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Table 2 Interventions used in the 25 RCTs

From: Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis

Study

Age at enrollment

Type of AACS

Intervention dose

Mode of delivery

Intervention treatment

AACs vs placebo

 Arnon [35]

1996

15 (0.6)a

14 (0.5)a

BUD

600 μg BID

MDI

7 days or until the infant had been extubated

 Bassler [16] 2015

within 12 h

BUD

400 μg Q12H for 14 days

200 μg Q12H for 15 days

MDI

Until extubation and no oxygen dependent or 32 weeks PMA

 Cao [36] 2016

within 6 h

BUD

250 μg Q8H

Airway instillation

Until FIO2 < 0.4 or extubation

 Cole [37] 1999

5.7 (3.4)a

5.4 (2.9)a

BDP

40 μg/kg for 7 days

30 μg/kg for 7 days

15 μg/kg for 7 days

5-10 μg/kg for 7 days

MDI

28 days

 Denjean [38] 1998

10 days

BDP

250 μg Q6H

MDI

28 days

 Fok [39] 1999

within 24 h of birth

FPP

250 μg

Q12H

MDI

14 days

 Giep [40] 1996

14 days

BDP

1 mg/kg/d

MDI

7 days

 Jangaard [41] 2002

3 years

BDP

0.2 mg/kg/d

MDI

Until 28 days of age

 Jonsson [42] 2000

6 days

BUD

0.5 mg/times

BID

Electronic dosimetric jet nebulizer

14 days

 Ke [43] 2016

within 6 h

BUD

250 μg Q12H

Airway instillation

Until stop respiratory support

 LaForce [44] 1993

14 days

BDP

50 μg Q8H

A Whisper Jet nebulizer system

28 days

 Merz [45] 1999

3 days

BUD

1.6 mg/d Q6H

MDI

10 days or until extubation

 Nakamura [24] 2016

within 24 h of birth

FPP

50 μg BID

MDI

Until 6 weeks of age or extubation

 Pappagallo [46] 1998

22.6 (3.0)a

19.1 (1.6)a

DXM

1 mg/kg Q8H for 7 days

0.5 mg/kg Q8H for 7 days

A jet nebulizer

10 days

 Townsend [47] 1998

at 48-96 h of age

FPP

500 μg TID

MDI

28 days or until extubation

Wen [48] 2016

within 24 h of birth

BUD

0.4 mg/kg

Q12H

MDI

14 days

 Yeh [49] 2008

Kuo [50] 2010

2.1 (2.2)a

BUD

0.25 mg/kg

Q8H

Airway instillation

Until the infant required ≤0.4 of FIO2 or until the infant was extubated

 Yeh [25]

2016

2.0 (1.5)a

1.8 (1.6)a

BUD

0.25 mg/kg

Q8H

Airway instillation

Until the infant required ≤0.4 of FIO2 or until extubation

 Yong [20]

1999

within 18 h of birth

FPP

250 μg

Q12H

MDI

14 days

 Zimmerman [51]

2000

within 24 h of birth

BDP

2MDI, Q6H for 3 days;

2MDI, Q8H for 3 days;

2MDI Q12H for 3 days;

2MDI QD for 3 days

MDI

12 days

Inhaled corticosteroids vs systemic corticosteroids

 Dimitriou [52]

1997

After 5 days

BUD

100 μg QD

A jet nebulizer

10 days

 Groneck [53]

1999

After 72 h

BDP

250 μg QD

MDI

10~28 days

 Halliday [54] 2001

Wilson [55] 2006

< 72 h or > 15d

BUD

<1000 g 0.4 mg BID

>1000 g 0.6 mg BID

MDI

12 days or until extubation

 Rozycki [56]

2003

at 14 days of age

BDP

High: 2.4-3.7 mg/kg/d

Mid: 1.0-1.8 mg/kg/d

Low: 0.5-0.7 mg/kg/d

MDI

7 days or until extubation

 Suchomski [57] 2002

12-21 days of age

BDP

High: 800 μg/d

Low: 400 μg/d

MDI

Until extubation

  1. RCTs Randomized controlled trials, BUD Budesonide, BDP Beclomethasone dipropionate, FPP Fluticasone propionate, MDI metered-dose inhaler, AACs Airway administration of corticosteroids, DXM Dexamethasone
  2. None of the trials were sponsored by the manufacturer
  3. ameans ± SD