DARE abstract 20031112
Effects of a single course of corticosteroids given more than 7 days before
birth: a systematic review
McLaughlin K J, Crowther C A, Walker N, Harding J E. Effects of a single
course of corticosteroids given more than 7 days before birth: a systematic
review. Australia and New Zealand Journal of Obstetrics and Gynaecology,
2003;43(2):101-106.
This record is a structured abstract written by CRD reviewers. The original
has met a set of quality criteria. Since September 1996 abstracts have been
sent to authors for comment. Additional factual information is incorporated
into the record. Noted as (A:....).
CRD summary
This review concluded that exposure to a single course of prenatal
corticosteroids administered more than 7 days before birth does not reduce
the incidence of respiratory distress syndrome, but can increase the risk of
perinatal mortality, earlier birth and maternal infectious morbidity. The
review was generally well-conducted and, despite a few methodological
considerations, the conclusions are likely to be reliable.
Author's objective
The authors' objective was to determine the effects of a single course of
prenatal corticosteroids administered more than 7 days before birth on
foetal, neonatal and maternal mortality and morbidity.
Type of intervention
Treatment, adverse events.
Specific interventions included in the review
Studies comparing a single course of prenatal corticosteroids (betamethasone
or dexamethasone) with no corticosteroids were eligible for inclusion in the
review.
Participants included in the review
Women who had not given birth 7 days after treatment were eligible for the
review. Women in one study who had been given more than one course of
treatment were excluded. No further details of the participants were
provided.
Outcomes assessed in the review
The outcomes of interest were clinically important infant and maternal
outcomes, including stillbirth, neonatal death, perinatal mortality,
respiratory distress syndrome, maternal morbidity, gestational age at birth,
birth weight, the number of infants with an Apgar score of less than seven
at 5 minutes, cerebroventricular haemorrhage, proven neonatal infection,
congenital anomalies, maternal chorioamnionitis, maternal pyrexia and mode
of delivery.
Study designs of evaluations included in the reviews
Randomised controlled trials (RCTs) were eligible for inclusion in the
review. However, one of the included studies was described as using
quasi-random treatment allocation.
What sources were searched to identify primary studies
Current Contents, MEDLINE and the Cochrane Controlled Trials Register (Issue
4, 2001) were searched; the search terms were stated. The reference lists of
all identified studies were checked for additional trials. Study authors
were contacted for unpublished data and information about any relevant
unpublished trials.
Criteria on which the validity (or quality) of studies was assessed
The methodological quality of the studies was assessed in terms of treatment
allocation and its concealment, blinding, intention-to-treat analyses and
loss to follow-up.
How were decisions on the relevance of primary studies made?
The authors did not state how the papers were selected for the review, or
how many reviewers performed the selection.
How were judgements on the validity (or quality) made?
The assessment of methodological quality was carried out independently of
the trial results. The authors did not state how many reviewers performed
the validity assessment.
How were the data extracted from primary studies?
Two reviewers extracted the data and any discrepancies were resolved by
discussion with a third reviewer. The reviewers were not blinded to study
authorship. Two of the review authors appear to have been involved in one of
the included studies and provided further unpublished data. Data were
extracted for each of the dichotomous outcomes, and the relative risk (RR)
and 95% confidence intervals were calculated. For continuous variables,
group means and the mean difference were calculated.
Number of studies included in the review
Seven RCTs with a total of 2,149 women carrying 2,176 unborn infants were
identified; 862 remained undelivered more than 7 days after treatment
allocation, and so were included in the review.
How were the studies combined?
The RRs were weighted and pooled using a fixed-effect model.
How were differences between studies investigated?
Statistical heterogeneity was assessed using the chi-squared statistic.
Analyses for neonatal mortality were carried out with the inclusion and
exclusion of infants with congenital anomalies. Subgroup analyses of trials
with a high level of methodological quality for treatment allocation were
performed.
