\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{A comparison of the effect of bi-level positive airway pressure and
synchronized intermittent mandatory ventilation in preterm infants with
respiratory distress syndrome}



\author[1]{xin lin}%
\author[1]{changyi yang}%
\affil[1]{Fujian Province Maternal and Child Health Hospital}%


\vspace{-1em}



  
  \date{May 04, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: Bi-level positive airway pressure (BiPAP) and synchronized
intermittent mandatory ventilation (SIMV) can be used to achieve peak
inspiratory pressure and positive end-expiratory pressure to avoid
alveolar collapse and improve oxygenation in preterm infants during the
treatment of respiratory distress syndrome (RDS), and there is an urgent
demand for evaluating the effects and prognoses of these two ventilation
modes. Methods: We conducted a retrospective study on preterm infants ([?]
32 weeks and \textless{} 2500 g) from March 2015 to March 2020 with
BiPAP (n = 63) and SIMV (n = 63). The primary outcomes were successful
treatment and weaning within 72 hours, the demand for a second pulmonary
surfactant supply and the need for a second respiratory support. The
secondary outcome was the incidence of complications. Results: There
were no significant differences (P\textgreater{}0.05) in the primary
outcomes or the incidence of complications (pneumonia, apnoea,
respiratory failure, air leak syndrome, persistence of patent ductus
arteriosus, neonatal sepsis, necrotizing enterocolitis, retinopathy of
prematurity, and intraventricular haemorrhage). There were significant
differences (P\textless{}0.05) in the incidence of pulmonary
haemorrhage, bronchopulmonary dysplasia and IVH ([?] grade II).
Conclusion: Although both BiPAP and SIMV achieved good early treatment
outcomes of RDS in preterm infants, BiPAP support is recommended for
reducing the incidence of pulmonary haemorrhage, bronchopulmonary
dysplasia and IVH ([?] grade II) if infants are tolerant. Attempts should
be made to prevent these complications from happening with the use of
SIMV support if infants are intolerant.%
\end{abstract}%



\sloppy


\textbf{Key Words}

Respiratory Distress Syndrome; Preterm infants; Bi-level positive airway
pressure; Synchronized intermittent mandatory ventilation

\textbf{Introduction}

Respiratory distress syndrome (RDS) remains a significant disease among
preterm infants, especially for infants with a gestational age of no
more than 32 weeks. Although the lung compliance of premature infants
with RDS can be improved after alveolar surfactant replacement
therapy\textsuperscript{1}, most infants need ventilation support to
maintain positive end-expiratory pressure (PEEP) and peak inspiratory
pressure (PIP) in order to avoid alveolar collapse and improve
oxygenation. An inappropriate mode of ventilation support leads to a
higher incidence rate of bronchopulmonary dysplasia (BPD) and chronic
lung diseases\textsuperscript{2}. The pathophysiology of RDS results in
the lungs being difficult to open and easy to collapse. Therefore,
applying PIP and PEEP via either non-invasive support (bi-level positive
airway pressure, BiPAP) or invasive support (synchronized intermittent
mandatory ventilation, SIMV) is effective for recruiting the lungs and
maintaining the functional residual capacity (FRC) and minute
ventilation volume (MVV)\textsuperscript{3,4}. Compared to the
traditional non-invasive support method of continuous positive airway
pressure (CPAP), BiPAP reduces the need for intubation within the first
72 hours of age\textsuperscript{5} and shortens the length of stay in
the hospital\textsuperscript{6}. Because of the difficulty in
maintaining ventilation capacity (VC), carbon dioxide retention and
sputum blockage in the airway easily occur. Compared to BiPAP, SIMV
decreases carbon dioxide retention due to the establishment of
artificial airways via intubation. However, it leads to a longer length
of stay in the hospital and a higher incidence rate of BPD in extremely
preterm infants\textsuperscript{7}.

As an increasing number of neonatologists are choosing non-invasive
support (BiPAP) rather than invasive support (SIMV)\textsuperscript{8},
there is an urgent demand for effective evaluations of treatments
related to these two ventilation modes. We made an effort to determine
the differences in treatment effects and prognoses between these two
ventilation modes by performing retrospective analyses on premature
infants with a gestational age of less than or equal to 32 weeks over
the past 5 years.

