Original Research

Journal of Intensive Care Medicine

1-9
Mortality in Pediatric Acute Respiratory ª The Author(s) 2017
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Distress Syndrome: A Systematic Review DOI: 10.1177/0885066617705109
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and Meta-Analysis

Judith Ju-Ming Wong, MBBCh, BAO, MRCPCH1,2, Mark Jit, BSc, PhD, MPH3,4,
Rehena Sultana, MSc5, Yee Hui Mok, MBBS, MRCPCH2,6,
Joo Guan Yeo, MBBS, MRCPCH2,6, Jia Wen Janine Cynthia Koh, GCE A-Levels7,
Tsee Foong Loh, MBBS, MRCPCH2,6, and Jan Hau Lee, MBBS, MRCPCH, MCI2,6

Abstract
Objective: Sparse and conflicting evidence exists regarding mortality risk from pediatric acute respiratory distress syndrome
(ARDS). We aimed to determine the pooled mortality in pediatric ARDS and to describe its trend over time.
Data Sources and Study Selection: MEDLINE, EMBASE, and Web of Science were searched from 1960 to August 2015.
Keywords or medical subject headings (MESH) terms used included “respiratory distress syndrome, adult,” “acute lung injury,” “acute
respiratory insufficiency,” “acute hypoxemic respiratory failure,” “pediatrics,” and “child.” Study inclusion criteria were (1) pediatric
patients aged 0 days to 18 years, (2) sufficient baseline data described in the pediatric ARDS group, and (3) mortality data. Randomized
controlled trials (RCTs) and prospective observational studies were eligible. Data Extraction and Synthesis: Data on study
characteristics, patient demographics, measures of oxygenation, and mortality were extracted using a standard data extraction
form. Independent authors conducted the search, applied the selection criteria, and extracted the data. Methodological quality of
studies was assessed. Meta-analysis using a random-effects model was performed to obtain pooled estimates of mortality. Meta-
regression was performed to analyze variables contributing to change in mortality over time. Eight RCTs and 21 observational studies
(n ¼ 2274 patients) were included. Pooled mortality rate was 24% (95% confidence interval [CI]: 19-31). There was a decrease in
mortality rates over 3 epochs (2000, 2001-2009, and 2010: 40% [95% CI: 24-59], 35% [95% CI: 21-51], and 18% [95% CI: 12-26],
respectively, P < .001). Observational studies reported a higher mortality rate than RCTs (27% [95% CI: 24-29] versus 16% [95% CI: 12-
20], P < .001). Earlier year of publication was an independent factor associated with mortality. Conclusion: Overall mortality rate in
pediatric ARDS is approximately 24%. Studies conducted and published later were associated with better survival.

Keywords
systematic review, meta-analysis, acute respiratory distress syndrome, acute lung injury, mortality, pediatric

