Maternal Betamethasone Administration Research Articles

Cardiovascular responses to maternal betamethasone administration in the intrauterine growth–restricted ovine fetus

The objective was to characterize the effect of glucocorticoid treatment on fetal organ blood flow and regional cerebral blood flow in normally grown fetuses and fetuses with intrauterine fetal growth restriction (IUGR). Studies were undertaken in both control and IUGR fetal sheep; growth restriction was induced by ligation of 1 umbilical artery. Fetuses received colored microspheres for organ blood flow calculations before and after 2 maternal betamethasone injections (BM1 and BM2). Following BM1, cardiac output was significantly decreased in the control fetuses and blood flow to the heart and placenta was unchanged, whereas total cerebral blood flow was significantly decreased (P<.001), consistent with cerebral vasoconstriction. In the fetuses with IUGR, the cardiac output was significantly increased at +33 hours relative to BM1, and blood flow was increased in all organs; notably, there was a 2-fold increase in cerebral blood flow (P=.03). The cardiovascular response of the fetus with IUGR to glucocorticoids is profoundly different from the control fetuses, which may induce both short- and long-term injury.

Fetal hemodynamic changes following maternal betamethasone administration in pregnancies with fetal growth restriction and absent end‐diastolic flow in the umbilical artery

To examine the effects of betamethasone administration on umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler flow. Longitudinal prospective study. Fetal Surveillance Unit, Department of Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil. Thirty-two singleton pregnancies complicated by fetal growth restriction with absent end-diastolic flow in the UA. Pulsatility index (PI) of the UA, MCA and DV was measured from 26 to 34 weeks prior to and within 24 or 48 hours after starting betamethasone treatment course. Analysis of variance for repeated measures was used to determine the changes in the fetal hemodynamic Doppler flow following maternal corticosteroid administration. Improvement of UA-PI within 24 hours and DV-PIV (venous pulsatility) within 48 hours from the first betamethasone dose. Mean gestational age at delivery was 29.3 (+/-1.8) weeks and birthweight was 806.6 (+/-228.2) g. A reduction in the UA-PI was observed in 29 (90.6%) cases, with return of end-diastolic flow in 22 (68.7%). The mean UA-PI were 2.84 (+/-0.52) before corticosteroid administration, 2.07 (+/-0.56) within 24 hours and 2.42 (+/-0.75) after 48 hours, with a significant difference along the evaluations (p<0.001). No significant changes in the MCA Doppler were observed. DV-PIV decreased from 1.06 (+/-0.23) prior corticosteroids administration to 0.73 (+/-0.16) within 24 hours and 0.70 (+/-0.19) after 48 hours (p<0.001). There was reduction in the umbilical artery and in the DV pulsatility indices within 24 hours from betamethasone administration that was maintained up to 48 hours.

35: Maternal administration of betamethasone inhibits pulmonary proliferation but stimulates maturation after fetal tracheal occlusion in the nitrofen rat model - A placebo controlled study

35: Maternal administration of betamethasone inhibits pulmonary proliferation but stimulates maturation after fetal tracheal occlusion in the nitrofen rat model - A placebo controlled study

Maternal administration of betamethasone inhibits proliferation induced by fetal tracheal occlusion in the nitrofen rat model for congenital diaphragmatic hernia: a placebo-controlled study

Fetal tracheal occlusion (TO) is offered to fetuses with severe pulmonary hypoplasia due to congenital diaphragmatic hernia (CDH). TO induces lung growth, but even when performed minimally invasive, there is a risk for iatrogenic preterm delivery. Whenever this is anticipated, maternal glucocorticoids (GC) may be given to enhance lung maturation. The pulmonary effects of GC in fetuses with CDH that underwent TO are yet poorly defined. Therefore, we conducted a placebo-controlled study in the nitrofen (NF) rat model for CDH. Pregnant rats were gavage fed NF or olive oil (OO) on ED9.5. At ED19.0, fetuses were either assigned to TO or left untouched. Maternal betamethasone (BM) or saline (PLAC) was administered on ED20. Necropsy was done on ED21.5 to obtain lung-to-body-weight ratio (LBWR), and perform quantitative RT-PCR and fluorescent immunostaining for Ki-67 and proliferating cell nuclear antigen (PCNA) in fetal lungs. CDH fetuses had a lower LBWR than normal fetuses, but comparable pulmonary PCNA and Ki-67 expression levels. TO increased LBWR, irrespective of maternal BM or PLAC. However, BM but not PLAC inhibited proliferation in TO and unoperated fetuses. Rats with NF-induced CDH have hypoplastic lungs with normal proliferation indices. TO triggers proliferation, an effect countered by BM.

Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs

Objectives: Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs. Study Design: 112 fetuses from 21 time-mated, pregnant, giant white rabbits received maternal injections of BM at either 0.05 or 0.1 mg/kg/day on days 25–26 of gestational age. Controls received either saline (10 does, 56 fetuses) or no injection (10 does, 59 fetuses). Fetuses were harvested from day 27 onwards until term (day 31). 44 additional fetuses (8 does) were harvested between days 23 and 26. Endpoints were wet lung-to-body weight ratio, vascular morphometric indices and immunohistochemistry staining for α-smooth muscle actin, Flk-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). ANOVA (Tukey’s test) and independent t test (p < 0.05) were used for comparison between BM and saline groups. Results: Maternal BM injected on days 25–26 to pregnant rabbits induced a significant decrease in fetal body and lung weight and the lung-to-body weight ratio in the preterm pups shortly after injection. BM led to a dose-dependent thinning of the arterial media and adventitia (pulmonary arteries with an external diameter (ED) of <100 µm), to an increase in the percentage of non-muscularized peripheral vessels (ED <60 µm), in eNOS and VEGF immunoreactivity of the endothelial and smooth muscle cells in the pulmonary vessels and to an increase in Flk-1-positive pulmonary epithelial cell density. Conclusions: Maternal administration of BM caused thinning of the arterial wall of pulmonary vessels (ED <100 µm) and a decrease in muscularization in peripheral vessels (ED <60 µm). This coincided with increased expression of Flk-1 in the endothelium and smooth muscle cells of the pulmonary arteries. All the effects studied were dose-dependent.

Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep

The placenta may mediate glucocorticoid-induced fetal growth restriction. Previous studies have examined effects of fetal cortisol in sheep, which reduces placental binucleate cell (BNC) number; the source of ovine placental lactogen (oPL). The effects of maternal GC are unknown. Therefore, this study examined the effects of maternal betamethasone (BET) administration on BNC number, distribution, placental oPL protein levels, and maternal and fetal plasma oPL levels. Pregnant ewes were randomized to receive injections of saline or one (104 days of gestation; dG), two (104 and 111 dG), or three (104, 111, and 118 dG) doses of BET (0.5 mg/kg). Placental tissue was collected before, during, and after the period of BET treatment. Fetal (121-146 dG) and placental (121 dG) weights were decreased after BET when compared with controls. In controls, the mean number of BNCs increased until 132 dG and decreased thereafter. Placental oPL protein levels peaked at 109 dG and remained stable thereafter. Maternal plasma oPL levels in controls increased across gestation; fetal plasma oPL levels decreased. BNCs were reduced by 24% to 47% after BET when compared with controls at all ages studied. Placental oPL protein levels, maternal, and fetal plasma oPL levels were also reduced after BET injections, but recovered to values that were not different to controls near term. BET disrupted the normal distribution of BNCs within the placentome. These data may suggest a placental role in growth restrictive effects of prenatal maternal BET exposure through alterations in placental output of oPL, a key metabolic hormone of pregnancy.

