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American Journal of Obstetrics and... Apr 2022Antenatal corticosteroid therapy is a standard of care for women at imminent risk of preterm labor. However, the optimal (maximum benefit and minimal risk of side...
Betamethasone phosphate reduces the efficacy of antenatal steroid therapy and is associated with lower birthweights when administered to pregnant sheep in combination with betamethasone acetate.
BACKGROUND
Antenatal corticosteroid therapy is a standard of care for women at imminent risk of preterm labor. However, the optimal (maximum benefit and minimal risk of side effects) antenatal corticosteroid dosing strategy remains unclear. Although conveying overall benefit when given to the right patient at the right time, antenatal corticosteroid treatment efficacy is highly variable and is not risk-free. Building on earlier findings, we hypothesized that when administered in combination with slow-release betamethasone acetate, betamethasone phosphate and the high maternal-fetal betamethasone concentrations it generates are redundant for fetal lung maturation.
OBJECTIVE
Using an established sheep model of prematurity and postnatal ventilation of the preterm lamb, we aimed to compare the pharmacodynamic effects of low-dosage treatment with betamethasone acetate only against a standard dosage of betamethasone phosphate and betamethasone acetate as recommended by the American College of Obstetricians and Gynecologists for women at risk of imminent preterm delivery between 24 0/7 and 35 6/7 weeks' gestation.
STUDY DESIGN
Ewes carrying a single fetus at 122±1 days' gestation (term=150 days) were randomized to receive either (1) maternal intramuscular injections of sterile saline (the saline negative control group, n=12), (2) 2 maternal intramuscular injections of 0.25 mg/kg betamethasone phosphate+betamethasone acetate administered at 24-hour dosing intervals (the betamethasone phosphate+betamethasone acetate group, n=12); or (3) 2 maternal intramuscular injections of 0.125 mg/kg betamethasone acetate administered at 24-hour dosing intervals (the betamethasone acetate group, n=11). The fetuses were surgically delivered 48 hours after treatment initiation and ventilated for 30 minutes to determine functional lung maturation. The fetuses were euthanized after ventilation, and the lungs were collected for analysis using quantitative polymerase chain reaction and Western blot assays. Fetal plasma adrenocorticotropic hormone levels were measured in the cord blood samples taken at delivery.
RESULTS
Preterm lambs were defined as either antenatal corticosteroid treatment responders or nonresponders using an arbitrary cutoff, being a PaCO level at 30 minutes of ventilation being more extreme than 2 standard deviations from the mean value of the normally distributed saline control group values. Compared with the animals in the saline control group, the animals in the antenatal corticosteroid treatment groups showed significantly improved lung physiological responses (blood gas and ventilation data) and had a biochemical signature (messenger RNA and surfactant protein assays) consistent with functional maturation. However, the betamethasone acetate group had a significantly higher treatment response rate than the betamethasone phosphate+betamethasone acetate group. These physiological results were strongly correlated to the amount of surfactant protein A. Birthweight was lower in the betamethasone phosphate+betamethasone acetate group and the fetal hypothalamic-pituitary-adrenal axis was suppressed to a greater extent in the betamethasone phosphate+betamethasone acetate group.
CONCLUSION
Low-dosage antenatal corticosteroid therapy solely employing betamethasone acetate was sufficient for fetal lung maturation. The elevated maternal-fetal betamethasone concentrations associated with the coadministration of betamethasone phosphate did not in addition improve lung maturation but were associated with greater fetal hypothalamic-pituitary-adrenal axis suppression, a lower antenatal corticosteroid treatment response rate, and lower birthweight-outcomes not desirable in a clinical setting. These data warranted a clinical investigation of sustained low-dosage antenatal corticosteroid treatments that avoid high maternal-fetal betamethasone exposures.
