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    Should we take another look at antenatal corticosteroids?


    A study by Poggi Davis et al reinforces these concerns.18 They studied 54 children, aged 6 to 10, who had received a single course of betamethasone at a mean gestational age of 29.3 weeks (+/- 3 weeks), delivered at term, and matched 1:2 to term infants not exposed to ACS. There were very concerning findings with ACS exposure: widespread differences in cortical thickness associated with significant thinning of the cortex, particularly the rostral anterior cingulate cortex (rACC), which is strongly associated with development of affective disorders, as well as HPA axis dysregulation. 

    These findings are consistent with every animal model of ACS exposure that has been studied.12 In particular, they mirror the findings of Uno et al who used different dexamethasone dosing regimens administered similarly to ACS to preterm macaques.19 In unpublished data, they demonstrated significant changes in the hippocampus, and neural damage in the cere tarded growth of the cerebellum. The finding on the cerebellum has been confirmed.20

    Before endorsing the use of ACS at gestational ages when severe morbidity and mortality is low, the onus is on clinician-scientists and policy-makers to require long-term follow-up studies. ACS administration has always been enigmatic. We have gone from under-using it to abusing it with prophylactic weekly administration, to salvage therapy. Clinicians should avoid elective late-term deliveries and delay elective cesareans whenever possible to 39 weeks to reduce the morbidity associated with these deliveries. 

    In 2013, SMFM published recommendations regarding early delivery for multiple maternal, fetal, and obstetrical complications.21 These recommendations were largely determined by consensus and not high-quality data. 

    What are clinicians to do? Are we to deliver an increasing number of women late preterm to reduce the potential risks of expectant management and expose them to a single course of ACS all in an effort to avoid admission to the NICU and reduce short-term respiratory morbidity? Or should we avoid iatrogenic delivery prior to 39 weeks and thus obviate the need for ACS exposure but possibly increase fetal and maternal risk from continuing the pregnancy?


    If parents were informed of the low risk of severe respiratory complications in the majority of late preterm or term infants and the unknown risk for irreversible changes in the brain and the hypopituitary axis, the majority would likely choose to avoid ACS therapy.

    ACS therapy should not be expanded until we fully understand the potential risk-benefit ratio of treatment, and better understand the long-term consequences of exposure to ACS late preterm or at term. <



    1.  Liggins GC, Howie RN.  A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants.  Pediatrics 1972; 50: 515.

    2.  ACOG Committee on practice bulletins-obstetrics.  ACOG practice bulletin no. 150:  management of preterm labor.  Obstet Gynecol 2016; 127 e29.

    3. Sotiradis A, Tsiami A, Papatheodorou S, Baschat A, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in children born preterm.  A systematic review and meta-analysis.  Obstet and Gynec 2015; 125 (6): 1385-

    4. Saccone G, Berghella V.  Antenatal corticosteroids for maturity of term or near term fetuses:  systematic review and meta-analysis of randomized controlled trials.  BMJ 2016; 355:IS044  

    5.  Stutchfield PR, Whitaker R, Gliddon AE, Hobson L, Kotecha S, Doull IJM.  Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean sect (ASTECS trial). Arch Dis Child Fetal Neonal Ed 2013; 98:F195-F200     

    6. Stutchfield, P, Whiaker R, Russell I.  Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section:  pragmatic randomized trial.  BMK, doi:10.1135/bmj.38547.41693.06 (published 22 August 2005)  BMJ 2005; 331: 662.

    7. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita ATN, Reddy UM, et al.  Antenatal betamethasone for women at risk for late preterm delivery.  NEJM 2016 SMFM Publications Committee, SMFM statement:  implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery.  Am J Obstet Gynec 2016: 

    8. SMFM Publications Committee, SMFM statement: implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016:

    9. Committee on Fetus and Newborn. Adarrkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011;127:575-9

    10. Dalziel SR, Lim VK, Lamber A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomized controlled trial. BMJ 2005;331 665.

    11. Dalziel SR, Walker NK, Parag V, Mantell C, Rea H, et al. Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomized controlled trial. Lancet 2005;365:1856-62. 

    12. Kemp MW, Newnham JP, Challis JG, Jobe AH, Stock SJ. The clinical use of corticosteroids in pregnancy. Human Reproduction Update 2015;22(2):240-259

    13. Kugelman A, Colin A. Late preterm infants: near term but still in a critical developmental time period. Pediatrics 2013:132(4):741-751.

    14. Kinney J. The near-term (late preterm) human brain and risk for periventricular leukomalacia: A review. Semin Perinatol 2006;30:81-88

    15. Chang YP. Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. Korean J Pediatr 2014:57(3):101-109.

    16. Champagne DL, de Kloet ER, Joels M. Fundamental aspects of the impact of glucocorticoids on the (immature) brain. Semin Fetal Neonatal Med 2009;14:136:142.

    17. Tegethoff M, Pryce C, Meinlschmidt G. Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary adrenal axis function in humans: a systematic review. Endocr Rev 2009;30:753-759.

    18. Davis EP, Sandman CA, Buss C, Wing DA, Head K. Fetal glucocorticoid exposure is associated with preadolescent brain development. Biol Psychiatry 2013;74(9)647-655. 

    19. Uno H, Lohmiller L, Thieme C, Kemnitz JW, Engle MJ, et al. Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus. Brain Res Dev Brain Res 1990;53(2):157-167.

    20. Noguchi K, Walls K, Wozniak D, Olney JW, Roth KA, et al. Acute neonatal glucorcorticoid Cautioexposure produces selective and rapid cerebellar neural progenitor cell apoptotic death. Cell Death Differ 2008;15(10):1582-92

    21. Medically indicated late preterm and early term deliveries. Committee opinion no 560. American College of Obstetricians and Gynecologists 2013;121:901-10




    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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