Fetal Tracheal Occlusion for the Treatment of Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) continues to be associated with significant mortality and morbidity rates despite advances in neonatal care. Fetal intervention for CDH has been studied for 25 years. After initial difficulties encountered with open fetal repair, attention has turned to tracheal occlusion (TO) as a method to correct pulmonary hypoplasia before birth. This article reviews our contribution to this field of research and outlines the current status of this treatment modality. Using the fetal lamb model, we have studied the effects of fetal TO on tracheal fluid pressure, lung growth and type II pneumocyte maturation, and surfactant production. We developed a minimally invasive and reversible technique of TO, using a detachable balloon placed using single-port tracheoscopy. We examined differential lung growth, structural maturation, pulmonary artery remodeling, and lung function during an 8-h resuscitation period in lambs, comparing normal controls, lambs with a surgically created CDH, those with CDH+TO, and those with CDH+TO and release of TO 1 week before delivery. We also studied the potential benefits of maternal betamethasone administration and the administration of surfactant at birth. Using a neonatal piglet model, we examined the effect of postnatal pulmonary distension with perfluorocarbon on lung growth. More recently, we turned to the rat nitrofen-induced CDH model to study the effects of TO on bronchial branching and some molecular markers of lung growth (Shh and LGL1). Fetal TO is being used to treat human CDH, but its application remains limited by the absence of reliable and widely reproducible prenatal prognostic criteria. A better understanding of the molecular events guiding the lung growth seen with TO may help to refine its use in humans.

Lack of effect of antenatal glucocorticoid therapy in the fetal baboon on cerebral cortical glucose transporter proteins

Maternal antenatal glucocorticoid therapy is used to accelerate lung maturation of immature babies at risk of preterm delivery. It acutely affects brain activity of the human fetus and reduces the immunoreactivity of neurocytoskeletal and synaptic proteins in the fetal baboon brain. These effects might be based on cerebral energy failure due to a decreased neuronal glucose uptake that has been shown in vitro. Glucose uptake into the brain is selectively facilitated by GLUT1 expressed in the blood-brain barrier and GLUT3 expressed in the neuronal membrane. Immunohistochemical distribution of GLUT1 and GLUT3 were examined in the frontal neocortex of the fetal baboon brain at 0.73 gestation (i.e. similar to 28 weeks of human gestation) after maternal betamethasone administration, mimicking the clinical dose regimen. Betamethasone did not alter GLUT1 and GLUT3 immunoreactivity. The results suggest that inhibition of glucose uptake is not the mechanism for the cerebral effects of antenatal glucocorticoids.

Transient Loss of the Diurnal Rhythms of Fetal Movements, Heart Rate, and Its Variation after Maternal Betamethasone Administration

Antenatal betamethasone administration to enhance fetal lung maturation is associated with transient reductions in fetal heart rate (FHR) variation, breathing, and body movements 2 d after the first dose (d 2). This study examines whether steroid administration affects the natural diurnal rhythms of fetal variables. Sixteen women at 27-32 wk of gestation received two doses of betamethasone 24 h apart. One-hour recordings of FHR, breathing, and body movements were made in the morning, afternoon, and evening of d 2, and again in the morning of d 3. Repeat recordings were obtained at 4-6 d later from 9/16 women. Maternal blood samples were obtained with each recording to determine ACTH and cortisol. No diurnal rhythm was present for FHR, FHR variation, breathing, and body movements on d 2. This resulted from suppression of the expected natural rise in body and breathing movements, and heart rate variation in the course of the day. Suppression of the diurnal rhythm of body movements depended on gestation (R = -0.89; p < 0.01). All variables showed diurnal rhythms 4-6 d later. Maternal ACTH and cortisol diurnal rhythms were completely suppressed on d 2. Four to six days later, the normal diurnal pattern was resumed, although absolute levels of ACTH and cortisol were still suppressed. We conclude that maternal betamethasone administration transiently abolishes the fetal diurnal rhythms of heart rate and its variation, breathing, and body movements.

