Criteria
Judgements
○ No
○ Probably
Benefits & harms of the options
Problem
no
Is there a
problem
priority?
What is the
overall
certainty of
this
evidence?
○ Uncertain
○ Probably
yes
Additional considerations
Bronchopulmonary dysplasia (BPD) is major morbidity of preterm infants
associated with post-discharge mortality, respiratory problems, and
neurodevelopmental impairment later in life.1 Ventilator-induced lung
injury is an important factor for the development of BPD and non-invasive
(non-ventilator) respiratory management such as continuous positive
airway pressure (CPAP) started soon after birth has been drawing attention
in recent years.2
● Yes
○ Varies
Ref. 1: Van Marter LJ. Semin Fetal Neonatal Med. 2009 Dec;14(6):358-66
Ref. 2: Carlo, WA. Early Hum Dev. 2012 May;88 Suppl 2:S81-3
○ No
GRADE Evidence profile Table
included
studies
○ Very low
○ Low
● Moderate
○ High
○ Important
uncertainty
or variability
Is there
important
uncertainty
about how
much people
value the
main
outcomes?
Research evidence
● Possibly
important
uncertainty
or variability
○ Probably
no important
uncertainty
of variability
○ No
important
uncertainty
of variability
○ No known
Event rates
Outcomes
NCPAP
Effect
Intubate Relative
& IPPV (95% CI)
Absolute
(95% CI)
Quality
Importance
41 fewer per 1000
⨁⨁⨁◯
(0 fewer−77
MODERATE
fewer)
Critical
(8)
RR 0.92
(0.82 to
1.03)
30 fewer per 1000
⨁⨁⨁◯
(11 more−68
MODERATE
fewer)
Critical
(7)
RR 0.82
(0.66 to
1.03)
23 fewer per 1000
⨁⨁⨁◯
(4 more−43
MODERATE
fewer)
Critical
(9)
Death or
BPD
493/1193 531/1165
RR 0.91
(41.3%) (45.6%) (0.83 to 1)
BPD
370/1070 384/1018
(34.6%) (37.7%)
Death
123/1193 147/1165
(10.3%) (12.6%)
BPD: Bronchopulmonary dysplasia, CI: confidence interval, RR: relative risk
Criteria
Judgements
undesirable
Research evidence
GRADE Evidence profile Table
Event rates
Outcomes
Severe
IVH
● No
○ Probably
no
Are the
desirable
anticipated
effects large?
○ Uncertain
○ Probably
yes
○ Yes
○ Varies
○ No
○ Probably
no
Are the
undesirable
anticipated
effects small?
● Uncertain
○ Probably
yes
○ Yes
○ Varies
Additional considerations
NCPAP
Intubate
& IPPV
Effect
Relative
(95% CI)
125/1167 112/1134
RR 1.09
(10.7%) (9.9%) (0.86 to 1.39)
Absolute
(95% CI)
9 more per 1000
(14 fewer−39
more)
Air leak
85/1192
(7.1%)
67/1165
RR 1.24
14 more per 1000
(5.8%) (0.91 to 1.69) (5 fewer−40 more)
Severe
ROP
80/703
(11.4%)
72/656
RR 1.03
(11.0%) (0.77 to 1.39)
NEC
3 more per 1000
(25 fewer−43
more)
Quality
Importance
⨁◯◯◯
VERY LOW
Critical
(7)
⨁⨁◯◯
LOW
Important
(5)
⨁⨁◯◯
LOW
Critical
(7)
⨁⨁⨁◯
113/1183 92/1148
RR 1.19
15 more per 1000
(9.6%)
(8.0%) (0.92 to 1.55) (6 fewer−44 more) MODERATE
Critical
(7)
CI: confidence interval, IVH: intraventricular hemorrhage, NEC: necrotizing enterocolitis,
ROP: retinopathy of prematurity, RR: relative risk
Criteria
Judgements
Research evidence
○ No
○ Probably
Are the
desirable
effects large
relative to
undesirable
effects?
no
● Uncertain
○ Probably
yes
○ Yes
○ Varies
○ No
○ Probably
no
Are the
resources
required
small?
○ Uncertain
● Probably
yes
Resource use
○ Yes
○ Varies
Is the
incremental
cost small
relative to
the net
benefits?
○ No
○ Probably
no
○ Uncertain
○ Probably
yes
● Yes
CPAP requires less resource and cost than intubation & IPPV because it
reduces the surfactant administration 1,2,3 and shorten the duration
receiving mechanical ventilation 1.
Ref 1: Morley CJ, et al.N Engl J Med. 2008 Feb 14;358(7):700-8
Ref 2: Finer NN, et al. N Engl J Med. 2010 May 27;362(21):1970-9
Ref 3: Dunn MS, et al. Pediatrics. 2011 Nov;128(5):e1069-76
Additional considerations
Criteria
Judgements
○ Varies
○ Increased
○ Probably
Equity
increased
What would
be the impact
on health
inequities?
○ Uncertain
● Probably
reduced
○ Reduced
○ Varies
Acceptability
○ No
○ Probably
no
○
●
Is the option
Uncertain
acceptable to
key
Probably
stakeholders? yes
○ Yes
○ Varies
Research evidence
Additional considerations
Criteria
Judgements
Research evidence
Additional considerations
Both CPAP and intubation and IPPV are widely used in neonatal units and
implementation would be straightforward.
○ No
○ Probably
Feasibility
no
Is the option
feasible to
implement?
○ Uncertain
○ Probably
yes
● Yes
○ Varies
Recommendation
Balance of
consequences
Type of
recommendation
Undesirable consequences
clearly outweigh desirable
consequences in most
settings
Undesirable consequences
probably outweigh desirable
consequences in most
settings
The balance between desirable
and undesirable consequences
is closely balanced or
uncertain
Desirable consequences
probably outweigh
undesirable consequences in
most settings
Desirable consequences
clearly outweigh undesirable
consequences in most
settings
○
○
○
●
○
We recommend against offering this
option
We suggest not offering this
option
We suggest offering this
option
We recommend offering this option
○
○
●
○
Recommendation

