Course Of Antenatal Betamethasone Research Articles

Effects of Antenatal Betamethasone on Maternal and Fetoplacental Matrix Metalloproteinases 2 and 9 Activities in Human Singleton Pregnancies

BackgroundA single course of antenatal betamethasone is administered to women at risk of preterm labor to advance fetal lung maturation. Matrix metalloproteinases (MMPs) are collagen-degrading enzymes that remodel extracellular matrix...

Cognition- and Anxiety-Related Behavior, Synaptophysin and MAP2 Immunoreactivity in the Adult Rat Treated with a Single Course of Antenatal Betamethasone

We investigated the effects of a single course of antenatal betamethasone on cognition- and anxiety-related behavior and synaptophysin and microtubule-associated protein 2 (MAP2) immunoreactivity in the adult rat hippocampus. On d 20 of gestation, pregnant rats were injected with either 1) 170 microg/kg body weight of betamethasone ("clinically equivalent dose," equivalent to 12 mg twice, 24 h apart); 2) half this dose; or 3) vehicle. Cognition- and anxiety-related behavior of the offspring was analyzed at an age of 5 mo using the Morris water maze, object recognition task, and open field test. Subsequently, synaptophysin and MAP2 immunoreactivity were measured in the hippocampus. We report no detrimental effects of antenatal betamethasone on cognition- and anxiety-related behavior and synaptophysin immunoreactivity in the adult rat. On the other hand, MAP2 immunoreactivity was decreased by betamethasone in males, suggesting a permanent impairment in the hippocampus. Interestingly, the lower dose appears to have less influence in terms of growth restriction, known to be associated with an increased risk of disease in adulthood. Further research might elucidate whether the betamethasone effect on hippocampal neurons persists later in life and could affect the aging process increasing the risk for neuropathology of the adult.

Lowering the dose of antenatal steroids: The effects of a single course of betamethasone on somatic growth and brain cell proliferation in the rat

We investigated the effects of a single course of antenatal betamethasone on neonatal somatic and brain development. On day 20 of gestation, pregnant rats were injected with either with 170 microg kg(-1) body weight of betamethasone ("clinically-equivalent dose," equivalent to 12 mg twice, 24 hours apart) or half this dose or vehicle. Pups (8-11 animals per experimental group per timepoint per gender) were analyzed at 1 (P1), 2, and 21 days after birth. We report that betamethasone induced a significant dose-dependent decrease of somatic measurements in both genders. At P1 cell proliferation was affected by the "clinically equivalent dose" only in the subventricular zone in both genders and in the hippocampus in males. In summary, we show for the first time that a lower dose (equivalent to 6 mg) induces fewer and less severe effects on somatic growth, whereas it does not affect cell proliferation within the brain.

Cardiac effects of a single course of antenatal betamethasone in preterm infants

Aim: To show the effects of a single course of antenatal betamethasone on cardiac measurements and systolic functions in premature newborn infants. Methods: Seventy six newborn infants with a gestational...

Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial

Objectives To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood.Design Follow-up of the...

A single course of antenatal betamethasone reduces neurotrophic factor S100B concentration in the hippocampus and serum in the neonatal rat

The effects of a single course of antenatal betamethasone on S100B protein concentration were investigated in Fisher 344 rats. On day 20 of gestation, pregnant rats were injected twice 8 h apart with either (1) 170 μg kg −1 body weight betamethasone (“clinically-equivalent dose”, equivalent to 12 mg twice, 24 h apart in humans), (2) half of this dose (equivalent to 6 mg) or (3) vehicle. We report reference values for S100B protein in the serum and different brain regions in both genders at 1, 2, and 21 days after birth. Interestingly, S100B concentration showed a time-dependent and brain region-specific pattern of expression. At P1, S100B was higher in the serum of males compared to females. In addition, we show that both doses of betamethasone decreased S100B concentration in the serum of males at P1, whereas in the hippocampus, it was reduced by the clinically-equivalent dose only. This suggests that lowering the dose of antenatal betamethasone may be less detrimental for brain maturation and therefore we reiterate the need for clinical trials with a low dose regimen.