Exogenous Corticosteroids andin UteroOxygenation Modulate Indices of Fetal Insulin Secretion

Low birth weight has long-term effects on glucose-insulin homeostasis. Factors that could mediate intra-uterine "programing" of glucose homeostasis include endogenous and exogenous glucocorticoids, adipose tissue-secreted factors such as adiponectin, and in utero hypoxia. Here, we studied 123 fetuses with gestational age (GA) between 25 and 37 wk and birth weight sd score (BW SDS) between -2.79 and 2.42. We measured proinsulin, C-peptide, insulin, and adiponectin in umbilical vein (UV) plasma and calculated the proinsulin to insulin ratio as a measure of beta-cell secretory function. These indices were related to GA, BW SDS, time since the last maternal betamethasone administration, and blood gas data. Insulin and C-peptide were correlated with BW SDS but not GA, whereas the proinsulin to insulin ratio was inversely correlated with BW SDS. The proinsulin to insulin ratio was raised (P = 0.002) in fetuses with UV PO(2) less than or equal to 21.3 mm Hg (i.e. the 50th percentile) compared with those with PO(2) more than 21.3 mm Hg, inferring that in utero hypoxia engenders beta-cell secretory dysfunction. Proinsulin, insulin, and C-peptide were markedly but transiently (<24 h) elevated after maternal betamethasone administration, returning thereafter to concentrations measured in noncorticosteroid-treated fetuses. However, there was considerable variability within the less than 24-h betamethasone group: the indices of insulin secretion were related to UV PO(2), suggesting that hypoxia attenuates the responsiveness of fetal beta-cells to corticosteroids. Adiponectin was not related to any of the insulin indices. In conclusion, we have identified two environmental signals that modulate fetal insulin output: maternal corticosteroids produce a transient surge in fetal insulin synthesis and secretion, whereas in utero hypoxia disturbs the insulin secretory process.

Short-Term (0–48 h) Effects of Maternal Betamethasone Administration on Fetal Heart Rate and Its Variability

The short-term (0-48 h) effects of maternal betamethasone administration on computerized fetal heart rate (FHR) parameters were studied in 36 pregnancies at increased risk for preterm delivery. FHR was recorded for 90 min immediately before the start of betamethasone treatment and again at 6-h intervals during the next 48 h. Multiple linear regression models were used to assess the possible effects on FHR parameters of gestational age, time of day, clinical indication for treatment, and use of tocolytic drugs. Within 12 h after the start of treatment, significant increases occurred in FHR accelerations, and short- and long-term FHR variability (36%, 28%, and 22%, respectively), whereas basal FHR showed a 5% decrease. FHR variability was decreased by 10% at 42-48 h. The observed changes were more pronounced in older (29-33 wk of gestation) compared with younger fetuses (25-28 wk of gestation). Decelerations occurred only in 4 out of 11 compromised fetuses during betamethasone therapy. We conclude that there are significant changes in FHR parameters during the first 48 h after betamethasone administration. These changes are transient in normal fetuses. However, the compromised fetus may be adversely affected by betamethasone.

The effects of antenatal betamethasone administration on fetal heart rate and behaviour depend on gestational age

Objective: We previously reported decreases in fetal heart rate (FHR) variability and body and breathing movements after maternal betamethasone administration. We now test the hypothesis that fetal responsiveness to betamethasone depends on the gestational age at which glucocorticoid therapy is started. Design of the study: 1-h recordings of FHR ( n=350) and fetal movements ( n=310) made during a 5-day period (days 0–4) were available for analysis. The recordings had been obtained from 63 pregnant women at high risk for preterm delivery who received betamethasone (two doses of 12 mg 24 h apart) between 26 and 34 weeks' gestational age (wGA). The response to betamethasone, i.e. the direction and magnitude of change in FHR and movement parameters compared with baseline (day 0), was studied in relation to gestational age at drug administration. Results: Fetuses exposed to betamethasone at 29–34 wGA showed a decrease in FHR on day 1 (indicative of baroreceptor reflex), and reduced breathing activity and prolonged episodes of quiescence with a concomitant decrease in body movements on days 1 and 2. However, these changes were not observed if betamethasone administration occurred at 26–28 wGA. Betamethasone-induced reductions in FHR variability were similar in young and older fetuses. Conclusions: Age-related differential responsiveness to betamethasone was found for all studied fetal processes (body and breathing movements, FHR, and quiescence), except FHR variability. Our results suggest ontogenic changes in the mechanisms presumed to underlie these processes (glucocorticoid receptor (GR) maturation, cardiovascular and neuro-endocrine development).

