Multiple Courses Of Antenatal Corticosteroids Research Articles

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial.

Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted..

One vs 2 courses of antenatal corticosteroids in pregnancies at risk of preterm birth: a secondary analysis of the MACS trial

Birth is unpredictable and many patients who receive antenatal corticosteroids for preterm birth remain pregnant. Some professional societies recommend rescue antenatal corticosteroids for those who remain pregnant ≥14 days following the initial course. This study aimed to explore a single vs a second course of antenatal corticosteroids in terms of severe neonatal morbidity and mortality. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS) trial. The MACS study was a randomized clinical trial conducted in 80 centers in 20 different countries from 2001 to 2006. Participants who received only 1 course of intervention (ie, either a second course of antenatal corticosteroids or placebo) were included in this study. The primary outcome was a composite of stillbirth, neonatal mortality in the first 28 days of life or before discharge, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage stage III and IV, periventricular leukomalacia, and necrotizing enterocolitis. Two subgroup analyses were planned to address the effect of a second course of antenatal corticosteroids on infants born before 32 weeks or within 7 days from the intervention. Moreover, a sensitivity analysis was performed to assess the effect of intervention on singleton pregnancies. Baseline characteristics were compared between the groups using chi-square and Student t tests. Multivariable regression analysis was performed to adjust for confounding variables. There were 385 and 365 participants included in the antenatal corticosteroid and placebo groups, respectively. The composite primary outcome occurred in 24% and 20% of participants in the antenatal corticosteroid and placebo groups, respectively (adjusted odds ratio, 1.09; 95% confidence interval, 0.76-1.57). Moreover, severe respiratory distress syndrome rate was similar between the 2 groups (adjusted odds ratio, 0.98; 95% confidence interval, 0.65-1.48). Newborns exposed to antenatal corticosteroids were more likely to be small for gestational age (14.9% vs 10.6%; adjusted odds ratio, 1.63; 95% confidence interval, 1.07-2.47). These findings remained true among singleton pregnancies for the primary composite outcome and birthweight <10th percentile (adjusted odds ratio, 1.29 [0.82-2.01]; and adjusted odds ratio, 1.74 [1.06-2.87]; respectively). Subgroup analyses of infants born before 32 weeks or within 7 days from the intervention did not show any benefits in terms of the composite primary outcome with antenatal corticosteroids vs placebo (50.5% vs 41.8% [adjusted odds ratio, 1.16; 95% confidence interval, 0.78-1.72]; and 42.3% vs 37.1% [adjusted odds ratio, 1.02; 95% confidence interval, 0.67-1.57]; respectively). Neonatal mortality and severe morbidities, including severe respiratory distress syndrome, were not improved by a second course of antenatal corticosteroids. Policy makers need to be thoughtful when recommending a second course of antenatal corticosteroids and consider whether not only short-term but also long-term benefits can be gained from such administration.

Antenatal corticosteroids for prevention of neonatal respiratory distress syndrome multiple vs simple doses

Objective: To analyze the major outcomes comparing single versus multiple courses of antenatal corticosteroids (ACS) therapy in women at high risk of premature delivery. Methods: This systematic review analyzed 20 articles that were selected from “Biblioteca Virtual em Saúde" of Pan American Health Organization. The terms “multiple courses” and “antenatal corticosteroids” were used to search in databases: MEDLINE, LILAC, CUMED and IBECS. Another 4 relevant articles outside this search and fit our inclusion criteria were added. Results: There is no consensus in literature about whether multiple doses of ACS are beneficial or harmful for the infant and women. The majority of the reviewed articles positioned against multiple corticosteroid therapy, due to possible neurological effects to the newborn and the no outstanding results compared to single dose. Although some studies demonstrated that multiple ACS might have benefits greater than harms. Independently of those opinions, there is one major difficulty to establish the benefits of multiple ACS: insufficient long-term evaluation of these infants. For this reason, there are several neutral articles. Conclusion: The different criteria of each study (e.g. gestational age, dosage of ACS, sample size), made it difficult to analyze the articles in a standard format. There might be advantages in corticoid therapy in lower gestational age. However, there is a lack of long-term studies with exposed infants, besides insufficient studies about the best methods to administer the ACS (dosage, number of doses, rescue dose, gestational age). More long-dated follow-up and studies about methodologies are necessary to conclude this hypothesis.