288 The Effect of Second Course of Antenatal Betamethasone (BM) on Neonatal Morbidity in Preterm Infants: A Randomized Trial

Background: Single course of BM decreases neonatal morbidity when administrated within 7 days before preterm delivery. The benefits of second course of BM are unknown.Aims: To evaluate the efficacy of second course of BM in increasing the intact survival of preterm infants.Methods: In this randomized, blinded trial, pregnant women (before 34.0 gestational weeks) were eligible if they had remained undelivered more than 7 days after antenatal BM. Single dose of BM (12 mg) or placebo was given, when the preterm delivery was anticipated. Primary outcome was intact survival without respiratory distress syndrome and/or intracerebral hemorrhage (grade 3–4).Results: 251 mothers participated the study. All infants were delivered prior to 35 weeks of gestation. At present the outcome of 285 infants has been analyzed. The intact survival was 48% in BM and 58% in placebo groups (P=0.1). The intact survival was non-significantly higher in BM group (58% vs. 41%, P=0.3), when the study drug was administered more than 24 h before birth (group 1). The incidence of intact survival was lower in BM group (44% vs. 61%, P=0.01), when the intervention took place less than 24 h before birth (group 2). In group 1, the risk of patent ductus arteriosus was 16% in BM and 41% in placebo group (P=0.04), vs. 29% and 27% in group 2. In group 2, systolic and diastolic blood pressures were increased in BM arm (P=0.02 and P=0.03). In group 1, blood pressure levels were similar between study groups. The second course of BM did not influence the acute outcome of preterm infants. The preterm infants benefited from antenatal BM, when treatment was given more than 24 h before delivery. BM given less than 24 hours before delivery was associated with increased blood pressure after birth and with a decrease in intact survival.

Maternal and feto-placental prostanoid responses to a single course of antenatal betamethasone

We tested the hypothesis that antenatal betamethasone alters prostanoid levels in the maternal and feto-placental compartments. Forty-three singleton pregnancies were studied. Group I were women treated with a single course of antenatal betamethasone and who delivered <37 weeks gestation; Group II were untreated women who delivered <37 weeks; and Group III were untreated women who delivered >38 weeks. Maternal and mixed cord blood; and placental samples were collected at delivery and analyzed for PGE 2, PGF 2α, 6-ketoPGF 1α, and TxB 2 levels. Antenatal betamethasone decreased maternal PGE 2 levels with concomitant increases in the feto-placental compartment. Umbilical cord TxB 2 levels in the treated group were significantly lower than the non-treated pre-term and term groups resulting in a higher 6-ketoPGF 1α:TxB 2 ratio. Considering the regulatory role of PGE 2 and PGI 2 in fetal lung development and neonatal transition homeostasis, these results suggest a mechanism, at least in part, for the beneficial effects of antenatal steroids on fetal lung maturation and neonatal cardio-pulmonary homeostasis at birth.

Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial

Antenatal betamethasone treatment is widely used for the prevention of neonatal respiratory distress syndrome in preterm infants and substantially reduces neonatal mortality and morbidity. Fetal exposure to excess glucocorticoids has been proposed as one of the core mechanisms of the fetal origins of adult disease hypothesis. We assessed whether antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome affects cardiovascular risk factors at 30 years of age. We followed up at age 30 years 534 individuals whose mothers participated in a double-blind, placebo-controlled, randomised trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Mothers received two doses of betamethasone or placebo given by intramuscular injection 24 h apart. Follow-up assessments included anthropometry; measurement of blood pressure, blood lipids (after overnight fasting), and early morning cortisol levels; and a 75 g oral glucose tolerance test. There were no differences between those exposed to betamethasone and to placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease. After a 75 g oral glucose tolerance test, participants exposed to betamethasone had higher plasma insulin concentrations at 30 min (60.5 vs 52.0 mIU/L; ratio of geometric means 1.16 [95% CI 1.03 to 1.31], p=0.02) and lower glucose concentrations at 120 min (4.8 vs 5.1 mmol/L; difference -0.26 mmol/L [-0.53 to 0.00], p=0.05) than did those exposed to placebo. Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no clinical effect on cardiovascular risk factors at 30 years of age. Thus, obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

