First Dose Of Betamethasone Research Articles

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants

Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

56: Association of timing from steroid administration to delivery and neonatal outcomes in the late-preterm period

Administration of antenatal steroids for women at risk of late preterm birth reduces neonatal morbidity but results in more frequent neonatal hypoglycemia. The objective was to evaluate if there is an association between time from steroid administration to delivery and neonatal hypoglycemia. Retrospective cohort of all women with singleton pregnancies admitted between 34-36 6/7 weeks’ from 4/2016-4/2017 and received at least one dose of antenatal steroids. The exposure was steroid latency, defined as the time from first dose of betamethasone to delivery, examined categorically as < 48 versus ≥ 48 hours from receipt of first dose of betamethasone. The primary outcomes were neonatal hypoglycemia ≤35 mg/dL in the first day of life, admission to the NICU, and neonatal dextrose administration. Of the 302 women eligible for inclusion, 49 (16.2%) had a steroid latency ≥48 hours. Women who received steroids ≥48 hours before delivery were more likely to have preeclampsia (8.2% vs. 1.2%; p=0.015) and were more likely to undergo cesarean (38.8% vs 24.5%; p=0.039). They received betamethasone at an earlier gestation(35.2 ± 0.8 vs 35.7 ± 0.8; p=0.001) but delivered at a more advanced gestation(36.2 ± 0.9 vs 35.8 ± 0.9; p=0.002) than women with a < 48 hour steroid latency. There was no difference in the frequency of hypoglycemia ≤35 mg/dL (14.3% vs. 19.0%; p=0.437) by steroid latency, which remained non-significant after accounting for potential confounders (aOR 0.40, 95% CI 0.12-1.30). Steroid latency remained non-associated with hypoglycemia when examined as a continuous variable. NICU admission and IV dextrose administration were also not associated with steroid latency (Table). Although administration of antenatal steroids for women at elevated risk of delivery in the late preterm period has been reported to increase the risk for neonatal hypoglycemia, in this cohort, the amount of time from steroid administration to delivery is not associated with a greater likelihood of neonatal hypoglycemia or related neonatal events.

Effects of Antenatal Betamethasone on Fetal Doppler Indices andShort Term Fetal Heart Rate Variation in Early Growth RestrictedFetuses.

To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001). Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.

Reduced short-term variation following antenatal administration of betamethasone: Is reduced fetal size a predisposing factor?

ObjectiveTo assess the association between fetal size and the incidence of reduced short-term variability (STV) following bethametasone administration for fetal lung maturity. Study designThis was a retrospective, multicenter, cohort study conducted in two Tertiary University Units. Only uncomplicated singleton pregnancies admitted for threatened preterm labor between 26 and 34 weeks and submitted to betamethasone for fetal lung maturity were included. Delivery occurring within 72h from betamethasone administration represented criteria for exclusion. Computerized cardiotocography was carried out on a daily basis. Cases were identified by persistently reduced STV, defined as <5th percentile for gestational age and lasting for at least 72h after the first dose of betamethasone. The primary outcome was estimated fetal weight (EFW) at ultrasound in fetuses with normal and in those with persistently reduced STV. Pregnancy outcomes were also evaluated. ResultsPersistently reduced STV occurred in 33/405 of the included patients (8.1%). Compared to women with normal STV, those with persistently reduced STV had significantly lower EFW (1472±435 vs 1812±532g, p 0.04), lower birthweight (2353±635 vs 2857±796g, p<0.01) and earlier gestational age at delivery (35.1±4.2 vs 37.3±2.4weeks, p<0.01), whereas all the other variables including gestational age on admission were comparable. ConclusionsReduced STV following maternal betamethasone administration among appropriately grown fetuses seems to correlate with lower fetal size. Furthermore, fetuses with such abnormal response to steroids seem to carry a higher risk of perinatal complications, including lower birthweight and earlier gestational age at delivery.

Effect of corticosteroids on cardiac function in growth-restricted fetuses.