Optimized Clustering Algorithm for Comparative Analysis of Different Prenatal Corticosteroid Neurological Deficits in Premature Infants through Magnetic Reasoning Imaging (MRI).

Objective This study aimed to explore the application of different prenatal corticosteroids in the assessment of neurological deficits and prognosis in premature infants through Magnetic Reasoning Imaging (MRI) under optimized cluster algorithm. Methods 100 pregnant women with threatened preterm labor were retrospectively analyzed, in which 38 pregnant women with lasting threatened preterm labor (group A) were treated with multiple courses of antenatal corticosteroids (dexamethasone treatment) and 62 cases of pregnant women with threatened preterm labor (group B) were treated with single course of dexamethasone treatment. Craniocerebral MRI images based on optimal clustering algorithm were used to examine neonates. Neonatal hypoxic-ischemic encephalopathy (HIE) rate, serum neuron-specific enolase (NSE) concentration, neonatal behavioral neurological score (NBNA), respiratory distress syndrome (RDS) rate, perinatal mortality, neonatal birth weight, and maternal complications rate of two groups were compared. Results Compared with other traditional image segmentation algorithms, this algorithm had the best segmentation effect, the shortest running time (1.43 s), the least number of iterations (5 times), and the highest segmentation accuracy (97.98%). There was no significant difference in the HIE rate, serum NSE concentration, NBNA score, RDS score, and perinatal mortality in group A and group B (P > 0.05). Compared with group B, neonates' body weight in group A was decreased, while the maternal complication rate in group A was increased (P < 0.05). Conclusion MRI images based on optimized clustering algorithm can be used in the diagnosis of neonatal hypoxic-ischemic encephalopathy. There is no significant difference in the application of different antenatal corticosteroids affecting premature nerve function defect and prognosis, but multiple courses of antenatal corticosteroids can affect neonatal body mass and increased maternal complications to a certain extent; therefore, before threatened premature delivery treatment, the pros and cons of multiple courses of antenatal corticosteroids should fully be considered and in the treatment, measures should be actively taken to alleviate the side effect.

805: Postpartum depression assessment in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS)

805: Postpartum depression assessment in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS)

Accounting for treatment by center interaction in sample size determinations and the use of surrogate outcomes in the pessary for the prevention of preterm birth trial: a simulation study

BackgroundThe Pessary for the Prevention of Preterm Birth Study (PS3) is an international, multicenter, randomized clinical trial designed to examine the effectiveness of the Arabin pessary in preventing preterm birth in pregnant women with a short cervix. During the design of the study two methodological issues regarding power and sample size were raised. Since treatment in the Standard Arm will vary between centers, it is anticipated that so too will the probability of preterm birth in that arm. This will likely result in a treatment by center interaction, and the issue of how this will affect the sample size requirements was raised. The sample size requirements to examine the effect of the pessary on the baby’s clinical outcome was prohibitively high, so the second issue is how best to examine the effect on clinical outcome. The approaches taken to address these issues are presented.ResultsSimulation and sensitivity analysis were used to address the sample size issue. The probability of preterm birth in the Standard Arm was assumed to vary between centers following a Beta distribution with a mean of 0.3 and a coefficient of variation of 0.3. To address the second issue a Bayesian decision model is proposed that combines the information regarding the between-treatment difference in the probability of preterm birth from PS3 with the data from the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study that relate preterm birth and perinatal mortality/morbidity. The approach provides a between-treatment comparison with respect to the probability of a bad clinical outcome. The performance of the approach was assessed using simulation and sensitivity analysis.Accounting for a possible treatment by center interaction increased the sample size from 540 to 700 patients per arm for the base case. The sample size requirements increase with the coefficient of variation and decrease with the number of centers. Under the same assumptions used for determining the sample size requirements, the simulated mean probability that pessary reduces the risk of perinatal mortality/morbidity is 0.98. The simulated mean decreased with coefficient of variation and increased with the number of clinical sites.ConclusionEmploying simulation and sensitivity analysis is a useful approach for determining sample size requirements while accounting for the additional uncertainty due to a treatment by center interaction. Using a surrogate outcome in conjunction with a Bayesian decision model is an efficient way to compare important clinical outcomes in a randomized clinical trial in situations where the direct approach requires a prohibitively high sample size.

