Table 1. Characteristics of the Included Studies.

Source (study location)	Birth weight, mean or median, g	Gestational age, mean (SD), wk	Intervention 1 (No.)	Intervention 2 (No.)	Time of randomization	Dose, mg/kg	Ventilated at enrollment?	Open-label systemic corticosteroid used?	ANS, %	Other comments
LIBUD vs late-initiated systemic dexamethasone
Dimitriou et al,23 1997 (United Kingdom)	833	Group 1: median (IQR), 27 (24-31) Group 2: median (IQR), 27 (24-30)	LaMdMcDX (20)a	LIBUD (20)	27 d	2.8	Yes	No	55-60	LIBUD: 100 μg 4 times daily; 10 d
Halliday et al,24 2001 (Ireland)	1007	Group 1: 27.1 (1.9) Group 2: 27.3 (1.8) Group 3: 27.0 (2.0)	LaMdMcDX (150)a	EIBUD (143) (LIBUD) (142)	>15 d	2.7	Yes	No	55-63	EIBUD/LIBUD: 400 μg/kg twice daily; 12 d 4-Group trial Early-initiated dexamethasone group excluded
EIBEC
Cole et al,25 1999 (United States)	800	Group 1: 26 (2) Group 2: 26 (2)	EIBEC (123)	Placebo (130)	5 d	NA	Yes	Yes	68-77	Tapering course 40-5 μg/kg/d; 28 d
Zimmerman et al,26 2000 (United States)	828	Group 1: 26 (2) Group 2: 26 (2)	EIBEC (20)	Placebo (19)	<8 h	NA	Yes	Yes	70-79	Tapering dose; exact dose not mentioned; 12 d
Jangaard et al,27 2002 (Canada)	900	Group 1: 27.2 (2) Group 2: 27.9 (2)	EIBEC (30)	Placebo (30)	<96 h	NA	Yes	Yes	50-53	200 μg/kg/d; 28 d
ITBUD + surfactant
Lin et al,28 2001 (China)	953	NA (mean: 27)	EIBUD (44)	Placebo (42)	<12 h	NA	NA	NA	NA	ITBUD: 500 μg/kg
Yeh et al,29 2008 (Taiwan); Kuo et al,30 2010 (Taiwan)	900	Group 1: 26.4 (2.2) Group 2: 26.7 (2.3)	ITBUD + surfactant (60)	Surfactant (56)	<2 h	NA	Yes	Yes	42-46	ITBUD: 0.25 mg/kg with 100 mg/kg Survanta, repeated administration every 8 h until FiO2 < 0.4
Yeh et al,31 2016 (United States and Taiwan)	908	Group 1: 26.5 (2.2) Group 2: 26.8 (2.2)	ITBUD + surfactant (131)	Surfactant (134)	<4 h	NA	Yes	Yes	79-85	ITBUD: 0.25 mg/kg with 100 mg/kg Survanta, repeated administration every 8 h until FiO2 < 0.3 or extubated, maximum dose: 6
Ke et al,32 2016 (China)	NA	NA	EIBUD (46) ITBUD + surfactant (46)	Surfactant (46)	4 h	NA	Yes	NA	NA	ITBUD: 0.25 mg/kg, surfactant 200 mg/kg, every 6-12h if needed EIBUD: 200 μg/d until weaning
Pan et al,33 2017 (China)	1310	Group 1: 30 (1.7) Group 2: 29.5 (1.8)	ITBUD + surfactant (15)	Surfactant (15)	4 h	NA	Yes	NA	60-67	ITBUD: mean (SD), 0.25 (70) mg pulmonary surfactant; surfactant dose of 70 mg/kg, repeated once if FiO2 > 0.4 or MAP >8 cm water
EIBUD
Merz et al,34 1999 (Germany)	1114	Group 1: median (IQR), 28 (27-32) Group 2: median (IQR), 29 (27-31)	EIBUD (12)	Placebo (11)	3 d	NA	Yes	Yes	58-63	1600 μg/d; 10 d
Bassler et al,35,36 2015, 2018 (multicenter Europe)	800	Group 1: 26.1 (1.3) Group 2: 26.1 (1.2)	EIBUD (437)	Placebo (419)	<24 h	NA	Yes	No	88-90	200 μg Twice daily; 14 d followed by 200 μg once daily until withdrawal of oxygen or positive pressure or 32 wk’ PMA
