We examined the hypothesis that a single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis.A prospective, observational, pilot study consisting of four groups of pregnant women: (I) received betamethasone and delivered <2 weeks post treatment; (II) received betamethasone and delivered >2 weeks post treatment; (III) untreated women who delivered <37 weeks (preterm controls); (IV) untreated women who delivered >37 weeks (term controls). Maternal and mixed umbilical cord blood was collected at delivery and analyzed for insulin, glucose, IGF-I, IGF-II, IGFBP-1, IGFBP-3, GH, and GHBP.Betamethasone increased maternal insulin, glucose and IGF-I levels without affecting IGFBPs. In the fetal compartment, betamethasone treatment was associated with a delayed suppressive effect on GH and a sustained suppressive effect on IGF-II levels. There were no differences in infant size or neonatal morbidities between patients who delivered <2 weeks or >2 weeks post betamethasone treatment. In Group IV, birth weight correlated positively with cord IGF-I levels (r2=0.41, p=0.0098) and negatively with cord IGFBP-1 levels (r2=0.51, p=0.0039), and ponderal index correlated negatively with cord IGFBP-1 levels (r2=0.27, p<0.05).A single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis, particularly fetal IGF-II levels, without measurable anthropometric changes at birth. Whether these effects have implications beyond the neonatal period remains to be determined.