Repeat Courses Of Antenatal Corticosteroids Research Articles

Reported adherence to current antenatal corticosteroid guidelines in Australia and New Zealand.

Antenatal corticosteroids (ANC) reduce mortality and morbidity in preterm babies, but prescription practices vary. To assess obstetricians' compliance with the recommendations of the Australian and New Zealand clinical practice guidelines on use of ANC. An anonymous online questionnaire was distributed to Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. All respondents reported prescribing an initial course of ANC according to the guidelines if preterm birth at 28weeks' gestation was expected within 24 or 72h. However, 22% reported prescribing ANC even if birth was not expected within sevendays. This was reported more often by practitioners not using adjunct tests to predict preterm birth (14% vs 69%; P < 0.001). An initial course of ANC at ≥35weeks was prescribed by 52% of respondents. However, 93% reported prescribing ANC at ≥35weeks prior to elective caesarean section. Repeat courses of ANC were prescribed by 76% of respondents. Of these, 89% reported prescribing repeat courses beyond the guideline recommendations at ≥33weeks and 29% exceeded the recommendations on number of repeat courses. For infants born at <35weeks, current ANC prescribing patterns in Australia and New Zealand are consistent with the guideline recommendations and result in high rates of administration in this group. However, administration of ANC to groups where benefits have not been demonstrated is commonly reported. Adherence to the guideline recommendations would decrease ANC exposure to babies for whom there is no strong evidence of benefit.

648: Single vs repeat courses of antenatal corticosteroids with twin gestations

648: Single vs repeat courses of antenatal corticosteroids with twin gestations

Repeat Antenatal Steroid Exposure and Later Blood Pressure, Arterial Stiffness, and Metabolic Profile

To determine the relationship between repeat courses of antenatal corticosteroids (ACS) and risk factors for cardiovascular disease in adolescents and young adults. We assessed body mass index, blood pressure, arterial stiffness, blood lipids, and insulin resistance (IR) in a Swedish population-based cohort (n = 100) at a median age of 18 (range 14-26) years. Fifty-eight subjects (36 males) had been exposed to 2-9 weekly courses of antenatal betamethasone and 42 (23 males) were unexposed subjects matched for age, sex, and gestational age (GA). There were no significant differences between the groups regarding body mass index, systolic or diastolic blood pressures, arterial stiffness measured by augmentation index, blood lipids, IR, or morning cortisol levels either in simple regression or in multivariable models. However, more subjects with elevated augmentation index had been exposed to repeat courses of ACS (n = 7) compared with unexposed subjects (n =1, P = .06), and glucose, insulin, and IR correlated inversely to GA at start of ACS (P < .01). Repeat courses of ACS did not correlate to adverse cardiovascular risk profile in adolescence and young adulthood, but long-standing effects on the arterial tree and glucose metabolism, the latter dependent on GA at ACS exposure, cannot be excluded. These observations have clinical implications for the ongoing discussion on short-term benefits and long-term safety of repeat ACS treatment.

Cognitive Outcome in Adolescents and Young Adults after Repeat Courses of Antenatal Corticosteroids

To investigate whether repeat courses of antenatal corticosteroids have long-term effects on cognitive and psychological functioning. In a prospective cohort study, 58 adolescents and young adults (36 males) who had been exposed to 2-9 weekly courses of betamethasone in utero were assessed with neuropsychological tests and behavior self-reports. Unexposed subjects (n = 44, 25 males) matched for age, sex, and gestational age at birth served as a comparison group. In addition, individuals exposed in utero to a single course (n = 25, 14 males) were included for dose-response analysis. Group differences were investigated using multilevel linear modeling. Mean scores obtained in 2 measures of attention and speed were significantly lower in subjects exposed to 2 or more antenatal corticosteroids courses (Symbol Search, P = .009; Digit Span Forward, P = .02), but these were not dose-dependent. Exposure to repeat courses of antenatal corticosteroids was not associated with general deficits in higher cognitive functions, self-reported attention, adaptability, or overall psychological function. Although this study indicates that repeat exposure to antenatal corticosteroids may have an impact on aspects of executive functioning, it does not provide support for the prevailing concern that such fetal exposure will have a major adverse impact on cognitive functions and psychological health later in life.

453 Repeat Courses of Antenatal Corticosteroids for Preterm Birth and Risk for Metabolic Syndrome in Young Adulthood

BackgroundPreterm birth is associated with later hypertension and diabetes. One explanation for this association could be that exposure to antenatal corticosteroids (ACS), especially if repeated, induce adverse long-term effects. There...

