Table 2. Assessment of the Quality of Evidence for the Different Comparisons for Bronchopulmonary Dysplasia (BPD) or Mortality at Postmenstrual Age (PMA) of 36 Weeks.
| Regimen comparison | Quality of evidence (reason for downgrading)a | Network meta-analysis | ||
|---|---|---|---|---|
| Indirect evidence | Direct evidence | RR (95% CrI) | Quality of evidencea | |
| Primary outcome: BPD or mortality at 36 wk’ PMA | ||||
| EHC:EIBEC | Low (risk of bias, imprecision) | NA | 0.90 (0.59-1.30) | Low |
| EHC:EIBUD | Moderate (imprecision) | NA | 1.01 (0.75-1.35) | Moderate |
| EHC:EIFLUT | Moderate (imprecision) | NA | 1.12 (0.79-1.54) | Moderate |
| EHC:ITBUD | Low (imprecision, heterogeneity) | NA | 1.15 (0.84-1.52) | Low |
| EHC:LaHdDXb | Moderate (imprecision) | NA | 1.20 (0.87-1.59) | Moderate |
| EHC:LaLdDXb | Low (severe imprecision) | NA | 0.93 (0.63-1.29) | Low |
| EHC:LaMdDXb | Low (severe imprecision) | NA | 0.90 (0.64-1.21) | Low |
| EHC:LHC | Moderate (imprecision) | NA | 0.83 (0.59-1.09) | Moderate |
| EHC:LIBEC | Very low (risk of bias, severe imprecision) | NA | 1.09 (0.71-1.51) | Very low |
| EHC:LIBUD | Very low (risk of bias, imprecision) | NA | 0.94 (0.62-1.36) | Very low |
| EHC:MoHdDXb | Moderate (imprecision) | NA | 1.31 (0.94-1.77) | Moderate |
| EHC:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 1.00 (0.62-1.53) | Very low |
| EHC:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.38 (0.98-1.89) | Low |
| EHC:Placebo | NA | Moderate (imprecision) | 0.82 (0.68-0.97)c | Moderate |
| EIBEC:EIBUD | Low (risk of bias, imprecision) | NA | 1.16 (0.75-1.77) | Low |
| EIBEC:EIFLUT | Low (risk of bias, imprecision) | NA | 1.29 (0.80-2.00) | Low |
| EIBEC:ITBUD | Low (risk of bias, imprecision) | NA | 1.32 (0.84-1.99) | Low |
| EIBEC:LaHdDXb | Low (risk of bias, imprecision) | NA | 1.38 (0.88-2.08) | Low |
| EIBEC:LaLdDXb | Low (risk of bias, imprecision) | NA | 1.07 (0.65-1.67) | Low |
| EIBEC:LaMdDXb | Low (risk of bias, imprecision) | NA | 1.04 (0.65-1.57) | Low |
| EIBEC:LHC | Low (risk of bias, imprecision) | NA | 0.95 (0.61-1.43) | Low |
| EIBEC:LIBEC | Very low (risk of bias, severe imprecision) | NA | 1.25 (0.74-1.94) | Very low |
| EIBEC:LIBUD | Very low (risk of bias, imprecision) | NA | 1.08 (0.64-1.74) | Very low |
| EIBEC:MoHdDXb | Low (risk of bias, imprecision) | NA | 1.51 (0.95-2.30) | Low |
| EIBEC:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 1.15 (0.64-1.91) | Very low |
| EIBEC:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.59 (0.99-2.45) | Low |
| EIBEC:Placebo | NA | Low (risk of bias, imprecision) | 0.95 (0.65-1.33) | Low |
| EIBUD:EIFLUT | Moderate (imprecision) | NA | 1.12 (0.76-1.59) | Moderate |
| EIBUD:ITBUD | Low (imprecision, heterogeneity) | NA | 1.15 (0.80-1.57) | Low |
| EIBUD:LaHdDXb | Moderate (imprecision) | NA | 1.20 (0.84-1.63) | Moderate |
| EIBUD:LaLdDXb | Low (severe imprecision) | NA | 0.93 (0.62-1.30) | Low |
| EIBUD:LaMdDXb | Low (severe imprecision) | Very low (risk of bias, imprecision) | 0.90 (0.66-1.15) | Low |
| EIBUD:LHC | Moderate (imprecision) | NA | 0.83 (0.57-1.13) | Moderate |
| EIBUD:LIBEC | Very low (risk of bias, severe imprecision) | NA | 1.09 (0.68-1.55) | Very low |
| EIBUD:LIBUD | Very low (risk of bias, imprecision) | Very low (risk of bias, imprecision) | 0.93 (0.66-1.26) | Very low |
| EIBUD:MoHdDXb | Moderate (imprecision) | NA | 1.31 (0.90-1.83) | Moderate |
| EIBUD:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 1.00 (0.60-1.57) | Very low |
| EIBUD:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.38 (0.95-1.94) | Low |
| EIBUD:Placebo | Very low (risk of bias, imprecision) | Moderate (imprecision) | 0.83 (0.63-1.02) | Moderate |
| EIFLUT:ITBUD | Low (imprecision, heterogeneity) | NA | 1.05 (0.70-1.49) | Low |
