Within the last decades, therapeutic advances have significantly improved the survival of extremely preterm infants. In contrast, the incidence of major neonatal morbidities, including bronchopulmonary dysplasia, has not declined. Given the well-established relationship between exposure to invasive mechanical ventilation and neonatal lung injury, neonatologists have sought for effective strategies of noninvasive respiratory support in high-risk infants. Continuous positive airway pressure has replaced invasive mechanical ventilation for the initial stabilization and the treatment of respiratory distress syndrome. Today, noninvasive respiratory support has been adopted even in the tiniest babies with the highest risk of lung injury. Moreover, different modes of noninvasive respiratory support supplemented by a number of adjunctive measures and rescue strategies have entered clinical practice with the goal of preventing intubation or reintubation. However, does this unquestionably important paradigm shift to strategies focused on noninvasive support lull us into a false sense of security? Can we do better in (i) identifying those very immature preterm infants best equipped for noninvasive stabilization, can we improve (ii) determinants of failure of noninvasive respiratory support in the individual infant and underlying etiology, and can we enhance (iii) success of noninvasive respiratory support and (iv) better prevent ultimate harm to the developing lung? With increased survival of infants at the highest risk of developing lung injury and an unchanging burden of bronchopulmonary dysplasia, we should question indiscriminate use of noninvasive respiratory support and address the above issues.

1.
Stoll
BJ
,
Hansen
NI
,
Bell
EF
,
Walsh
MC
,
Carlo
WA
,
Shankaran
S
, et al.
Trends in care practices, morbidity, and mortality of extremely preterm neonates
.
JAMA
.
2015
;
314
:
1039
51
.
2.
Van Marter
LJ
,
Allred
EN
,
Pagano
M
,
Sanocka
U
,
Parad
R
,
Moore
M
, et al.
Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network
.
Pediatrics
.
2000
;
105
(
6
):
1194
201
. .
3.
Laughon
M
,
Bose
C
,
Allred
EN
,
O'Shea
TM
,
Ehrenkranz
RA
,
Van Marter
LJ
, et al.
Antecedents of chronic lung disease following three patterns of early respiratory disease in preterm infants
.
Arch Dis Child Fetal Neonatal Ed
.
2011
;
96
(
2
):
F114
20
. .
4.
Courtney
SE
,
Durand
DJ
,
Asselin
JM
,
Hudak
ML
,
Aschner
JL
,
Shoemaker
CT
, et al.
High-frequency oscillatory ventilation versus conventional mechanical ventilation for very-low-birth-weight infants
.
N Engl J Med
.
2002
;
347
(
9
):
643
52
. .
5.
Ramanathan
R
.
Optimal ventilatory strategies and surfactant to protect the preterm lungs
.
Neonatology
.
2008
;
93
(
4
):
302
8
. .
6.
Wheeler
K
,
Klingenberg
C
,
McCallion
N
,
Morley
CJ
,
Davis
PG
.
Volume-targeted versus pressure-limited ventilation in the neonate
.
Cochrane Database Syst Rev
.
2010
;
10
(
11
):
CD003666
. .
7.
Wright
CJ
,
Polin
RA
,
Kirpalani
H
.
Continuous positive airway pressure to prevent neonatal lung injury: how did we get here, and how do we improve?
J Pediatr
.
2016
;
173
:
17
e2
. .
8.
Wright
CJ
,
Sherlock
LG
,
Sahni
R
,
Polin
RA
.
Preventing continuous positive airway pressure failure: evidence-based and physiologically sound practices from delivery room to the neonatal intensive care unit
.
Clin Perinatol
.
2018
;
45
(
2
):
257
71
. .
9.
Morley
CJ
,
Davis
PG
,
Doyle
LW
,
Brion
LP
,
Hascoet
JM
,
Carlin
JB
, et al.
Nasal CPAP or intubation at birth for very preterm infants
.
N Engl J Med
.
2008
;
358
(
7
):
700
8
. .
10.
Finer
NN
,
Finer
NN
,
Carlo
WA
,
Walsh
MC
,
Rich
W
,
Gantz
MG
, et al.
Early CPAP versus surfactant in extremely preterm infants
.
N Engl J Med
.
2010
;
362
(
21
):
1970
9
. .
11.
Dunn
MS
,
Kaempf
J
,
de Klerk
A
,
de Klerk
R
,
Reilly
M
,
Howard
D
, et al.
Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates
.
Pediatrics
.
2011
;
128
(
5
):
e1069
76
. .
12.
Davidson
LM
,
Berkelhamer
SK
.
Bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary o.utcomes
.
J Clin Med
.
2017
;
6
(
1
):
4
.
13.
Doyle
LW
,
Carse
E
,
Adams
AM
,
Ranganathan
S
,
Opie
G
,
Cheong
JLY
, et al.