Growth in the neonatal period after repeat courses of antenatal corticosteroids: data from the ACTORDS randomised trial

ObjectiveTo determine the effect of repeated antenatal corticosteroids on postnatal changes in weight, linear growth and head circumference.MethodsMothers who entered the repeated dose of antenatal steroids (ACTORDS) trial were randomised...

Review: multiple doses of antenatal corticosteroids prevent preterm neonatal respiratory disease more than a single dose

ED FROM Crowther CA, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2007;(3):CD003935. Correspondence to:...

Long-Term Outcomes after Repeat Doses of Antenatal Corticosteroids

Previous trials have shown that repeat courses of antenatal corticosteroids improve some neonatal outcomes in preterm infants but reduce birth weight and increase the risk of intrauterine growth restriction. We report long-term follow-up results of children enrolled in a randomized trial comparing single and repeat courses of antenatal corticosteroids. Women at 23 through 31 weeks of gestation who remained pregnant 7 days after an initial course of corticosteroids were randomly assigned to weekly courses of betamethasone, consisting of 12 mg given intramuscularly and repeated once at 24 hours, or an identical-appearing placebo. We studied the children who were born after these treatments when they were between 2 and 3 years of corrected age. Prespecified outcomes included scores on the Bayley Scales of Infant Development, anthropometric measurements, and the presence of cerebral palsy. A total of 556 infants were available for follow-up; 486 children (87.4%) underwent physical examination and 465 (83.6%) underwent Bayley testing at a mean (+/-SD) corrected age of 29.3+/-4.6 months. There were no significant differences in Bayley results or anthropometric measurements. Six children (2.9% of pregnancies) in the repeat-corticosteroid group had cerebral palsy as compared with one child (0.5% of pregnancies) in the placebo group (relative risk, 5.7; 95% confidence interval, 0.7 to 46.7; P=0.12). Children who had been exposed to repeat as compared with single courses of antenatal corticosteroids did not differ significantly in physical or neurocognitive measures. Although the difference was not statistically significant, the higher rate of cerebral palsy among children who had been exposed to repeat doses of corticosteroids is of concern and warrants further study. (ClinicalTrials.gov number, NCT00015002 [ClinicalTrials.gov].).

The Need to Go Beyond: Evaluating Antenatal Corticosteroid Trials With Long-Term Outcomes

A single course of antenatal corticosteroids (ACS) reduces the risk of severe neonatal morbidity and is associated with a strong trend towards a reduced risk of abnormal neurodevelopmental outcome. However, because 50% of women given ACS remain undelivered and continue to be at risk for preterm delivery, the question remains: would these women benefit from repeated courses of ACS, and, if so, how do repeated courses of ACS affect the fetus and long-term neurodevelopmental outcome? The serious consequences of this effect on the developing brain justify the need for long-term outcome studies (beyond two years of age) before repeat courses of ACS become standard care in the management of pregnant women who are at risk of preterm delivery throughout pregnancy.

Single Versus Repeat Courses of Antenatal Steroids to Improve Neonatal Outcomes: Risks and Benefits

Recent additions to the literature provide evidence supporting the use of repeat courses of antenatal steroids. Both human and animal studies offer evidence that repeat courses of corticosteroids improve neonatal pulmonary outcomes, especially for the infants delivered at earlier gestational ages. Although there is also evidence to suggest altered neuronal maturation and intrauterine growth restriction in animals treated with repeat steroids, randomized controlled studies in humans have shown that birth weight reduction was only seen in those infants treated with 4 or more courses of corticosteroids. In addition, the reduction in neonatal birth weight and head circumference seen after multiple courses of antenatal corticosteroids normalizes by the time of hospital discharge. Studies are ongoing to investigate the 24-month post delivery physical and neurodevelopmental outcomes in infants exposed to repeat courses of antenatal corticosteroids. Although there is evidence demonstrating the safety of a single repeat, or 'rescue', dose of antenatal corticosteroids, this must be tempered against the adverse effects seen after multiple courses of weekly repeat steroids. Randomized controlled trials are needed to determine the optimal number of courses of antenatal steroids to reduce the frequency of neonatal respiratory distress syndrome (RDS) without adversely affecting other neonatal outcomes.

