Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants

Brigitte Lemyre; Matthew Laughon; Carl Bose; Peter G Davis

doi:10.1002/14651858.CD005384.pub2

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Figure 1

Study flow diagram.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 3

Forest plot of comparison: 1 NIPPV vs NCPAP (by population), outcome: 1.1 Respiratory failure.

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Figure 4

Forest plot of comparison: 1 NIPPV vs NCPAP (by population), outcome: 1.2 Need for intubation.

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Figure 5

Forest plot of comparison: 1 NIPPV vs NCPAP (by population), outcome: 1.3 Mortality during study period.

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Figure 6

Forest plot of comparison: 1 NIPPV vs NCPAP (by population), outcome: 1.4 Chronic lung disease.

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Analysis 1.1

Comparison 1 NIPPV vs NCPAP (by population), Outcome 1 Respiratory failure.

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Analysis 1.2

Comparison 1 NIPPV vs NCPAP (by population), Outcome 2 Need for intubation.

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Analysis 1.3

Comparison 1 NIPPV vs NCPAP (by population), Outcome 3 Mortality during study period.

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Analysis 1.4

Comparison 1 NIPPV vs NCPAP (by population), Outcome 4 Chronic lung disease.

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Analysis 1.5

Comparison 1 NIPPV vs NCPAP (by population), Outcome 5 Pneumothorax.

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Analysis 1.6

Comparison 1 NIPPV vs NCPAP (by population), Outcome 6 Intraventricular hemorrhage (all grades).

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Analysis 1.7

Comparison 1 NIPPV vs NCPAP (by population), Outcome 7 Severe intraventricular hemorrhage (grade III/IV).

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Analysis 1.8

Comparison 1 NIPPV vs NCPAP (by population), Outcome 8 Necrotizing enterocolitis (≥ Bell's stage 2).

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Analysis 1.9

Comparison 1 NIPPV vs NCPAP (by population), Outcome 9 Sepsis.

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Analysis 1.10

Comparison 1 NIPPV vs NCPAP (by population), Outcome 10 Retinopathy of prematurity (≥ stage 3).

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Analysis 1.11

Comparison 1 NIPPV vs NCPAP (by population), Outcome 11 Local upper airway injury.

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Analysis 2.1

Comparison 2 NIPPV vs NCPAP (by device), Outcome 1 Respiratory failure.

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Analysis 2.2

Comparison 2 NIPPV vs NCPAP (by device), Outcome 2 Need for intubation.

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Analysis 2.3

Comparison 2 NIPPV vs NCPAP (by device), Outcome 3 Mortality.

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Analysis 2.4

Comparison 2 NIPPV vs NCPAP (by device), Outcome 4 Chronic lung disease.

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Analysis 2.5

Comparison 2 NIPPV vs NCPAP (by device), Outcome 5 Pneumothorax.

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Analysis 2.6

Comparison 2 NIPPV vs NCPAP (by device), Outcome 6 Severe intraventricular hemorrhage (grade III/IV).

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Analysis 3.1

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 1 Respiratory failure.

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Analysis 3.2

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 2 Need for intubation.

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Analysis 3.3

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 3 Mortality.

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Analysis 3.4

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 4 Chronic lung disease.

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Analysis 3.5

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 5 Pneumothorax.

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Analysis 3.6

Comparison 3 NIPPV vs NCPAP (by synchronization), Outcome 6 Severe intraventricular hemorrhage (grade III/IV).

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Analysis 4.1

Comparison 4 NIPPV vs NCPAP high‐quality studies only (by device), Outcome 1 Respiratory failure (high‐quality studies).

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Summary of findings for the main comparison. NIPPV versus NCPAP (by population)

