Dynamics of the fetal adrenal, cholesterol, and apolipoprotein B responses to antenatal betamethasone therapy,☆☆,,★★

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Abstract

OBJECTIVE: Prior studies suggest that fetal plasma cholesterol is regulated in part by the rate of uptake and utilization of low-density lipoprotein cholesterol by the fetal adrenals for use in steroid biosynthesis. Direct evidence for this phenomenon and the kinetics of this process is, however, virtually impossible to obtain in a controlled experiment 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 glucocorticosteroids, to evaluate the temporal relationship between fetal adrenal steroids and plasma lipoprotein cholesterol levels in umbilical cord blood at delivery. STUDY DESIGN: Umbilical cord serum was obtained at delivery from 136 infants (30.5 ± 2.7 weeks' gestation) who previously 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 representative fetal adrenal steroids and also measured the total cholesterol and apolipoprotein B; the relationship between the steroids and lipids as a function of the interval between initial treatment and delivery was analyzed. RESULTS: Umbilical cord levels of dehydroepiandrosterone sulfate and cortisol were significantly reduced within the first 24 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 generally followed the same pattern as cholesterol. Cholesterol levels also were higher than normal in infants delivered >1 week after initial 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 part, by the rate of uptake of low-density lipoprotein cholesterol and utilization by the fetal adrenals as substrate for steroidogenesis. Betamethasone also may influence cholesterol and lipoprotein synthesis in the fetus. (AM J OBSTET GYNECOL 1996;174:562-5.)

Section snippets

MATERIAL AND METHODS

Umbilical venous serum was obtained at delivery from 136 infants whose mothers had been given a partial or complete course of betamethasone: 1 to 2 intramuscular doses of 12 mg given 12 or 24 hours apart in an attempt to facilitate lung maturation before expected preterm delivery.17 Infants exposed to multiple courses of therapy (usually conducted if delivery did not occur within 1 week of completion of the initial course of treatment) were excluded from these analyses. Twenty-one infants were

RESULTS

Umbilical cord steroids, cholesterol, and apolipoprotein B levels in the betamethasone-treated infants were subdivided according to broad time intervals after initial therapy (Table I). Most of the infants (102/136, 75%) were delivered within the first week after initiation of betamethasone therapy; their serum levels of DHEAS and cortisol were reduced, whereas their total cholesterol concentrations were increased compared with the control group. DHEAS levels were also subnormal among the 16

COMMENT

The acute response of adrenal steroids in the preterm human fetus to intrauterine betamethasone treatment that we found in this study is in general agreement with that described by Ballard et al.15 and that predicted from the studies of others.13, 14 As has been suggested in prior studies of more limited scope,11, 12 we observed that umbilical cord serum levels of cholesterol and apolipoprotein B, the apoprotein of LDL particles, are increased in some infants exposed in utero to synthetic

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  • Cited by (0)

    From the Department of Obstetrics and Gynecology, University of Alabama at Birmingham.

    ☆☆

    Supported by National Institutes of Health grant No. HD 22969.

    Reprint requests: C. Richard Parker, Jr., PhD, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 35233-7333.

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    0002-9378/96 $5.00 + 0 6/1/66854

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