Ventilation in extremely preterm infants and respiratory function at 8 years
.
N Engl J Med
.
2017
;
377
(
4
):
329
37
. .
14.
Gregory
GA
,
Kitterman
JA
,
Phibbs
RH
,
Tooley
WH
,
Hamilton
WK
.
Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure
.
N Engl J Med
.
1971
;
284
(
24
):
1333
40
. .
15.
Avery
ME
,
Tooley
WH
,
Keller
JB
,
Hurd
SS
,
Bryan
MH
,
Cotton
RB
, et al.
Is chronic lung disease in low birth weight infants preventable? A survey of eight centers
.
Pediatrics
.
1987
;
79
(
1
):
26
30
.
16.
Gittermann
MK
,
Fusch
C
,
Gittermann
AR
,
Regazzoni
BM
,
Moessinger
AC
.
Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants
.
Eur J Pediatr
.
1997
;
156
(
5
):
384
8
. .
17.
Stoll
BJ
,
Hansen
NI
,
Bell
EF
,
Walsh
MC
,
Carlo
WA
,
Shankaran
S
, et al.
Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012
.
JAMA
.
2015
;
314
(
10
):
1039
51
. .
18.
Schmolzer
GM
,
Kumar
M
,
Pichler
G
,
Aziz
K
,
O'Reilly
M
,
Cheung
PY
.
Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis
.
BMJ
.
2013
;
347
:
f5980
.
19.
Fischer
HS
,
Bührer
C
.
Avoiding endotracheal ventilation to prevent bronchopulmonary dysplasia: a meta-analysis
.
Pediatrics
.
2013
;
132
(
5
):
e1351
60
. .
20.
Committee on Fetus and Newborn, American Academy of Pediatrics
.
Respiratory support in preterm infants at birth
.
Pediatrics
.
2014
;
133
(
1
):
171
4
. .
21.
Sweet
DG
,
Carnielli
V
,
Greisen
G
,
Hallman
M
,
Ozek
E
,
Te Pas
A
, et al.
European consensus guidelines on the management of respiratory distress syndrome: 2019 update
.
Neonatology
.
2019
;
115
(
4
):
432
50
. .
22.
Dargaville
PA
,
Aiyappan
A
,
De Paoli
AG
,
Dalton
RG
,
Kuschel
CA
,
Kamlin
CO
, et al.
Continuous positive airway pressure failure in preterm infants: incidence, predictors and consequences
.
Neonatology
.
2013
;
104
(
1
):
8
14
. .
23.
Roberts
CT
,
Owen
LS
,
Frøisland
DH
,
Doyle
LW
,
Davis
PG
,
Manley
BJ
.
Predictors and outcomes of early intubation in infants born at 28–36 weeks of gestation receiving noninvasive respiratory support
.
J Pediatr
.
2020
;
216
:
109
e1
. .
24.
Ammari
A
,
Suri
M
,
Milisavljevic
V
,
Sahni
R
,
Bateman
D
,
Sanocka
U
, et al.
Variables associated with the early failure of nasal CPAP in very low birth weight infants
.
J Pediatr
.
2005
;
147
(
3
):
341
7
. .
25.
Fuchs
H
,
Lindner
W
,
Leiprecht
A
,
Mendler
MR
,
Hummler
HD
.
Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of mechanical ventilation in preterm infants of <29 weeks
.
Arch Dis Child Fetal Neonatal Ed
.
2011
;
96
(
5
):
F343
7
. .
26.
Dargaville
PA
,
Gerber
A
,
Johansson
S
,
De Paoli
AG
,
Kamlin
CO
,
Orsini
F
, et al.
Australian, New Zealand Neonatal Network. Incidence and outcome of CPAP failure in preterm infants
.
Pediatrics
.
2016
;
138
(
1
):
e20153985
.
27.
Gulczynska
E
,
Szczapa
T
,
Hozejowski
R
,
Borszewska-Kornacka
MK
,
Rutkowska
M
.
Fraction of inspired oxygen as a predictor of CPAP failure in preterm infants with respiratory distress syndrome: a prospective multicenter study
.
Neonatology
.
2019
;
116
:
171
8
.
28.
Bancalari
EH
,
Jobe
AH
.
The respiratory course of extremely preterm infants: a dilemma for diagnosis and terminology
.
J Pediatr
.
2012
;
161
(
4
):
585
8
. .
29.
Lemyre
B
,
Davis
PG
,
de Paoli
AG
.
Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity
.
Cochrane Database Syst Rev
.
2002
(
1
):
CD002272
. .
30.
Lemyre
B
,
Laughon
M
,
Bose
C
,
Davis
PG
.
Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants
.
Cochrane Database Syst Rev
.