Sadeghnia et al,37 2018 (Iran)	915	Group 1: 26.9 (1.3) Group 2: 27.3 (0.8)	EIBUD (35)	Placebo (35)	2 h	NA	No	NA	38-49	500 μg Every 12 h; 7 d
Cao et al,38 2018 (China)	NA	NA (inclusion ≤32 w)	EIBUD (40)	Placebo (40)	NA	NA	NA	NA	NA	250 μg/kg, Duration not mentioned
EIFLUT
Fok et al,39 1999 (China)	987	Group 1: 27.9 (0.5) Group 2: 27.1 (0.5)	EIFLUT (27)	Placebo (26)	<24 h	NA	Yes	Yes	50-55	250 μg Twice daily every 12 d
Yong et al,40 1999 (NA)	972	Group 1: 27.4 (1.7) Group 2: 27.7 (1.7)	EIFLUT (20)	Placebo (20)	<18 h	NA	Yes	NA	NA	500 μg/d; 14 d
Nakamura et al,41 2016 (Japan)	784	Group 1: median (IQR), 26.1 (25.1-27.3) Group 2: median (IQR), 26.2 (25.1-27.3)	EIFLUT (107)	Placebo (104)	<24 h	NA	Yes	NA	40-42	50 μg Twice daily; 6 wk or until extubation
EHC
Watterberg et al,42 1999 (United States)	746	Group 1: 25.2 (1.3) Group 2: 25.4 (1.5)	EHC (20)	Placebo (20)	<48 h	10.5	Yes	Yes	85	1 mg/kg/d for 9 d; 0.5 mg/kg/d for 3 d
Efird et al,43 2005 (United States)	783	Group 1: 26 (1) Group 2: 26 (1)	EHC (16)	Placebo (18)	<3 h	5.8	NA	No	>94	1 mg/kg Twice daily for 2 d; 0.3 mg/kg twice daily for 3 d Neonates treated for hypotension
Watterberg et al,44,45 2004, 2007 (United States)	733	Group 1: 25.2 (1.5) Group 2: 25.3 (1.7)	EHC (180)	Placebo (180)	12-48 h	13.5	Yes	Yes	77-81	1 mg/kg/d for 12 d; 0.5 mg/kg/d for 3 d
Peltoniemi et al,46,47 2005, 2009 (Finland)	895	Group 1: 26.7 (1.6) Group 2: 26.5 (2.8)	EHC (25)	Placebo (26)	<36 h	11.5	Yes	No	92-96	2 mg/kg/d for 2 d; 1.5 mg/kg/d for 2 d; 0.75 mg/kg/d for 6 d
Bonsante et al,48 2007 (Italy)	860	Group 1: median (IQR), 26.2 (25.2-27.4) Group 2: median (IQR), 26.5 (25.0-28.1)	EHC (25)	Placebo (25)	<48 h	10.5	Yes	Yes	52-68	1 mg/kg/d for 9 d; 0.5 mg/kg/d for 3 d
Ng et al,49 2006 (Hong Kong)	919	Group 1: median (IQR), 27.2 (25.4-29.1) Group 2: median (IQR), 26.0 (25.2-29.9)	EHC (24)	Placebo (24)	12 h	15	NA	Yes	NA	1 mg/kg 3 Times daily; 5 d
Hochwald et al,50 2014 (United States)	844	Group 1: 26.1 (1.5) Group 2: 25.6 (1.37)	EHC (11)	Placebo (11)	≤48 h	7	NA	NA	63	2 mg/kg Followed by 1 mg/kg every 6 h for 3 doses 0.5 mg/kg every 6 h for 4 doses Neonates treated for hypotension
Baud et al,51,52 2016, 2019 (France)	850	Group 1: median (IQR), 29.9 (26.5-34.5) Group 2: median (IQR), 29.9 (26.5-34.7)	EHC (255)	Placebo (266)	16 h	8.5	Yes	No	88-95	1 mg/kg/d for 7 d; 0.5 mg/kg/d for 3 d
LIBEC
LaForce and Brudno,53 1993 (United States)	<1500	NA	LIBEC (6)	Placebo (7)	≥14 d	NA	Yes	NA	NA	50 μg 3 Times daily; 28 d
Giep et al,54 1996 (United States)	768	Group 1: 26 (2) Group 2: 25 (1.6)	LIBEC (10)	Placebo (9)	19 d	NA	Yes	Yes	22-40	1000 μg/kg/d