1
Department of Pediatrics, KK Women’s and Children’s Hospital, Singapore,
Introduction Singapore
2
Duke-NUS Medical School, Singapore, Singapore
Traditionally, acute respiratory distress syndrome (ARDS) in 3
Department of Infectious Disease Epidemiology, London School of Hygiene &
children is diagnosed using the American-European Consensus Tropical Medicine, London, United Kingdom
4
Conference (AECC) criteria.1 More recently, the Berlin and the Modelling and Economics Unit, Public Health England, London, United
Kingdom
Pediatric Acute Lung Injury Consensus Conference (PALICC) 5
Centre for Quantitative Medicine, Duke-NUS Medical School, The Academia,
definitions have been proposed.2,3 Studies on pediatric ARDS Singapore, Singapore
report an incidence of approximately 1% to 4% of all pediatric 6
Children’s Intensive Care Unit, Department of Pediatric Subspecialties, KK
intensive care unit (PICU) admissions.4-6 Compared to those Women’s and Children’s Hospital, Singapore, Singapore
7
without lung injury, critically ill children with ARDS have Yong Loo Lin School of Medicine, National University of Singapore, Singa-
pore, Singapore
significantly increased morbidity and mortality.7 Short-term
consequences include increased duration of mechanical venti- Received December 10, 2016. Received revised March 7, 2017. Accepted
lation, PICU, and hospital stay.8 Long-term consequences for publication March 27, 2017.
include diminished lung function and exercise tolerance,
Corresponding Author:
reduced quality of life, and diminished neurocognitive func- Judith Ju-Ming Wong, Department of Pediatrics, KK Women’s and Children’s
tion.9-11 These patients also incur a significant financial burden Hospital, 100 Bukit Timah Road, 229899 Singapore, Singapore.
due to hospitalization costs and pediatric intensive care Email: judith.wjm@gmail.com
2 Journal of Intensive Care Medicine XX(X)
therapies.12 Moreover, mortality in pediatric ARDS is high,
with previous estimates varying widely between 22% and
65%.6,13,14
Conflicting data exist regarding the mortality trend of pedia-
tric ARDS over time.14-17 A recent systematic review and
meta-analysis in pediatric ARDS reported a pooled mortality
of 33.7%.17 In contrast to adult data, this systematic review did
not demonstrate declining mortality rate in children with
ARDS over time.18 In addition, this pediatric systematic review
found that geographical location had an impact on mortality of
children with ARDS. This systematic review was performed
using a search strategy that included retrospective study
designs. Because previous investigators have demonstrated that
data from randomized controlled trials (RCTs) usually report
lower mortality due to stringent selection criteria, we postulate
that the choice of included study designs is an important influ-
ence on the mortality outcome.18
In view of limitations in existing medical literature, we
conducted a systematic review using a comprehensive search
strategy and performed a meta-analysis to (1) determine the
current overall mortality of ARDS in critically ill children,
(2) evaluate whether mortality has changed over time, and
(3) determine whether study design was independently associ-
ated with mortality.
Materials and Methods
This systematic review and meta-analysis was conducted in
close accordance with the Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analyses guidelines.19 We identi-
fied the Patient, Intervention, Control, Outcome, Study design
as critically ill children with ARDS, with the primary outcome
of interest being mortality. With the help of an experienced
librarian, the search strategy was developed using the appro-
priate keywords and MESH terms. MESH terms used include
“respiratory distress syndrome, adult,” “acute lung injury,”
“acute respiratory insufficiency,” “acute hypoxemic respira-
tory failure,” “pediatrics,” “child,” “infant,” and “adolescent.”
We did not use “mortality” as a search term because many
studies that report clinical outcomes were not indexed with
“mortality” as a keyword or MESH term. A complete descrip-
tion of the search strategy for PubMed/MEDLINE is outlined
in Supplemental Appendix 1. Language was not restricted.
Studies up to August 15, 2015, were included.
Two authors (J.J-M.W., J.H.L.) independently carried out an
online search in MEDLINE, EMBASE, and Web of Science
using the predetermined keywords and MESH terms from 1960
to August 2015. The authors screened potential studies by
examining the title and abstract. The full-text articles of the
shortlisted studies were then assessed for eligibility and data
extracted independently. Reference lists of obtained articles
and relevant review articles were also hand searched. We con-
tacted authors of non-English publications and publications
with insufficient baseline data to obtain missing data that were
not reported. A standardized data collection form was used to
extract the following data by 3 authors (J.J-M.W., J.C.J.K.,
J.H.L.): definition used, demographics, baseline measures of
oxygenation, ventilator settings, and mortality. We adapted the
data collection form from one that was previously utilized in a
prior systematic review performed in adult ARDS.18 Disagree-
ments were resolved by consensus.
A priori, we defined eligible studies to be those that meet
the following criteria: (1) pediatric patients aged 0 days to
18 years, (2) sufficient baseline data described in the ARDS
group, and (3) survival data in the ARDS group. Any definition
of ARDS was accepted as long as the label of ARDS was used.
We deemed a study to have “sufficient baseline data” if age,
severity scores, oxygenation measures (eg, partial pressure of
arterial oxygen:fraction of inspired oxygen ratio [P/F ratio] and
oxygenation index [OI]), and risk factors for ARDS were
reported. We included all RCTs and prospective observational
studies. Studies involving adults, specific pediatric populations
(eg, bronchiolitis), post hoc analysis of another existing RCT
(if there were no duplicate data), database/registry studies, and
studies that involved a retrospective arm and a prospective arm
were included if they fulfilled the previously mentioned inclu-
sion criteria. Studies involving neonatal/perinatal respiratory
distress, prematurity, retrospective studies, abstracts, studies
with less than 20 patients, and studies on follow-up of ARDS
survivors were excluded. The primary outcome was the pro-
portion of death among patients with ARDS. For primary out-
come, we also planned subgroup analysis a priori: year of
publication and study design.
Methodological quality of RCTs was assessed using the
Cochrane Collaboration’s tool for assessing risk of bias.20 The