Topics: Animals; Betamethasone; Birth Weight; Female; Glucocorticoids; Hypothalamo-Hypophyseal System; Lung; Pituitary-Adrenal System; Pregnancy; Sheep
PubMed: 34626553
DOI: 10.1016/j.ajog.2021.10.001 -
Acta Obstetricia Et Gynecologica... Jul 2011To systematically review the efficacy and safety of repeated antenatal corticosteroid on neonatal morbidity, growth and later development. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review the efficacy and safety of repeated antenatal corticosteroid on neonatal morbidity, growth and later development.
DESIGN
MEDLINE, Cochrane database and a bibliography of identified articles were searched for English language studies. Design. Meta-analysis of randomized controlled trials.
SAMPLE
Randomized, controlled trials studying the efficacy and safety of repeat antenatal corticosteroid treatment on neonatal morbidity and early childhood development.
MAIN OUTCOME MEASURES
Respiratory distress syndrome, intrauterine growth, neurodevelopment.
METHODS
Two reviewers independently assessed titles, abstracts and full studies, extracted data and assessed quality. Meta-analyses were performed, calculating risk ratios and weighted differences of means with 95% confidence intervals using a random-effects model.
RESULTS
Eight trials were included. Repeated betamethasone treatment decreased the risk of respiratory distress syndrome (relative risk 0.85, 95% confidence interval 0.77-0.93). Trials involving weekly or biweekly repeated betamethasone and those involving a single rescue dose decreased the risk of respiratory distress syndrome. Intrauterine growth was significantly restricted among preterm infants exposed to weekly or biweekly repeated betamethasone. A single rescue course did not affect growth. Four follow-up studies did not reveal any disturbances in neurodevelopment or growth at two years of corrected age.
CONCLUSIONS
Repeated corticosteroid treatment decreased the risk of respiratory distress syndrome among preterm infants. Weekly or biweekly repeated betamethasone restricted intrauterine growth, which raises concerns about long-term consequences on neurodevelopment and metabolism. More follow-up studies are needed to confirm the long-term safety of repeated betamethasone.
Topics: Adrenal Cortex Hormones; Betamethasone; Child Development; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fetal Development; Finland; Humans; Incidence; Infant Mortality; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pregnancy; Pregnancy Outcome; Premature Birth; Prenatal Care; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Survival Rate
PubMed: 21426310
DOI: 10.1111/j.1600-0412.2011.01132.x -
JPMA. the Journal of the Pakistan... Nov 2023
Topics: Humans; Betamethasone; Blindness; Vision Disorders
PubMed: 38013581
DOI: 10.47391/JPMA.9815 -
Journal of Perinatology : Official... Dec 2022Assess if maternal betamethasone administration at 34-35 weeks accelerated neonatal amplitude integrated EEG (aEEG) maturation. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Assess if maternal betamethasone administration at 34-35 weeks accelerated neonatal amplitude integrated EEG (aEEG) maturation.
STUDY DESIGN
Nested, observational cohort in 7 centers participating in the Antenatal Late Preterm Steroid randomized trial. Up to 2 aEEGs were obtained in neonates born from 34-35 weeks gestation before 72 h (aEEG 1) and at 5-7 days (aEEG 2) if hospitalized. Personnel and aEEG central readers were masked to the intervention. The primary outcome was maturation reflected by cycle frequency; secondary outcomes were border voltage, span, and discontinuity.
RESULTS
58 neonates were enrolled (betamethasone, 28, placebo, 30). On aEEG 1, cycle frequency did not differ, but betamethasone exposed infants had a greater lower border voltage and a broader span. On aEEG 2, both groups displayed increases in lower border voltage.
CONCLUSIONS
Betamethasone associated changes in lower border voltage support accelerated electrical activity. Further investigation is needed to understand the broader span.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Betamethasone; Cohort Studies; Electroencephalography; Gestational Age; Premature Birth
PubMed: 35618748
DOI: 10.1038/s41372-022-01415-4 -
American Journal of Ophthalmology Sep 2023To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular...
PURPOSE
To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase.
DESIGN
Retrospective case series.
METHODS
Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed.
RESULTS
This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed.
CONCLUSIONS
In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.