To determine the acute effects of corticosteroids on the cardiovascular system in growth-restricted fetuses. This was a prospective cohort study conducted at a tertiary hospital between January 2011 and October 2013. Fetal cardiovascular function in fetuses with intrauterine growth restriction (IUGR) was assessed immediately before and 24 h after the first dose of betamethasone, administered in routine management of IUGR. Fetal arterial and venous Dopplers were assessed. Fetal cardiac function was evaluated by tissue Doppler echocardiography, with the assessment of both left and right ventricular function by calculating myocardial performance index (MPI') and E':A' ratios. Values were compared before and after exposure. Seventeen patients were included at a mean gestational age of 34 + 1 (range, 29 + 1 to 37 + 4) weeks. Fifteen fetuses were below the 5(th) percentile and two were below the 10(th) percentile for estimated fetal weight and abdominal circumference and all had no interval growth during a 2-week period. There was a decrease in right MPI' (from 0.56 to 0.47; P = 0.007) after corticosteroid exposure but no change in left MPI' (from 0.49 to 0.48). Right MPI' was higher than left MPI' before exposure (0.56 vs 0.49, respectively; P = 0.001), but not after exposure (P = 0.55). There was no change in left or right ventricular E':A' ratios and no difference was detected in umbilical artery, middle cerebral artery or ductus venosus pulsatility index following administration of corticosteroids. Corticosteroids altered right-sided, but not left-sided, tissue Doppler MPI' in IUGR fetuses, with no detectable change in arterial or venous Doppler pulsatility indices. Before exposure, the mean right MPI' was higher than the left. However, after exposure, there was no difference, suggesting that corticosteroids may reverse the negative effect of IUGR on fetal heart function. Large prospective studies with a larger sample size are needed to confirm this finding. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study.

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.

Effect of antenatal betamethasone administration on Doppler velocimetry of fetal and uteroplacental vessels: a prospective study.

To examine the effect of antenatal betamethasone administration on Doppler parameters of fetal and uteroplacental circulation. Seventy-six singleton pregnancies that received betamethasone therapy were prospectively evaluated. Doppler measurements of pulsatility indices (PI) in fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus and maternal uterine arteries were performed before (0 h) and 24, 48, 72 and 96 h after the first dose of betamethasone. Women with positive end-diastolic flow (EDF) in UA and those with absent or reversed EDF in UA were evaluated separately. Fifty-two women with EDF in UA and 24 women with absent or reversed flow in UA were examined. Administration of maternal betamethasone was followed by a significant decrease in the PI of the MCA at 24 h (P<0.05). Additionally, return of absent to positive, reversed to absent or from reversed to positive diastolic flow in UA was detected within 24 h in 19 (79.2%) fetuses with absent or reversed UA-EDF. All alterations were transient and maintained up to 72 h. Antenatal administration of betamethasone is associated with significant but transient changes in the fetal blood flow. Hence, intensive surveillance of fetuses with Doppler ultrasonography is warranted following betamethasone therapy.

The effect of maternal betamethasone administration on Doppler flow velocity parameters of the fetal branch pulmonary artery

To investigate the effects of antenatal betamethasone on fetal pulmonary blood flow velocity waveforms. The study comprised 28 women with singleton pregnancies at high risk for preterm delivery. They were treated with two doses of 12 mg betamethasone intramuscularly 24 h apart to enhance lung maturity. Flow velocity waveforms were recorded with Doppler ultrasound from the middle segment of pulmonary artery (PA). Compared with the pretreatment mean value, a significant decrease in the pulmonary artery pulsatility (PI) and the resistance indexes (RI) was noted at 24 h and 48 h after the administration of first dose of betamethasone (p = 0.022 and p = 0.018 for PI and p = 0.001 and p = 0.004 for RI, respectively). After 7 days, the pulmonary artery velocity waveforms returned to the types of waveform observed before treatment (p = 0.216 for PI and p = 0.249 for RI). Maternal antenatal betamethasone resulted in a significant transient decrease in the pulsatility and the resistance indexes in the pulmonary artery. These findings indicate a direct effect of betamethasone on fetal pulmonary circulation.

Fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective growth restriction and abnormal umbilical artery Doppler

To evaluate fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective intrauterine growth restriction (sIUGR) and absence of end-diastolic velocity in umbilical artery (UA) Doppler. sIUGR was defined as fetal weight below the 10th percentile in one twin and inter-twin birth weight discordance >25%. The results of Doppler examinations including UA, middle cerebral artery (MCA) and ductus venosus directly prior to (D0), at 24 h (D1) and 48 h (D2) after administration of the first dose of betamethasone were recorded. Cerebral-placenta ratio was defined as MCA pulsatility index (PI) divided by UA-PI. In four (20%) of the 20 cases, the UA Doppler of the growth-restricted twin returned to positive end-diastolic velocity after betamethasone administration. The UA-PI and MCA-PI of the sIUGR twin changed significantly after betamethasone administration: UA-PI was decreased at D1, the MCA-PI was reduced at both D1 and D2, and the cerebral-placenta ratio was not altered after betamethasone administration in the sIUGR twin. The hemodynamic changes after betamethasone administration were different between the two monochorionic twin fetuses where one presented with sIUGR and absence of UA end-diastolic velocity. The etiology of a low rate of return of end-diastolic velocity in the sIUGR twin needs further evaluation.