495: Preterm premature rupture of membranes and adverse neurodevelopmental outcomes at 5 years of age: a multiple courses of antenatal corticosteroids for preterm birth study secondary analysis

495: Preterm premature rupture of membranes and adverse neurodevelopmental outcomes at 5 years of age: a multiple courses of antenatal corticosteroids for preterm birth study secondary analysis

Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)

BackgroundThe Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age.MethodA total of 1719 children, with the breakdown into groupings of <30, 30–36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis.ResultsGestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037.ConclusionPreterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research.Trial registrationThis study has been registered at (identifier NCT00187382)Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2393-14-272) contains supplementary material, which is available to authorized users.

656: Multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5): association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years of age

656: Multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5): association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years of age

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study

A single course of antenatal corticosteroid therapy is recommended for pregnant women at risk of preterm birth between 24 and 33 weeks' gestational age. However, 50% of women remain pregnant 7 to 14 days later, leading to the question of whether additional courses should be given to women remaining at risk for preterm birth. The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) was an international randomized clinical trial that compared multiple courses of antenatal corticosteroids with a single course in women at risk of preterm birth. To determine the effects of single vs multiple courses of antenatal corticosteroid therapy on death or neurodevelopmental disability (neuromotor, neurosensory, or neurocognitive/neurobehavioral function) at 5 years of age in children whose mothers participated in MACS. Our secondary aims were to determine the effect on height, weight, head circumference, blood pressure, intelligence, and specific cognitive (visual, spatial, and language) skills. Cohort follow-up study of children seen between June 2006 and May 2012 at 55 centers. In total, 1724 women (2141 children) were eligible for the study, of whom 1728 children (80.7% of the 2141 eligible children) participated and 1719 children contributed to the primary outcome. Single and multiple courses of antenatal corticosteroid therapy. The primary outcome was death or survival with a neurodevelopmental disability in 1 of the following domains: neuromotor (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for visual/hearing aids), or neurocognitive/neurobehavioral function (abnormal attention, memory, or behavior). There was no significant difference between the groups in the risk of death or neurodevelopmental disability: 217 of 871 children (24.9%) in the multiple-courses group vs 210 of 848 children (24.8%) in the single-course group (odds ratio, 1.02 [95% CI, 0.81 to 1.29]; P = .84). Multiple courses, compared with a single course, of antenatal corticosteroid therapy did not increase or decrease the risk of death or disability at 5 years of age. Because of a lack of strong conclusive evidence of short-term or long-term benefits, it remains our opinion that multiple courses not be recommended in women with ongoing risk of preterm birth. clinicaltrials.gov Identifier: NCT00187382.

Gestational age–specific risks vs benefits of multicourse antenatal corticosteroids for preterm labor

The purpose of this study was to estimate a gestational age threshold at which the benefits of treatment with weekly courses of antenatal corticosteroids (ACS) during preterm labor outweigh the risks. Risk-benefit ratios by gestational age were determined with the use of a Markov microsimulation decision-analysis model with a 1-week cycle length. Single course and multiple (weekly to a maximum of 4) courses of ACS by gestational age of entry (23 weeks to 31 weeks 6 days' gestation) were compared. Benefits were composite events (respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, or stillbirth) averted. Risks were small head circumference and small for gestational age. More composite events are averted (benefits) than risks acquired (ratio, 6:1) when multiple courses of ACS are initiated at 26weeks' gestation. When multiple courses of ACS are initiated at 29weeks' gestation, the risk-benefit ratio is 1. Beyond 29 weeks, there is a suggestion of more risk than benefit. The model suggests that multiple courses of ACS that are initiated at <29 weeks' gestation may have increased benefit compared with risks. Further analyses are needed to determine the long-term clinical significance of these findings.

2: Multiple Courses of Antenatal Corticosteroids for preterm birth study: 5-year outcomes (MACS-5)

2: Multiple Courses of Antenatal Corticosteroids for preterm birth study: 5-year outcomes (MACS-5)

Effect of Antenatal Corticosteroids on Fetal Growth and Gestational Age at Birth

To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. II.

