Down Syndrome and the Risk of

Severe RSV Infection: A Meta-analysis

Andrea A. Beckhaus, MD, Jose A. Castro-Rodriguez, MD, PhD

CONTEXT: Down syndrome (DS) is the most common chromosomal condition in live-born
abstract
infants worldwide, and lower respiratory infection caused by respiratory syncytial virus
(RSV) is a leading cause of hospital admissions.
OBJECTIVE: To evaluate RSV-associated morbidity among children with DS compared with a
population without DS.
DATA SOURCES: Four electronic databases were searched.

STUDY SELECTION: All cohorts or case-control studies of DS with an assessment of RSV infection
and the associated morbidity or mortality were included without language restriction.
DATA EXTRACTION: Two reviewers independently reviewed all studies. The primary outcomes
were hospital admission and mortality. Secondary outcomes included length of hospital
stay, oxygen requirement, ICU admission, need for respiratory support, and additional
medication use.
RESULTS: Twelve studies (n = 1 149 171) from 10 different countries met the inclusion criteria;
10 studies were cohort studies, 1 study was retrospective, and 1 study had both designs. DS
was associated with a higher risk of hospitalization (odds ratio [OR]: 8.69; 95% confidence
interval [CI]: 7.33–10.30; I2 = 11%) and mortality (OR: 9.4; 95% CI: 2.26–39.15; I2 = 38%)
compared with what was seen in controls. Children with DS had an increased length of
hospital stay (mean difference: 4.73 days; 95% CI: 2.12–7.33; I2 = 0%), oxygen requirement
(OR: 6.53; 95% CI: 2.22–19.19; I2 = 0%), ICU admission (OR: 2.56; 95% CI: 1.17–5.59; I2 = 0%),
need for mechanical ventilation (OR: 2.56; 95% CI: 1.17–5.59; I2 = 0%), and additional medication
use (OR: 2.65 [95% CI: 1.38–5.08; I2 = 0%] for systemic corticosteroids and OR: 5.82 [95% CI:
2.66–12.69; I2 = 0%] for antibiotics) than controls.
LIMITATIONS: DS subgroups with and without other additional risk factors were not reported in
all of the included studies.
CONCLUSIONS: Children with DS had a significantly higher risk of severe RSV infection than
children without DS.

Division of Pediatrics, Department of Pediatric Pulmonology and Cardiology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

Dr Beckhaus reviewed and collected the data, conducted the analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Castro-Rodriguez
conceptualized and designed the study, reviewed the data, drafted the initial manuscript, and reviewed and revised the manuscript; and all authors approved the
final manuscript as submitted and agree to be accountable for all aspects of the work.
DOI: https://​doi.​org/​10.​1542/​peds.​2018-​0225

To cite: Beckhaus AA and Castro-Rodriguez JA. Down Syndrome and the Risk of Severe RSV Infection: A Meta-analysis. Pediatrics. 2018;142(3):e20180225

