Elsevier

Obstetrics & Gynecology

Volume 94, Issue 2, August 1999, Pages 213-218
Obstetrics & Gynecology

Original Articles
Effect of corticosteroids on brain growth in fetal sheep

https://doi.org/10.1016/S0029-7844(99)00265-3Get rights and content

Abstract

Objective: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep.

Methods: Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days’ gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters).

Results: In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 ± 1.81 g) and controls (42.5 ± 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 ± 1.70 g; P = .022) compared with controls (53.4 ± 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 ± 1.65 g; P = .005) compared with controls (42.5 ± 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 ± 1.52 g; P = .001) compared with controls (53.4 ± 1.73 g) as were all other measures (P < .05).

Conclusion: Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Section snippets

Materials and methods

The effects of corticosteroids on organ weights were reported on animals in this study.16 Ewes were date-mated, then singleton pregnancy was confirmed in each case by ultrasound examination at 85 days’ gestation. All ewes were injected intramuscularly at 100 days’ gestation with 150 mg medroxyprogesterone acetate (Depo Provera; Upjohn, Rydalmere, Australia) to minimize risks of preterm births.

Pregnant ewes were ear-tagged at mating; then, a random number sequence was used to assign them to one

Results

Table 1 provides the data of maternal body weights, lamb birth weights, and gestational ages. As we reported, lamb weights were significantly reduced.16 There were no significant differences in baseline variables of maternal weight or gestational age. Table 2, Table 3 summarize brain growth data for the preterm and term animals in the control and single - and repeated-corticosteroid groups, respectively.

In the single corticosteroid group, after delivery at 125 days’ preterm gestation,

Discussion

Single and repeated doses of corticosteroids retarded brain growth in fetal sheep; repeated doses had more profound effects, particularly at term.

The clinical dose of betamethasone (Table 4) 17, 18, 19, 20, 21 results in a 75% occupancy of corticosteroid receptors in the lung; higher or more frequent doses have little additional benefit.5 The dosage for the current study was similar to that used clinically (Table 4) and conformed to previous studies in sheep in which fetal lung maturation was

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    Supported by Women and Infants Research Foundation, Western Australia, Australian Government Overseas Postgraduate Research Scholarship (to WLH); and National Health and Medical Research Council (NH and MRC) of Australia Program Grant (952304) and Project Grant (980578).

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