For spontaneously breathing preterm infants with respiratory distress requiring respiratory support in the delivery room
we suggest initial use of CPAP rather than intubation and IPPV (weak recommendation, moderate quality of evidence).

Values and preference statement: In making this suggestion we recognize that the absolute reduction in risk of adverse
outcome associated with starting with CPAP is small and that infants recruited to the trials had a high rate of treatment
with antenatal steroids but we favor the less invasive approach. The balance of risks and benefits of this approach in
infants who have not received antenatal steroids is unknown.

For the critical composite outcome of “death or bronchopulmonary dysplasia” we have identified moderate quality
evidence (downgraded for imprecision) from 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) enrolling
2358 preterm infants born at < 30 weeks gestation in the first 15 minutes after birth showing modest potential benefit to
starting treatment with CPAP (R.R. 0.91, 95% CI 0.83 – 1.00).

For the critical outcome of “death” we have identified moderate quality evidence (downgraded for imprecision) from the
same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing modest potential benefit to starting
treatment with CPAP (R.R. 0.82, 95% CI 0.66 – 1.03).

For the critical outcome of “bronchopulmonary dysplasia” we have identified moderate quality evidence (downgraded for
imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing modest potential
benefit to starting treatment with CPAP (R.R. 0.92, 95% CI 0.82 – 1.03).

For the critical outcome of “air leak” we have identified low quality evidence (downgraded for inconsistency and
imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing no benefit to
starting treatment with CPAP (R.R 1.24, 95% CI 0.91 – 1.69).

For the critical outcome of “severe intraventricular haemorrhage” we have identified very low quality evidence
(downgraded for inconsistency and very serious imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970,
Dunn 2011 e1069) showing no benefit to starting treatment with CPAP (R.R 1.09, 95% CI 0.86 – 1.39).

For the important outcome of “necrotizing enterocolitis” we have identified moderate quality evidence (downgraded for
imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing no benefit to
starting treatment with CPAP (R.R 1.19 95% CI 0.92 – 1.55).

For the important outcome of “severe retinopathy of prematurity” we have identified low quality evidence
(downgraded for very serious imprecision) from 2 RCTs (Finer 2010 1970, Dunn 2011 e1069) enrolling 1359 infants
showing no benefit to starting treatment with CPAP (R.R 1.03 95% CI 0.77-1.39).
Justification
Ref 1: Morley CJ, et al.N Engl J Med. 2008 Feb 14;358(7):700-8
Ref 2: Finer NN, et al. N Engl J Med. 2010 May 27;362(21):1970-9
Ref 3: Dunn MS, et al. Pediatrics. 2011 Nov;128(5):e1069-76
Subgroup
considerations
Implementation
considerations
Monitoring and
evaluation

A further trial of CPAP versus intubation and IPPV in high risk preterm infants at lower gestations is required to
determine the risks and benefits more clearly. It is not clear whether there is a significant effect on mortality. The
confidence intervals for the other morbidities of prematurity leave open the possibility that any benefit in relation to
bronchopulmonary dysplasia might still be balanced by a small increase in risk of severe intraventricular haemorrhage or
necrotizing enterocolitis.

The utility of using an INSURE approach to facilitate early stabilization on CPAP soon after birth has been compared
with CPAP alone in at least 2 trials and this should be the subject of a future worksheet.
Research
possibilities