| EIFLUT:LaHdDXb | Moderate (imprecision) | NA | 1.09 (0.74-1.56) | Moderate |
| EIFLUT:LaLdDXb | Low (severe imprecision) | NA | 0.84 (0.54-1.25) | Low |
| EIFLUT:LaMdDXb | Low (severe imprecision) | NA | 0.82 (0.54-1.18) | Low |
| EIFLUT:LHC | Moderate (imprecision) | NA | 0.76 (0.50-1.07) | Moderate |
| EIFLUT:LIBEC | Very low (risk of bias, severe imprecision) | NA | 0.99 (0.61-1.46) | Very low |
| EIFLUT:LIBUD | Low (severe imprecision) | NA | 0.86 (0.53-1.31) | Low |
| EIFLUT:MoHdDXb | Moderate (imprecision) | NA | 1.19 (0.79-1.73) | Moderate |
| EIFLUT:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 0.91 (0.53-1.47) | Very low |
| EIFLUT:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.26 (0.83-1.84) | Low |
| EIFLUT:Placebo | NA | Moderate (imprecision) | 0.75 (0.55-0.98)c | Moderate |
| ITBUD:LaHdDXb | Low (imprecision, heterogeneity) | NA | 1.06 (0.75-1.47) | Low |
| ITBUD:LaLdDXb | Low (imprecision, heterogeneity) | NA | 0.82 (0.54-1.18) | Low |
| ITBUD:LaMdDXb | Low (imprecision, heterogeneity) | NA | 0.80 (0.55-1.11) | Low |
| ITBUD:LHC | Low (imprecision, heterogeneity) | NA | 0.73 (0.51-1.01) | Low |
| ITBUD:LIBEC | Very low (risk of bias, severe imprecision) | NA | 0.96 (0.61-1.38) | Very low |
| ITBUD:LIBUD | Low (risk of bias, imprecision) | NA | 0.83 (0.53-1.24) | Low |
| ITBUD:MoHdDXb | Low (imprecision, heterogeneity) | NA | 1.16 (0.80-1.63) | Low |
| ITBUD:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 0.88 (0.53-1.39) | Very low |
| ITBUD:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.22 (0.84-1.74) | Low |
| ITBUD:Placebo | NA | Low (imprecision, heterogeneity) | 0.73 (0.57-0.91)c | Low |
| LaHdDX:LaLdDXb | Low (severe imprecision) | NA | 0.78 (0.52-1.13) | Low |
| LaHdDX:LaMdDXb | Low (severe imprecision) | Low (severe imprecision) | 0.76 (0.53-1.04) | Low |
| LaHdDX:LHC | Moderate (imprecision) | NA | 0.70 (0.49-0.96)c | Moderate |
| LaHdDX:LIBEC | Very low (risk of bias, severe imprecision) | Low (risk of bias, imprecision) | 0.91 (0.67-1.15) | Low |
| LaHdDX:LIBUD | Low (severe imprecision) | NA | 0.79 (0.52-1.18) | Low |
| LaHdDX:MoHdDXb | Moderate (imprecision) | Low (risk of bias, imprecision) | 1.10 (0.79-1.51) | Moderate |
| LaHdDX:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 0.84 (0.51-1.32) | Very low |
| LaHdDX:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.16 (0.81-1.64) | Low |
| LaHdDX:Placebo | Low (severe imprecision) | Moderate (imprecision) | 0.70 (0.54-0.87)c | Moderate |
| LaLdDX:LaMdDXb | Low (severe imprecision) | Low (severe imprecision) | 0.99 (0.69-1.38) | Low |
| LaLdDX:LHC | Low (severe imprecision) | NA | 0.92 (0.60-1.32) | Low |
| LaLdDX:LIBEC | Very low (risk of bias, severe imprecision) | NA | 1.20 (0.73-1.78) | Very low |
| LaLdDX:LIBUD | Low (severe imprecision) | NA | 1.03 (0.66-1.57) | Low |
| LaLdDX:MoHdDXb | Low (severe imprecision) | NA | 1.45 (0.95-2.13) | Low |
| LaLdDX:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 1.10 (0.64-1.80) | Very low |
| LaLdDX:MoMdDXb | Low (severe imprecision) | NA | 1.52 (1.00-2.27) | Low |
| LaLdDX:Placebo | Low (severe imprecision) | Low (severe imprecision) | 0.91 (0.66-1.21) | Low |
| LaMdDX:LHC | Low (severe imprecision) | NA | 0.92 (0.60-1.32) | Low |
| LaMdDX:LIBEC | Low (risk of bias, imprecision) | NA | 1.03 (0.66-1.57) | Low |
| LaMdDX:LIBUD | Very low (risk of bias, imprecision) | Low (risk of bias, imprecision) | 1.05 (0.78-1.42) | Low |
| LaMdDX:MoHdDXb | Low (severe imprecision) | NA | 1.48 (1.01-2.10)c | Low |
| LaMdDX:MoLdDXb | Low (severe imprecision) | NA | 1.12 (0.67-1.79) | Low |
| LaMdDX:MoMdDXb | Low (severe imprecision) | Low (severe imprecision) | 1.55 (1.06-2.24)c | Low |
| LaMdDX:Placebo | Very low (risk of bias, imprecision) | Low (severe imprecision) | 0.93 (0.71-1.19) | Low |