\textbf{Methods}

\textbf{Subjects}

We performed a retrospective study on preterm infants with a gestational
age of less than or equal to 32 weeks who were admitted to our neonatal
intensive care unit (NICU) from March 2015 to March 2020 and who were
treated with BiPAP or SIMV without tranquilizers in Fujian Province
Maternal and Child Health Hospital within 6 hours after birth. All
preterm infants were diagnosed with RDS by chest X-ray and clinical
characteristics within 6 hours after birth. The surfactants were
administered at a dose of 100-200 mg/kg (Curosurf, Chiesi, Parma, Italy)
immediately one or more times. The chest X-ray results of preterm
infants with RDS were categorized as grades 1 to 4 according to the
degree of disease. The exclusion criteria were preterm infants with the
following conditions: infants who had respiratory tract malformations,
diaphragmatic hernia, congenital oesophageal atresia, tracheoesophageal
fistula, chromosomal disease or inherited metabolic diseases; and
infants who did not survive eventually or were discharged automatically
within 72 hours after birth. A total of 224 preterm infants ([?] 32 weeks
and \textless{} 2500 g) were previously included in the study. However,
for various reasons, 98 infants were eventually excluded (15 of
respiratory tract malformations, 18 of diaphragmatic Hernia, 12 of
esophageal fistula, 11 of chromosomal or inherited metabolic diseases,
and 42 of not survival or discharged automatically \textless{} 72 h).

\textbf{Ventilator parameters}

A total of 126 preterm infants were divided into two groups: a BiPAP
group and a SIMV group. BiPAP support was delivered using the
infant-driver device (Infant Flow System, CareFusion Corp, Palm Springs,
California, USA). To maintain an oxygen saturation
(SaO\textsubscript{2}) of 89-93\%, the initial ventilator parameters
were as follows: positive end-expiratory pressure and peak inspiratory
pressure of 3-6 and 6-8 cmH\textsubscript{2}O, a fraction of inspired
oxygen (FiO\textsubscript{2}) of 0.21-0.60, an inspiratory time (Ti) of
0.30-0.50 seconds and a respiratory rate (RR) of 20-40 movements per
minute (mpm). Weaning was started with a progressive reduction of the
respiratory rate to 20 mpm with a set fraction of inspired oxygen ([?]
0.25) and SaO\textsubscript{2} of 89-93\%, followed by a reduction in
the positive end-expiratory pressure down to 3 cmH\textsubscript{2}O and
a reduction in the peak inspiratory pressure down to 6
cmH\textsubscript{2}O. SIMV support was delivered using the intubation
ventilator device (SLE5000 System, SLE Corp, South Croydon Surrey CR2
6PL, UK). To maintain an SaO\textsubscript{2} of 89-93\%, the initial
ventilator parameters were PEEP and PIP values of 3-7 and 16-25
cmH\textsubscript{2}O, an FiO\textsubscript{2} of 0.25-1.00, a Ti of
0.30-0.50 s and an RR of 30-45 mpm. Weaning from SIMV was performed when
patients tolerated a reduction in RR to 30 mpm with a progressive
reduction of the set FiO\textsubscript{2} [?] 0.40 and
SaO\textsubscript{2} of 89-93\%, followed by a reduction in the positive
end-expiratory pressure down to 3 cmH\textsubscript{2}O and a reduction
in the peak inspiratory pressure down to 15 cmH\textsubscript{2}O.
Successful treatments were defined as follows: a. the symptoms of
dyspnoea in infants were significantly improved; b. the results of chest
X-ray re-examination indicated an improvement in lung transparency or
returned to normal within 24 hours; c. compared to the initial results
of the arterial partial pressure of oxygen
(PaO\textsubscript{2})/FiO\textsubscript{2}, the final results were
higher and more than 250 at 72 hours after birth; d. blood gas analysis
indicated no carbon dioxide retention, hypoxemia, or acid-base balance
disorders; e. after respiratory support for 72 hours, the ventilator
parameters were decreased, or infants were weaned with the saturation
maintained at 89-93\%. However, during the entire treatment, when there
was a progressive increase in breathing rates and an occurrence of
complications (e.g., severe pulmonary haemorrhage, severe pneumonia,
severe sepsis, and repeated apnoea), and when the current ventilator
parameters were unable to maintain a saturation of 89-93\%, we adjusted
to a ventilation mode of high frequency oscillatory ventilation (HFOV).