2016
;
12
:
CD005384
. .
31.
Lemyre
B
,
Davis
PG
,
De Paoli
AG
,
Kirpalani
H
.
Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation
.
Cochrane Database Syst Rev
.
2017
;
2
(
9
):
CD003212
. .
32.
Sahni
R
,
Schiaratura
M
,
Polin
RA
.
Strategies for the prevention of continuous positive airway pressure failure
.
Semin Fetal Neonatal Med
.
2016
;
21
(
3
):
196
203
. .
33.
Patel
RM
,
Zimmerman
K
,
Carlton
DP
,
Clark
R
,
Benjamin
DK
,
Smith
PB
.
Early caffeine prophylaxis and risk of failure of initial continuous positive airway pressure in very low birth weight infants
.
J Pediatr
.
2017
;
190
:
108
e1
. .
34.
Collaborative European Multicenter Study Group
.
Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial
.
Pediatrics
.
1988
;
82
:
683
91
.
35.
Yost
CC
,
Soll
RF
.
Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome
.
Cochrane Database Syst Rev
.
2000
;
11
(
2
):
CD001456
. .
36.
Morley
CJ
.
Systematic review of prophylactic vs rescue surfactant
.
Arch Dis Child Fetal Neonatal Ed
.
1997
;
77
(
1
):
F70
4
. .
37.
Soll
RF
,
Morley
CJ
.
Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants
.
Cochrane Database Syst Rev
.
2001
(
2
):
CD000510
. .
38.
Rojas-Reyes
MX
,
Morley
CJ
,
Soll
R
.
Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants
.
Cochrane Database Syst Rev
.
2012
;
3
(
3
):
CD000510
. .
39.
Horbar
JD
,
Carpenter
JH
,
Buzas
J
,
Soll
RF
,
Suresh
G
,
Bracken
MB
, et al.
Timing of initial surfactant treatment for infants 23 to 29 weeks’ gestation: is routine practice evidence based?
Pediatrics
.
2004
;
113
(
6
):
1593
602
. .
40.
Herting
E
,
Härtel
C
,
Göpel
W
.
Less invasive surfactant administration (LISA): chances and limitations
.
Arch Dis Child Fetal Neonatal Ed
.
2019
;
104
(
6
):
F655
9
. .
41.
De Jaegere
AP
,
van der Lee
JH
,
Canté
C
,
van Kaam
AH
.
Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation
.
Acta Paediatr
.
2012
;
101
(
4
):
374
9
. .
42.
Rocha
G
,
Flôr-de-Lima
F
,
Proença
E
,
Carvalho
C
,
Quintas
C
,
Martins
T
, et al.
Failure of early nasal continuous positive airway pressure in preterm infants of 26 to 30 weeks gestation
.
J Perinatol
.
2013
;
33
(
4
):
297
301
. .
43.
Kakkilaya
V
,
Wagner
S
,
Mangona
KLM
,
Steven Brown
L
,
Jubran
I
,
He
H
, et al.
Early predictors of continuous positive airway pressure failure in preterm neonates
.
J Perinatol
.
2019
;
39
(
8
):
1081
8
. .
44.
Sandri
F
,
Plavka
R
,
Ancora
G
,
Simeoni
U
,
Stranak
Z
,
Martinelli
S
, et al.
Prophylactic or early selective surfactant combined with nCPAP in very preterm infants
.
Pediatrics
.
2010
;
125
(
6
):
e1402
9
. .
45.
Tagliaferro
T
,
Bateman
D
,
Ruzal-Shapiro
C
,
Polin
RA
.
Early radiologic evidence of severe respiratory distress syndrome as a predictor of nasal continuous positive airway pressure failure in extremely low birth weight newborns
.
J Perinatol
.
2015
;
35
(
2
):
99
103
. .
46.
Seger
N
,
Soll
R
.
Animal derived surfactant extract for treatment of respiratory distress syndrome
.
Cochrane Database Syst Rev
.
2009
(
2
):
CD007836
. .
47.
Ng
EH
,
Shah
V
.
Guidelines for surfactant replacement therapy in neonates
.
Paediatr Child Health
.
2021
;
26
(
1
):
35
49
. .
48.
Dietrich
CF
,
Buda
N
,
Ciuca
IM
,
Dong
Y
,
Fang
C
,
Feldkamp
A
, et al.
Lung ultrasound in children, WFUMB review paper (part 2)
.
Med Ultrason
.
2021 Mar 3
[Online ahead of print]. .
49.
Jaworska
J
,
Buda
N
,
Ciuca
IM
,
Dong
Y
,
Fang
C
,
Feldkamp
A
, et al.
Ultrasound of the pleura in children, WFUMB review paper
.
Med Ultrason
.
2021 Feb 1
[Online ahead of print]. .
