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Updated: Dec 21, 2025
Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
Does Antenatal Betamethasone Alter White Matter Brain Development in Growth Restricted Fetal Sheep?
Amy E Sutherland1, Tamara Yawno1, Margie Castillo-Melendez1
1Department of Obstetrics and Gynaecology, The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC, Australia.
Insights
Fetal growth restriction (FGR) adversely affects the fetal brain, particularly white matter development. Antenatal betamethasone treatment exacerbated growth restriction but did not worsen brain injury in FGR fetuses.
Area of Science:
- Neuroscience
- Developmental Biology
- Obstetrics
Background:
- Fetal growth restriction (FGR) is a common pregnancy complication linked to neurological impairments.
- Antenatal glucocorticoids are used to reduce neonatal mortality but their impact on the fetal brain in FGR is not well understood.
Purpose of the Study:
- To investigate the effects of antenatal betamethasone on the fetal brain in both FGR and appropriately grown sheep models.
- To assess both short- and long-term impacts of betamethasone exposure.
Main Methods:
- Fetal growth restriction was induced in sheep via single umbilical artery ligation (SUAL).
- Ewes received betamethasone or saline treatment during gestation.
- Fetal brains were collected at two time points (48 hours and 10 days post-treatment) for analysis of myelin, glial cells, and neuronal markers.
Main Results:
- FGR fetuses were significantly smaller than controls, and betamethasone reduced body weight in both groups.
- FGR led to reduced myelin staining and increased glial activation in specific white matter regions.
- Betamethasone treatment altered myelin and glial cell staining in specific white matter areas but did not exacerbate FGR-induced brain injury.
Conclusions:
- Fetal growth restriction has progressive adverse effects on fetal brain white matter development.
- While betamethasone exacerbates growth restriction, it does not appear to worsen white matter brain injury in this FGR model.
Abstract:
Fetal growth restriction (FGR) is a common complication of pregnancy often associated with neurological impairments. Currently, there is no treatment for FGR, hence it is likely these babies will be delivered prematurely, thus being exposed to antenatal glucocorticoids. While there is no doubt that antenatal glucocorticoids reduce neonatal mortality and morbidities, their effects on the fetal brain, particularly in FGR babies, are less well recognized. We investigated the effects of both short- and long-term exposure to antenatal betamethasone treatment in both FGR and appropriately grown fetal sheep brains. Surgery was performed on pregnant Border-Leicester Merino crossbred ewes at 105-110 days gestation (term ~150 days) to induce FGR by single umbilical artery ligation (SUAL) or sham surgery. Ewes were then treated with a clinical dose of betamethasone (11.4 mg intramuscularly) or saline at 113 and 114 days gestation. Animals were euthanized at 115 days (48 h following the initial betamethasone administration) or 125 days (10 days following the initial dose of betamethasone) and fetal brains collected for analysis. FGR fetuses were significantly smaller than controls (115 days: 1.68 ± 0.11 kg vs. 1.99 ± 0.11 kg, 125 days: 2.70 ± 0.15 kg vs. 3.31 ± 0.20 kg, P < 0.001) and betamethasone treatment reduced body weight in both control (115 days: 1.64 ± 0.10 kg, 125 days: 2.53 ± 0.10 kg) and FGR fetuses (115 days: 1.41 ± 0.10 kg, 125 days: 2.16 ± 0.17 kg, P < 0.001). Brain: body weight ratios were significantly increased with FGR (P < 0.001) and betamethasone treatment (P = 0.002). Within the fetal brain, FGR reduced CNPase-positive myelin staining in the subcortical white matter (SCWM; P = 0.01) and corpus callosum (CC; P = 0.01), increased GFAP staining in the SCWM (P = 0.02) and reduced the number of Olig2 cells in the periventricular white matter (PVWM; P = 0.04). Betamethasone treatment significantly increased CNPase staining in the external capsule (EC; P = 0.02), reduced GFAP staining in the CC (P = 0.03) and increased Olig2 staining in the SCWM (P = 0.04). Here we show that FGR has progressive adverse effects on the fetal brain, particularly within the white matter. Betamethasone exacerbated growth restriction in the FGR offspring, but betamethasone did not worsen white matter brain injury.
