Inhaled steroids compared with systemic steroids for BPD (infants randomised at < 72 hours of age)

Patient or population: Neonates with developing BPD

Settings: Neonatal intensive care unit

Intervention: Inhaled steroids

Comparison: Systemic steroids

Death or BPD at 36 weeks' postmenstrual age

RR 1.04 (95% CI 0.86 to 1.26)

292 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this single study was high. The study was not blinded at all sites. Only 35/150 infants randomised to systemic steroids received full course while 33/142 infants randomised to inhaled steroids received full course. Results were presented in intention to treat analyses including deaths occurring after 72 hours of age. We downgraded the quality of the evidence by one step.
Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was acceptable

Presence of publication bias: N/A.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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; RR: Risk Ratio; BPD: Bronchopulmonary dysplasia; N/A: Not applicable

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Inhaled steroids compared with systemic steroids for BPD (infants randomised between 12 and 21 days of age)

Patient or population: Neonates with developing BPD

Settings: Neonatal intensive care unit

Intervention: Inhaled steroids

Comparison: Systemic steroids

Death or BPD at 36 weeks' postmenstrual age

RR 0.94 (95% CI 0.83 to 1.05)

78 (1)

⊕⊕⊝⊝
low

Bias: The risk of bias for this single study was high. There was no blinding of the intervention or outcome measurements. We downgraded the quality of the evidence by one level.
Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: The precision for the point estimate was low as the sample size was small

Presence of publication bias: N/A.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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; RR: Risk Ratio; BPD: Bronchopulmonary dysplasia; N/A: Not applicable

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Inhaled steroids compared with systemic steroids for BPD (infants randomised at < 72 hours or between 12 and 21 days of age)

Patient or population: Neonates with developing BPD

Settings: Neonatal intensive care unit

Intervention: Inhaled steroids

Comparison: Systemic steroids

BPD at 36 weeks' postmenstrual age

RR 1.08 (95% CI 0.88 to 1.32)

429 (3)

⊕⊕⊝⊝
low

Bias: The risk of bias for these three studies was high. There was blinding of randomisation in all three studies. There was no blinding of the intervention or outcome measurements at all sites in the largest study (Halliday 2001). In Rozycki 2003 there was blinding of the intervention but blinding of outcome assessment was unclear. In Suchomski 2002 there was no blinding of the intervention or outcomes measurements. We downgraded the quality of the evidence by two levels.
Heterogeneity/consistency: Heterogeneity was low (I² = 39%).
Directness of the evidence: The studies were conducted in the target population of newborn infants.

Precision: The precision for the point estimate was high as the sample size was quite large.

Presence of publication bias: N/A. We did not create a funnel plot as there were only three trials included in the analysis.

Hyperglycaemia

RR 0.86 (95% CI 0.61 to 1.22)

429 (3)

⊕⊕⊝⊝
low

Bias: The risk of bias for these three studies was high. There was blinding of randomisation in all three studies. There was no blinding of the intervention or outcome measurements at all sites in the largest study (Halliday 2001). In Rozycki 2003 there was blinding of the intervention but blinding of outcome assessments was unclear. In Suchomski 2002 there was no blinding of the intervention or outcome measurements. We downgraded the quality of the evidence by two levels.

Heterogeneity/consistency: There was no heterogeneity (I² = 8%).
Directness of the evidence: The studies were conducted in the target population of newborn infants.

Precision: The precision for the point estimate was high as the sample size was quite large.

Presence of publication bias: N/A. We did not create a funnel plot as there were only three trials included in the analysis.

Hypertension

RR (RR 0.86, 95% CI 0.73 to 1.01)

429 (3)

⊕⊕⊝⊝
low

Bias: The risk of bias for these three studies was high. There was blinding of randomisation in all three studies. There was no blinding of the intervention or outcome measurements at all sites in the largest study (Halliday 2001). In Rozycki 2003 there was blinding of the intervention but blinding of outcome assessments was unclear. In Suchomski 2002 there was no blinding of the intervention or outcome measurements. We downgraded the quality of the evidence by two steps.

Heterogeneity/consistency: There was no heterogeneity (I² = 0%).
Directness of the evidence: The studies were conducted in the target population of newborn infants.

Precision: The precision for the point estimate was high as the sample size was quite large.

Presence of publication bias: N/A. We did not create a funnel plot as there were only three trials included in the analysis.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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; RR: Risk Ratio; BPD: Bronchopulmonary dysplasia; N/A: Not applicable

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Inhaled steroids compared with systemic steroids for BPD ‐ long‐term outcomes at 7 years of age (infants randomised at < 72 hours of age)

Patient or population: Neonates with developing BPD

Settings: NICU

Intervention: Inhaled steroids

Comparison: Systemic steroids

General conceptual ability (GCA) score at 7 years

The test has a standardisation mean of 100 and SD of 15

MD ‐3.40 (95% CI ‐12.38 to 5.58)

74 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the Quality of the evidence by one step.

Presence of publication bias: N/A.

Moderate/severe disability at 7 years

RR 1.40 (95% CI 0.49 to 4.01)

74 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the Quality of the evidence by one step.

Presence of publication bias: N/A.

Death or moderate/severe disability at 7 years

RR 1.01 (95% CI 0.65 to 1.58)

107 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the Quality of the evidence by one step.

Presence of publication bias: N/A.

Systolic blood pressure > 95th percentile at 7 years

RR 0.55 (95% CI 0.25 to 1.23)

70 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the quality of the evidence by one step.

Presence of publication bias: N/A.

Diastolic blood pressure > 95th percentile at 7 years

RR (1.38, 95% CI 0.43 to 4.45)

69 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the quality of the evidence by one step.

Presence of publication bias: N/A.

Ever diagnosed as asthmatic by 7 years

RR 0.87 (95% CI 0.55 to 1.39)

73 (1)

⊕⊕⊕⊝
moderate

Bias: The risk of bias for this outcome was low. This outcome was reported in a subset of infants, who had been enrolled in the trial in Ireland and the UK. The assessors of all the long‐term outcomes were blinded to the original treatment group allocation.

Heterogeneity/consistency: Heterogeneity was N/A as there was only one study included in the analysis.
Directness of the evidence: The study was conducted in the target population of newborn infants.

Precision: Precison for the point estimate was low because of the small sample size. We downgraded the quality of the evidence by one step.

Presence of publication bias: N/A.

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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; RR: Risk Ratio; BPD: Bronchopulmonary dysplasia; NICU: Neonatal intensive care unit; N/A: Not applicable

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.