PEDIATRICS Volume 142, number 3, September 2018:e20180225 REVIEW ARTICLE

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 Acute lower respiratory tract
infections (LRTIs) are a leading cause
of hospital admissions and pediatric
mortality worldwide.‍1 Respiratory
syncytial virus (RSV) accounts for
a great majority of cases, affecting
70% of children <1 year of age and
nearly 100% of children <2 years of
age.‍2 Acute respiratory infections
caused by RSV, particularly acute
bronchiolitis, create an important
economic burden (with a high
number of visits to emergency units
and outpatient clinics), requiring
hospital admissions in up to 3% of
cases.‍3,​4‍
Down syndrome (DS) is the most
common chromosomal condition,
with a worldwide estimated
incidence of 1 in 800 live births.‍5
In the United States, the live birth
prevalence of DS in recent years
(2006–2010) was estimated at
12.6 per 10 000 live births (95%
confidence interval [CI]: 12.4–12.8),
with ∼5300 births annually.‍6
Respiratory problems are a frequent
cause of morbidity and mortality
in this population. Respiratory
morbidity includes airway
obstruction with consequent sleep-
related breathing disorders as well as
recurrent respiratory infections with
a wide range of severity, including
viral upper respiratory tract
infections, viral or bacterial LTRIs,
and wheezing disorders.‍5 Children
with DS may suffer from certain
anatomic abnormalities, such as
macroglossia, pharyngeal hypotonia,
adenoid enlargement, and airway
malacia, which may be associated
with other underlying conditions,
such as gastroesophageal reflux,
swallowing dysfunction, congenital
heart disease (CHD), hypotonia,
and immunologic dysfunction.‍5
All these factors contribute to the
respiratory morbidity observed in
DS. Respiratory infections are the
leading cause of hospitalization in
children with DS.7 Most individuals
who are affected have at least 1
hospital admission, with multiple
2 BECKHAUS and CASTRO-RODRIGUEZ
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hospitalizations being common.
A high proportion of these occur
during the first year of life‍8 and are
associated with significant costs.‍9
Therefore, our objective in this
systematic review is to evaluate RSV-
associated morbidity in children with
DS compared with those without DS.
METHODS
Search and Selection Criteria
We searched 4 electronic databases
(Medline, the Cochrane Central
Register of Controlled Trials, Latin
American and Caribbean Literature
on Health Sciences database, and
the Cumulative Index to Nursing and
Allied Health Literature) up to May
2017. The search was conducted
by using the following keywords:
(Down syndrome) AND (respiratory
syncytial virus) OR (respiratory
infection). We also searched other
nonbibliographic data sources, such
as through Web searching, references
of the included publications, and
pharmaceutical industry Web sites.
The inclusion criteria were (1)
cohorts or case-control (C-C) studies
of DS, (2) assessment of RSV infection
(by any laboratory diagnosis test)
and the associated morbidity, and
(3) no language restriction. The
exclusion criteria were (1) no specific
RSV analysis, (2) a DS morbidity
description with an absence of a
control group (CG) with which to
compare, and (3) reviews, letters,
or abstracts because of the lack of
full information about the included
studies. The primary outcomes in
this systematic review were hospital
admission and mortality. Secondary
outcomes included length of hospital
stay (LOS), oxygen requirement,
admission to the ICU, need for
respiratory support, and additional
medication use (ie, in addition to
the patient’s baseline). When data
from participants with DS without
additional risk factors (eg, CHD or
prematurity) were reported, the
group without any additional risk
factors was used for calculations.
Data Abstraction and Assessment
of Risk of Bias
Titles, abstracts, and citations
were independently analyzed by 2
independent investigators (A.A.B.
and J.A.C.R.), and any disagreement
was resolved after discussion.
From the full texts, the reviewers
independently assessed all studies
for inclusion on the basis of the
criteria for population intervention,
study design, and outcomes.
After obtaining full reports about
potentially relevant trials, they
independently assessed eligibility. If
the information was incomplete, they
attempted to contact the authors. The
risk of bias from including certain
studies was assessed according to the
Newcastle–Ottawa scale.‍10
Data Analysis
We calculated pooled odds ratios
(ORs) with 95% CIs for categorical
outcomes and mean differences with
95% CIs for continuous outcomes.
Heterogeneity was assessed by
using the I2 test (≤25% absence
of bias, 26%–39% unimportant,
40%–60% moderate, and 60%–
100% substantial bias).‍11 For all
outcomes measured, a fixed-effects
meta-analysis was used when low
heterogeneity was present (I2 <
40%), and a random-effects meta-
analysis was performed when high
heterogeneity was detected (I2
≥ 40%) to address the variation
across the included studies. Data
from cohort and retrospective
studies were pooled together and
into separate meta-analyses. The
meta-analyses were performed by
using Review Manager 5.3 software
(The Nordic Cochrane Centre, The
Cochrane Collaboration, Copenhagen,
Denmark).
RESULTS
A total of 36 studies were initially
identified in the databases and other
 Records idenfied by searching databases Addional records idenfied in other sources
(n = 36) (n = 0)

Records aer duplicates were eliminated

(n = 33)