Denjean et al,55 1998 (France)	1050	Group 1: 27.8 (1.6) Group 2: 27.6 (1.5)	LIBEC (43)	Placebo (43)	10 d	NA	Yes	Yes	14-26	250 μg 4 Times daily; 28 d
LIBEC vs late-initiated systemic dexamethasone
Suchomski and Cummings,56 2002 (United States)	845	Group 1: 26 (1.5) Group 2: 26 (2)	LIBEC (51)	LaHdLcDX (27)a	17 d	7.6	Yes	Yes	48-84	LIBUD: 400 or 800 μg/d until extubation, same dose for 48 h postextubation, dose halved every other day for 6 d Dexamethasone: 0.5 mg/kg/d tapered over 42 d
Rozycki et al,57 2003 (United States)	760	Group 1: median (IQR), 26 (23-31) Group 2: median (IQR), 26 (24-27)	LIBEC (15)	LaHdLcDX (15)a	>14 d	7.6	Yes	Yes	59-67	LIBUD: 42 μg/dose twice daily to 3 times daily; 7 d Dexamethasone: same as Suchomski and Cummings56
LIBUD
Arnon et al,58 1996 (United Kingdom)	1024	Group 1: 27.5 (0.7) Group 2: 27.1 (0.9)	LIBUD (9)	Placebo (11)	14 d	NA	Yes	NA	73-78	600 μg Twice daily for 7 d or until extubation
Jónsson et al,59 2000 (Sweden)	806	Group 1: median (IQR), 25 (23-27) Group 2: median (IQR), 26 (24-29)	LIBUD (15)	Placebo (15)	7 d	NA	Yes	Yes	67-80	1000 μg/d for 14 d Neonates could be excluded if they required FiO2 > 0.6 or Pco2 > 65 mm Hg
LHC
Parikh et al,60,61 2013, 2015 (United States)	666	Group 1: median (IQR), 25 (24-26) Group 2: median (IQR), 25 (24-27)	LHC (31)	Placebo (33)	16 d	17	Yes	Yes	61-81	3 mg/kg/d for 3 d; 2 mg/kg/d for 2 d; 1 mg/kg/d for 1 d
Onland et al,62 2019 (Netherlands)	742	Group 1: median (IQR), 25.4 (24.9-26.4) Group 2: median (IQR), 25.6 (24.7-26.4)	LHC (181)	Placebo (190)	10 d	72.5	Yes	NA	87-91	5 mg/kg/d in 4 Divided doses for 7 d; 3.75 mg/kg/d in 3 divided doses for 5 d; lowering frequency 1 dose every 5 d Total duration: 22 d
Late-initiated systemic dexamethasone
Cummings et al,63 1989 (United States)	827	Group 1: 26 (2) Group 2: 26 (2) Group 3: 26 (2)	LaHdLcDX (13)a	LaMdLcDX (12)a Placebo (11)	15 d	3 vs 7.98	Yes	NA	25-38	Course duration: 18 and 42 d
Kothadia et al,64 1999 (United States)	750	Group 1: median (IQR), 25 (23-29) Group 2: median (IQR), 26 (23-31)	LaHdLcDX (50)a	Placebo (45)	19 d	7.98	Yes	NA	16-48	0.5 mg/kg/d for 3 d; 0.3 mg/kg/d for 3 d; dose reduced by 10% every 3rd d to reach 0.1 mg/kg/d on 34th d;, same dose on alternate d for 1 wk
Malloy et al,65 2005 (United States)	770	Group 1: 25.8 Group 2: 26.1	LaMdScDX (8)a	LaLdScDX (8)a	15 d	2.7 vs 0.56	Yes	Yes	63-75	LaMdScDX: 0.5 mg/kg/d for 3 d, 0.3 mg/kg/d for 4 d LaLdScDX: 0.08 mg/kg/d for 7 d
Doyle et al,66,67 2006, 2007 (Australia)	676	Group 1: median (IQR), 24 (24-25) Group 2: median (IQR), 25 (24-26)	LaLdMcDX (35)a	Placebo (35)	4 wk	0.89	Yes	Yes	89	0.15 mg/kg/d for 3 d; 0.10 mg/kg/d for 3 d; 0.05 mg/kg/d for 2 d; 0.02 mg/kg/d for 2 d
Moderately early-initiated systemic dexamethasone