The perinatal characteristics of the infants were recorded: gestational
age (GA) and birth weight (BW), small for gestational age (SGA), sex,
amniotic fluid traits, mode of delivery, multiple pregnancies, grade of
chest X-ray, occurrence of premature rupture of membranes and severe
asphyxia, use of dexamethasone (DXM) before delivery, arterial partial
pressure of carbon dioxide (PCO\textsubscript{2}) and
SaO\textsubscript{2} in the beginning, and main maternal pregnancy
diseases, including placental abruption, gestational diabetes mellitus
(GDM), intrauterine infection (IAI), and hypertension during pregnancy.
Intrauterine infection was defined as cervical or palace cavity
secretions tested positive, mother fever (axillary temperature [?]
37.3-degree Celsius) or increased in C-reactive protein and white blood
cell count ([?] 1.5*10\textsuperscript{9}/L) during pregnancy. Other time
variables were recorded for each infant, including the hours of oxygen
use and the days of stay in the hospital. Preterm infants were monitored
by using oxygen saturation monitoring (BeneVision N12 Neo, Mindray Corp,
Guangdong Province, China). The following ventilator parameters were
recorded for each infant: FiO\textsubscript{2}, RR, PEEP, PIP, and Ti.
The primary outcomes were successful treatment and weaning within 72
hours, the demand for a second pulmonary surfactant (PS) supply and the
need for a second respiratory support. The secondary outcome was the
incidence of complications: pneumonia, apnoea, respiratory failure, air
leak syndrome, pulmonary haemorrhage, BPD, persistence of patent ductus
arteriosus (PDA), neonatal sepsis, necrotizing enterocolitis (NEC),
retinopathy of prematurity (ROP), and intraventricular haemorrhage
(IVH).

\textbf{Statistical analysis}

The statistical analyses were performed using SPSS Statistics version
26.0 (IBM Corp, Armonk, NY, USA). The clinical characteristics of the
infants are expressed as the mean \selectlanguage{ngerman}± SD (standard deviation). In analyses
of continuous data, if fit to a normal distribution, the variables were
analysed by t-tests; if not, they were analysed by the Wilcoxon test.
Chi-square tests or Fisher's exact tests were used in the analyses of
categorical variables as appropriate. Results with P\textless{}0.05 were
considered statistically significant.

All patients were contacted by telephone to obtain verbal informed
consent.

\textbf{Results}

In the BiPAP group, the mean gestational age was 29.5 ± 1.3 weeks, and
the mean birth weight was 1357.3 ± 263.8 g. In the SIMV group, the mean
gestational age was 29.1 ± 2.0 weeks, and the mean birth weight was 1299
± 337.3 g. The perinatal characteristics of the infants (\selectlanguage{english}[?] 32 weeks and
\textless{} 2500 g) in the two groups are reported in Table 1, and there
were no significant differences (P\textgreater{}0.05) for all variables.
The initial PCO\textsubscript{2} values in the SIMV group and the BiPAP
group were not different (P=0.124), and after 72 hours of ventilation
support, the final PCO\textsubscript{2} values were similar (44.76 +- 8
vs 43.38 +- 8) (P=0.224). As shown in Table 2, we found that the hours of
oxygen use and the number of days of stay in the hospital in the SIMV
group were longer than those in the BiPAP group. There was much more
oxidative damage in the preterm infants from the SIMV group during the
treatment of RDS, which resulted in detriments to the functions of some
important organs, such as the eyes and lungs.

