Single Course Of Antenatal Corticosteroids Research Articles

Committee Opinion No. 475: Antenatal Corticosteroid Therapy for Fetal Maturation

A single course of corticosteroids is recommended for pregnant women between 24 weeks and 34 weeks of gestation who are at risk of preterm delivery within 7 days. A single course of antenatal corticosteroids should be administered to women with premature rupture of membranes before 32 weeks of gestation to reduce the risks of respiratory distress syndrome, perinatal mortality, and other morbidities. The efficacy of corticosteroid use at 32–33 completed weeks of gestation for preterm premature rupture of membranes is unclear, but treatment may be beneficial, particularly if pulmonary immaturity is documented. Sparse data exist on the efficacy of corticosteroid use before fetal age of viability, and such use is not recommended. A single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than 2 weeks prior, the gestational age is less than 32 6/7 weeks, and the women are judged by the clinician to be likely to give birth within the next week. However, regularly scheduled repeat courses or multiple courses (more than two) are not recommended. Further research regarding the risks and benefits, optimal dose, and timing of a single rescue course of steroid treatment is needed.

The effect of maternal body mass index on neonatal outcome in women receiving a single course of antenatal corticosteroids

The aim of this study was to determine the effect of maternal body mass index on the incidence of neonatal prematurity morbidities in those who receive corticosteroids. This was a secondary analysis of a trial of corticosteroids in women at risk for preterm birth. Women receiving a single course of corticosteroids were classified by their prepregnancy body mass index (<25 and > or = 25) and compared on a composite outcome comprised of several neonatal morbidities and on each individual outcome. Of 183 eligible women, 96 (52.5%) had a body mass index of <25 and 87 (47.5%) had a body mass index of > or = 25. The composite outcome occurred more frequently in the body mass index of > or = 2 5 group (28.7%), compared with those with a body mass index of <25 (18.8%), although this was not statistically significant (odds ratio, 1.75; 95% confidence interval, 0.83-3.72). Body mass index was not associated with outcomes after adjusting for confounding. Maternal body mass index did not affect neonatal prematurity morbidities in those receiving corticosteroids.

472: Influence of the interval between antenatal corticosteroid administration and preterm labor on the occurrence of respiratory morbidity

The aim of this study was to determine whether the effectiveness of a single complete course of antenatal corticosteroids (ACS) in the prevention of neonatal respiratory morbidity depends on the interval between ACS administration and delivery. A retrospective cohort study was performed in two perinatal centres among all women with threatened preterm labor who completed a single course of antenatal corticosteroids (betamethasone) before a gestational age of 34 weeks. We excluded women with a triplet pregnancy, women who delivered more than 21 days after completion of the ACS and antenatal deaths. Each neonate born from a twin pregnancy was analysed separately. We categorized the patients in three groups: ACS-delivery interval <7 days (1), between 7 and 14 days (2) and >14 days (3). Neonatal respiratory morbidity was defined as intubation of the neonate. We performed a logistic regression analysis to control for differences in gestational age at delivery. We included 254 neonates, of which 155 (61%) neonates were born <7 days after ACS, 64 (25%) neonates were born 7-14 days after ACS and 35 (14%) neonates were born >14 days after ACS. In total 76 (33%) neonates needed intubation. The risk for intubation in group 2 and group 1 was comparable (odds ratio 1.7 [95% CI 0.77-3.8]). However, neonates delivered >14 days after ACS (group 3) had an increased risk of needing intubation (odds ratio 4.6 [95% CI 1.6 – 14]). This effect was mainly found in the subgroup of neonates born between 28 and 32 weeks. As the effect of ACS administration is decreasing in time, administration of the first dose of ACS in women with threatened preterm labor should be considered carefully.

Blood pressure support in extremely premature infants is affected by different courses of antenatal steroids

To examine the effects of partial, single and multiple courses of antenatal corticosteroids (ANS) on the need for blood pressure support in extremely premature infants. Extremely premature infants with gestational age of 24 to 28 weeks were included in this study during a 5-year period. The main outcome measure of the study was the amount of blood pressure support during the first 3 days of life. The study infants (n = 163) were divided into: infants not exposed (ANS; n = 27) and exposed to ANS (ANS; n = 136). Blood pressure support was significantly lower in ANS compared with No ANS (65% vs 96%; p = 0.003) and in single course (SANS; n = 73) and >or=2 courses (MANS; n = 34) compared with partial course of ANS (PANS; n = 29) (62%, 56% vs 86%; p = 0.03). The number of infants who received volume support and the amount of volume support were significantly lower in ANS compared with that in No ANS (p < 0.001) and in SANS and MANS compared with that in PANS (p < 0.02). Exposure to multiple courses of ANS was as beneficial as single course of ANS in decreasing the need for blood pressure support in extremely premature infants.

