O International Journal of GYNECOLOGY & OBSTETRICS International Journal of Gynecology & Obstetrics 78 (2002) 95-97 www.elsevier.com/Iocate/ijgo ACOG committee opinion Antenatal Corticosteroid Therapy for Fetal Maturation Number 273, May 2002 Committee on Obstetric Practice This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Copyright © May 2002 by the American College of Obstetricians and Gynecologists.All rights reserved.No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. ABSTRACT." The National Institute of Child Health and Human Development and the Office of Medical Applications of Research of the National Institutes of Health convened consensus conferences in 1994 and 2000 that recommended giving a single course of corticosteroids to all pregnant women between 24 and 34 weeks of gestation who are at risk of preterm delivery. within 7 days. Because of insuffic&nt sc&ntific evidence, the consensus panel also recommended that repeat corticosteroid courses, including so-called "rescue therapy," should not be routinely used but should be reserved for women enrolled in clinical trials. Betamethasone and dexamethasone have been most widely studied and have generally been the preferred corticosteroids for antenatal treatment to accelerate fetal organ maturation. The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice supports the conclusions of the consensus conferences. In August 2000, the National Institute of Child Health and Human Development and the Office of Medical Applications of Research of the National Institutes of Health reconvened a consensus conference on antenatal steroids, entitled "Consensus Development Conference on Antenatal Corticosteroids Revisited: Repeat Courses," to address the issue of repeated courses o f corticosteroids for fetal maturation, The consensus panel from this conference reaffirmed the 1994 consensus panel's recommendation o f giving a single course of corticosteroids to all pregnant women between 24 and 34 weeks o f gestation who are at risk of preterm delivery within 7 days (1). Requests for authorizationto make photo- Because o f insufficient scientific evidence, the panel also recommended that repeat corticosteroid courses, including so-called "rescue therapy," should not copies should be directed to: be routinely used but should be reserved for w o m e n enrolled in clinical trials. Copyright Clearance Center Several o f these randomized trials are in progress, The American College of 222 Rosewood Drive Obstetricians and Gynecologists' C o m m i t t e e on Obstetric Practice supports Danvers, MA 01923 the conclusions of the consensus conferences. (978) 750-8400 There is no convincing scientific evidence that antenatal corticosteroid therapy increases the risk o f neonatal infection, although multiple courses The American College of have been associated with fetal adrenal suppression (2). Follow-up studies o f Obstetricians and Gynecologists children aged 12 years and younger exposed to at least one course o f 409 12th Street, SW PO Box 96920 corticosteroid treatment indicate there is no apparent risk o f adverse neuWashington, DC 20090-6920 rodevelopmental outcome associated with antenatal corticosteroids. There are 96 ACOG committee opinion/International Journal of Gynecology & Obstetrics 78 (2002) 95-97 inconclusive data that repeated courses of antenatal corticosteroids have been associated with a decrease in birth weight and neonatal head circumference (3, 4). The 2000 consensus panel concluded that studies regarding the possible benefits and risks of repeat courses of corticosteroids are limited because of their study design and "methodologic inconsistencies?' The 2000 consensus panel noted that, although there is a suggestion of possible benefit from repeated doses (especially in the reduction and severity of respiratory distress), there also are animal and human data that suggest deleterious effects on the fetus regarding cerebral myelination, lung growth, and function of the hypothalamic-pituitary-adrenal axis. Maternal effects include increased infection and suppression of the hypothalamic-pituitaryadrenal axis (5, 6). Betamethasone and dexamethasone are the most widely studied and have generally been the preferred corticosteroids used for antenatal treatment to accelerate fetal organ maturation. Both cross the placenta in their active form and have nearly identical biologic activity. Both lack mineralocorticoid activity and have relatively weak immunosuppressive activity with short-term use. Although betamethasone and dexamethasone differ only by a single methyl group, their phannacokinetics differ. Betamethasone has a longer half-life because of its decreased clearance and larger volume of distribution (7). Meta-analyses of randomized trials have shown that, although both agents decrease the frequency of respiratory distress syndrome, only betamethasone decreases neonatal mortality (8). A recent large, uncontrolled retrospective study suggested that betamethasone also may have significant benefit in decreasing the rate of newborn cystic periventricular leukomalacia by approximately 50% compared with untreated and dexamethasone-treated women (9). The offspring of pregnant mice who were given betamethasone performed neurobehavioral developmental tasks better than the offspring of pregnant mice given dexamethasone (10). Furthermore, betamethasone requires fewer intramuscular injections. Betamethasone use, however, has been associated with a significant transient decrease in fetal movements and heart rate variability (11, 12). The 2000 consensus panel reviewed all available reports on the safety and efficacy of betamethasone and dexamethasone. It did not find significant scientific evidence to support a recommendation that betamethasone should be used preferentially instead of dexamethasone. Thus, based on this information, the Committee on Obstetric Practice recommends either of the following corticosteroid regimens: • Betamethasone (12 mg) given intramuscularly every 24 hours for two doses • Dexamethasone (6 mg) given intramuscularly every 12 hours for four doses in patients at risk for preterm delivery between 24 and 34 weeks of gestation with intact membranes or between 24 and 32 weeks of gestation for patients with ruptured membranes The use of corticosteroids after 34 weeks of gestation is not recommended unless there is evidence of fetal pulmonary immaturity. References I. Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement 2000; 17(2): 1-10 2. Kairalla AB. Hypothalamic-pituitary-adrenal axis function in premature neonates after extensive prenatal treatment with betamethasone: a case history. Am J Perinatol 1992;9:428-430 3. French NP, Hagan R, Evans SF, Godfrey RN, Newnham JP. Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 1999; 180:114-121 4. Guinn DA, Atkinson MW, Sullivan L, Lee M, MacGregor S, Parilla BV et al. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: a randomized controlled trial. JAMA 2001 ;286:1581-1587 5. McKenna DS, Wittber GM, Nagaraja HN, Samuels P. The effects of repeat doses of antenatal corticosteroids on maternal adrenal function. Am J Obstet Gynecol 2000; 183:669-673 6. Abbasi S, Hirsch D, Davis J, Tolosa J, Stouffer N, Debbs R, et al. Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome. Am J Obstet Gynecol 2000; 182:1243-1249 7. Fanaroff AA, Hack M. Periventricular leukomalacia-prospects for prevention [letter]. N Engl J Med 1999;341: 1229-1231 8. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol 1995; 173:254-262 9. Baud O, Foix-L'Helias L, Kaminski M, Audiberet F, Jarreau PH, Papiernik E, et al. Antenatal gtucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med 1999;341:1190-1196 10. Rayburn WF, Christensen HD, Gonzalez CL. A placebocontrolled comparison between betamethasone and dexamethasone for fetal maturation: differences in neurobehavioral development of mice offspring. Am J Obstet Gynecol 1997; 176:842-850; discussion 850-851 ACOG committee opinion / International Journal of Gynecology & Obstetrics 78 (2002) 95-97 11. Mulder EJ, Derks JB, Visser GH. Antenatal corticosteroid therapy and fetal behavior: a randomised study of the effects of betamethasone and dexamethasone. Br .1Obstet Gynaecol 1997;104:1239-1247 97 12. Senat MV, Minoui S, Multon O, Fernandez H, Frydman R, Ville Y. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomised study. Br J Obstet Gynaecol 1998:105:749-755
