Cochrane Update
Abstracts from Cochrane Reviews that relate to the practice of obstetrics and gynecology
Antenatal Corticosteroids for Accelerating
Fetal Lung Maturation for Women at Risk of
Preterm Birth
COCHRANE ABSTRACT
BACKGROUND: Respiratory distress syndrome (RDS) is
a serious complication of preterm birth and the primary
cause of early neonatal mortality and disability.
OBJECTIVE: To assess the effects on fetal and neonatal
morbidity and mortality, on maternal mortality and mor-
bidity, and on the child in later life of administering
corticosteroids to the mother before anticipated preterm
birth.
SEARCH STRATEGY: We searched the Cochrane Preg-
nancy and Childbirth Group Trials Register (October 30,
2005).
SELECTION CRITERIA: Randomized controlled compar-
isons of antenatal corticosteroid administration (beta-
methasone, dexamethasone, or hydrocortisone) with
placebo or with no treatment given to women with a
singleton or multiple pregnancy, expected to deliver
preterm as a result of either spontaneous preterm labor,
preterm prelabor rupture of the membranes, or elective
preterm delivery.
DATA COLLECTION AND ANALYSIS: Two review au-
thors assessed trial quality and extracted data indepen-
dently.
MAIN RESULTS: Twenty-one studies (3,885 women and
4,269 infants) are included. Treatment with antenatal
corticosteroids does not increase risk to the mother of
death, chorioamnionitis, or puerperal sepsis. Treatment
with antenatal corticosteroids is associated with an over-
all reduction in neonatal death (relative risk [RR] 0.69,
Address correspondence to: James P. Neilson, Professor of Obstetrics and
Gynaecology, Head of School of Reproductive & Developmental Medicine,
University of Liverpool, Co-ordinating Editor, Cochrane Pregnancy & Child-
birth Group, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS,
UK; e-mail: jneilson@liverpool.ac.uk.
Cochrane Reviews are regularly updated as new evidence emerges and in response
to feedback, and the Cochrane Library (http://www.thecochranelibrary.com)
should be consulted for the most recent version of the review.
© 2006 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/06
VOL. 109, NO. 1, JANUARY 2007
CLINICAL IMPLICATIONS
A single course of corticosteroids, such as beta-
methasone 12 mg intramuscularly twice at a 24-
hour interval, should be given to women between
24 and 34 weeks in whom there is reason to
anticipate early delivery, including women:
• with ruptured membranes,
• with preeclampsia,
• with multiple pregnancies, and
• in whom delivery is likely in less than 24 hours.
95% confidence interval [CI] 0.58 – 0.81, 18 studies, 3,956
infants), RDS (RR 0.66, 95% CI 0.59 – 0.73, 21 studies,
4,038 infants), cerebroventricular hemorrhage (RR 0.54,
95% CI 0.43– 0.69, 13 studies, 2,872 infants), necrotizing
enterocolitis (RR 0.46, 95% CI 0.29 – 0.74, eight studies,
1,675 infants), respiratory support, intensive care admis-
sions (RR 0.80, 95% CI 0.65– 0.99, two studies, 277 in-
fants), and systemic infections in the first 48 hours of life
(RR 0.56, 95% CI 0.38 – 0.85, five studies, 1,319 infants).
Antenatal corticosteroid use is effective in women with
premature rupture of membranes and pregnancy-related
hypertension syndromes.
REVIEWERS’ CONCLUSION: The evidence from this
new review supports the continued use of a single course
of antenatal corticosteroids to accelerate fetal lung mat-
uration in women at risk of preterm birth. A single course
of antenatal corticosteroids should be considered routine
for preterm delivery with few exceptions. Further infor-
mation is required concerning optimal dose-to-delivery
interval, optimal corticosteroid to use, and effects in
multiple pregnancies and to confirm the long-term ef-
fects into adulthood.
Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal
lung maturation for women at risk of preterm birth. Cochrane
Database of Systematic Reviews 2006, Issue 3. Art. No.:
CD004454. DOI: 10.1002/14651858. CD004454.pub2. Copyright
The Cochrane Collaboration, reproduced with permission.
OBSTETRICS & GYNECOLOGY 189
COMMENTARY data from 24 –25 weeks), 2) even when delivery