quality of observational studies was assessed using the RTI
item bank that addresses the risk of bias, confounding, and
precision at the study level.21
Statistical Analysis
We performed a meta-analysis using random-effects model to
obtain DerSimonian-Laird pooled estimates of mortality and
associated exact binomial 95% confidence intervals (95% CIs).
When pooling the estimates of mortality, we excluded the treat-
ment arm of the RCTs because all randomized treatments were
not standard of care.18 A continuity correction of 0.5 was added
to zero counts. The I2 statistics was used to quantify hetero-
geneity across studies, and an I2 statistics of 50% or more
indicates a considerable amount of heterogeneity. Separate
pooled estimates were then obtained for studies classified
according to (1) year of publication (2000, 2001-2009,
2010) and (2) study design (observational vs RCT). We also
obtained a cumulative forest plot–based year of publication.
The simultaneous effect of both variables was explored using
a random-effects logistic meta-regression. Univariate and mul-
tivariate random-effects meta-regressions were performed to
assess for other potential covariates that could predict the het-
erogeneity and summarized as odd ratio (OR) with correspond-
ing 95% CI. The included covariates were year of publication,
study design, and geographical location. Using the PF ratio as a
marker of severity of lung disease, we also conducted a
Wong et al
Figure 1. Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) flowchart of the number of studies in each
stage of search.
stratified analysis to assess the effect of time on studies with
mean/median PF ratio 100 and >100.
Bubble plots were performed based on year of publication
stratified by study design. Bubble sizes in those plots were
proportional to the total patient recruited in the study. Linear
regression lines were fit to estimate the mortality rate over the
year of publication stratified by study design and geographical
location separately. We performed sensitivity analyses exclud-
ing smaller studies with <50 patients. Statistical analysis was
performed using Statistical Analysis System (SAS version 9.3;
SAS Institute, Cary, North Carolina) and Comprehensive
Meta-Analysis software (version 3). A P value of <.05 was
considered to indicate statistical significance.
Results
The search from the 3 major databases yielded a total of 4026
studies and 1 more was found from hand searching reference
lists. Twenty-nine studies were finally included (Figure 1).
Excluded studies with reasons were summarized in Supple-
mental Table 1. There were 8 RCTs and 21 observational stud-
ies with a total number of 2274 patients with ARDS.
Four RCTs included in this systematic review studied the
efficacy of surfactant and 1 RCT each studied the efficacy of
prone positioning, inhaled nitric oxide, immunomodulatory
feeds, and a lung recruitment maneuver, respectively
(Table 1).22-29 There were 2 RCTs that studied the same patient
cohort. One study reported the use of bovine surfactant (cal-
factant) and the other reported the impact of fluid balance on
outcomes; we have included only the former in this meta-
analysis due to overlapping patient population.26,30
There were 21 observational studies (Supplemental Table 2).
There was 1 non-randomized controlled study, 1 population-
based study, 12 cohort studies, and 7 descriptive studies on
ARDS.8,13,14,16,31-46 Four studies included only specific popu-
lations: postcardiopulmonary bypass, infants with human
3
immunodeficiency virus exposure, patients with ARDS who
had the complication of pulmonary barotrauma, and children
with immunosuppression.28,35,40,47 Of note, 1 study utilized
very high tidal volumes (22 + 8 mL/kg) and ventilator pres-
sures (peak inspiratory pressures up to 73 + 15 cm water and
positive end-expiratory pressures 14 + 4 cm water).34
Most studies (24 [83%] of 29) used the AECC definition for
ARDS (Table 1 and Supplemental eTable2). The remaining
(5 [17%] of 29) used the following to define ARDS: the
description of “diffuse alveolar disease with hypoxemia,” lung
injury score >2.5, and OI >12; 2 studies did not provide any
specific definition except the label of acute lung injury (ALI)/
ARDS.27-29,34,41 The degree of hypoxemia as described by the
P/F ratio and OI across studies was mostly in the moderate to
severe category.
All included RCTs had moderate to low risk of bias (Sup-
plemental Digital Content, eTable 3). Two studies did not state
clear primary and secondary outcome measures.28,29 In addi-
tion, these 2 studies used no specific definition except the label
of ALI. Three studies were stopped early. Two RCTs studying
the role of surfactant in pediatric ARDS was stopped early due
to slow patient recruitment.22,23 One RCT studying prone posi-
tioning was stopped early due to futility.24 Only 1 RCT was
powered to detect a statistically significant outcome.25
Included observational studies had a moderate to high risk of
bias (Supplemental Digital Content, eTable 4). Only 2 studies
reported both standard ventilation and weaning strategies.45,48
Nine studies carried out some form of stratification or multi-
variate analysis.8,12-14,35,37-39,47 Follow-up was complete or near
complete in most studies except in Yapicioğlu et al, which cen-
sored data after 14 days.42 Two studies by Kong et al were not
explicit in the duration of follow-up and the type of
mortality.36,37
Mortality in Pediatric ARDS
Overall pooled mortality including the control arm of RCTs
and all observational studies was 24% (95% CI: 19-31; Figure
2). Mortality reported in observational studies was higher than
in RCTs (27% [95% CI: 24-29] vs 16% [12-20], P < .001).
Mortality in studies published in years 2000, 2001 to 2009,
and 2010 onward showed stepwise improvement: 40% (95%
CI: 24-59), 35% (95% CI: 21-51), and 18% (95% CI: 12-26);
P < .001, respectively (Figure 3).
In the multivariate meta-regression model, a later year of
study was significantly associated with survival (adjusted odds
ratio [OR]: 0.94; 95% CI: 0.94-0.95; P < .001). When stratified
according to the type of study design, a later year of study for
RCTs (OR: 0.88; 95% CI: 0.86-0.91; P < .001) and observa-
tional studies (OR: 0.95; 95% CI: 0.94-0.95; P < .001) were
still significantly associated with survival (Figure 4). Com-
pared to RCT, observational study design itself was not asso-
ciated with increased mortality (adjusted OR: 0.91; 95% CI:
0.83-1.01; P ¼ .062). There were insufficient randomized stud-
ies conducted in each continent to include geographical loca-
tion into the meta-regression. Instead, a summary of studies
4 Journal of Intensive Care Medicine XX(X)

Table 1. Characteristics of Included Randomized Controlled Trials.

Study Definition of ARDS Risk Factors Intervention Control Primary Outcome

Moller et al22 AECC Mixed Bovine surfactant (Alveofact; Standard of care (n ¼ 16) P/F ratio at 48 hours
n ¼ 22) Mean P/F ratio: (reported 30-day
Mean P/F ratio: 71.3 + 13.7 64.3 + 16.2 mortality)
Willson et al23 AECC Predominantly Bovine surfactant Air placebo (n ¼ 75) 28 VFD (reported
pulmonary (Calfactant; n ¼ 77) Mean P/F ratio: hospital mortality)
Mean P/F ratio: 128 + 54 126 + 73
Mean OI: 20.0 + 12.9 Mean OI: 20.5 + 14.7
Curley et al24 AECC Predominantly Prone nursing (n ¼ 51) Supine nursing (n ¼ 51) 28 VFD (reported
pulmonary Mean P/F ratio: 153 + 65 Mean P/F ratio: hospital mortality)
Mean OI: 18 + 18 147 + 60
Mean OI: 15 + 12
Cui et al28 No specific Cardiopulmonary Lung recruitment maneuver Standard of care (n ¼ 32) Unclear
definition except bypass only (n ¼ 32) Mean P/F ratio:
the label of ALI Mean P/F ratio: 109 + 5.4 112.5 + 10.2
Thomas et al25 AECC; S/F ratio Predominantly Synthetic surfactant Air placebo (n ¼ 81) Duration of mechanical
250 pulmonary (Lucinactant; n ¼ 84) Mean P/F ratio: ventilation (reported
Mean P/F ratio: 211 + 157 178 + 79 14-day mortality)
Mean OI: 9.2 + 5.0 Mean OI: 9.8 + 6.4
Willson et al26 AECC Predominantly Bovine surfactant Air placebo (n ¼ 53) 90-day mortality
pulmonary (Calfactant; n ¼ 56) Median P/F ratio
Median P/F ratio: 120 (IQR 125 (IQR: 115-140)
115-135)
Jacobs et al29 No specific Mixed EPA þ GLA feeds (n ¼ 19) Pediasure (n ¼ 18) Unclear
definition except Mean P/F ratio: 176.9 + 19.4 Mean P/F ratio:
the label of ALI (SEM) 202.3 + 22.7 (SEM)
Mean OI: 14.5 + 2.7 (SEM) Mean OI: 11.5 + 2.1
(SEM)
Bronicki et al27 OI  12 Mixed Inhaled nitric oxide (n ¼ 26) Air placebo (n ¼ 29) 28 VFD (reported
Mean OI: 22.0 + 8.4 Mean OI: 25.6 + 14.9 28-day mortality)
Abbreviations: AECC, America-European Consensus Conference; ARDS, acute respiratory distress syndrome; EPA, eicosapentaenoic acid; GLA, gamma-linolenic
acid; IQR, interquartile range; OI, oxygenation index (mean airway pressure  fraction of inspired oxygen)/partial pressure of inspired oxygen; P/F ratio, partial
pressure of inspired oxygen:fraction of inspired oxygen ratio; S/F ratio, oxygen saturation:fraction of inspired oxygen ratio; SEM, standard error of mean;
VFD, ventilator-free days.

according to geographical location without taking into account
study design showed improving mortality trend over time in
North America, Europe, and Asia (Supplemental Figure 1).
In studies with PF ratio >100, a later year of study had an
OR of 0.94 (0.94-0.95), P < .001, and in studies with PF ratio
100, a later year of study had an OR of 0.98 (0.97-0.99),
P < .001. There were no RCTs with a mean/median PF ratio
100, and hence, we could not examine the impact of type of
study design with this stratification. We conducted a sensitivity
analysis including only studies with 50 patients (n ¼ 12). There
remained a decrease in the odds of mortality with a later year of
study (adjusted OR: 0.98; 95% CI: 0.97-0.98; P < .001) and
RCT design (adjusted OR: 0.73; 95% CI: 0.67-0.81; P < .001).
Discussion
To date, our meta-analysis involved the largest number of
patients with pediatric ARDS. It confirmed previous findings
of high mortality risk (pooled mortality of 24%) in children
with ARDS. In addition, we demonstrated that mortality rates
declined over time regardless of study design. Our systematic
review highlighted the paucity of good-quality data in pediatric
ARDS. The majority of included studies was observational and
had small sample sizes.
Our pooled mortality rate of pediatric ARDS (24%; 95% CI:
19-31) is lower than previously reported in another meta-
analysis (34%; 95% CI: 29-40). 17 In addition, although
Schouten et al demonstrated lack of improvement of mortality
over time, we found a declining mortality rate over time in
children with ARDS.17 We postulate that the differences in
findings may be due to methodological differences. In the
search strategy of the prior systematic review, investigators
included the search term “mortality.” We made an assumption
that some studies that reported mortality outcomes may not
include “mortality” as a keyword. In this current systematic
review that did not use “mortality” as a keyword, we managed
to identify an additional 8 RCTs that were not included in the
prior published systematic review.
Another methodological difference is the inclusion of retro-
spective studies (18 of the 32 studies were retrospective) and
studies with less than 20 patients in the report by Schouten et al.
A subgroup analysis by Schouten et al found no significant
Wong et al
Figure 2. Cumulative forest plot of mortality in all included studies.
difference in mortality between retrospective and prospective
designs.17 However, this finding must be interpreted in the
context that retrospective studies are inherently exposed to
patient and treatment selection biases.49 We excluded studies
with less than 20 patients because we assumed that these cen-
ters see a low volume of patients with ARDS and may affect the
pooled mortality adversely.50,51 A sensitivity analysis with a
more stringent threshold of more than 50 patients showed con-
sistent results demonstrating decreasing mortality over time
and now RCT design as well. However, this could have created
a bias in the assessment of ARDS mortality as the number of
PICUs across the world that does not see much ARDS is not
known. We postulated, a priori, that there would be a difference
in mortality between RCTs and prospective observational stud-
ies, but we did not find any difference. Conduct and reporting
in RCTs are tightly governed by checklists and guidelines;
hence, we assume information generated is more robust.49 Ran-
domized controlled trials apply more stringent inclusion/exclu-
sion criteria and study protocols to improve safety and
maximize therapeutic effects.18,50 This may inadvertently
exclude certain subgroups of patients (eg, bone marrow trans-
plant patients or extracorporeal membrane oxygenation) that
may affect reported mortality rate. We decided to report the
overall mortality in pediatric ARDS without including the
treatment arm of the RCTs because these treatments were col-
lectively not the current standard of care in pediatric ARDS.3,18
5
We demonstrated that there is an improving mortality trend
in pediatric ARDS. There are several plausible explanations for
this. In the past, the incidence of pediatric ARDS was under-
estimated as most patients were diagnosed according to their
underlying diseases.52 With increasing awareness, there is pos-
sibly an increase in prompt recognition/diagnosis of pediatric
ARDS enabling earlier treatment. Moreover, since the advent
of peripheral capillary oxygen saturation (SpO2)-based indices,
clinicians are able to diagnose ARDS without the need for
measurement of arterial oxygenation.53,54 As a result, studies
over time may have included a patient population with lower
disease severity and thus lower mortality. We attempted to
address this confounder by stratifying studies with a mean/
median PF ratio 100 and >100. However, in our stratified
analysis based on the PF ratio, consistent decrease in mortality
risk was demonstrated in later studies. The improving mortality
trend may also signify the development of effective ARDS treat-
ments. For example, the use of lower tidal volumes (6-8 mL/kg)
has been shown to reduce mortality in adult ARDS and is now
a standard of care in pediatric patients.3,55 Lastly, improve-
ments in mortality may reflect general improvements in
pediatric critical care support.56
One of the main strengths of this systematic review is the
inclusion of a comprehensive search conducted without the
search term “mortality,” which identified many relevant studies
that would have otherwise been missed. For example, the
6 Journal of Intensive Care Medicine XX(X)

Figure 3. Forest plot of mortality by time periods.

Figure 4. Bubble plot showing mortality rate against the year of study publication stratified by study design. Bubble sizes in those plots were
proportional to the total patient recruited in the study.
Wong et al
Figure 5. World map showing the distribution of studies across
continents. Red stars signify the number of randomized controlled
trials. Blue pentagons signify the number of prospective observational
studies. All countries involved in multicenter studies were counted
separately to reflect the research energy in each continent.
MEDLINE search generated 2558 articles with the current
search strategy and this subsequently yielded 23 relevant stud-
ies that were included. When search terms such as “mortality,”
“child mortality,” “hospital mortality,” or “infant mortality”
were added, only 801 articles were generated and this yielded
only 8 relevant studies.
It is also timely to determine the pooled mortality following
the publication of the PALICC group recommendations
that promote optimization and consistency of care for children
with pediatric ARDS so as to provide a baseline for compar-
ison for future trials.3 However, the findings of our review
should be interpreted in the context of the limitations. Firstly,
many studies did not report important details like ventilation
strategies (eg, tidal volumes, prone positioning) and nonpul-
monary treatments (eg, sedation, paralysis, nutrition, fluid
management). Additionally, due to the small number of eli-
gible studies, we were unable to enter these important clinical
variables into the meta-regression model as well as other vari-
ables such as geographical location and case mix. The studies
also reported various mortality rates (eg, PICU mortality,
hospital mortality, and 60-day mortality) that could have cre-
ated bias in our pooled analysis. Secondly, studies in this
meta-analysis were highly heterogeneous. Some studies
included enrolled patients with specific risk factors (eg, car-
diopulmonary bypass), while other studies included all
patients. Thirdly, there is possible publication bias since the
funnel plot generated is mildly skewed (Supplemental Digital
Content, eFigure 2). This may be contributed by heterogeneity
mentioned earlier and poor methodological quality of the
smaller studies; 2 studies did not state a clear primary and
secondary outcome measure, and 5 studies used unconven-
tional criteria to define ARDS. Lastly, there is a paucity of
good-quality data in pediatric ARDS, with the majority of
studies originating from North America (Figure 5). This can
potentially limit generalizability of the results.
7
Conclusion
The overall pooled mortality rate in pediatric ARDS is approx-
imately 24% and is lower than previously published reports.
Earlier year of publication was an independent factor adversely
affecting mortality in pediatric ARDS regardless of study
design.
Acknowledgments
The authors thank Ms Peggy Fong Bih Yuh, head librarian of KK
Women’s and Children’s Hospital, Singapore, for assisting with the
formulation of the search strategy. The authors also thank Dr Jason
Phua from the National University Hospital, Singapore, for sharing the
data collection form used for a previous adult ARDS review that was
adapted for use in this systematic review.18
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
Supplemental Material
The online [appendices/data supplements/etc] are available at http://
journals.sagepub.com/doi/suppl/10.1177/0885066617705109.
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