Examined abstracts Excluded records

(n = 33) (n = 18)

Full-text arcles excluded; did not

Full-text arcles in which eligibility was evaluated meet inclusion criteria or met
(n = 15) exclusion criteria
(n = 3)

Studies included in qualitave synthesis

(n = 12)

Studies included in quantave synthesis

(meta-analysis)
(n = 12)

FIGURE 1
Process of study selection.

sources (‍Fig 1). After excluding 3
duplicates, we reviewed 33 abstracts.
Eighteen studies were excluded
because they did not meet inclusion
criteria. Fifteen full-text articles
were evaluated, and after excluding
3 studies, 12 studies fulfilled the
inclusion criteria for the qualitative
and quantitative synthesis. These
12 studies (n = 1 149 171 children:
3662 children with DS and 1 145 509
children without DS) were published
from 2004 to 2017.‍12–‍‍‍‍‍‍‍‍ 23
‍ Ten studies
were cohort studies,​‍12–‍‍ 16,​‍ 18–
‍ 20,​
‍ 22,​
‍ 23
‍ higher odds of admission (pooled
1 study was a C-C study,​‍ and 1 21
study had both designs.17 Most
studies included participants up to
2 years of age,​‍12–‍ 14,​
‍ 16,​
‍ 17,​22,​
‍ 23
‍ whereas
some studies included all pediatric
‍ –‍ 21
ages.‍15,​18 ‍ Six studies were
conducted in Europe,​‍12–14,​ ‍ 16,​
‍ 22,​
‍ 23
‍ risk factors, the same results were
3 studies were conducted in Asia,​‍15,​18,​21 ‍
2 studies were conducted in the
United States,​‍17,​19
‍ and 1 study was
conducted in Latin America.‍20 A
detailed description of these 12
studies is shown in Table 1, and a
description of our quality assessment
is presented in ‍Table 2.
Primary Outcomes
Hospital Admissions
The authors of 6 studies reported
differences in RSV hospital
admissions between children
with DS and children without
DS.‍12,​13,​
‍ 16,​
‍ 19,​
‍ 22,​23
‍ DS was associated with
OR: 8.69; 95% CI: 7.33–10.30; I2 =
11%) with the absence of bias (‍Fig 2).
Excluding studies with no description
of additional risk factors and
studies that included a population
with DS with known additional
obtained (pooled OR: 16.66; 95%
CI: 7.22–38.46; I2 = 0%).‍13,​22
‍ The
authors of 1 study reported that
the age distribution also tended to
be different between both groups,
with children with DS continuing
to have more hospitalizations for
RSV during their second year of
life than controls.22 Similar results
were obtained when only data from
prospective studies were analyzed
(data not shown).
The authors of 1 study compared
children with CHD with children
with DS who had CHD or did not
have CHD. The study revealed that
DS appeared to be associated with
a higher risk of hospital admission
compared with CHD without DS (OR:
1.89; 95% CI: 1.30–2.74).‍14
Mortality
The authors of 5 studies reported
‍ –23
RSV mortality.‍12,​20‍‍ Children with
DS had a statistically increased risk
of mortality than children without DS
(pooled OR: 9.4; 95% CI: 2.26–39.15;