The primary outcome characteristics are shown in Table 3. There were no
significant differences (P\textgreater{}0.05) in the primary outcomes,
including successful treatment and weaning within 72 hours, the demand
for a second pulmonary surfactant (PS) supply and the need for a second
ventilation support in either group. Although the rates of successful
treatment of RDS in the two groups were approximately equal, the number
of infants weaned within 72 hours in the BiPAP group was higher than
that in the SIMV group (5 vs 1), and the number of infants who demanded
a second PS supply (3 vs 9) and further respiratory support (23 vs 29)
were lower than those in the SIMV group. The secondary outcome
characteristics are also shown in Table 3. No significant differences
(P\textgreater{}0.05) in the incidence of complications were observed:
pneumonia, apnoea, respiratory failure, air leak syndrome, persistence
of PDA, neonatal sepsis, NEC, ROP or IVH. Through further analysis of
the incidence of ROP, the morbidity of ROP (\selectlanguage{english}[?] stage II) in the SIMV
group was higher than that in the BiPAP group (80.0\% vs 50.0\%).
Moreover, through further analysis of the incidence of IVH, the
morbidity of IVH (\selectlanguage{english}[?] grade II) in the SIMV group was higher than that in
the BiPAP group (26.1\% vs 5.6\%).The incidences of pulmonary
haemorrhage and BPD were lower in preterm infants in the BiPAP group
than in the SIMV group (P\textless{}0.05). No infants in the BiPAP group
had pulmonary haemorrhage.

\textbf{Discussion}

Previous studies have reported the effects of some modes of ventilation
in the treatment of RDS in prematurity, such as BiPAP vs nasal
synchronized intermittent positive pressure ventilation
(NSIPPV)\textsuperscript{9}; nasal bi-level PAP (N-BiPAP) vs sigh-PAP
(n-SiPAP) \textsuperscript{10}; and nasal intermittent positive pressure
ventilation (NIPPV) vs nasal continuous positive airway pressure
(NCPAP)\textsuperscript{11}. This is the first report to compare
normal-frequency-assisted ventilation for preterm infants (\selectlanguage{english}[?] 32 weeks
and \textless{} 2500 g) followed by RDS between invasive ventilation
with SIMV and non-invasive ventilation with BiPAP. Although SIMV can
reduce the mean arterial pressure, improve oxygenation, coordinate
spontaneous breathing with ventilators, and exercise the function of
respiratory muscles, it requires intubation, and the long-term
establishment of artificial airways increases the incidence rate of
ventilator-associated pneumonia (VAP)\textsuperscript{12}. The
intubation procedure in SIMV support is extremely distressing, causing
an increase in the pro-inflammatory cytokines implicated in pain
responses\textsuperscript{13}. In contrast, the avoidance of airway
intubation in BiPAP support is associated with a reduction in the
incidence of chronic lung disease among preterm infants with respiratory
distress syndrome\textsuperscript{3}.

