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    Should we take another look at antenatal corticosteroids?





    Despite Liggins’ landmark paper in 1972 and more than 44 years of active research, we are still at a loss to define which pregnancies are most likely to benefit from antenatal corticosteroids (ACS) and which may be harmed.1 While much attention has been focused on the impact of ACS on the preterm lung, the long-term impact of ACS on other organ systems has not been adequately studied in humans, even though glucocorticoids affect every human organ system. 

    The efficacy and relative safety of a single course of ACS in pregnancies delivered prior to 32–34 weeks is well established and one of the most powerful interventions in obstetric medicine.2,3 The value of ACS in late preterm pregnancies and before elective cesarean at term is less clear. Here I review the latest data from clinical trials on this topic and the risks of expanding use of ACS therapy.

    What the evidence says

    Use of ACS at ≥34 weeks’ gestation  was evaluated in a 2016 meta-analysis that included 6 randomized controlled trials (RCTs).4 The RCTs looked at 2 groups: women who were candidates for ACS with delivery anticipated between 35 and 37 weeks’ gestation (N=3204) and women undergoing planned elective cesarean at term (≥37 weeks’ gestation, N=2498). The primary outcome of all the RCTs in the meta-analysis was neonatal respiratory outcomes and/or NICU admissions. Only 3 trials were blinded and long-term outcomes are available from one study.5,6 The group of women randomized between 34 and 36 6/7 weeks for “imminent preterm delivery” demonstrated statistically significant reductions in severe respiratory distress syndrome (1.4% vs 2.3%; RR 0.60, 95% CI 0.24–0.98) and transient tachypnea of the newborn (8.2% vs 10.9%; RR 0.72, 95% CI 0.50–0.98), but not RDS overall or mechanical ventilation. ACS treatment increased the risk for neonatal hypoglycemia (22.8% vs 14.2%; RR 1.61, 95% CI 1.16–2.12).4

    The meta-analysis was dominated by the Antenatal Late Preterm Steroids Trial (ALPS),7 in which women at 34 0/7 to 36 5/7 weeks’ gestation at high risk for late preterm birth were randomly assigned to receive a first course of antenatal corticosteroids (2 injections of betamethasone 24 hrs apart) or placebo. No tocolytics were administered. The primary outcome was a composite of neonatal respiratory treatment in the first 72 hrs (continuous positive airway pressure [CPAP] or high-flow nasal cannula for ≥2 hours, supplemental oxygen with FIO2 ≥0.30 for ≥4 hrs, extracorporeal membrane oxygenation, or mechanical ventilation), stillbirth, or neonatal death within 72 hrs of delivery. See sidebar at left for major findings. 

    No data are available about the long-term neurodevelopmental outcomes of children exposed to corticosteroids between 34 0/7 and 36 5/7 weeks. A 2-year follow-up study is currently being performed. 

    Women randomized at term prior to cesarean received either betamethasone or dexamethasone administered 48 hrs before planned cesarean delivery at ≥37 weeks’ gestation. RDS (2.7% vs 6.7%; RR 0.40, 95% CI 0.27–0.59) and use of mechanical ventilation (0.7% vs 3.6%; RR 0.19, 95% CI 0.08–0.43) were reduced, as were time on oxygen, maximum inspired oxygen, and length of stay in the NICU.4

    Long-term follow-up is available from the ASTECS (ACS for term cesarean section) and ASTECS2 trials.5,6 In ASTECS2, 998 women undergoing planned cesarean delivery at term were randomly assigned to receive a course of betamethasone (12 mg IM q 24 hrs x2) or usual treatment prior to delivery.6 The primary outcome was admission to a special care unit with respiratory problems. 

    The ASTECS-2 study provided follow-up data on participants of the ASTEC trial at ages 8 to 15 years.5 About 50% of participants were lost to follow-up; children available for study were disproportionately represented by the betamethasone group and those admitted to the special care nursery for respiratory complications (5% vs 2%, P=0.01). Long-term assessment was based on parental responses to the strengths and difficulties questionnaire (SDQ), standardized scholastic testing results, and teacher responses. Overall there was no difference in behavioral characteristics based on SDQ, school performance, health issues, asthma, or atopic disease. The authors concluded that “parents can be reassured that the administration of a single course of ACS is not only beneficial in the short term, but does not have any adverse long term consequences.” Based on these findings, use of ACS prior to term cesarean became accepted practice in the United Kingdom. 


    Debra A. Guinn, MD
    Dr Guinn is Director, Montana Perinatal Center, and Director, Maternal Fetal Medicine, Kalispell Regional Medical Center, Kalispell, ...


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    • UBM User
      I am very concerned about the widespread use of steroids in the late preterm period. The issue is well covered by Dr Guinn. The data on long term follow up is weak; but the results of neuro imaging (MRI) studies are not. The neonatologists knew of the studies, Human and animal, I did not. As I looked at absolute numbers, and not just percentages I was surprised: RDS decreased from 6.7% to 2.7%... 93% of babies did not get RDS even without steroids, and only 4/100 babies benefited! Mechanical Ventilation decreased from 3.6% to 0.7%..... 96% of babies did not need mechanical ventilation only 3/100 babies benefited! However 100/100 babies were potentially exposed to steroids that, at least on MRI, affect brain development. What risk would you take with your baby, potential small short term benefit or unknown long term risk?
    • UBM User
      I enjoy reading articles that challenge our sometimes tortured reasoning. It is not my intention to rain on the parade of progress but to measure the rainfall. Thank you Dr. Guinn! I've been alluding to this for years. Unfortunately and inherent to our specialty is the lack of good quality prospective RCTs that look at the short and long term benefits and risks of not only ACS but much of what we do. Yet, we tend to intervene. Why? I believe it's in our DNA, we desire to improve the clinical situation and sometimes become myopic to the big picture. Also, some colleagues (mostly MFMs) believe that "doing something is better than doing nothing." The current debate of ACS at near term may be an example of such an intervention in search of an indication. Even after 40 years of study we lack precise information with regard to the pharmacological induction of the desired biologic effects. We have been assured about the standard two dose protocol of B-methasone, 24 hours apart but, at the same time, we know nothing about the latent phase of one dose with regard to clinical relevance. Finally, whatever we do know, the studies are confined to singleton pregnancies. There are no prospective RCTs using ACS in twin pregnancies. Let's walk slowly and carry a big stick - said differently: let's be deliberate, with evidence so we can provide a provable benefit and promote false hope that ultimately harms our patients as well as ourselves and our specialty.......


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