGFBP) in fetal and postnatal progeny in the sheep. Pregnant sheep carrying male fetuses were injected with saline or
betamethasone at 104, 111, and 118 days of gestation (dG, term approximately 150 dG). Plasma samples were collected postmortem from fetuses before (75, 84, 101 dG) or after one (109 dG), two (116 dG), or three (121-122, 132-133, 145-147 dG) doses of saline or
betamethasone and from progeny at 42 and 84 days of age.
Fetal weight was reduced after two or more maternal
betamethasone injections, and this effect persisted to term. Repeated
betamethasone exposures reduced plasma
IGF-I and total
IGFBP in fetuses at 133 dG and progeny at 84 days, and reduced plasma
IGFBP-3 at 84 days. Fetal plasma
IGF-II tended to increase transiently at 109 dG following the first
betamethasone injection. Fetal, placental, and/or postnatal weights correlated positively with concomitant plasma
IGF-I,
IGF-II, and total
IGFBP. We conclude that repeated exposure to synthetic
glucocorticoids in utero programs the IGF axis before and after birth, which may contribute to the adverse effects of
betamethasone exposure on growth and metabolism.