Kari et al,68 1993 (Finland)	880	Group 1: 27 (2) Group 2: 27 (2)	MoMdScDX (17)a	Placebo (24)	14 d	3.5	Yes	Yes	4-6	0.5 mg/kg/d; 7 d
Ramanathan et al,69 1994 (United States)	NA	NA (mean, 27 wk)	MoMdScDX (15)a	MoLdScDX (13)a	10-14 d	1.9 vs 1	NA	NA	NA	MoMdScDX: 0.4 mg/kg/d for 2 d and tapered for the succeeding 5 d MoLdScDX: 0.2 mg/kg/d for 2 d, then tapered for 5 d
Brozanski et al,70 1995 (United States)	804	Group 1: 25.6 (0.3) Group 2: 26 (0.3)	MoHdLcDX (39)a	Placebo (39)	7 d	3-10.5	Yes	NA	20-23	Pulse regimen 0.25 mg/kg/dose Twice daily for 3 d; repeated after 10 d until 36 wk’ PMA or oxygen or ventilator support no longer required
Durand et al,71 1995 (United States)	<1500	NA	MoMdScDX (23)a	Placebo (20)	7-14 d	2.35	Yes	NA	NA	0.5 mg/kg/d for 3 d and then 0.25 mg/kg/d for 3 d and 0.10 mg/kg for 1 d
Scott et al,72 1997 (United States)	NA	NA	MoMdScDX (10)a	Placebo (5)	11-14 d	1.9	Yes	NA	NA	0.5 mg/kg/d for 2 d and then 0.3 mg/kg/d for 3 d
Bloomfield et al,73 1998 (New Zealand); Armstrong et al,74 2002 (New Zealand)	782.5	Group 1: 25.8 (0.3) Group 2: 25.8 (03)	MoHdMcDX (19)a	LaHdLcDX (21)a	14 d	5.3 vs 7.1	Yes	NA	62-68	Pulse regimen (MoHdMcDX) vs long course (LaHdLcDX) Pulse regimen started 7 d; long course regimen started >14 d
Kovács et al,75 1998 (Canada)	763	Group 1: 25.8 (1.6) Group 2: 25.9 (1.8)	MoLdScDX (30)a	Placebo (30)	7 d	1.5	Yes	Yes	73	0.25 mg/kg Twice daily for 3 d
Merz et al,34 1999 (Germany)	960	Group 1: 27 Group 2: 27.5	MoMdLcDX (15)a	LaMdLcDX (15)a	7 d vs 14 d	2.9	Yes	NA	73-87	0.5 mg/kg/d for 3 d; 0.3 mg/kg/d for 3 d; 0.1 mg/kg/d, followed by this dose alternatively every 2nd d until day 16
Romagnoli et al,76,77 1999, 2002 (Italy)	899	Group 1: 27.4 (1.4) Group 2: 27.1 (1.4)	MoHdMcDX (15)a	Placebo (15)	10 d	4.75	Yes	NA	40-47	0.5 mg/kg/d for 6 d; 0.25 mg/kg/d for 6 d; 0.125 mg/kg/d for 2 d
Durand et al,78 2002 (United States)	895	Group 1: 27.1 (1.8) Group 2: 26.9 (1.6)	MoMdScDX (23)a	MoLdScDX (24)a	NA	2.35 vs 1	Yes	Yes (after study period)	50-52	MoMdScDX: 0.5 mg/kg/d for 3 d; 0.25 mg/kg/d for 3 d; 0.1 mg/kg/d for 1 d MoLdScDX: 0.2 mg/kg/d for 3 d; 0.1 mg/kg/d for 4 d
Walther et al,79 2003 (United States)	1011	Group 1: 28.5 (1.7) Group 2: 28.6 (1.9)	MoMdMcDX (17)a	Placebo (19)	7-14 d	1.9	Yes	Yes	42-76	0.2 mg/kg/d for 4 d; 0.15 mg/kg/d for 4 d; 0.10 mg/kg/d for 4 d; 0.05 mg/kg/d for 2 d
McEvoy et al,80 2004 (United States)	834.5	Group 1: 26.1 (2) Group 2: 26.3 (1.8)	MoMdMcDX (29)a	MoLdScDX (33)a	7-14 d	2.35 vs 1	Yes	Yes (after study period)	34-48	MoMdMcDX: 0.5 mg/kg/d for 3 d; 0.25 mg/kg/d for 3 d; 0.1 mg/kg/d for 1 d MoLdScDX: 0.2 mg/kg/d for 3 d; 0.1 mg/kg/d for 4 d