Doppler Measurements in Fetoplacental Vessels after Maternal Betamethasone Administration

Objective: To observe the influence of maternal betamethasone administration for fetal lung maturation on the arterial, venous and intracardiac blood flow of the fetus and the uterine arteries. Methods: Twenty-seven women with singleton pregnancies were examined before the first, and 30 min and 8, 24, 48 and 72 h after the second of two single doses of 8 mg of betamethasone. We recorded blood flow velocity waveforms of the umbilical artery (UA), the middle cerebral artery, the uterine arteries, the ductus venosus, the inferior vena cava and the right hepatic vein, the pulmonary trunk, the ductus arteriosus and the right and left intraventricular inflow of the heart. Results: The resistance index of the UA showed a significant transient decrease 30 min (p = 0.024) after the second betamethasone dose. The peak systolic velocity of the ductus arteriosus increased significantly 30 min after the 2nd dose (p = 0.009) and then returned to non-significant values. No significant change was observed in any of the other vessels. Conclusion: Betamethasone causes short-term changes in fetal blood flow. However, this effect seems to be mild and reversible and does not appear to contraindicate the use of corticosteroids to promote fetal lung maturation.

Visual interpretation of the effect of maternal betamethasone administration on the fetal heart rate pattern

This study was performed to interpret visually the effect of maternal betamethasone administration on the fetal heart patterns in women at risk for preterm delivery. These effects had previously only been described using computer analysis. It was a retrospective study of 54 women who had received two doses of betamethasone 12 hours apart and had fetal heart tracings before, and on the first and second days after steroid administration. The primary outcome measure was change in short-term variability and secondary outcome measures were change in long-term variability, baseline fetal heart rate, accelerations and decelerations. Inter-observer variation of fetal heart rate variability was also measured. Betamethasone caused a significant reduction in short-term variability 1 and 2 days after administration. There was no effect on baseline fetal heart rate or on variable decelerations. A transient decrease in fetal heart rate accelerations was observed on the first day after steroid administration but not on the second day. Inter-observer variability was good between the two observers (GJH and BVI). In most clinical settings, surveillance of fetal wellbeing is achieved most commonly by visual inspection of the fetal heart tracings and not by computer analysis. Clinicians should be aware of the effects of betamethasone on these tracings when considering interventions and/or other tests of fetal wellbeing.

Gestation-related and betamethasone-induced changes in 11β-hydroxysteroid dehydrogenase types 1 and 2 in the baboon placenta

Objective: We determined developmental and labor-related changes in 11β-hydroxysteroid (HSD) 1 and 2 expression in baboon placentas during the final third of gestation and labor. We examined whether maternal glucocorticoid administration alters placental 11β-HSD 2 expression. Study Design: Maternal and fetal plasma cortisol concentrations were measured in five animals. Types 1 and 2 11β-HSD messenger RNA (mRNA) and protein in placentas obtained at 121 to 185 days' gestation (dGA, term approximately 185 dGA, n = 16), during labor between 141 and 193 dGA (n = 8), and after maternal administration of four doses of 87.5 μg/kg betamethasone (n = 5) at 12-hour intervals at 121 to 135 dGA were analyzed by Northern and Western blot. Results: Cortisol levels were higher in maternal plasma than fetal (4-fold, P < .mob031). Placental 11β-HSD 2 mRNA and protein decreased after 0.9 gestation (P < .001). 11β-HSD 1 mRNA remained unchanged. There was no effect of labor on placental 11β-HSD 1 and 2 mRNA and protein levels. Maternal betamethasone administration dramatically increased (P < .05) 11β-HSD 2 mRNA as well as protein without effect on 11β-HSD 1 mRNA and protein expression. Conclusions: The late-gestation baboon maternal plasma cortisol concentration is four times the fetal plasma concentration. Decreased placental 11β-HSD 2 may enhance maternal cortisol passage to the fetus at the end of gestation, thereby contributing to cortisol-mediated changes within the placenta and cortisol in fetal plasma at this stage of fetal development. The positive effect of betamethasone on placental 11β-HSD 2 induction further suggests an ability of the placenta to regulate glucocorticoid transfer in the presence of elevated maternal glucocorticoid. (Am J Obstet Gynecol 2003;188:13-21.)