Results of the review
There was no statistically significant difference in the risk of stillbirths
between those exposed to a course of prenatal corticosteroids and the
control group, (3 trials; RR 1.67, 95% CI: 0.86, 3.25, P=0.13). The risk of
neonatal death was three times greater in the group that had been exposed to
corticosteroids than in the control group (1 trial; RR 3.24, 95% CI: 1.32,
7.96, P=0.01). The higher number of neonatal deaths in the treatment group
was not explained by one cause of death alone, but there was a higher number
of congenital anomalies in the treatment group. After removing infants with
congenital anomalies from the analysis, there was still a greater number of
deaths in the treatment group than the control group, but this difference
was no longer statistically significant (RR 2.53, 95% CI: 0.91, 7.05,
P=0.11). The risk of perinatal mortality was more than twice as high in the
corticosteroid-exposed group than the control (3 trials; RR 2.13, 95% CI:
1.27, 3.57, P<0.01). When infants with congenital anomalies were excluded
from the analysis, the difference between groups remained statistically
significant (RR 1.86, 95% CI: 1.08, 3.22, P<0.03). There was no
statistically significant difference in the risk of respiratory distress
syndrome between infants exposed to a course of prenatal corticosteroids and
infants in the control group, (7 trials; RR 0.72, 95% CI: 0.49, 1.07,
P=0.11). Other infant outcomes were only reported in one trial. Infants
exposed to corticosteroids had a significantly lower gestational age than
infants in the control group; the mean difference was -5.00 days (95% CI:
-9.15, -0.85, P=0.02). No statistically significant differences in birth
weight, low Apgar scores, neonatal infection, or cerebroventricular
haemorrhage were found between the two groups. Mothers who received
corticosteroids more than 7 days before giving birth were at almost three
times greater risk of chorioamnionitis than mothers in the control group, (1
trial; RR 2.91, 95% CI: 1.25, 6.74, P=0.01). No significant differences were
found in pyrexia or type of delivery between the two groups. The removal of
trials with inadequate or unreported methods of treatment allocation from
the analysis had little effect on the results. There was no evidence of
statistical heterogeneity in the pooled analyses. There was some evidence of
imbalance in gestational age, race and the use of alcohol as a tocolytic
across treatment groups in some studies.
Was any cost information reported?
No.
Authors' conclusions
Exposure to a single course of corticosteroids more than 7 days before birth
does not reduce the incidence of respiratory distress syndrome, but it can
increase the risk of perinatal mortality, earlier birth and maternal
infectious morbidity.
CRD commentary
The authors set out a clear objective at the beginning of the review and
clearly stated the inclusion criteria used. Three electronic databases were
searched and an effort was made to obtain unpublished data, which helps
reduce publication bias. It was unclear how the studies were selected for
review. Two independent reviewers extracted the data, and the methodological
assessment was carried out blind to the trial results; both of these help
reduce bias. Appropriate criteria were assessed for validity, and the effect
of adequate randomisation procedures on the results was assessed. Few
details of the participants in the primary studies were provided, which
makes it difficult for the findings to be generalised to a wider population.
The pooling of the results seems appropriate, particularly given the absence
of statistical heterogeneity. However, some studies had only small numbers
of participants, and the number of studies pooled was small. This means that
the size of treatment effects might have been underestimated. In general,
this was a well-conducted review and, despite a few methodological
considerations, the authors' conclusions are likely to be reliable.
What are the implications of the review?
Practice: The authors stated that until more is known about the safety and
efficacy of repeat courses of prenatal corticosteroids, only a single course
should be used and this should be administered within 7 days of the
predicted pre-term birth. Research: The authors stated that the safety and
efficacy of repeat courses of prenatal corticosteroids should be assessed in
future trials. In addition, the possibility of a causal relationship between
earlier birth, seen in infants exposed to corticosteroids who remained
undelivered 7 days later, and the risk of chorioamnionitis should be
investigated.
Subject index terms
Subject indexing assigned by NLM: Adult; Betamethasone/tu [therapeutic-use];
Female; Glucocorticoids/tu [therapeutic-use]; Infant-Mortality;
Infant,-Newborn; Pregnancy; Pregnancy-Outcome; Randomized-Controlled-Trials;
Respiratory-Distress-Syndrome,-Newborn/pc [prevention-&-control];
Time-Factors
Language of original publication: English
Authors' address for correspondence: Ms. C A Crowther, Department of
Obstetrics and Gynaecology, University of Adelaide, 1st Floor, Queen
Victoria Building, Women's and Children's Hospital, 72 King William Road,
North Adelaide, S. Australia 5006, Australia. E-
mail:[EMAIL PROTECTED]
Copyright: University of York, 2005.
Leanne Wynne
Midwife in charge of "Women's Business"
Mildura Aboriginal Health Service Mob 0418 371862
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