NIPPV versus NCPAP (by population)
Patient or population: preterm infants Setting: neonatal intensive care units Intervention: NIPPV Comparison: NCPAP
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with NCPAP	Risk with NIPPV
Respiratory failure	Study population		RR 0.62 (0.47 to 0.82)	876 (9 RCTs)	Moderate^a	Risk of bias: unblinded intervention Meets optimal information size (OIS) (N = 377)
	251 per 1000	155 per 1000 (120 to 200)
	Moderate
	175 per 1000	109 per 1000 (84 to 140)
Need for intubation	Study population		RR 0.79 (0.64 to 0.97)	766 (8 RCTs)	Moderate^a	Risk of bias: unblinded intervention Does not meet OIS (N = 838)
	300 per 1000	237 per 1000 (192 to 291)
	Moderate
	175 per 1000	138 per 1000 (112 to 170)
Pneumothorax	Study population		RR 0.69 (0.35 to 1.34)	876 (9 RCTs)	Low^a,b	Risk of bias: unblinded intervention Imprecision: wide confidence intervals
	43 per 1000	29 per 1000 (15 to 57)
	Moderate
	44 per 1000	30 per 1000 (15 to 58)
Severe intraventricular hemorrhage (grade III/IV)	Study population		RR 1.26 (0.53 to 3.01)	430 (4 RCTs)	Very low^a,b	Risk of bias: unblinded intervention Imprecision: extremely wide confidence intervals
	37 per 1000	46 per 1000 (19 to 110)
	Moderate
	49 per 1000	61 per 1000 (26 to 147)
Chronic lung disease	Study population		RR 0.67 (0.47 to 0.94)	727 (8 RCTs)	Moderate^a	Risk of bias: unblinded intervention Does not meet OIS (N = 1250)
	179 per 1000	120 per 1000 (84 to 168)
	Moderate
	170 per 1000	114 per 1000 (80 to 160)
Mortality during study period	Study population		RR 0.77 (0.51 to 1.17)	876 (9 RCTs)	Low^a,b	Risk of bias: unblinded intervention Imprecision: wide confidence intervals
	89 per 1000	69 per 1000 (46 to 105)
	Low
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	26 per 1000	20 per 1000 (13 to 30)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aUnblinded intervention. ^bImprecision: wide confidence intervals.

Summary of findings for the main comparison. NIPPV versus NCPAP (by population)

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Comparison 1. NIPPV vs NCPAP (by population)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Respiratory failure Show forest plot	10	1060	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.51, 0.82]

1.1 Surfactant (via INSURE) before enrollment	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.15, 0.90]
1.2 No surfactant treatment before enrollment	6	774	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]
1.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.24, 0.91]
2 Need for intubation Show forest plot	9	950	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.64, 0.94]

2.1 Surfactant (via INSURE) before enrollment	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.12, 3.57]
2.2 No surfactant treatment before enrollment	6	774	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.69, 1.02]
2.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.24, 0.91]
3 Mortality during study period Show forest plot	10	1061	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.51, 1.15]

3.1 Surfactant (via INSURE) before enrollment	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.07, 16.76]
3.2 No surfactant treatment before enrollment	6	775	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.52, 1.30]
3.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.21, 1.42]
4 Chronic lung disease Show forest plot	9	899	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.58, 1.06]

4.1 Surfactant (via INSURE) before enrollment	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.29, 1.00]
4.2 No surfactant treatment before enrollment	5	627	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.64, 1.32]
4.3 Mixed population (re: surfactant treatment) before enrollment	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.08, 1.91]
5 Pneumothorax Show forest plot	10	1061	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.42, 1.48]

5.1 Surfactant (via INSURE) before enrollment	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.07, 2.94]
5.2 No surfactant treatment before enrollment	6	775	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.52, 2.91]
5.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.13, 1.41]
6 Intraventricular hemorrhage (all grades) Show forest plot	5	370	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.54, 1.16]

6.1 Surfactant (via INSURE) before enrollment	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 3.92]
6.2 No surfactant treatment before enrollment	3	270	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.56, 1.22]
6.3 Mixed population (re: surfactant treatment) before enrollment	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Severe intraventricular hemorrhage (grade III/IV) Show forest plot	4	430	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.53, 3.01]

7.1 Surfactant (via INSURE) before enrollment	1	110	Risk Ratio (M‐H, Fixed, 95% CI)	5.37 [0.26, 109.35]
7.2 No surfactant treatment before enrollment	3	320	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.39, 2.59]
7.3 Mixed population (re: surfactant treatment) before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Necrotizing enterocolitis (≥ Bell's stage 2) Show forest plot	7	718	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.34, 1.31]

8.1 Surfactant (via INSURE) before enrollment	2	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.10, 2.82]
8.2 No surfactant treatment before enrollment	4	492	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.25, 1.33]
8.3 Mixed population (re: surfactant treatment) before enrollment	1	76	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.28, 8.93]
9 Sepsis Show forest plot	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.36, 1.70]

9.1 Surfactant (via INSURE) before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 No surfactant treatment before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.36, 1.70]
10 Retinopathy of prematurity (≥ stage 3) Show forest plot	2	245	Risk Ratio (M‐H, Fixed, 95% CI)	1.50 [0.65, 3.44]

10.1 Surfactant (via INSURE) before enrollment	1	110	Risk Ratio (M‐H, Fixed, 95% CI)	3.22 [0.13, 77.41]
10.2 No surfactant treatment before enrollment	1	135	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.58, 3.30]
10.3 Mixed population (re: surfactant treatment) before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Local upper airway injury Show forest plot	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.03, 0.41]

11.1 Surfactant (via INSURE) before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.2 No surfactant treatment before enrollment	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.3 Mixed population (re: surfactant treatment) before enrollment	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.03, 0.41]