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TABLE 1 Summary of Included Studies
Author, y Country Study Design Included Participants Outcomes No. Participants, n Age
Fjaerli et al,​‍12 Norway RC Children <2 y of age hospitalized for RSV bronchiolitis Hospital admissions, mortality, DS: 52; CG: 58 127 DS median: 9 mo; CG median:
2004 compared with all children <2 y of age living in need of mechanical 6 mo
same area identified from official populations ventilation, LOS
statistics and hospital records (DS: 52; CG: 58 127);
DS group included participants with additional risk
factors (4 children with CHD)
Bloemers et al,​‍13 Netherlands RC and PC RC: children with DS managed by DS study group, Hospital admissions, mortality, DS: 216; CG: 276 DS range: 0–24 mo; CG range:
2007 data obtained from medical records; PC: birth need of mechanical 0–24 mo
prospective cohort of children with DS managed ventilation, need of
until 2 y of age. DS: without additional risk supplemental oxygen, LOS
factors 216 (103 in retrospective study and 113 in
prospective study); CG: 276 siblings of the birth
cohort. Participants with CHD and prematurity were
included in this study, but only the non–high-risk
population with DS was included in analysis.
Medrano López Spain PC Multicentric study including individuals with CHD and Hospital admissions, need DS: 279; CG: 805 DS median: 10 mo; CG median:
et al,​‍14 2009 participants with DS (with and without CHD) <2 of mechanical ventilation, 8.5 mo
y of age with LRTI. DS: 279 (105 without CHD); CG: admission to PICU, LOS
805. Individuals with CHD were studied, but the
prematurity condition was excluded.
Megged and Israel RC Review of medical records of 222 children with DS Mortality, need of mechanical DS: 222; CG: not reported —
Schlesinger,​‍15 hospitalized because of unspecified reasons; CG ventilation, LOS
2010 was the general population with RSV infection (DS:

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222; CG: not reported); no description of additional
risk factors
Kristensen et al,​‍16 Denmark PC Population-based cohort study to evaluate risk and Hospital admissions, mortality, DS: 399; CG: 451 806 DS range: 0–23 mo; CG range:
2012 severity of RSV hospitalization in children with LOS 0–23 mo
chronic conditions <2 y of age (DS: 399; CG: 451 806);
no description of additional risk factors
Zachariah et al,​‍17 United RC and C-C RSV hospitalization data and birth data of children Hospital admissions, need of Database 1: DS 630; CG not Database 1: DS range: 0–23 mo
2012 States with and without DS <2 y of age (2 different mechanical ventilation, LOS, reported. Database 2: DS not
databases and state census). Database 1: DS 630; use of bronchodilators, use reported; CG not reported.
CG not reported. Database 2: DS not reported; CG of systemic corticosteroids, C-C: DS 35 (16 without other
not reported. C-C study of clinical features of RSV use of antibiotics risk factors); CG 48
between DS and non-DS admissions: DS 35 (16
without other risk factors); CG 48. Participants with
CHD and prematurity were included in this study,
but only the non–high-risk population with DS was
included in analysis.
Zhang et al,​‍18 China PC Children 1 mo to 14 y of age admitted to the PICU Need of ventilatory support, LOS DS: 13; CG: 158 Total: median 3 mo (1 mo to 3 y)
2013 for severe RSV LRTI were managed during in PICU, mortality
hospitalization (DS: 13 [9 without other risk
factors]; CG 158); individuals with chronic
preexisting conditions were excluded in this study.

BECKHAUS and CASTRO-RODRIGUEZ

by maria ordonez
TABLE 1 Continued
Author, y Country Study Design Included Participants Outcomes No. Participants, n Age
Stagliano et al,​‍19 United RC RSV hospitalization data of children with and without Hospital admissions, need of DS: 842; CG: 632 358 —
2015 States DS within Tricarea <3 y of age (DS: 842; CG: 632 358); respiratory support, LOS
participants with additional risk factors were
included (23% hemodynamically significant CHD,
28% prematurity, and 2% chronic lung disease)
Galleguillos Chile RC RSV hospitalization data of children <14 y of age Mortality, need of respiratory DS: 58; CG: 58 DS median: 26.4 mo; CG median:
et al,​‍20 2016 with and without DS (DS: 58; CG: 58); participants support, need of 11.8 mo
with additional risk factors were included (15% supplemental oxygen,
hemodynamically significant CHD and 10% chronic admission to PICU, LOS, use
lung disease) of systemic corticosteroids,
use of antibiotics
Lee et al,​‍21 2016 Taiwan C-C Children <18 y of age admitted to the PICU for Mortality, need of respiratory DS: 9; CG: 177 Total median: 5.3 mo
severe RSV LRTI (DS: 9; CG: 177); no description of support, LOS in PICU