Répétition des cures de corticoïdes chez les femmes à risque d’accouchement prématuré : un consensus difficile

A single course of antenatal corticosteroids in women at risk of preterm delivery reduces the risk of neonatal mortality and morbidity. Recent experimental and clinical studies have stated early, medium and long term consequences of single or repeated courses of antenatal corticosteroids. Betamethasone and dexamethasone are the two molecules usually used. Benefits are observed until the first 24 hours after the first injection. Single-course corticosteroids are not effective in babies born more than 7 days after initial treatment. Benefits of corticosteroids were evaluated between 22 and 35 weeks of gestation. Antenatal exposure to single-course betamethasone might result in disruption on glucose metabolism in adult offspring. Weekly courses of prenatal corticosteroids therapy are not recommended. Repeat prenatal corticosteroids given to women at continuing risk of preterm birth 7 or more days after an initial course reduced the inherent respiratory complications of prematurity and improved health outcomes of preterm infants. However, adverse outcomes have been reported concerning cognitive development. Although repeat course may have short term benefits, whether there are effects on health into childhood and beyond must await later assessment. Long term data are needed to recommend repeated courses.

Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS): A Randomized Controlled Trial

Although a single course of antenatal corticosteroids for women at risk of preterm birth reduces the risk of respiratory distress syndrome (RDS), neonatal mortality and morbidity, the benefits may diminish over time. The effects of weekly doses have been investigated but the benefits are unclear, and there is evidence of decreased fetal growth and other short-term and long-term adverse effects. MACS is an international, multicenter, double-blind, randomized controlled trial designed to determine whether multiple courses of antenatal corticosteroids provide short-term respiratory benefits and minimize the risk of neonatal morbidity and mortality. This trial enrolled 1858 women at 25 to 32 weeks' gestation who had not delivered 14 to 21 days after an initial course of antenatal corticosteroids and remained at high risk for preterm birth. The study was conducted at 80 centers in 20 countries. The study subjects were randomized to receive either antenatal corticosteroids (n = 937) or placebo (n = 921), every 14 days until week 33 or delivery, whichever came first. The primary study outcome was a composite of perinatal or neonatal mortality, or clinically significant neonatal morbidity, which was defined as severe RDS, bronchopulmonary dysplasia intraventricular hemorrhage grade III or IV, cystic periventricular leucomalacia, or necrotizing enterocolitis. All patients and caregivers were blinded as to the treatment given. No difference in primary outcomes of morbidity and mortality was found between infants receiving multiple courses of antenatal corticosteroids or placebo (150 [12.9%] vs. 143 [12.5%], P = 0.83). At birth, in comparison to the placebo, infants who received multiple courses of antenatal corticosteroids weighed less (2216 vs. 2330 g, P < 0.0026), were shorter (44.5 vs. 45.4 cm, P < 0.001), and had a smaller head circumference (31.1 vs. 31.7 cm, P < 0.001). These data show that multiple courses of antenatal corticosteroids given every 14 days are associated with decreased growth in utero and provide no neonatal benefits compared with 1 course of antenatal corticosteroids. The investigators conclude from these findings that multiple courses every 14 days are not recommended.

Impact of a ‘rescue course’ of antenatal corticosteroids: a multicenter randomized placebo-controlled trial

Previous studies using repetitive courses of antenatal corticosteroids (ACS) have demonstrated marginal or no benefit and concern over potential risk. No prior prospective or randomized studies have evaluated the option of a single rescue course of ACS on neonatal outcome. A multicenter randomized double-blind placebo-controlled trial was performed from May 2003 through February 2008 in 18 private (15) and university (3) medical centers. Patients with singletons or twins < 33 weeks who had completed a single course of ACS before 30 weeks and at least 14 days before inclusion, and were judged to have a recurring threat of preterm delivery in the coming week, were included. Patients were randomized to receive a single rescue course of betamethasone, 2 12-mg doses 24 hours apart, or placebo. Exclusion criteria included: premature rupture of membranes, advanced dilation (> 5 cm), chorioamnionitis, and other steroid use. In all, 437 patients were randomized (223 rescue steroid group and 214 placebo group). A total of 55% of patients in each group delivered at < 34 weeks. There was a significant reduction in the primary outcome of composite neonatal morbidity < 34 weeks in the rescue steroid group vs placebo (43.9% vs 63.6%; odds ratio, 0.45; 95% confidence interval, 0.27-0.75; P = .002) and significantly decreased respiratory distress syndrome, ventilator support, and surfactant use. Perinatal mortality and other morbidities were similar in each group. Including all neonates in the analysis (regardless of gestational age at delivery) still demonstrated a significant reduction in composite morbidity in the rescue course group (32.1% vs 42.6%, odds ratio, 0.65; 95% confidence interval, 0.44-0.97; P = .0034) and improvement in respiratory morbidities. Administration of a single rescue course of ACS before 33 weeks improves neonatal outcome without apparent increased short-term risk.