Comparison 1. NIPPV vs NCPAP (by population)

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Comparison 2. NIPPV vs NCPAP (by device)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Respiratory failure Show forest plot	10		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ventilator‐generated NIPPV	6	606	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.47, 0.86]
1.2 Bilevel NIPPV	2	160	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.44, 2.27]
1.3 Mixed devices	2	294	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.38, 0.93]
2 Need for intubation Show forest plot	10		Risk Difference (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Ventilator‐generated NIPPV	6	606	Risk Difference (M‐H, Fixed, 95% CI)	‐0.08 [‐0.14, ‐0.02]
2.2 Bilevel NIPPV	2	160	Risk Difference (M‐H, Fixed, 95% CI)	0.0 [‐0.10, 0.10]
2.3 Mixed devices	2	294	Risk Difference (M‐H, Fixed, 95% CI)	‐0.11 [‐0.20, ‐0.02]
3 Mortality Show forest plot	9	977	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.51, 1.15]

3.1 Ventilator‐generated NIPPV	5	522	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.52, 1.23]
3.2 Bilevel NIPPV	2	160	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.08]
3.3 Mixed devices	2	295	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.21, 2.83]
4 Chronic lung disease Show forest plot	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Ventilator‐generated NIPPV	5	457	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.47, 1.15]
4.2 Bilevel NIPPV	2	160	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.24, 2.13]
4.3 Mixed devices	2	282	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.54, 1.32]
5 Pneumothorax Show forest plot	10		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Ventilator‐generated NIPPV	6	606	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.21, 1.11]
5.2 Bilevel NIPPV	2	160	Risk Ratio (M‐H, Fixed, 95% CI)	2.5 [0.49, 12.67]
5.3 Mixed devices	2	295	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.28, 7.29]
6 Severe intraventricular hemorrhage (grade III/IV) Show forest plot	3	346	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.51, 3.62]

6.1 Ventilator‐generated NIPPV	2	236	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.35, 3.04]
6.2 Mixed devices	1	110	Risk Ratio (M‐H, Fixed, 95% CI)	5.37 [0.26, 109.35]

Comparison 2. NIPPV vs NCPAP (by device)

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Comparison 3. NIPPV vs NCPAP (by synchronization)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Respiratory failure Show forest plot	10	1060	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.51, 0.81]

1.1 Nonsynchronized NIPPV	5	572	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.44, 0.83]
1.2 Synchronized NIPPV	4	304	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.41, 1.02]
1.3 Mixed methods	1	184	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.44, 1.22]
2 Need for intubation Show forest plot	10	1060	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.61, 0.87]

2.1 Nonsynchronized NIPPV	5	572	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.60, 0.92]
2.2 Synchronized NIPPV	4	304	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.42, 1.06]
2.3 Mixed methods	1	184	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.44, 1.22]
3 Mortality Show forest plot	9	977	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.51, 1.15]

3.1 Synchronized NIPPV	3	220	Risk Ratio (M‐H, Fixed, 95% CI)	0.25 [0.03, 2.19]
3.2 Nonsynchronized NIPPV	5	572	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.54, 1.27]
3.3 Mixed methods	1	185	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.16, 3.09]
4 Chronic lung disease Show forest plot	9	899	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.58, 1.06]

4.1 Nonsynchronized NIPPV	4	423	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.51, 1.08]
4.2 Synchronized NIPPV	4	304	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.18, 1.01]
4.3 Mixed methods	1	172	Risk Ratio (M‐H, Fixed, 95% CI)	1.38 [0.70, 2.72]
5 Pneumothorax Show forest plot	10	1061	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.42, 1.48]

5.1 Nonsynchronized NIPPV	5	572	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.24, 1.40]
5.2 Synchronized NIPPV	4	304	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.30, 2.43]
5.3 Mixed methods	1	185	Risk Ratio (M‐H, Fixed, 95% CI)	4.74 [0.23, 97.39]
6 Severe intraventricular hemorrhage (grade III/IV) Show forest plot	3	346	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.51, 3.62]

6.1 Synchronized NIPPV	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.2 Nonsynchronized NIPPV	3	346	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.51, 3.62]

Comparison 3. NIPPV vs NCPAP (by synchronization)

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Comparison 4. NIPPV vs NCPAP high‐quality studies only (by device)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Respiratory failure (high‐quality studies) Show forest plot	8	902	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.50, 0.82]

1.1 Ventilator‐generated NIPPV	4	448	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.45, 0.85]
1.2 Bilevel NIPPV	2	160	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.44, 2.27]
1.3 Mixed devices	2	294	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.38, 0.93]

Comparison 4. NIPPV vs NCPAP high‐quality studies only (by device)

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