Topics: Betamethasone; Humans; Stevens-Johnson Syndrome; Administration, Topical; Retrospective Studies; Anti-Inflammatory Agents; Visual Acuity; Glucocorticoids; Pulse Therapy, Drug; Eye Diseases; Male; Female; Child; Adolescent; Adult; Middle Aged; Aged
PubMed: 37182731
DOI: 10.1016/j.ajo.2023.05.010 -
JAMA Pediatrics Dec 2022
Topics: Infant, Newborn; Pregnancy; Female; Humans; Betamethasone; Gestational Age; Premature Birth
PubMed: 36121659
DOI: 10.1001/jamapediatrics.2022.3251 -
Current Opinion in Obstetrics &... Apr 2014The beneficial effects of antenatal steroids in women at risk of preterm birth are evident. A dose of 24 mg appears sufficient, but there are insufficient data to... (Review)
Review
PURPOSE OF REVIEW
The beneficial effects of antenatal steroids in women at risk of preterm birth are evident. A dose of 24 mg appears sufficient, but there are insufficient data to recommend betamethasone or dexamethasone, a single steroid dose, the optimal interval between doses and repeated courses, the gestational age at which treatment is beneficial and the long-term effects of steroid treatment. This review addresses these aspects of antenatal steroid treatment.
RECENT FINDINGS
Although the 12-h and 24-h dosing intervals are equivalent with respect to prevention of respiratory distress syndrome, the former enables the completion of treatment in 50% more neonates delivered prematurely. Reducing the single steroid dose in patients at risk for premature birth reduces the associated maternal side effects. An inverse relationship has been demonstrated between the number of corticosteroid courses and foetal growth. The reduced size of exposed foetuses has been attributed to birth at earlier gestational ages and decreased foetal growth. Evidence suggests that antenatal exposure to synthetic glucocorticoids in term-born children has long-lasting effects, which may have important implications in the recommendation of steroids before elective caesarean at term.
SUMMARY
The short-term and long-term effects of the dosage regimen on the pregnant mother and foetus remain unclear.
Topics: Anti-Inflammatory Agents; Betamethasone; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fetal Development; Gestational Age; Glucocorticoids; Humans; Infant, Newborn; Practice Guidelines as Topic; Pregnancy; Pregnancy Outcome; Premature Birth; Respiratory Distress Syndrome, Newborn
PubMed: 24463225
DOI: 10.1097/GCO.0000000000000047 -
American Journal of Obstetrics and... Sep 2010Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect medication distribution volume. We evaluated whether maternal or neonatal cord betamethasone concentrations differed in twin gestations or obese patients.
STUDY DESIGN
Participants receiving betamethasone in a randomized controlled trial of weekly ACS were identified. We analyzed maternal delivery and cord serum betamethasone concentrations comparing singletons with twins and obese (BMI > or =30 kg/m(2)) with nonobese women.
RESULTS
Fifty-five maternal and 45 cord blood samples were available. Unadjusted median maternal serum concentrations appeared paradoxically higher in both twin gestations and the obese. However, after controlling for confounders, there were no differences in betamethasone concentrations in maternal serum or cord blood between singletons and twins (P = .61 vs P = .14) or nonobese and obese women (P = .67 vs .12).
CONCLUSION
Maternal and umbilical cord blood serum betamethasone concentrations are not different in twin gestations or obese women.
Topics: Betamethasone; Body Mass Index; Female; Fetal Blood; Glucocorticoids; Humans; Multivariate Analysis; Obesity; Pregnancy; Pregnancy, Multiple; Premature Birth; Twins
PubMed: 20579955
DOI: 10.1016/j.ajog.2010.04.047 -
PloS One 2022Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less than 35 weeks' gestation. If women remain at risk of preterm birth seven or more days after an initial course of ACS, most guidelines recommend administration of a repeat dose(s). No randomised trials have assessed the efficacy of dexamethasone as a repeat steroid compared to betamethasone.
