O
International Journal of
GYNECOLOGY
& OBSTETRICS
International Journal of Gynecology & Obstetrics 78 (2002) 95-97
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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,
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in any form or by any means, electronic,
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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.
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Several o f these randomized trials are in progress, The American College of
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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
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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;
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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
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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
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