Odd et al,81 2004 (New Zealand)	695	Group 1: median (IQR), 24 (23-27) Group 2: median (IQR), 24 (23-26)	MoMdLcDX (17)a	MoHdLcDX (16)a	10-12 d	3.8 vs 6.5	Yes	Yes	NA	MoHdLcDX (long course): 0.5 mg/kg/d for 3 d; 0.3 mg/kg/d for 3 d; dose reduced by 10% every 3rd d to reach 0.1 mg/kg/d on 34th d; same dose on alternate d for 1 wk MoMdLcDX (individualized): 0.5 mg/kg/d for 3 d; 0.3 mg/kg/d for 3 d; 0.1 mg/kg/d for 3 d; 0.1 mg/kg every 72 h until the infant was extubated and required FiO2 < 0.25 for 3 doses
Alishiri and Mosavi,82 2015 (Iran)	1456	Group 1: 30.07 (2.01) Group 2: 30.8 (2.17)	MoMdScDX (27)a	Placebo (31)	8 d	3.5	No	Yes	33-39	0.25 mg/kg Twice daily from 7 d
Marr et al,83 2019 (United States)	777	Group 1: 25.2 (1.2) Group 2: 25.2 (1.1)	MoHdLcDX (30)a	MoMdMcDX (29)a	14 d	7.98 vs 4	Yes	NA	62-63	MoHdLcDX: 0.5 mg/kg/d for 3 d; 0.3 mg/kg/d for 3 d; dose reduced by 10% every 3rd d to reach 0.1 mg/kg/d on 34th d; same dose on alternate d for 1 wk MoMdMcDX: 0.5 mg/kg/d for 3 d; 0.25 mg/kg/d for 3 d; 0.125 mg/kg/d for 3 d

Abbreviations: ANS, antenatal corticosteroids; EHC, early-initiated systemic hydrocortisone; EIBEC, early-initiated inhaled beclomethasone; EIBUD, early-initiated inhaled budesonide; EIFLUT, early-initated inhaled fluticasone; IQR, interquartile range; ITBUD, intratracheal budesonide; LaHdLcDX, late-initiated, high cumulative dose, long course of systemic dexamethasone; LaLdMcDX, late-initiated, low cumulative dose, medium course of systemic dexamethasone; LaLdScDX, late-initiated, low cumulative dose, short course of systemic dexamethasone; LaMdLcDX, late-initiated, medium cumulative dose, long course of systemic dexamethasone; LaMdMcDX, late-initiated, medium cumulative dose, medium course of systemic dexamethasone; LaMdScDX, late-initiated, medium cumulative dose, short course of systemic dexamethasone; LHC, late-initiated systemic hydrocortisone; LIBEC, late-initated inhaled beclomethasone; LIBUD, late initiated inhaled budesonide; MAP, mean arterial pressure; MoHdLcDX, moderately early-initiated, high cumulative dose, long course of systemic dexamethasone; MoHdMcDX, moderately early-initiated, high cumulative dose, medium course of systemic dexamethasone; MoLdScDX, moderately early-initiated, low cumulative dose, short course of systemic dexamethasone; MoMdLcDX, moderately early-initiated, medium cumulative dose, long course of systemic dexamethasone; MoMdMcDX, moderately early-initiated, medium cumulative dose, medium course of systemic dexamethasone; MoMdScDX, moderately early-initiated, medium cumulative dose, short course of systemic dexamethasone; NA, not applicable; Pco2, partial pressure of carbon dioxide; PMA, postmenstrual age.

^aEarly-initiated: less than 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 and low cumulative dose: less than 2 mg/kg; medium cumulative dose: 2 to 4 mg/kg.