AIM
We aimed to determine if there were differences between the use of dexamethasone or betamethasone as repeat ACS, for women who remain at risk of preterm birth after an initial course, on maternal, infant, and childhood health outcomes.
METHODS
We performed a secondary analysis of data from the ASTEROID randomised trial, where women at risk of preterm birth were allocated to either betamethasone or dexamethasone. Infant, childhood, and maternal outcomes were compared according to whether women received a repeat dose(s) of dexamethasone or betamethasone. The primary outcome was a composite outcome of death or any neurosensory disability at age two years (corrected for prematurity). The ASTEROID trial is registered with ANZCTR, ACTRN12608000631303.
RESULTS
168 women and their infants were included, with 86 women receiving dexamethasone and 82 women receiving betamethasone as a repeat dose. Women in the two ACS groups had similar baseline characteristics. We observed little to no difference in the incidence of death or any neurosensory disability at age two years (OR 0.89, 95% CI 0.39 to 2.06, p = 0.79) or in the incidence of other infant, childhood, and maternal adverse health outcomes between women who received dexamethasone and those who received betamethasone.
CONCLUSION
Use of dexamethasone for a repeat dose(s) compared to betamethasone did not result in any differences in infant, childhood, and maternal health outcomes. These results can be used to support clinical practice guideline recommendations.
Topics: Adult; Betamethasone; Dexamethasone; Female; Glucocorticoids; Humans; Infant; Infant Mortality; Infant, Newborn; Maternal Mortality; Premature Birth
PubMed: 35192656
DOI: 10.1371/journal.pone.0263927 -
Journal of the European Academy of... May 2020Psoriasis is a disease that commonly manifests in adolescence. Up to half of adults with psoriasis develop it before the age of 20. Topical formulations containing...
Safety and efficacy of topical, fixed-dose combination calcipotriene (0.005%) and betamethasone (0.064% as dipropionate) gel in adolescent patients with scalp and body psoriasis: a phase II trial.
BACKGROUND
Psoriasis is a disease that commonly manifests in adolescence. Up to half of adults with psoriasis develop it before the age of 20. Topical formulations containing corticosteroids and/or vitamin D3 analogs are recommended for treatment.
OBJECTIVE
This phase II study aimed to evaluate the safety, including any potential effect on the hypothalamic-pituitary-adrenal axis and calcium metabolism, and efficacy of fixed-dose combination calcipotriene (0.005%) and betamethasone (0.064% as dipropionate) (Cal/BD) gel in adolescents with psoriasis.
METHODS
Patients aged 12 to <17 years, with at least mild psoriasis on the body and scalp, received topical Cal/BD gel once daily for ≤8 weeks. Safety response criteria included adverse drug reactions [ADRs; any adverse event (AE) possibly or probably related to treatment as determined by the investigator; a primary response criterion] and AEs (a secondary response criterion). Only treatment-emergent AEs (events that occurred after the first application of Cal/BD gel or events which started before this and increased in intensity after the first application of Cal/BD gel) are presented here. Efficacy response criteria included controlled disease, by physician's global assessment of disease severity (PGA), following Cal/BD gel treatment.
RESULTS
A total of 107 patients (median age 14 years; range 12-16) were enrolled and treated. Eight ADRs were observed in 7 (7%) patients and 38 (36%) patients experienced ≥1 AE. The most common AEs were headache [6 (6%) patients], nasopharyngitis [6 (6%) patients] and blood parathyroid hormone increased [4 (4%) patients]. One severe AE was reported (attempted suicide) but was considered unrelated to treatment. At the end of treatment, 58% of patients had controlled disease on the body and 69% on the scalp according to PGA.
CONCLUSION
In this uncontrolled phase II study, Cal/BD gel was well tolerated and effective for treating scalp and body psoriasis in adolescents.
Topics: Adolescent; Betamethasone; Calcitriol; Child; Dermatologic Agents; Drug Combinations; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Psoriasis; Scalp; Treatment Outcome
PubMed: 31721327
DOI: 10.1111/jdv.16077