50.
Raimondi
F
,
Migliaro
F
,
Sodano
A
,
Ferrara
T
,
Lama
S
,
Vallone
G
, et al.
Use of neonatal chest ultrasound to predict noninvasive ventilation failure
.
Pediatrics
.
2014
;
134
(
4
):
e1089
94
. .
51.
Brat
R
,
Yousef
N
,
Klifa
R
,
Reynaud
S
,
Shankar Aguilera
S
,
De Luca
D
.
Lung ultrasonography score to evaluate oxygenation and surfactant need in neonates treated with continuous positive airway pressure
.
JAMA Pediatr
.
2015
;
169
(
8
):
e151797
. .
52.
Perri
A
,
Riccardi
R
,
Iannotta
R
,
Di Molfetta
DV
,
Arena
R
,
Vento
G
, et al.
Lung ultrasonography score versus chest x-ray score to predict surfactant administration in newborns with respiratory distress syndrome
.
Pediatr Pulmonol
.
2018
;
53
(
9
):
1231
6
. .
53.
Rodriguez-Fanjul
J
,
Jordan
I
,
Balaguer
M
,
Batista-Muñoz
A
,
Ramon
M
,
Bobillo-Perez
S
.
Early surfactant replacement guided by lung ultrasound in preterm newborns with RDS: the ULTRASURF randomised controlled trial
.
Eur J Pediatr
.
2020
;
179
(
12
):
1913
20
. .
54.
Aldecoa-Bilbao
V
,
Balcells-Esponera
C
,
Herranz Barbero
A
,
Borràs-Novell
C
,
Izquierdo Renau
M
,
Iriondo Sanz
M
, et al.
Lung ultrasound for early surfactant treatment: development and validation of a predictive model
.
Pediatr Pulmonol
.
2021
;
56
(
2
):
433
41
. .
55.
Badurdeen
S
,
Kamlin
COF
,
Rogerson
SR
,
Kane
SC
,
Polglase
GR
,
Hooper
SB
, et al.
Lung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants
.
Resuscitation
.
2021 Feb 3
[Online ahead of print]. .
56.
De Martino
L
,
Yousef
N
,
Ben-Ammar
R
,
Raimondi
F
,
Shankar-Aguilera
S
,
De Luca
D
.
Lung ultrasound score predicts surfactant need in extremely preterm neonates
.
Pediatrics
.
2018
;
142
(
3
):
e20180463
. .
57.
Raschetti
R
,
Yousef
N
,
Vigo
G
,
Marseglia
G
,
Centorrino
R
,
Ben-Ammar
R
, et al.
Echography-guided surfactant therapy to improve timeliness of surfactant replacement: a quality improvement project
.
J Pediatr
.
2019
;
212
:
137
e1
. .
58.
Rojas
MA
,
Lozano
JM
,
Rojas
MX
,
Laughon
M
,
Bose
CL
,
Rondon
MA
, et al.
Very early surfactant without mandatory ventilation in premature infants treated with early continuous positive airway pressure: a randomized, controlled trial
.
Pediatrics
.
2009
;
123
(
1
):
137
42
. .
59.
Ho
JJ
,
Subramaniam
P
,
Davis
PG
.
Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants
.
Cochrane Database Syst Rev
.
2020
;
10
:
CD002271
. .
60.
Pape
KE
,
Armstrong
DL
,
Fitzhardinge
PM
.
Central nervous system patholgoy associated with mask ventilation in the very low birthweight infant: a new etiology for intracerebellar hemorrhages
.
Pediatrics
.
1976
;
58
(
4
):
473
83
.
61.
Wilkinson
D
,
Andersen
C
,
O’Donnell
CP
,
De Paoli
AG
,
Manley
BJ
.
High flow nasal cannula for respiratory support in preterm infants
.
Cochrane Database Syst Rev
.
2016
;
2
:
CD006405
. .
62.
Nielsen
KR
,
Ellington
LE
,
Gray
AJ
,
Stanberry
LI
,
Smith
LS
,
DiBlasi
RM
.
Effect of high-flow nasal cannula on expiratory pressure and ventilation in infant, pediatric, and adult models
.
Respir Care
.
2018
;
63
(
2
):
147
57
. .
63.
Ejiofor
BD
,
Carroll
RW
,
Bortcosh
W
,
Kacmarek
RM
.
PEEP generated by high-flow nasal cannula in a pediatric model
.
Respir Care
.
2019
;
64
(
10
):
1240
9
. .
64.
Stevens
TP
,
Finer
NN
,
Carlo
WA
,
Szilagyi
PG
,
Phelps
DL
,
Walsh
MC
, et al.
SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT)
.
J Pediatr
.
2014
;
165
:
240
9.e4
.
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