Antenatal Corticosteroids: A Risk Factor for the Development of Chronic Disease

Preterm birth remains a major health issue worldwide. Since the 1990s, women at risk for preterm birth received a single course of exogenous antenatal corticosteroids (ACSs) to facilitate fetal lung maturity. More recently, repeated or multiple courses of ACS have been supported to provide continued fetal maturity support for women with continued risk of preterm birth. However, exogenous ACS reduces birth weight which, in turn, is associated with adverse adult outcomes such as coronary heart disease, stroke, hypertension, and type 2 diabetes. The long-term effects of ACS exposure on HPA axis activity and neurological function are well documented in animal studies, and it appears that ACS, regardless of dose exposure, is capable of affecting fetal HPA axis development causing permanent changes in the HPA axis that persists through life and is manifested by chronic illness and behavioral changes. The challenge in human studies is to demonstrate whether an intervention such as ACS administration in pregnancy contributes to developmental programming and how this is manifested in later life.

498: Do antenatal corticosteroids reduce fetal growth or gestational age at birth? A secondary analysis from the multiple courses of antenatal corticosteroids for preterm birth study (MACS)

Multiple courses of Antenatal Corticosteroids for preterm birth Study (MACS) was an international multi-centered double-blind randomized controlled trial of single vs. multiple courses of antenatal corticosteroids (ACS). Infants exposed to ACS experienced similar composite morbidity and mortality as compared to placebo (12.9 % ACS vs. 12.5% placebo) OR 1.04 (CI 0.77-1.39 p=0.83). Infants in the ACS group were smaller. They weighed less (2216 g vs. 2330 g, p=0.0026), were shorter (44.5 cm vs. 45.4 cm, p=0.001) and had a smaller head circumference (31.1 cm vs.

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes

Multiple courses of antenatal corticosteroids for preterm birth study: 2-year outcomes (1)

Multiple courses of antenatal corticosteroids for preterm birth study: 2-year outcomes (1)

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes

Antenatal corticosteroids for preterm birth: dose‐dependent reduction in birthweight, length and head circumference

This study was undertaken to evaluate the effects of repeated courses of antenatal corticosteroids (ACS) on foetal growth. We studied 94 infants exposed to 2-9 courses of ACS. Mean gestational age (GA) at first exposure was 29 and at birth 34 weeks. Exposure data were retrieved from case record files. Information on potential confounders was collected from the Swedish Medical Birth Registry. Standard deviation scores (SDS) for birthweight (BW), birthlength (BL) and head circumference (HC) were calculated and considered as outcomes. GA at start of ACS did not affect outcome. BW-SDS, BL-SDS and HC-SDS were -0.21, -0.19 and +0.25 in infants exposed to two courses, compared to -1.01, -1.04 and -0.23 in infants exposed to ≥ 4 courses of ACS (p = 0.04-0.07). In multiple regression analyses, ≥ 4 courses were associated with lower BW-SDS, BL-SDS and HC-SDS (p = 0.007-0.04) compared to SDS after 2-3 courses. The effects from ≥ 4 courses on BW and BL were comparable to reduction in birth size seen in twins and on HC to that observed after maternal smoking. Multiple courses of ACS are associated with a dose-dependent decline in foetal growth, which may affect later development and health.

Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study: 2-Year Outcomes

The aim of this study was to determine the effects of repeated courses of prenatal corticosteroid therapy versus placebo on death or neurologic impairment among the children enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, at 18 to 24 months of age. A total of 2305 infants were eligible for follow-up evaluation; 2104 infants (1069 in the prenatal corticosteroid therapy group and 1035 in the placebo group) were monitored. The primary outcome was death or neurologic impairment, defined as either cerebral palsy or cognitive delay, at 18 to 24 months of age. The secondary outcomes were measurements of growth (height, weight, and head circumference). Children exposed to multiple courses of prenatal corticosteroid therapy had similar rates of death or neurologic impairment, compared with children exposed to placebo (148 children [13.8%] vs 142 children [13.7%]; odds ratio: 1.001[95% confidence interval: 0.75-1.30]; P = .95). They had a mean weight of 11.94 kg, compared with 12.14 kg in the placebo group (P = .04), a mean height of 85.51 cm, compared with 85.46 cm (P = .87), and a mean head circumference of 48.18 cm, compared with 48.25 cm (P = .45). Multiple courses of prenatal corticosteroid therapy, given every 14 days, did not increase or decrease the risk of death or neurologic impairment at 18 to 24 months of age, compared with a single course of prenatal corticosteroid therapy. Continued follow-up monitoring of these children is necessary to assess neurobehavioral function, school performance, and possible susceptibility to disease.