T he first meta-analysis of trials of prenatal cortico-

steroid use took place in 1989, and widespread
implementation of this effective therapy into clinical
practice took even longer. Before 1982, there were
seven published clinical trials, starting with the semi-
nal study of Liggins and Howie in Auckland, New
Zealand, in 1972.1 Had a meta-analysis been done in
1982, it would have shown a statistically significant
reduction in neonatal deaths.
The iconic systematic review of prenatal cortico-
steroids has been updated recently by Roberts and
Dalziel. It includes five new trials, a reanalysis of the
1972 New Zealand study based on “intention to
treat,” and data on long-term follow-up into
adulthood.
The new review demonstrates a significant reduc-
tion in necrotizing enterocolitis and early systemic
neonatal infection, as well as the previously recog-
nized reductions in neonatal death, respiratory dis-
tress, and cerebroventricular hemorrhage. Only 21
women need to be treated to avoid one neonatal
death. Long-term follow-up findings in humans are
reassuring, important in light of the adverse effects of
corticosteroids on fetal brain growth in some animal
experiments.
The review also shows that treatment is beneficial
1) from 26 weeks (possibly earlier but there are few
occurs within 24 hours of treatment, 3) in the presence
of preterm rupture of membranes or maternal hyper-
tension, and 4) in modern neonatal practice where
surfactant is available. There are few data from mul-
tiple pregnancies, so the findings have to be extrapo-
lated from singleton pregnancies.
Separate Cochrane reviews address the related
issues of the effectiveness and safety of multiple doses
of prenatal corticosteroids (still controversial2— but
may be beneficial3), the adjunctive use of thyroid-
releasing hormone with corticosteroids (does not
help), and the use of corticosteroids before planned
cesarean delivery at term (review pending).
REFERENCES
1. Wellcome Trust Centre. Prenatal corticosteroids for reducing
morbidity and mortality after preterm birth. Witness Seminar,
Wellcome Trust Centre for the History of Medicine, June
2004. Available at: http://library.wellcome.ac.uk/witnesssemi-
nars/wit25.pdf. Retrieved October 31, 2006.
2. Crowther CA, Harding J. Repeat doses of prenatal corticoste-
roids for women at risk of preterm birth for preventing
neonatal respiratory disease (Cochrane Review). In: The
Cochrane Library, Issue 3, 2003. Oxford: Update Software.
3. Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS;
for ACTORDS Study Group. Neonatal respiratory distress
syndrome after repeat exposure to antenatal corticosteroids: a
randomised controlled trial. Lancet 2006;367:1913–9.

VISIT THE COCHRANE COLLABORATION WEB SITE FOR

THE FULL TEXT OF THIS MONTH’S FEATURED REVIEW:
http://www.cochrane.org/reviews/index.htm
Other recent reviews of interest to obstetricians and gynecologists from the
Cochrane Library:
• Alfirevic Z, Devane D, Gyte GML. Continuous cardiotocography for fetal
assessment during labour (Issue 3, 2006).
• van Doorn HC, Ansink A, Verhaar-Langereis M, Stalpers L. Neoadjuvant
chemoradiation for advanced primary vulvar cancer. (Issue 3, 2006)
• van Vliet HAAM, Grimes DA, Lopez LM, Schulz KF, Helmerhorst FM.
Triphasic versus monophasic oral contraceptives for contraception. (Issue 3,
2006).
• Fernando R, Sultan AH, Kettle C, Thakar R, Radley S. Methods of repair for
obstetric anal sphincter injury. (Issue 3, 2006).
• Meher S, Duley L. Garlic for preventing pre-eclampsia and its complications.
(Issue 3, 2006).

190 Cochrane Update OBSTETRICS & GYNECOLOGY