Changes in Umbilical Artery Flow Velocity Waveforms Following Maternal Administration of Betamethasone

In a retrospective cohort study we have previously shown that administration of betamethasone to women with a pregnancy complicated by absent end-diastolic flow in the umbilical artery (UA) is associated with altered UA flow velocity waveforms. To examine this phenomenon further we undertook a prospective study of 30 similar singleton pregnancies. Umbilical artery FVWs were recorded before and after betamethasone administration using real-time pulsed wave colour flow Doppler. The results of this prospective cohort were similar to those of the retrospective study allowing pooling of the data. Of the 55 total pregnancies with umbilical artery AEDF studied betamethasone administration was associated with the return of end-diastolic flow in 39 (71 per cent; 95 per centCI: 59–83 per cent). The median (range) duration of this change was 3 (1–10) days. There is no evidence that this change has either a beneficial or detrimental effect on foetal health. Administration of betamethasone to women with a pregnancy complicated by umbilical artery AEDF is associated with the transient return of end-diastolic flow in most cases. While the mechanisms underlying this effect are yet to be fully elucidated it has implications for foetal surveillance in these high-risk pregnancies.

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep.

Prenatal glucocorticoid exposure has been associated with a reduction in birth weight and postnatal alterations in glucose homeostasis and hypothalamic-pituitary-adrenal (HPA) axis function. The mechanisms underlying these responses are unknown, although changes in fetal hepatic development may play an important role. The fetal liver produces key regulators of fuel metabolism and of the developing HPA axis that are altered by glucocorticoids. The local availability of glucocorticoids is regulated, in part, by corticosteroid-binding protein (CBG), glucocorticoid receptors (GR) and by the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD), but the effects of maternal glucocorticoid administration on the expression of these genes in the fetal liver are unknown. 11betaHSD1 is the predominant form of this enzyme present in the liver and is responsible for the conversion of cortisone to cortisol. To determine if prenatal glucocorticoid exposure alters fetal hepatic regulation of CBG, 11betaHSD1 and GRs, we treated pregnant ewes with betamethasone (0.5 mg/kg) intramuscularly at 104, 111 and 118 days of gestation (term 150 days). Animals were killed at 125 or 146 days of gestation. Maternal betamethasone administration did not alter mean cord plasma glucose but significantly decreased cord plasma insulin levels (P<0.05) at 125 days of gestation. At 146 days of gestation, cord plasma glucose levels were significantly increased without alterations in insulin levels following maternal betamethasone treatment (P<0.05). Maternal betamethasone administration resulted in a significant increase in fetal hepatic 11betaHSD1 mRNA and protein levels at 125 days of gestation (P<0.05). CBG mRNA levels were significantly elevated over control at 125 days although levels of CBG protein were not significantly different. GR protein levels were not statistically different at either 125 or 146 days of gestation following glucocorticoid administration. These data suggest that prenatal betamethasone exposure in the ovine fetus results in alterations in cord glucose and insulin levels as well as alterations in hepatic 11betaHSD1 mRNA and protein expression. These changes in 11betaHSD1 increase the potential to generate local cortisol from circulating cortisone. We speculate that this could affect expression of glucocorticoid-dependent hepatic enzymes involved with the regulation of glucose production and HPA responsiveness.

Changes in fetoplacental vessel flow velocity waveforms following maternal administration of betamethasone.

