Influence of a single course of antenatal betamethasone on the maternal–fetal insulin-IGF-GH axis in singleton pregnancies

Abstract

Objective. We examined the hypothesis that a single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis.Design. 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, GHBP.Results. 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).Conclusions. 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.Irfan Ahmad, MD 1 Running Title: Betamethasone and the insulin-IGF-GH axis. INFLUENCE OF A SINGLE COURSE OF ANTENATAL BETAMETHASONE ON THE MATERNAL-FETAL INSULIN-IGF-GH AXIS IN SINGLETON PREGNANCIES * ManuscriptIrfan Ahmad, MD 2 ABSTRACTObjective. We examined the hypothesis that a single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis.Design. 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, GHBP. Results. Betamethasone increased maternal insulin, glucose and IGF-I levels without affectingIGFBPs. 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 (r 2 =0.41, p=0.0098) and negatively with cord IGFBP-1 levels (r 2 =0.51, p=0.0039), and ponderal index correlated negatively with cord IGFBP-1 levels (r...

Transient Catabolic State with Reduced IGF-I after Antenatal Glucocorticoids

“…The decrement in IGF-I concentrations was observed regardless of BW z score (Fig. 2B); in a recent study that also examined the effect of antenatal betamethasone, there was no effect on IGF-I levels at birth, but the group that received GC Ͻ2 wk before birth was not subdivided (28). IGF-I is a distinct protein-anabolic hormone in the ovine fetus, stimulating protein synthesis while suppressing proteolysis and AA oxidation (19 -21).…”

“…The relative hyperglycemia observed in newborns exposed to GC Ͻ24 h before birth may well be the result of the rise in maternal glucose levels following GC administration (28). In addition, transplacental passage of GC may affect glucose metabolism in the fetus and neonate by down-regulating glucose disposal in peripheral tissues (29) while stimulating hepatic glucose production, as suggested by experiments in sheep fetuses (30).…”

Early-Life Glucocorticoid Exposure: The Hypothalamic-Pituitary-Adrenal Axis, Placental Function, and Long-term Disease Risk

“…IGFBP3 mRNA expression levels were significantly decreased, whereas placental IGF2 mRNA expression was significantly increased (165,173). In humans, antenatal treatment with a single course of betamethasone did not influence IGF-1 or IGFBP3 in umbilical cord serum or umbilical vein plasma in infants born at Ͻ37 weeks but significantly decreased IGF2 and IGFBP1 levels (174,175). These differences persisted even when betamethasone exposure occurred 2 weeks before delivery.…”

Loss of the pregnancy-induced rise in cortisol concentrations in the ewe impairs the fetal insulin-like growth factor axis

“…Although clinical treatment with synthetic glucocorticoids has been associated with marked changes in the fetal IGF axis (Kajantie et al 2001; Li et al 2002; Ahmad et al 2006; Gatford et al 2008), experimental data are mixed. In fetal sheep, cortisol levels similar to those reached near birth inhibit IGF-I production in the skeletal muscle, but stimulate IGF-I in liver (Li et al 2002; Fowden and Forhead 2009).…”