DYNAMICS OF THE FETAL ADRENAL, CHOLESTEROL, AND APOLIPOPROTEIN-B RESPONSES TO ANTENATAL BETAMETHASONE THERAPY

OBJECTIVE: Prior studies suggest that fetal plasma cholesterol is regu lated in part by the rate of uptake and utilization of low-density lip oprotein cholesterol by the fetal adrenals for use in steroid biosynth esis. Direct evidence for this phenomenon and the kinetics of this pro cess is, however, virtually impossible to obtain in a controlled exper iment in the developing human. In the current study we sought to take advantage of the anticipated transient inhibition of the hypothalamic- pituitary-adrenal axis that occurs after antenatal therapy with glucoc orticosteroids, to evaluate the temporal relationship between fetal ad renal steroids and plasma lipoprotein cholesterol levels in umbilical cord blood al delivery. STUDY DESIGN: Umbilical cord serum was obtaine d at delivery from 136 infants (30.5 +/- 2.7 weeks' gestation) who pre viously had been treated in utero with betamethasone, 12 mg per 12 or 24 hours for one or two doses and from 308 preterm infants (30.5 +/- 2 .1 weeks) who had not been exposed to such therapy. We quantified the concentrations of dehydroepiandrosterone sulfate and cortisol as repre sentative fetal adrenal steroids and also measured the total cholester ol and apolipoprotein B; the relationship between the steroids and lip ids as a function of the interval between initial treatment and delive ry was analyzed. RESULTS: Umbilical cord levels of dehydroepiandroster one sulfate and cortisol were significantly reduced within the first 2 4 hours after initial treatment and remained significantly lower than in control infants through 4 days after initial treatment. In contrast , serum levels of cholesterol were significantly increased 3 to 4 days after treatment but fell on day 5. Serum levels of apolipoprotein B g enerally followed the same pattern as cholesterol. Cholesterol levels also were higher than normal in infants delivered 21 week after initia l betamethasone treatment. CONCLUSIONS: The results of this study are consistent with the view that the plasma cholesterol pool in the fetus is regulated, at least in pari, by the rate of uptake of low-density lipoprotein cholesterol and utilization by the fetal adrenals as subst rate for steroidogenesis. Betamethasone also may influence cholesterol and lipoprotein synthesis in the fetus.