Preterm Labour and Birth: A Survey of Clinical Practice Regarding Use of Tocolytics, Antenatal Corticosteroids, and Progesterone

ObjectivesWe wished to determine prescribing practices of obstetricians in Canada regarding tocolytics, antenatal corticosteroids, and progesterone for women at increased risk of preterm labour and birth, and to determine whether these practices changed between 1997–98 and 2004. MethodsTwo cross-sectional surveys of Canadian obstetricians were conducted. The initial survey was in 1997–98 (N = 1313); the follow-up survey was in 2004 (N = 1508). ResultsResponse rates were 46.4% in 1997–98 and 43.3% in 2004. Most respondents reported that they prescribed tocolytics to women with signs and symptoms of preterm labour (97.4% in 1997–98; 92.2% in 2004; P < 0.001) but use had decreased. In 1997–98, 20.0% of respondents used tocolytics for > 48 hours during one course of treatment, whereas in 2004, only 9.6% did this (P = 0.06). The tocolytic prescribed most frequently was magnesium sulphate in 1997–98 (40.6% of respondents), whereas in 2004, it was indomethacin (47.5% of respondents). The use of repeat courses of antenatal corticosteroids decreased from 72.9% in 1997–98 to 18.7% in 2004 (P < 0.001). In 2004, only a few respondents (7.0%) prescribed progesterone for women at increased risk of preterm birth. ConclusionsMost Canadian obstetricians continue to use tocolytics for women in preterm labour, although use has decreased over time, and the most frequently prescribed tocolytic has changed from magnesium sulphate to indomethacin. The use of repeat courses of antenatal corticosteroids decreased substantially during this time, and in 2004, progesterone was not in frequent use.

Long term follow-up of infants receiving single vs repeat courses of antenatal corticosteroids (ACS) from the MFMU RCT

Long term follow-up of infants receiving single vs repeat courses of antenatal corticosteroids (ACS) from the MFMU RCT

Maternal and fetal adrenal function following single and repeat courses of antenatal corticosteroids (ACS)

A RANDOMIZED CONTROLLED TRIAL ANDREW ELIMIAN, DAVID GARRY, REINALDO FIGUEROA, ALAN R. SPITZER, VANDY WIENCEK, PAUL OGBURN, J. GERALD OUIRK, State University of New York at Stony Brook, Obstetrics, Gynecology and Reproductive Medicine, Stony Brook, New York OBJECTIVE: No human randomized study has formally compared betamethasone anddexamethasone, thepreferred corticosteroids forantenatal therapy,with regards to their effectiveness in reducing neonatal morbidities and mortality. Our objective was to compare betamethasone with dexamethasone in terms of effectiveness in reducing perinatal morbidities and mortality among preterm infants. STUDY DESIGN: We enrolled 299 women at risk for preterm delivery in a double blind placebo-controlled randomized trial of antenatal betamethasone compared to dexamethasone 8/1/2002-7/31/2004. We excluded women with clinical chorioamnionitis, major fetal structural and chromosomal abnormalities, prior antenatal steroid exposure, and use of betamethasone or dexamethasone for other medical indications. Consenting women were randomly allocated to one of two groups by the Pharmacy using computer generated random numbers. The statistical analysis was performed in accordance of the intention-to-treat principle. Student t test, Chi square and Fisher exact test were used for analysis. A P value of ! .05 was considered statistically significant. RESULTS: There were no significant differences between the groups with regards to baseline characteristics including maternal age, gestational age (GA) at steroid administration, GA at delivery, birth weight, fetal gender, antibiotic exposure, surfactant therapy, mode of delivery, and histologic chorioamnionitis. The rate of respiratory distress syndrome, neonatal mortality, need for vasopressor, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus and neonatal sepsis were not significant different between the groups. However the rate of intraventricular hemorrhage (IVH) was significantly lower in the dexamethasone group compared to the betamethasone group [6/105(5.7%) versus 16/98(16.3%), P=.027] CONCLUSION: Betamethasone and dexamethasone are comparable in reducing the rate of most major neonatal morbidities and mortality in preterm neonates. However dexamethasone appears to be more effective in reducing the rate of IVH.

Repeat courses of antenatal corticosteroids: The controversy continues

confirming the initial findings. 1 Despite what appears to be overwhelming evidence that a single course of antenatal corticosteroids improves outcomes and has a highly favorable risk to benefit ratio, obstetricians throughout the world slowly incorporated the use of corticosteroids into their practice. The reluctance to use corticosteroids was based on the risk of infection, inability to identify the pregnancies that would benefit most, and data from several animal models that suggested that exposure to exogenous corticosteroids resulted in intrauterine growth restriction and permanent damage to the central nervous system. In an attempt to review the scientific evidence and dispel unfounded myths regarding corticosteroids, the National Institutes of Health (NIH) held a consensus conference in 1994. The panel published a consensus statement that strongly supported the use of a single course of corticosteroids in pregnancies between 24 and 34 weeks gestation at risk for delivery within 7 days. 3 They also presented longterm pediatric follow-up data to prove its safety. After the dissemination of the NIH consensus statement, clinical practice appeared to change overnight. Administration of antenatal corticosteroids became the ‘‘standard of care’’ for women at risk for preterm birth and the use of repeat courses of corticosteroids became commonplace. 4 The practice of repeat courses was not

Repeat prenatal corticosteroids: who still recommends their use and why?