To determine the timing of the onset of the umbilical artery flow velocity waveform changes following maternal administration of betamethasone in pregnancies complicated by umbilical artery absent end-diastolic flow, and to explore whether these changes are associated with flow velocity waveform changes in other fetoplacental vessels. This was a prospective study of 12 women with pregnancies complicated by umbilical artery absent end-diastolic flow. Flow velocity waveforms were recorded from the umbilical artery, fetal middle cerebral artery, renal artery, aorta and ductus venosus, before and after maternal betamethasone administration, using real-time pulsed wave Doppler. In all 12 pregnancies, the administration of maternal betamethasone was followed by the return of end-diastolic flow within 24 h. End-diastolic flow was first observed at 4 h and was present in all women studied at 8 h. In addition, there was a statistically significant decrease in the pulsatility index in the fetal aorta at 8 h and the middle cerebral artery at 24 h. No change was observed in the ductus venosus or the renal artery flow velocity waveforms. The findings suggest that, in pregnancies complicated by absent end-diastolic flow in the umbilical artery, maternally administered betamethasone induces a return in umbilical artery end-diastolic flow as early as 4 h, along with widespread vasodilatation throughout the fetoplacental vasculature.

Effects of maternal betamethasone administration on fetal and maternal blood pressure and heart rate in the baboon at 0.7 of gestation

Objective: We sought to determine the effects of the intramuscular maternal administration of betamethasone to the pregnant baboon at 0.7 of gestation on fetal blood pressure and heart rate. Study design: We treated pregnant baboons at 0.7 of gestation with intramuscular betamethasone (n = 4), at a weight-adjusted dose equivalent to the daily dose administered to women in preterm labor or with saline solution (n = 5). Four injections were given at 12-hour intervals. Fetal and maternal blood pressure and heart rate were recorded continuously. Within-group differences and between-group differences were analyzed with repeated measures analysis of variance. Results: Fetal blood pressure increased significantly after betamethasone treatment. Fetal heart rate, maternal blood pressure, and heart rate did not change. Conclusion: Exposure of the developing primate fetus to exogenous glucocorticoid at 0.7 of gestation elevates fetal blood pressure. These findings confirm and extend the observations in the fetal sheep. Further studies are needed to evaluate the mechanisms that are involved and possible long-term consequences of these cardiovascular effects of antenatal glucocorticoid exposure in the fetal primate. (Am J Obstet Gynecol 2002;186:812-7.)

The effect of steroids on the biophysical profile and Doppler indices of umbilical and middle cerebral arteries in healthy preterm fetuses

Objective: To examine the effect of antenatal steroids on the biophysical profile and the Doppler parameters of umbilical and middle cerebral arteries of healthy fetuses. Study Design: Thiry-five singleton pregnancies between the gestational ages of 28 and 34 weeks, who received two consecutive doses of betamethasone 24 h apart to accelerate pulmonary maturation were prospectively studied. Fetal biophysical profile and Doppler assessment were performed at 0 (pre-steroid), 24, 48, 72, 96 and 120 h after the administration of first dose. We compared the percentage of the fetuses with biophysical parameters present for each of the five components of the biophysical profile and the Doppler indices, using Cochran’s Q-test, Friedman’s test and one way analysis of variance of repeated measures where appropriate. The statistical significance was defined as P<0.05. Results: The mean delivery time was 36.9(±1.8) weeks. There was a statistically significant difference in the frequency of the following findings in the pre- compared to post-steroid measurements: absence of body movements (48 h, P<0.05), non-reassuring fetal heart rate tracings (24, 48 and 72 h, P<0.05) and absence of breathing movements (24, 48 and 72 h, p<0.05). Initially none of the biophysical profile score was ≤6, whereas at 24, 48 and 72 h, 13.3, 76.7, 16.7% of them, respectively, were ≤6 ( P<0.05). None of the Doppler indices was found to be affected by the steroid administration. Conclusion: Maternal betamethasone administration can cause a significant but transient, reduction in biophysical profile scores, however the middle cerebral and umbilical artery Doppler indices were found to be unaffected suggesting the reliability of this modality for the evaluation of the fetuses previously exposed to the antenatal steroids.