Repeated courses of antenatal corticosteroids have adverse effects on aspects of brain development in naturally delivered baboon infants.
ABSTRACT Repeated courses of antenatal steroids in women at risk of preterm delivery have beneficial effects on lung maturation, but concern exists about the effects on brain development. We aimed to determine whether repeated courses of corticosteroids increased the risk of neuropathology as compared with single courses or no treatment.
Single-course animals received a 6-mg dose of steroids at 123 and 124 d of gestation (dg; term, 185 dg; n = 6). Repeated-course animals received additional doses at 137 and 138 dg (n = 7). Controls received no steroids (n = 5). Baboons delivered naturally at term and necropsy was performed. Brains were assessed histologically for parameters of development and neuropathology.
Body weights did not differ between the groups (P > 0.05); neither did brain/body weight ratio. Density of glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes in white matter (WM) was increased in the single- (P < 0.05) and repeated-course (P < 0.01) groups as compared with controls. Density of myelin basic protein (MBP)-IR oligodendrocytes was reduced in the repeated-course animals as compared with both the control and single-course groups (P < 0.05); oligodendrocyte transcription factor 2 (Olig2)-IR showed no difference between groups.
Repeated courses of antenatal corticosteroids have effects on myelination in the developing nonhuman primate brain, which should be taken into account when determining a dosing regimen.
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ABSTRACT: The aim of this study was to determine the effects of a clinically relevant single course of prenatal betamethasone in the rat on growth parameters with particular reference to brain cell proliferation and apoptosis. We report that administration of 170 microg kg-1 betamethasone twice within 4 h to E20 pregnant rats conveys moderate somatic growth retardation. Further, using a measure of brain cell proliferation independent of blood-brain barrier (BBB) permeability, we demonstrate for the first time that betamethasone is chronically anti-proliferative to brain cells without inducing caspase-3-mediated apoptosis. More importantly we show that there is a significant and sexually divergent rebound of neural proliferation which occurs earlier in males than in females and continues until at least 21 days of postnatal life. BBB permeability to [3H]thymidine was significantly increased by steroid treatment re-iterating the fact that tracer studies not correcting for BBB permeability, such as bromodeoxyuridine (BrdU), may be questionable in this type of study. Further, prenatal steroid treatment did not alter postnatal corticosterone levels. In summary we show that prenatal betamethasone conveys significant and long-lasting side effects and that its human clinical application in preterm labour needs more careful consideration as compared to the relative ease with which it is prescribed today.The Journal of Physiology 11/2003; 552(Pt 1):163-75. · 4.38 Impact Factor
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ABSTRACT: Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. To assess the effects on fetal and neonatal morbidity and mortality, on maternal mortality and morbidity, and on the child in later life of administering corticosteroids to the mother before anticipated preterm birth. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 October 2005). Randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery. Two review authors assessed trial quality and extracted data independently. Twenty-one studies (3885 women and 4269 infants) are included. Treatment with antenatal corticosteroids does not increase risk to the mother of death, chorioamnionitis or puerperal sepsis. Treatment with antenatal corticosteroids is associated with an overall reduction in neonatal death (relative risk (RR) 0.69, 95% confidence interval (CI) 0.58 to 0.81, 18 studies, 3956 infants), RDS (RR 0.66, 95% CI 0.59 to 0.73, 21 studies, 4038 infants), cerebroventricular haemorrhage (RR 0.54, 95% CI 0.43 to 0.69, 13 studies, 2872 infants), necrotising enterocolitis (RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants), respiratory support, intensive care admissions (RR 0.80, 95% CI 0.65 to 0.99, two studies, 277 infants) and systemic infections in the first 48 hours of life (RR 0.56, 95% CI 0.38 to 0.85, five studies, 1319 infants). Antenatal corticosteroid use is effective in women with premature rupture of membranes and pregnancy related hypertension syndromes. The evidence from this new review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. Further information is required concerning optimal dose to delivery interval, optimal corticosteroid to use, effects in multiple pregnancies, and to confirm the long-term effects into adulthood.Cochrane database of systematic reviews (Online) 02/2006; · 5.70 Impact Factor
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ABSTRACT: To determine effects of maternal or fetal injections of betamethasone on postnatal growth and arterial pressure. We measured body weight, arterial pressure, and heart rate serially in sheep born after single or repeated maternal or fetal betamethasone injections. At approximately 3.5 years, organ weights were measured. Repeated maternal betamethasone injections caused intrauterine growth restriction, and low body weight and blood pressure at 3 months. From 6 months to 3 years, body weight, blood pressure, and heart rate were not affected by treatment. At approximately 3.5 years, brain weight was reduced after single or repeated maternal betamethasone by 13% and 18%, respectively (P = .001). Fetal betamethasone reduced brain weight by 7% to 8% (P = .018). Weights of other organs were not affected by treatment. Brain weight was unrelated to body weight at approximately 3.5 years (P = .649) but was related to birth weight (P = .029). Prenatal betamethasone does not have long-term effects on blood pressure but causes a persistent deficit in brain weight.American Journal of Obstetrics and Gynecology 02/2005; 192(1):146-52. · 3.88 Impact Factor