Responsiveness of placental prostaglandin E2 (PGE2) and PGF2 receptors to a single course of antenatal betamethasone

RECEPTORS TO A SINGLE COURSE OF ANTENATAL BETAMETHASONE WILBERT FORTSON JR, KAY BEHARRY, PAM RUMNEY, HOUCHANG MODANLOU, DEBORAH WING, MICHAEL P. NAGEOTTE, University of California, Irvine, Maternal Fetal Medicine, Irvine, California, University of California, Irvine, Pediatrics, Orange, California, Long Beach Memorial Medical Center, Maternal Fetal Medicine, Long Beach, California, University of California, Irvine, Orange, California, Long Beach Memorial Medical Center, Obstetrics and Gynecology, Long Beach, California OBJECTIVE: Prostaglandin E2 (PGE2) and PGF2aare increased in the placenta for normal transition to labor. Their biological effects are mediated via EP and FP receptors, respectively. A single course of antenatal betamethasone (B) is administered to women at risk for preterm birth and may influence prostanoid signaling. We conducted a prospective pilot study to examine the responsiveness of placental EP and FP receptors to antenatal B. a STUDY DESIGN: Group I (n = 21): women antenatally treated with a single course of antenatal B and who delivered!36 weeks gestation; Group II (n = 7): untreated women who delivered !36 weeks; and Group III (n = 15): untreated women who delivered > 38 weeks. Group I was divided into women delivering: (a) !2 weeks (IA), and (b) >2 weeks (IB), post B treatment. Placentas were collected at the time of delivery for PGE2 and PGF2 levels; and EP-2, EP3-3, EP3-6, & FP receptor mRNA expression. RESULTS: PGE2 (pg/mg protein) and PGF2a (ng/mg protein) levels were elevated in Group I (177G 36.6, P ! .05 and 24.9 G 6.1, P ! .01) and II (168.8 G 39.3, P ! .05 and 28.7 G 6.2, P ! .01) vs. Group III (65.5 G 28.4 and 9.7 G 2.3), respectively. In Group IB, EP3-2 was induced (P! .05 vs Group IA), while EP3-6 was suppressed (P ! .05 vs Groups IA, II, and III). FP receptor mRNA was lower in Groups I and II, than III (P ! .05). CONCLUSION: Preterm labor is associated with increased PGE2 and PGF2 levels, and decreased FP mRNA transcripts in the placenta. While antenatal B had no effect on the FP receptor, it may have opposing latent effects on placental EP3-2 and EP3-6 mRNA transcripts.

A single course of antenatal betamethasone has a delayed suppressive effect on placental progesterone and estrogen receptor mRNA transcripts

A single course of antenatal betamethasone has a delayed suppressive effect on placental progesterone and estrogen receptor mRNA transcripts

Response of vascular endothelial growth factor (VEGF) to a single course of antenatal betamethasone in preterm pregnancy

Antenatal betamethasone (AB) is administered to women at risk for preterm birth. VEGF is a mitogen, which contributes to fetal development. We examined the effects of a single course of antenatal betamethasone on maternal and placental VEGF protein levels and mRNA expression.

Effect of a single course of antenatal betamethasone on vascular endothelial growth factor (vegf) receptor-1 (sflt-1) and receptor-2 (sflk-1/kdr)

VEGF is a mitogen that promotes vasodilation through stimulation of Flk-1 and Flt-1 receptors. Soluble flt-1 (sFlt-1) is a splice variant of the Flt-1 receptor and acts to antagonizeVEGF activity. We prospectively examined the effect of a single course of antenatal betamethasone (B) on soluble VEGF receptor levels.