| LHC:LIBEC | Very low (risk of bias, severe imprecision) | NA | 1.33 (0.85-1.92) | Very low |
| LHC:LIBUD | Low (severe imprecision) | NA | 1.15 (0.74-1.75) | Low |
| LHC:MoHdDXb | Moderate (imprecision) | NA | 1.60 (1.11-2.28)c | Moderate |
| LHC:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 1.22 (0.74-1.95) | Very low |
| LHC:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.69 (1.16-2.45)c | Low |
| LHC:Placebo | NA | Moderate (imprecision) | 1.01 (0.79-1.28) | Moderate |
| LIBEC:LIBUD | Very low (risk of bias, imprecision) | NA | 0.89 (0.55-1.43) | Very low |
| LIBEC:MoHdDXb | Low (risk of bias, imprecision) | NA | 1.24 (0.83-1.86) | Low |
| LIBEC:MoLdDXb | Very low (risk of bias, severe imprecision) | NA | 0.94 (0.55-1.58) | Very low |
| LIBEC:MoMdDXb | Very low (risk of bias, severe imprecision) | NA | 1.30 (0.86-2.01) | Very low |
| LIBEC:Placebo | Low (risk of bias, imprecision) | Very low (risk of bias, severe imprecision) | 0.78 (0.57-1.09) | Low |
| LIBUD:MoHdDXb | Low (risk of bias, imprecision) | NA | 1.44 (0.91-2.16) | Low |
| LIBUD:MoLdDXb | Low (risk of bias, imprecision) | NA | 1.09 (0.61-1.82) | Low |
| LIBUD:MoMdDXb | Low (risk of bias, imprecision) | NA | 1.51 (0.95-2.30) | Low |
| LIBUD:Placebo | Low (severe imprecision) | NA | 0.91 (0.62-1.25) | Low |
| MoHdDX:MoLdDXb | Low (severe imprecision) | NA | 0.77 (0.47-1.20) | Low |
| MoHdDX:MoMdDXb | Low (risk of bias, imprecision) | Low (severe imprecision) | 1.06 (0.83-1.35) | Low |
| MoHdDX:Placebo | Low (severe imprecision) | Moderate (imprecision) | 0.64 (0.48-0.82)c | Moderate |
| MoLdDX:MoMdDXb | Very low (risk of bias, severe imprecision) | Low (severe imprecision) | 1.44 (0.90-2.19) | Low |
| MoLdDX:Placebo | Low (severe imprecision) | Very low (risk of bias, severe imprecision) | 0.87 (0.55-1.27) | Low |
| MoMdDX:Placebo | Low (severe imprecision) | Low (risk of bias, imprecision) | 0.61 (0.45-0.79)c | Low |
Abbreviations: CrI, credible interval; EHC, early-initiated systemic hydrocortisone; EIBEC, early-initiated inhaled beclomethasone; EIBUD, early-initiated inhaled budesonide; EIFLUT, early-initiated inhaled fluticasone; ITBUD, intratracheal budesonide; LaHdDX, late-initiated, high cumulative dose of systemic dexamethasone; LaLdDX, late-initiated, low cumulative dose of systemic dexamethasone; LaMdDX, late-initiated, medium cumulative dose of systemic dexamethasone; LHC, late-initiated systemic hydrocortisone; LIBEC, late-initiated inhaled beclomethasone; LIBUD, late-initiated inhaled budesonide; MoHdDX, moderately early-initiated, high cumulative dose of systemic dexamethasone; MoLdDX, moderately early-initiated low cumulative dose of systemic dexamethasone; MoMdDX, moderately early-initiated, medium cumulative dose of systemic dexamethasone; NA, not applicable; PMA, postmenstrual age; RR, risk ratio.
a
Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group approach: high (high confidence in the evidence: the true effect [or the reality, as defined by the GRADE group] is close to the estimated effect), moderate (moderate confidence: the true effect is likely close to but likely substantially different from the estimated effect), low (some confidence: the true effect is likely substantially different from the estimated effect), and very low (little confidence: the true effect is substantially different from the estimated effect).
b
Early-initiated: <8 days of postnatal age; late-initiated: 15 to 27 days of postnatal age; moderately early-initiated: 8 to 14 days of postnatal age; long course: more than 14 days; medium course: 8 to 14 days; short course: less than 8 days; high cumulative dose: greater than 4 mg/kg; low cumulative dose: less than 2 mg/kg; medium cumulative dose: 2 to 4 mg/kg.
c
Values are statistically significant.