European consensus guidelines on the management of RDS in
2019\textsuperscript{1} mentioned that if intubated, babies can often be
extubated to CPAP (BiPAP), HFNC or NIPPV immediately following
surfactant, and judgement needs to be made if an individual baby will
tolerate this. However, if infants are intolerant, invasive ventilation
is requisite. The successful treatment rate of RDS was highly supported
by either BiPAP or SIMV (60.3\% vs 54.0\%) within 72 hours after birth
in our study (Table 3). Not only were the hours of oxygen use and the
number of days of stay in the hospital longer, but the incidence of BPD
was also higher in the SIMV group than in the BiPAP group (Tables 2 and
3). Long-term oxidative stress is more likely to damage lung tissues and
cause BPD\textsuperscript{14}. Exposure to high concentrations of oxygen
resulted in significant damage to the developing lung. It has been
demonstrated that even a period of two hours under invasive mechanical
ventilation associated with higher oxygen levels may lead to lung
inflammation\textsuperscript{15}. Therefore, during the treatments of
RDS, the lower oxygen concentrations (30--60\%) were used to protect the
developing lung, and we maintained the SaO\textsubscript{2} around
89-93\%. Oxidative stress can result in ROP because of the
susceptibility of the phospholipid-rich retina to reactive oxygen
species that can be generated in high or low oxygen\textsuperscript{16}.
Only less than a quarter of infants had ROP in both groups (22.2\% of
BiPAP vs 23.8\% of SIMV), and the incidence was not significantly
different in our retrospective analysis (Table 3). Although we could not
confirm whether BiPAP or SIMV had a relationship with ROP, more
instances of ROP (\selectlanguage{english}[?] stage II) occurred in preterm infants in the SIMV
group. Further prospective clinical research needs to be done in preterm
infants with RDS. In extremely low-birth-weight infants, Munro et
al.\textsuperscript{17} found that cerebral blood flow (CBF) was
autoregulated above (and pressure-passive below) a breakpoint that
averages approximately 30 mmHg, and lower CBF was related to
IVH\textsuperscript{18}. With different ventilation approaches, the
median CBF in the SIMV group was 14.44 (2.70--32.10) and that in the
CPAP group was 31.69 (13.59--34.93) for preterm
infants\textsuperscript{19}. A network
meta-analysis\textsuperscript{20}found that SIMV (OR=8.22, 95\%, CI:
1.25-29.44, P\textless{}0.05) schemes seemed to have increased the risk
of IVH in preterm infants with RDS. We also found that the morbidity of
IVH (\selectlanguage{english}[?] grade II) in the SIMV group was higher than that in the BiPAP
group. An article\textsuperscript{21} mentioned that the complication
rate of pulmonary haemorrhage was 2.5\% with mechanical ventilation. If
the pressure associated with ventilation is too high, the incidence of
pulmonary haemorrhage can be significantly increased. In our study, we
found that the required initial levels of PIP in the SIMV group were
significantly higher than those in the BiPAP group (19.1 +- 1.8 vs 6.8 +-
0.5, P\textless{}0.05), which might be one of the reasons for an
increased risk of pulmonary haemorrhage. After receiving haemostatic
drugs and assisted ventilation with HFOV, all preterm infants with
pulmonary haemorrhage in the SIMV group survived and were eventually
successfully weaned.

The triggering of BiPAP is initiated by the patient's spontaneous
breathing using a pressure or flow rate trigger mechanism, and good
man-machine cooperation can provide adequate ventilation support and
reduce the work of breathing. The mode of BiPAP support might be an
advantage to spontaneously breathing patients and reduced early
extubation failure in very preterm neonates with RDS within seven\selectlanguage{english} days
from extubation\textsuperscript{22}. It is a way of using a single
airway with low resistance to reduce the length of stay in the
NICU\textsuperscript{23} and weaning as soon as possible. We found that
7.9\% of preterm infants were successfully weaned in the BiPAP group,
and only 1.6\% of preterm infants were successfully weaned in the SIMV
group within 72 hours (Table 2). No establishment of an artificial
airway in BiPAP support avoids the harms associated with normal feeding
and swallowing and retains the functions of heating, humidification and
filtering in the upper airway. In accordance with SIMV, BiPAP provides a
constant PEEP and PIP to infants assisted with ventilation each time,
which can ensure that the airway pressure is constant at the pre-set
level and avoid volume injuries. In our study, the incidence rates of
air leakage syndrome were at a low level, only 4.8\% in the BiPAP group
and 1.6\% in the SIMV group (Table 2). Because of the insufficient peak
inspiratory pressure of BiPAP, it is difficult for infants with severe
RDS to release carbon dioxide while the airway resistance is high, and
the alveolar compliance is probably poor. SIMV provides a relatively
higher peak inspiratory pressure during ventilation, and the
establishment of an artificial airway can also ensure the patency of the
main trachea, which is more beneficial to the release of carbon dioxide.
In our retrospective study, we found that the clearance of carbon
dioxide in the BiPAP group was not worse than that in the SIMV group
after 72 hours of respiratory support (P\textgreater{}0.05). An article
reported\textsuperscript{24} that infants with RDS in the BiPAP group
had better clearance of carbon dioxide and lower FiO2 requirements than
other types of NIV, such as CPAP.