Review and meta-analysis: Benefits and risks of multiple courses of antenatal corticosteroids

Preterm birth causes infant morbidity and mortality. A single course of antenatal corticosteroids (ACS) should be considered routine for preterm delivery. Benefits of therapy before 34 weeks' gestation have been established for infants born between 24 h and 7 days after treatment. It is still unclear whether multiple courses (MC) of ACS should be performed in women at risk of preterm delivery 7 days or more after initial treatment. To determine the risks and benefits of MC of ACS. Search and selection for human randomized controlled trials were conducted in PubMed and The Cochrane Central Register of Controlled Trials. Statistical analysis was performed using the Review Manager 4.3 software. MC of ACS were associated with a statistically decrease in the occurrence of respiratory distress syndrome, patent ductus arteriosus, use of surfactant, ventilation support, and any maternal side effects. This treatment was also associated with a significant reduction in birth weight and head circumference. MC of ACS in women at risk of preterm birth do not offer significant benefits concerning the composite neonatal morbidity. Data on long-term safety are still insufficient. Further evaluations, most by follow-up studies, are required to study the long-term effects.

812: The effect of maternal obesity on neonatal outcome in women receiving a single course of antenatal corticosteroids

Given the increasing prevalence of obesity in the United States, we sought to determine the effect of maternal obesity on the incidence of fetal prematurity morbidities, in those who receive antenatal corticosteroids. This could provide insight to whether a weight-based dose of antenatal corticosteroid should be pursued to improve clinical outcomes.

2: Multiple courses of antenatal corticosteroids for preterm birth study

A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome (RDS) and neonatal death. Trials of weekly vs. single courses of ACS suggest benefits (less respiratory morbidity) but also harm (reduced growth in utero). The aim of this trial was to see if multiple courses of ACS, every 14 days, would be associated with benefits in terms of reduced neonatal morbidity and mortality but without the risk of decreased growth in utero. 1858 women were randomized to receive multiple courses of antenatal corticosteroids vs. placebo every 14 days until 33 6/7 weeks or delivery which ever came first. The primary outcome was a composite of mortality, severe RDS, intraventricular haemorrhage (grade III or IV), periventricular leukomalacia, bronchopulmonary dysplasia or necrotizing enterocolitis. Infants born to women who received multiple courses of ACS incurred similar morbidity and mortality (12.9 % vs. 12.5%) as compared to the single course group 1.04 OR (CI 0.77-1.39 p=0.83). Infants born to women who received multiple courses of ACS weighed less (2216 grams vs. 2330 grams, p=0.0026), were not as long (44.5 cm vs. 45.4 cm, p=0.00075) and had a smaller head circumference (31.1 cm vs. 31.7 cm, p=<0.0001) as compared to those who received a single course of therapy. For women who continue to be at high risk of preterm delivery following an initial course of ACS, multiple courses of ACS, every 14 days until 336/7 weeks or delivery which ever comes first, does not offer additional benefits to their infants and appears to be associated with a decrease in birth weight, birth length and head circumference. Therefore multiple courses of ACS, every 14 days, should not be recommended for women who remain undelivered after their initial course of therapy. (ClinicalTrials.gov number, NCT 00187382)

The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Beneficial Effects of Antenatal Repeated Steroids study: impact of repeated doses of antenatal corticosteroids on placental growth and histologic findings

In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings. In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS. One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at < 32 or > or = 32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at > or = 32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036). Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.

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.

Use of systemic glucocorticosteroids in pregnancy: Be alert but not alarmed

SUMMARY Concerns have been raised regarding the use of repeated courses of systemic glucocorticosteroids given to pregnant women with threatened premature labour to improve fetal lung maturity. Most worrying are animal studies showing detrimental effects on the developing brain, though human data to date are conflicting. Additional concerns relate to the fetal origins of adult diseases, particularly vascular diseases such as hypertension and atherosclerosis. It is currently recommended that obstetricians give only a single course of antenatal corticosteroids to pregnant women to enhance lung maturity instead of giving repeated doses, which was previously a common practice. Other clinicians including dermatologists, gastroenterologists and rheumatologists may have reason to provide systemic glucocorticosteroids to pregnant women. Although systemic glucocorticosteroids all cross the placenta to some degree, the extent to which they do so depends on the drug involved. The choice of systemic glucocorticosteroid for the pregnant women in light of this evolving literature is discussed.

Effect of maternal BMI, number of courses and timing of antenatal corticosteroids: Association with neonatal anthropometric measurements

Effect of maternal BMI, number of courses and timing of antenatal corticosteroids: Association with neonatal anthropometric measurements

Lungenreifeinduktion mit Glukokortikoiden - einmalige oder wiederholte Applikation?

The discussion on the application of multiple versus single courses of antenatal corticosteroids (ANC) for the prevention of respiratory distress syndrome (RDS) in newborns is still controversial. Since the benefits of ANC have been shown to be most significant within 7 to 10 days after treatment, many obstetricians tend to treat women with repeated courses of ANC if the risk of premature delivery persists. However, data from animal as well as from clinical studies suggest detrimental effects of multiple courses of ANC: an increase of neonatal mortality, low birth weight, retardation of mental, and psychomotoric development, an increase in infectious morbidity of the mother and the newborn, alterations of intra-uterine programming by modification of the hypothalamic-pituitary-adrenal axis with the consequence of an increased rate of diabetes and hypertension in later life. However, a detailed review of the literature fails to prove a causal relationship between multiple courses of ANC and the complications mentioned above. Conversely, only gradual decreases in the severity of RDS do not justify routine application of repeated courses of ANC. Until publication of the results of larger prospective randomised controlled trials, each pregnant woman at significant risk for premature delivery (24-34 weeks of gestation) should receive a single course of ANC (e.g. betamethasone, 2 x 12 mg in a 24-hour interval). Based on the data pub-lished, a second course ofANC can be considered as efficient and harmless.

The effect of a single course of antenatal corticosteroids on maternal adrenal function at term

Objective: To determine if one course of antenatal corticosteroids at 32 weeks produces maternal adrenal suppression at term.Methods: The adrenocorticotropic hormone (ACTH) stimulation test was administered at 38 weeks to 11 pregnant women who had received a single course of antenatal betamethasone prior to 33 weeks and to six control subjects.Results: There was no difference in basal cortisol levels (mean ± standard deviation) between the two groups: 41.6 ± 6.9 μg/dl for controls versus 36.0 ± 7.8 μg/dl for the steroid group, p = 0.16. Peak cortisol levels at 45 min following ACTH stimulation were not different: 61.6 ± 3.5 μg/dl for controls versus 55.0 ± 2.6 μg/dl for the steroid group, p = 0.16. The power of the study to detect a statistical difference in the observed peak cortisol levels was greater than 95%. None of the study subjects had laboratory criteria or clinical signs of adrenal suppression.Conclusions: A single course of betamethasone for women at risk for preterm delivery does not produce adrenal insufficiency at term and stress dose steroids are not recommended.

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

Repeated courses of antenatal corticosteroids: is it justified?

The benefits of a single course of antenatal corticosteroids on neonatal outcomes are well established. There is, however, much controversy about how long this treatment should continue, and whether repeated courses should be administered if the women remain at risk for preterm delivery 7 days after the initial therapy. This review aims to discuss current evidence on the effectiveness and safety of repeated courses of antenatal corticosteroids.

The Use and Abuse of Steroids in Perinatal Medicine

Corticosteroids are one of the most powerful drugs increasingly used in the perinatal and neonatal period. This review discusses the merits and demerits of antenatal as well as postnatal use of steroids. A single course of antenatal corticosteroids in women at risk of premature delivery is highly effective in reducing respiratory distress syndrome (RDS), intraventricular haemorrhage and neonatal mortality and also neurodevelopmental sequelae including cerebral palsy. However, there is less evidence to support the practice of multiple courses of corticosteroids, with some animal and retrospective human studies suggesting an association with neurological impairment and reduction in birth weight as well as lung weight. Postnatal systemic corticosteroids have shown benefits in reducing chronic lung disease and improving survival for infants. However, besides short-term adverse effects, the follow-up studies have raised concern that they may increase the risk of neurodevelopmental disability, particularly cerebral palsy in survivors. Systemic corticosteroids may have a role in infants who had repeated and prolonged intubations and those with pressor-resistant hypotension. Alternative strategies for prevention of chronic lung disease, such as inhaled steroids, methylprednisolone and hydrocortisone, may need further studies with larger sample sizes. Data from animal research have revealed that fetal glucocorticoid exposure may have a role in programming the individual to adult degenerative diseases. Based on the current evidence, it is recommended that women at risk of preterm delivery receive a single course of glucocorticoids. Randomised controlled trials are needed to establish the true effects of multiple courses of antenatal corticosteroids. More research is also needed to study the long-term neurodevelopmental outcome of both multiple courses of antenatal corticosteroids, as well as postnatal corticosteroid therapy.

Repeated courses of antenatal corticosteroids: Is it justified?

The benefits of a single course of antenatal corticosteroids on neonatal outcomes are well established. There is, however, much controversy about how long this treatment should continue, and whether repeated courses should be administered if the women remain at risk for preterm delivery 7 days after the initial therapy. This review aims to discuss current evidence on the effectiveness and safety of repeated courses of antenatal corticosteroids.