Clinical Review

This simple and inexpensive treatment can cut neonatal

OBG Manag. 2002 September;14(9):50-58

References

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3. Liggins GC. Premature delivery of fetal lambs infused with glucocorticoids. J Endocrinol. 1969;45:515-523.

4. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972;50:515-525.

5. The National Institutes of Health Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. NIH Consens Statement. Feb 28-Mar 2 1994;12(2):1-24.

6. Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. Br J Obstet Gynaecol. 1990;97(1):11-25.

7. Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995;173(1):322-335.

8. Ballard PL, Granberg JP, Ballard RA. Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. J Clin Invest. 1975;56:1548-1554.

9. Smolders-de Haas H, Neuvel J, Schmand B, et al. Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up. Pediatrics. 1990;86:65-70.

10. The National Institutes of Health Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. Antenatal Corticosteroids Revisited: Repeat Courses. NIH Consens Statement. Aug 17-18 2000;17(2):1-18.

11. Ikegami M, Jobe AH, Newnham J, Polk DH, Willet KE, Sly P. Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs. Am J Respir Crit Care Med. 1997;156:178-184.

12. Jobe AH, Wada N, Berry LM, Ikegami M, Ervin MG. Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep. Am J Obstet Gynecol. 1998;178:880-885.

13. Polk DH, Ikegami M, Jobe AH, Sly P, Kohan R, Newnham J. Preterm lung function after retreatment with antenatal betamethasone in preterm lambs. Am J Obstet Gynecol. 1997;176:308-315.

14. Quinlivan JA, Beazley LD, Evans SF, Newnham JP, Dunlop SA. Retinal maturation is delayed by repeated, but not single, maternal injections of betamethasone in sheep. Eye. 2000;14:93-98.

15. McEvoy C, Bowling S, Sontag B, Stewart M. Timely repetitive antenatal steroids (AS) versus single-course AS: effect on functional residual capacity (FRC) and respiratory compliance (CRS) in preterm infants. Pediatr Res. 1996;39:229A, abstract 1357.-

16. Guinn DA, Atkinson MW, Sullivan L, et al. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: a randomized controlled trial. JAMA. 2001;286(13):1581-1587.

Since repeat courses did not offer a clearly demonstrated benefit and were associated with potential adverse effects in both animal and human studies, the consensus report concluded that repeat courses of antepartum corticosteroids for fetal maturation should only be used in the context of randomized clinical trials.

At the time of the consensus conference, 4 such trials were underway or planned. Thus far, only 1 has been completed. Guinn and colleagues conducted a randomized, double-blind, placebo-controlled, intention-to-treat trial at 13 US institutions from February 1996 through April 2000. They found that weekly doses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment, and therefore concluded that weekly regimens should not be routinely prescribed for women at risk for preterm delivery.¹⁶

The remaining 3 studies comparing single- and multiple-dose courses of antenatal corticosteroids are expected to be completed in 2004. A randomized, double-blind, placebo-controlled trial started in March 2000 and sponsored by the NIH Maternal Fetal Medicine Units Network will involve 2,400 women. The Multiple Antenatal Corticosteroid Study (MACS)—a randomized, controlled trial funded by the Canadian Health Research Institute and launched in March 2001—will report on 1,900 American and Canadian women. Finally, the Trial of the Effects of Antenatal Multiple Courses of Steroids (TEAMS), organized by England’s National Perinatal Epidemiology Unit, will look at the regimens in 4,000 women.

Conclusion

Until these randomized clinical trials have been completed and can offer conclusive results, physicians must administer antenatal glucocorticoids only in contexts supported by the evidence. To that end, only women who are clearly in preterm labor should receive this treatment, and then only in the doses outlined in the table. Since the fetus gets the most benefit from antenatal corticosteroid treatment when the drug is given between 2 and 7 days before delivery, clinicians should make every attempt to administer therapy in that time frame.

Dr. Clewell reports no affiliation or financial arrangement with any of the companies that manufacture drugs or devices in any of the product classes mentioned in this article.