Multiple courses of antenatal steroids: risks and benefits.To review the existing literature regarding the effect of multiple courses of antenatal corticosteroids in reducing the occurrence of complications arising because of lung immaturity. A systematic review of the English-language literature was conducted using a computerized database. The search terms used were antenatal steroids, prenatal steroids, and respiratory distress syndrome. We screened abstracts and found relevant articles, which we independently reviewed. Only prospective well-designed animal studies were corticosteroid side effects hiccups. In humans, no well-designed randomized controlled trials Multiple courses of antenatal steroids risks and benefits were identified.
Multiple courses of antenatal steroids: risks and benefits. - Semantic Scholar
The objective of this study is to evaluate the impact of one versus two courses of antenatal steroids on the incidence of major neonatal morbidity including respiratory distress syndrome in patients delivering prior to 34 weeks' gestation in a randomized prospective fashion. Numerous studies have evaluated the safety and efficacy of antenatal corticosteroid ANC administration in threatened preterm labor. National Institutes of Health NIH first consensus conference in evaluated the research in this field.
Conclusions included the clear evidence that antenatal corticosteroids decrease the incidence of RDS in infants born at weeks gestation, with a decrease in RDS severity for infants born at weeks gestation and a decrease in the incidence of intraventricular hemorrhage in infants born at weeks gestation without harm to mother or fetus.
Their recommendation was to give a single course of corticosteroids to all pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days 3. Since the studies on the duration of the effects of antenatal corticosteroids in the fetus are not conclusive 4 , many obstetricians repeat corticosteroids weekly or bi-weekly to patients continuing to be at risk for preterm delivery.
Lacking scientific evidence, many investigators have performed retrospective analyses regarding the effects of single-course versus multiple-course antenatal corticosteroids. The NIH consensus panel reconvened in and concluded that studies regarding repeated courses of corticosteroids are suggestive of possible benefits, especially in reduction of RDS, however, design flaws limit their validity.
Retrospective case-control and cohort studies lack the scientific evidence needed for changing current recommendations. Therefore, NIH recommendations remain as previously stated in with repeat courses reserved for research studies.
Additionally, they call for well designed randomized controlled studies 5. Walfisch et al reviewed the existing literature regarding the effects of multiple courses of antenatal corticosteroids. Their systematic review of all English-language published articles and abstracts revealed only twelve prospective animal studies and no human studies. Retrospective human studies showed possible benefits from reduction of RDS and suggest possible harmful effects such as decreases in birth weight and head circumference.
They call for the completion of well-designed prospective randomized trials 6. Jazayeri et al also performed a retrospective chart review of neonates delivering prior to 35 weeks' gestation. The number of antenatal corticosteriods varied, but there was no difference in outcomes between weekly versus single-course 7. Early evidence showed the effects of steroids lasted only 7 days, thereby fueling the trend of weekly repeat administration.
However, current reports do not show improved outcomes with weekly ANC and variable views on harmful effects for mother and fetus. So, the starndard of care pendulum has left the extreme of weekly ANC and is searching for the optimal dosage and timing.
Only through continued research can this be accomplished 8. This is the only prospective randomized trial since the NIH statement. Statistically significant differences were not shown, with a composite neonatal morbidity occurring On average the weekly-course group received 3. Aghajafari et al compiled a meta analysis of eight observational studies. They found selection bias was present in all studies. They concluded it was not possible to establish the true effects of multiple courses of ANC by review of observational studies due to confounding variables.
Randomized clinical trials are needed to address this important issue Another post hoc analysis of neonates from the Thyrotropin-Releasing Hormone trial performed by Banks et al revealed increase mortality from early severe lung disease associated with three or more courses of antenatal corticosteroids without relation to maternal risk factors Finally, the most recent publication from Caughey and Parer examined the literature for evidence regarding a dose response of the benefits and detriments of antenatal corticosteroids.
Based on their complex mathematical analysis they recommend all fetus' between 24 and 34 weeks' gestation at risk for preterm delivery should be given a first course of ANC. If the risk of preterm delivery persists the next course should be given 2 weeks later, for a maximum of two courses. Consistent with all previous articles, the call for a well designed randomized, controlled trial is made Since Pediatrix has grown to manage over Neonatology practices throughout the United States.
Completion of collaborative research studies is effective and productive in this setting. Recently, Obstetrix and Pediatrix have merged. Obstetrix currently manages 19 Perinatalogy practices throughout the United States.
The common goal of performing collaborative research studies is as true for Obstetrix as is for Pediatrix. Principal Investigators for this study Dr. Since current standard of care does not advocate administrion of a second course of antenatal corticosteroids, patients and their insurer must be protected from any research related cost. This is a randomized double-blinded placebo-controlled trial.
Participating hospitals will obtain approval from their Institutional Review Board. Eligible subjects with continued threat of preterm delivery within next 7 days who initiated their first course of betamethasone at least 14 days ago and prior to 30 weeks' gestation will be randomized to either a repeat course of betamethasone or placebo.
Written informed consent will be obtained. Subjects will be followed through delivery and discharge of both mother and baby from the hospital. Randomization will be completed by computer generated randomization logs distributed to the research pharmacist at each site.
The syringes will be covered by a label, to conceal the contents. The second dose of randomized medication will be prepared in the same manner. Site may add Lidocaine to the betamethasone syringe as long as equal amount of normal saline is added to placebo syringe.
Historically, betamethasone has been out of stock and back ordered in many US hospitals. Should this occur, dexamethasone may be substituted. The protocol for dexamethasone is 6 mg IM q 12 hours x 4 doses total, with the placebo group receiving and equal amount of normal saline IM q 12 hours x 4 doses total.
Both dexamethasone and normal saline will be prepared in a syringe, covered with a label to conceal the contents. Composite neonatal morbidity - respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death.
An internal safety monitoring committee will be used, which will include three individuals who are not participating in the study. The safety monitoring committee will review, after cases or sooner, the maternal and neonatal data. If there is a significant increase or trend toward major complications that develops in either group the study will be terminated after consultation with the investigators. Saunders, , pp American College of Obstetricians and Gynecologists.
Effect of antenatal steroids for fetal maturation on perinatal oucomes. Is betamethasone effective longer than 7 days after treatment?
NIH Consens Statement ;17 2: Multiple corses of antenatal steroids: Repeated antenatal corticosteroid treatments. Do they reduce neonatal morbidity? J Reprod Med Sep;46 9: Antenatal Corticosteriods - too much of a good thing?
Single versus weekly courses of antenatal corticosteroids for women at risk of preterm delivery: Multiple courses of antenatal corticosteroids: Am J Obstet Gynecol Nov; 5: Multiple courses of antenatal corticosteroids are associated with early severe lung disease in preterm neonates. J Perinatol Mar;22 2: Recommendations for repeat courses of antenatal corticosteroids: Am J Obstet Gynecol Jun; 6: