No of Mean no
Gestational
pts in of
Initial
Power
age
weekly additional
treatment
Primary Sample analysis
(weeks)
ACS courses
Trial
outcome size
grp
(ACS)
Composite
neonatal
1000
morbidity,
patients
Single dose
severe
needed for
Guinn et
betamethasone/
RDS,
90% power
al
dexamethasone
severe
to detect a
24-32
256
2.8
500
7 days earlier
IVH, NEC,
33%
sepsis,
reduction in
perinatal
morbidity
death
Composite
neonatal
morbidity,
2400
severe
Single dose
required for
RDS,
betamethasone/
80% power
Wapner
severe
dexamethasone
to detect a
et al
IVH,
7-10 days
30%
23-31
252
4
495
chronic
earlier
reduction in
lung
morbidity
disease,
perinatal
death
980 required
Single dose
for 80%
Crowther
betamethasone/
power to
982
et al
dexamethasone
detect a 25%
Frequency
<32
570
3.5
7+ days earlier
reduction in
of RDS
morbidity
Garite et
al
<33
Study
Guinn et al
Single dose
dexamethasone
14 days earlier 223
Treatment
Composite
morbidity
Placebo
ACS
28%
22.5%
Comments Non sig*
Placebo 8%
Wapner et
ACS
9.1%
al
Comments
Placebo
Crowther et
ACS
al
Comments
Placebo 63.6%
Garite et al ACS
43.9%
Comments P=0.02
*Non sig= Not statistically significant
Composite
neonatal
morbidity,
severe RDS,
severe IVH,
437
NEC,
perinatal
death
1
217
required
for 80%
power to
detect a
40%
reduction
in
morbidity
24.5%
15.3%
P=0.01,
significant
876
856
Mean head
circumferences
(cm)
29.4
29.1
Non sig*
Non sig*
(reduced)
Reduced by 95 (not affected)
33%
41%
(reduced)
(reduced)
2821
2803
32.5
33.0
Severe RDS
61.6%
41.4%
P=0.02
Mean birth
weights (g)
Composite
morbidity
Guinn et
reduced
al
Severe RDS
reduced
(better
Wapner et
No difference pulmonary
al
outcomes)
Crowther
et al
(better
pulmonary
outcomes)
Garite et
reduced
al
reduced
Birth
weight
Small
effect
Long term
Head
circumference concerns
Small effect
-
Age 2-3:
concerns
reduced reduced
over
cerebral
palsy
Age 2:
Reduced
concerns
Reduced (short
(short
over
term)
term)
attention
problems
No
No difference difference
Considerations for Education & Practice
Limit the number of absolute courses of ACS given.
Only treat babies most likely to deliver at a gestational age where they
would benefit mostly from ACS treatment.
Best approach is a ‘rescue course’: initial course of ACS administered
when preterm birth is likely.
If the patient does not deliver over the next 7 or more days, a repeat ACS
course can be given up to 32 weeks’ gestation.
Considerations for further research
Although a great deal of research exists, there is still a need for RCT’s to determine the best possible
number of courses of ACS to reduce neonatal RDS without adversely affecting other neonatal outcomes.
Searching for the best dosage and timing, and the risk-benefit ratio can only be accomplished through
continued research.
Well structured RCT’s that evaluate single and multiple courses are needed to answer important
questions such as:
Do repeat ACS doses maintain the production of surfactant in the foetal lung?
Do the effects of ACS change with time to delivery?
What are possible long-term consequences of repeat ACS in terms of behaviour?
The primary goal of perinatal medicine is to minimize neonatal morbidity and mortality, but we need a
better understanding of the mechanisms of preterm birth for more effective prevention, in order to
prevent all complications associated with premature birth, including RDS.