The comparison between BiPAP and SIMV in RDS was the first to involve
preterm infants (\selectlanguage{english}[?] 32 weeks and \textless{} 2500 g) with similar
characteristics over a period of five years. By combining the results of
this study, the advantages and disadvantages of the two different
ventilation supports were elaborated, which might be useful for helping
neonatologists choose appropriate ventilation support during the
treatment of RDS in preterm infants (\selectlanguage{english}[?] 32 weeks and \textless{} 2500 g).
We retrospectively enumerated the complications that were likely to
result from SIMV support compared with BiPAP support during the
treatment of RDS (e.g., BPD, pulmonary haemorrhage, IVH \selectlanguage{english}[?] grade II),
which might help to prevent these complications from occurring in the
future.

Because of the strictly selected inclusion criteria for preterm infants,
only 126 of them were included in the study. Further prospective
research should be done to confirm these results. Additionally, the
long-term follow-up and comparison of outcomes of infants in the SIMV
and BiPAP groups throughout childhood is necessary, and we will track
these data continuously. Because multiple confounding factors existed,
we were unable to analyse the relationship between ventilator-associated
pneumonia and two different ventilation supports in the treatment of
RDS. Therefore, it is necessary to carry out further prospective
studies.

\textbf{Conclusion}

Both BiPAP and SIMV achieved good early treatment of RDS in preterm
infants. Although the incidence of some complications, including
pneumonia, apnoea, respiratory failure, air leak syndrome, the
persistence of PDA, neonatal sepsis, NEC, ROP and IVH caused by the two
ventilation supports were not significantly different, there was a
higher incidence rate of complications, including BPD, pulmonary
haemorrhage, and IVH \selectlanguage{english}[?] grade II, in the SIMV group. To reduce the
occurrence of these complications, BiPAP support is recommended if
infants are tolerant. We retrospectively enumerated the complications
that were likely to result from SIMV support during the treatment of RDS
and aimed to prevent these complications from happening with the use of
SIMV support if infants are intolerant in the future.

\textbf{Acknowledgement:}

The authors want to thank the hospital Head of the Neonatal Department,
Fujian Province Maternal and Child Health Hospital for their permission
and also the nurses and medical officers who were working during the
study period in the NICU Fujian Province Maternal and Child Health
Hospital for their support. This study was carried out without grant.

\textbf{Conflict of Interests:}

The authors declare that they have no conflict of interest.

\textbf{Reference}

1. Sweet DG, Carnielli V, Greisen G, et al. European Consensus
Guidelines on the Management of Respiratory Distress Syndrome - 2019
Update.~Neonatology. 2019;115 (4):432-450.

2. Sun Y, Zhang H. Ventilation strategies in transition from neonatal
respiratory distress to chronic lung disease. Semin Fetal Neonatal Med.
2019;24(5):101035.

3. Alexiou S, Panitch HB. Physiology of non-invasive respiratory
support. Semin Fetal Neonatal Med. 2016;21(3):174-180.

4. Unal S, Ergenekon E, Aktas S, et al. Effects of Volume Guaranteed
Ventilation Combined with Two Different Modes in Preterm Infants. Respir
Care. 2017;62(1 2):1525-1532.

5. Rong ZH, Li WB, Liu W, et al. Nasal bi-level positive airway pressure
(BiPAP) versus nasal continuous positive airway pressure (CPAP) in
preterm infants \selectlanguage{english}[?]32\selectlanguage{english} weeks: A retrospective cohort study. J Paediatr
Child Health. 2016;52(5):493-498.

6. Lista G, Castoldi F, Fontana P, et al. Nasal continuous positive
airway pressure (CPAP) versus bi-level nasal CPAP in preterm babies with
respiratory distress syndrome: a randomised control trial.~Arch Dis
Child Fetal Neonatal Ed. 2010;95(2): F85-F89.

7. Abreu-Pereira S, Pinto-Lopes R, Flor-de-Lima F, Rocha G, Guimaraes H.
Ventilatory practices in extremely low birth weight infants in a level
III neonatal intensive care unit. Pulmonology. 2018;24(6):337-344.

8. Owen LS, Manley BJ, Davis PG, Doyle LW. The evolution of modern
respiratory care for preterm infants. Lancet. 2017;389(10079):1649-1659.