Effect of maternal betamethasone on fetal and uteroplacental blood flow velocity waveforms

To investigate the effects of antenatal betamethasone on fetal and uteroplacental hemodynamics. The study comprised 33 women with singleton high-risk pregnancies (23-33 weeks; 27 pregnancies < 30 weeks) not in labor, but at risk for preterm delivery based on fetal or maternal indications. They were treated with two doses of 12 mg betamethasone intramuscularly 24 h apart to enhance fetal lung maturity. Flow velocity waveforms were recorded with Doppler ultrasound from the umbilical artery, the fetal middle cerebral artery, the ductus venosus and both maternal uterine arteries, once before and twice after betamethasone administration. Twenty-one (64%) women delivered within 4 days, nine (27%) women within 5-7 days and three (9%) within 8-15 days after the first dose of betamethasone. Two days after betamethasone, a decrease in pulsatility index was found in the umbilical artery (P = 0.0002) and ductus venosus (P = 0.003). Changes in the umbilical artery waveform from reversed to absent, and from absent to positive diastolic flow, were noted in 12 of 15 cases (P < 0.01). After 4 days, umbilical artery and ductus venosus velocity waveforms in the undelivered fetuses either returned to the type of waveform observed before treatment or showed further deterioration. No significant effects of betamethasone were observed in the fetal middle cerebral artery and uteroplacental circulation. Maternal antenatal betamethasone resulted in a significant transient change in the velocity waveform and a decrease in the pulsatility index in the umbilical artery and ductus venosus, but did not influence uteroplacental circulation. These findings indicate a direct effect of betamethasone on fetal circulation.

Effect of antenatal betamethasone on maternal and fetal amino acid concentration

To determine the concentration of amino acids in women receiving the first course of antenatal betamethasone and to evaluate the umbilical venous and arterial amino acid concentrations at the time of elective cesarean section after betamethasone administration. Blood samples were collected from 34 pregnant women at risk of premature delivery before and 24 and 48 hours after the first course of betamethasone. In addition, maternal and cord blood samples were collected in 13 women undergoing an elective cesarean section between 24 and 192 hours after betamethasone. Maternal amino acid concentrations were significantly increased after the first dose of betamethasone. Overall total amino nitrogen increased 17.5% 24 hours after betamethasone administration and 20.5% after 48 hours. The concentration of most amino acids was increased both in the umbilical vein and artery after maternal betamethasone administration. The concentration of maternal and fetal amino acids increases significantly after betamethasone administration.

P242: Assessment of fetal cerebral arterial and venous blood flow before and after birth according to type of delivery

Objective: To determine whether antenatal steroids administration alter the Doppler flow indices of the umbilical, middle cerebral and uterine arteries and to determine the exact time that antenatal steroid administration affects the biophysical profile in fetuses. Methods: A prospective study was conducted in 20 fetuses between 26 and 34 weeks’ menstrual age at risk of preterm delivery. Two intramuscular injections of 12 mg of betamethasone were given to the mother 24 hours apart. The Doppler examination included the assessment of the pulsatility index of the umbilical artery (UA PI), the middle cerebral artery (MCA PI) and the pulsatility index of uterine arteries (Ut PI) before treatment, and 24, 48 and 72 hours after the first dose of betamethasone. All fetuses underwent biophysical profile testing prior to and on 24, 48 and 72 hours after steroid administration. We compared the percentage of fetuses with biophysical profile parameters present for each of the five components of the BP using statistical methods where appropriate. Neonatal outcome, including Apgar score, menstrual age at delivery, admission to and length of stay in the neonatal intensive care unit and mortality were analysed in all subjects. Results: The mean delivery time was 32.4 (27–36 weeks). There was a statistically significant difference in the frequency of the following findings in the precompared to post-steroid measurements: absence of body movements, non-reassuring fetal heart rate tracings, and absence of breathing movements. Initially none of the biophysical profile score was < or =8 whereas at 24, 48, and 72 hrs 10, 40 and 50% of them were respectively < or =8. No significant variation was noted in both the fetal and maternal Doppler velocimetry indices. Conclusion: Biophysical profile scores were decreased in more than 40% of fetuses within 48 hours of antenatal steroid administration, but neonatal outcome was not affected. On the contrary, Doppler velocimetry of the umbilical and fetal cerebral circulation appears to be reliable for the assessment of fetuses previously exposed to antenatal steroids. It seems that Doppler studies have the potential to differentiate the steroid induced changes in fetal biophysical profile from those due to fetal compromise.

Pharmacokinetics of betamethasone in twin and singleton pregnancy

The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone. We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies. The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4 versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus 5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons). The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.

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 …