Repeat prenatal corticosteroids have been in common use worldwide, even though the National Institutes of Health recommends that 'Until data establish a favourable benefit-to-risk ratio, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.' To describe the current use/recommendations for the use of repeat prenatal corticosteroids by obstetricians and neonatologists and to examine the sources of evidence on which their practice is based. Postal questionnaire. All Trainees, Members and Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and neonatologists in Australia and New Zealand. The questionnaire was mailed to obstetricians and neonatologists in August-September 2001. Practitioner use/recommendations for the use of repeat prenatal corticosteroids and the sources of evidence on which their practice was based. Use of repeat prenatal corticosteroids was recommended by 332 (44%) obstetricians and 19 (21%) neonatologists. Obstetricians were twice as likely to recommend their use compared with neonatologists (relative risk, 2.04; 95% confidence intervals, 1.36-3.06; P < 0.001). Over half of the respondents (483, 57%) reported they had changed their use/recommendations in the previous 3 years. The sources of evidence behind these practices differed between obstetricians and neonatologists and between those practitioners who recommended the use of repeat prenatal corticosteroids and those who did not. Fewer practitioners recommend repeat prenatal corticosteroids compared with previous surveys. Sources of evidence behind the practice of groups of obstetricians and neonatologists differ.

Recommendations for repeat courses of antenatal corticosteroids: A decision analysis

Objective: The objective was to review the evidence regarding multiple versus single courses of antenatal corticosteroids (ACS), devise dosing regimens based on this evidence, and then, by using decision analysis, compare 5 ACS regimens: (1) single course, (2) weekly courses, (3) every-other-week dosing, (4) every-other-week dosing with no more than 2 courses, and (5) an every-other-week dosing regimen with no third courses after 30 weeks and no second course after 32 weeks. Study Design: The literature was examined for evidence regarding a dose response of the benefits and detriments of ACS. A decision analytic model was designed by using odds ratios, risks of morbidity and mortality, and birth rates from the literature. Mathematic modeling, based on data in the literature, was used to estimate the number of patients who would present at risk for preterm delivery and at what gestational age they would subsequently be delivered. A sensitivity analysis was performed to account for uncertainties in the data. Results: Of approximately 4 million annual births in the United States, a conservative estimate of 138,000 patients will present between 24 and 34 weeks of gestation at risk for preterm delivery, with 91,915 deliveries. If the 5 different dosing regimens are applied to these patients, strategy 1, the single course of ACS, would result in 30,232 cases of respiratory distress syndrome (RDS) and 4032 neonatal deaths. Three of the other dosing regimens (2, 3, and 5) would all decrease the number of cases of RDS but would concomitantly increase neonatal deaths. Only dosing regimen 4 would decrease the cases of RDS by 2187 without increasing the number of neonatal deaths. Conclusion: There is evidence that there may be a decrease in the incidence of RDS secondary to the use of multiple doses of ACS; however, a concomitant increase in neonatal deaths may also occur. On the basis of our results, we recommend the following: (1) all fetuses between 24 and 34 weeks' gestation at risk for preterm delivery should be given the first course, (2) if there is a persisting risk of preterm delivery subsequent to this, the next course should be given 2 weeks later, and (3) no more than 2 courses should be given. These recommendations need to be examined in a randomized, controlled trial. (Am J Obstet Gynecol 2002;186:1221-9.)

Antenatal corticosteroids revisited: repeat courses— National Institutes of Health Consensus Development Conference Statement, August 17–18, 2000

Objective: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the benefits and risks of repeat courses of antenatal corticosteroids. Participants: A non-Federal, non-advocate, 16-member panel representing the fields of obstetrics and gynecology, pediatrics, maternal and fetal medicine, neonatology, medical ethics, community health, pharmacology, psychology, and reproductive biology. In addition, 13 experts in these same fields presented data to the panel and to a conference audience of approximately 200. Evidence: The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts of their conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel’s final revisions. Conclusions: The collective international data continue to support unequivocally the use and efficacy of a single course of antenatal corticosteroids using the dosage and interval of administration specified in the 1994 Consensus Development Conference report. The current benefit and risk data are insufficient to support routine use of repeat or rescue courses of antenatal corticosteroids in clinical practice. Clinical trials are in progress to assess potential benefits and risks of various regimens of repeat courses. Until data establish a favorable benefit-to-risk ratio, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.