9. Salvo V, Lista G, Lupo E, et al. Noninvasive ventilation strategies
for early treatment of RDS in preterm infants: an RCT. Pediatrics.
2015;135(3):444-451.

10. Sadeghnia A, Danaei N, Barkatein B. A Comparison of the Effect of
Nasal bi-level Positive Airway Pressure and Sigh-positive Airway
Pressure on the Treatment of the Preterm Newborns Weighing Less than
1500 g Affiliated with Respiratory Distress Syndrome. Int J Prev Med.
2016; 7:21. Published 2016 Jan 13.

11. 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(12):CD005384.

12. Lee PL, Lee WT, Chen HL. Ventilator-Associated Pneumonia in Low
Birth Weight Neonates at a Neonatal Intensive Care Unit: A Retrospective
Observational Study. Pediatr Neonatol. 2017;58(1):16-21.

13. Gitto E, Aversa S, Salpietro CD, et al. Pain in neonatal intensive
care: role of melatonin as an analgesic antioxidant. J Pineal Res.
2012;52(3):291-295.

14. Marseglia L, D'Angelo G, Granese R, et al. Role of oxidative stress
in neonatal respiratory distress syndrome. Free Radic Biol Med. 2019;
142:132-137.

15. Carvalho CG, Procianoy RS, Neto EC, Silveira RC. Preterm Neonates
with Respiratory Distress Syndrome: Ventilator-Induced Lung Injury and
Oxidative Stress. J Immunol Res. 2018; 2018:6963754.

16.Hartnett ME. Pathophysiology and mechanisms of severe retinopathy of
prematurity. Ophthalmology. 2015;122(1):200-210.

17. Munro MJ, Walker AM, Barfield CP. Hypotensive extremely low birth
weight infants have reduced cerebral blood flow {[}published correction
appears in Pediatrics. 2005 Jun;115(6):1794-5{]}. Pediatrics.
2004;114(6):1591-1596.

18. Watkins AM, West CR, Cooke RW. Blood pressure and cerebral
haemorrhage and ischaemia in very low birthweight infants. Early Hum
Dev. 1989;19(2):103-110.

19. Milan A, Freato F, Vanzo V, Chiandetti L, Zaramella P. Influence of
ventilation mode on neonatal cerebral blood flow and volume. Early Hum
Dev. 2009;85(7):415-419.

20. Wu, J; Wen, ZH; Liu, DD; et al. Safety evaluation on different
ventilation strategies set for neonatal respiratory distress syndrome: a
network Meta-analysis. Zhonghua Liu Xing Bing Xue Za
Zhi.2020,41(2):249-260

21. Torres-Castro C, Valle-Leal J, Martinez-Limon AJ, Lastra-Jimenez Z,
Delgado-Bojorquez LC. Complicaciones pulmonares asociadas a ventilacion
mecanica en el paciente neonatal {[}Pulmonary complications associated
with mechanical ventilation in neonates{]}. Bol Med Hosp Infant Mex.
2016;73(5):318-324.

22. Capasso L, Borrelli AC, Cerullo J, et al. Reducing post-extubation
failure rates in very preterm infants: is BiPAP better than CPAP?
{[}published online ahead of print, 2020 Apr 7{]}. J Matern Fetal
Neonatal Med. 2020;1-6.

23. Solevag AL, Kann IC. N-BiPAP treatment in infants with respiratory
distress syndrome: A population study. Early Hum Dev.
2015;91(10):577-581.

24. Cimino C, Saporito MAN, Vitaliti G, et al. N-BiPAP vs n-CPAP in term
neonate with respiratory distress syndrome. Early Hum Dev. 2020;
142:104965.

\textbf{Hosted file}

\verb`Table1.docx`  available at \url{https://authorea.com/users/352158/articles/476517-a-comparison-of-the-effect-of-bi-level-positive-airway-pressure-and-synchronized-intermittent-mandatory-ventilation-in-preterm-infants-with-respiratory-distress-syndrome}

\selectlanguage{english}
\FloatBarrier
\end{document}