Preterm premature rupture of the membranes is associated with a reduction in neonatal respiratory distress syndrome

Objective: The purpose of this study was to evaluate the effect of preterm premature rupture of the membranes on the frequency of respiratory distress syndrome among singleton pregnancies that are complicated with preterm delivery. Study Design: We performed a retrospective analysis of singleton pregnancies that were delivered between 24 and 34 weeks of gestation. Patients were categorized on the basis of membrane integrity into two groups: ruptured versus intact. All patients received prophylactic antibiotics and a single course of antenatal betamethasone. Data were analyzed with the Student t test, the χ2 test, and the Fisher exact test. Multiple logistic regression analysis was performed to examine the effect of possible confounding variables that were considered risk factors for respiratory distress syndrome. Probability values of <.05 for all two-tailed tests were considered significant. Results: A total of 366 patients were included (99 patients in the preterm premature rupture of the membranes group and 267 patients in the intact membranes group). Patients were delivered at 30.7 ± 2.9 and 30.1 ± 2.7 (mean ± SD) weeks of gestation, with birth weights of 1620 ± 594 and 1417 ± 501 g, respectively. The frequency of respiratory distress syndrome in the neonate was significantly lower in the preterm premature rupture of the membranes group than in their intact counterparts (17% vs 39%, P <.001). Multiple logistic regression analysis confirmed that preterm premature rupture of the membranes (odds ratio, 0.16; 95% CI, 0.08-0.34) was independently associated with a reduction in the frequency of respiratory distress syndrome. Conclusion: In the clinical setting of delivery before 34 weeks of gestation, preterm premature rupture of the membranes is associated with a significant decrease in the frequency of neonatal respiratory distress syndrome. (Am J Obstet Gynecol 2002;187:268-72.)

Multiple courses of antenatal betamethasone and cognitive development of mice offspring.

To measure the effect of multiple courses of antenatal betamethasone, used for lung maturation, on long-term cognition of mice offspring. Forty gravid CD-1 mice were randomly assigned to receive one of four treatments (n = 10 per group): 0.1 mg betamethasone or saline placebo, given subcutaneously either once daily on gestational days 13-16 or twice daily on days 14 and 15. This dose of betamethasone given on gestational day 14 causes fetal lung maturation in mice. Three offspring per gender in each litter underwent standard cognitive tasks as juveniles and as adults. Analysis of variance or Kruskal-Wallis testing was used to compare data. Learning acquisition and memory were indistinguishable between the betamethasone-exposed and the corresponding placebo-exposed offspring when performing the following tasks: juvenile runway with adult memory, adult water runway and Morris spatial maze. This lack of difference in task performance between treatment groups persisted after controlling for gender and for each multiple-course regimen. Multiple courses of antenatal corticosteroids did not impact the mouse offsprings' long-term learning and memory.

Influence of a Single Course of Antenatal Betamethasone on Placental and Umbilical Cord Prostanoid Levels in Pregnancies Delivering &lt; 2 Weeks and &gt; 2 Weeks after Treatment

Influence of a Single Course of Antenatal Betamethasone on Placental and Umbilical Cord Prostanoid Levels in Pregnancies Delivering &lt; 2 Weeks and &gt; 2 Weeks after Treatment

Multiple courses of antenatal betamethasone and cognitive development of mice offspring

Multiple courses of antenatal betamethasone and cognitive development of mice offspring

Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy

Objective: This study was undertaken to compare the effects of single versus multiple courses of betamethasone therapy on the frequencies of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. Study Design: We performed a nonconcurrent prospective analysis of singleton pregnancies delivered between 24 and 34 weeks’ gestation after antenatal betamethasone exposure. Patients were categorized into two groups according to betamethasone exposure: (1) two 12-mg doses in a 24-hour interval on admission (single-course group) and (2) repeated dosing after the initial single course (multiple-course group). All patients received prophylactic antibiotics for group B streptococci. Any patients with ruptured membranes for >24 hours before delivery were excluded. Data were analyzed with the Student t test, the χ 2 test, and the Fisher exact test. Multiple logistic regression analyses were performed to examine the effect of each steroid dosing regimen on early-onset neonatal sepsis and neonatal death. P < .05 was considered significant for all 2-tailed tests. Results: A total of 453 patients were included, with 267 in the single-course group and 186 in the multiple-course group. The two groups were similar with respect to maternal demographic characteristics, gestational age at delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization. Multiple courses were significantly associated with early-onset neonatal sepsis (odds ratio, 5.00; 95% confidence interval, 1.3-23.2), chorioamnionitis (odds ratio, 9.96; 95% confidence interval, 2.1-64.6), endometritis (odds ratio, 3.61; 95% confidence interval, 1.7-8.1), and neonatal death (odds ratio, 2.92; 95% confidence interval, 1.3-6.9). The frequencies of the other neonatal outcomes analyzed, including respiratory distress syndrome and grade III or IV intraventricular hemorrhage, were similar between the 2 groups. Multiple logistic regression analyses confirmed that multiple courses of antenatal betamethasone were independently associated with early-onset neonatal sepsis (odds ratio, 1.25; 95% confidence interval, 1.1-1.9) and neonatal death (odds ratio, 1.70; 95% confidence interval, 1.1-1.9). Conclusions: Multiple courses of antenatal betamethasone are associated with increased risks of perinatal infectious morbidity and neonatal death. (Am J Obstet Gynecol 2000;183:810-4.)

The effects of repeat doses of antenatal corticosteroids on maternal adrenal function

Objective: The purpose of this study was to determine whether repeated doses of maternal corticosteroids suppress the maternal hypothalamic-pituitary-adrenal axis. Study Design: The low-dose corticotropin stimulation test (1.0 μg intravenously) was administered a median of 3 days after the last betamethasone dose to 18 pregnant women who had received at least 2 weekly courses of antenatal betamethasone and to 6 control subjects matched for gestational age who had not received antenatal corticosteroids. Results: The mean basal cortisol level was significantly depressed among women who had received betamethasone with respect to control subjects (1.9 ± 1.5 vs 26.5 ± 6.2 μg/dL; P <.001). The maternal cortisol level after corticotropin stimulation was significantly lower in all women who had received betamethasone (P <.001). The mean time to attainment of peak cortisol level was significantly longer among women who had received betamethasone than among control subjects (37 ± 6.8 vs 27.4 ± 1.6 minutes; P <.001). Conclusions: Repeated courses of betamethasone lead to barely detectable maternal basal cortisol levels and secondary adrenal insufficiency. (Am J Obstet Gynecol 2000;183:669-73.)

Clinical use of antenatal corticosteroids: benefits and risks.

After completing this article, readers should be able to: 1. Describe the rationale for the use of antenatal corticosteroids for human fetal maturation. 2. Delineate recommendations of the 1994 National Institutes of Health Consensus Conference on Antenatal Corticosteroids. 3. Review areas of controversy in the clinical use of antenatal corticosteroids. 4. Describe the potential risks of multiple courses of antenatal corticosteroids. 5. Delineate current recommendations for clinical use of antenatal corticosteroids to promote fetal maturation. Glucocorticoid administration initially was appreciated as a method for accelerating development of the intestine more than 40 years ago. Since that time, developmental effects of these agents have been defined in at least 16 tissues of mammals. More than 30 years ago, while studying the mechanism of initiation of labor in sheep, Liggins made the observation that infusion of corticosteroids into fetal lambs was associated with improved survival and decreased lung disease in animals delivered preterm. Subsequently, numerous studies in cell culture, animal models, and human fetal tissue have delineated the multiple effects of glucocorticoids on the developing lung. These include increases in both the total tissue and alveolar surfactant pools; a decrease in vascular permeability, with less protein leak into the alveolar spaces; enhanced clearance of lung water; maturation of parenchymal structure; increase in lung compliance and maximal lung volume; enhanced response to surfactant treatment; and improvement in respiratory function, outcome, and survival. (See accompanying article on scientific rationale for use of antenatal glucocorticoids.) In 1972, the first randomized clinical trial of administration of antenatal corticosteroids (ANCS) in humans demonstrated decreased mortality and a decreased incidence of respiratory distress syndrome (RDS) in preterm infants born at less than 34 weeks’ gestation, who were treated with betamethasone for at least 24 hours before delivery. Over the ensuing 20 years, multiple clinical investigations continued to document the effectiveness of ANCS on …