PEDIATRICS Volume 142, number 3, September 2018

additional risk factors
Sánchez-Luna Spain PC Individuals with DS recruited after birth and matched Hospital admissions, mortality, DS: 93; CG: 68 DS mean ± SD: 7.4 ± 5.4 mo; CG
et al,​‍22 2017 with 1 control (exclusion of individuals with other need of respiratory support, mean ± SD: 8.4 ± 6.1 mo
risk factors); RSV hospitalization for children with need of supplemental oxygen,
DS <1 y of age and assessment of disease severity admission to PICU, LOS in
(DS: 93; CG: 68); individuals with chronic preexisting PICU, LOS
conditions were excluded in this study.
Grut et al,​‍23 Sweden RC RSV hospitalization and birth data for children with Hospital admissions, mortality DS: 814; CG: 1628 —
2017 DS, matched with 2 controls each, <2 y of age,
3 different databases (DS: 814; CG: 1628); no

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description of additional risk factors
PC, prospective cohort; RC, retrospective cohort; —, not applicable.
a US Department of Defense’s health care program.
LOS

not shown).

ICU Admissions
severe RSV LRTI.‍18

Oxygen Requirement
meta-analysis.‍12–14,​
Secondary Outcomes

‍ 16,​
‍ 17,​
‍ 19,​
in controls, but not enough

‍ 20

individuals with DS without

(‍Fig 3). When only data from

were limited to 2 studies‍15,​22

with more days being seen in
revealed no mortality in both

(pooled mean difference: 4.73

‍ ),

revealed similar results.‍22 The

When only data of prospective

(pooled OR: 6.53; 95% CI: 2.22–
data were available to perform a
I2 = 38%) with unimportant bias

19.19; I2 = 0%) without bias (‍Fig

were obtained (data not shown).

children with DS than in controls

‍
The authors of 2 studies reported
The authors of 3 studies reported
days; 95% CI: 2.12–7.33; I2 = 0%)

DS without additional risk factors

DS without additional risk factors

for mortality among children with

and without bias. The single study

similar findings, with a longer LOS

The authors of 9 studies evaluated
(data not shown). The single study

groups.‍22 Additionally, the authors

ICU admissions as an outcome.‍20,​22

that only included individuals with
that only included individuals with
prospective studies were analyzed,

4A). When only data of prospective

similar results were obtained (data

being seen in children with DS than

oxygen use during RSV infection.‍13,​20,​

‍

studies or studies that only included

results maintained their significance

authors of the rest of the studies had

Children with DS had a higher risk of

Children with DS were more likely to
LOS (although data for meta-analysis

‍ 22

require oxygen support than controls

of 1 study found DS to be a risk factor

additional risk factors were analyzed,

studies were analyzed, similar results

5
 ICU admission than controls (pooled
OR: 2.56; 95% CI: 1.17–5.59; I2 = 0%)
Adequacy of
Follow-up
without bias. Additionally, 1 study

—
—
√
√
√
√
√
√
√
√
√
√
√
revealed that in children with CHD,
having DS was not associated with
a higher risk of ICU admission (OR:
1.42; 95% CI: 0.77–2.63).‍14 The single
Follow-up Long

Outcomes to
Enough for
Outcome

study that only included individuals

Occur

—
√
√

√
√
√
√
√
√
√
√

√
√
with DS without additional risk
factors revealed no difference
between both groups.‍22
Assessment of
Outcome

Need for Respiratory Support

√
√
√
√
√
√
√
√
√
√
√

√
√
The authors of 6 studies reported
the necessity for respiratory support
during RSV infection.‍12,​13,​
‍ 17,​
‍ 19,​
‍ 20,​22
‍
Comparability of Cohorts

DS was associated with a higher risk

Based on the Design or

of needing mechanical ventilation

Analysis

compared with what was seen in

—
—
√
√

√
√
√
√
√
√
√

√
√

controls (pooled OR: 4.56; 95% CI:

2.17–9.58; I2 = 57%) although with
moderate bias (‍Fig 4B). When only
data of prospective studies or studies
that only included individuals with
Interest Was Not
That Outcome of

Present at Start
Demonstration

DS without additional risk factors

of Study

were analyzed, similar results were

√
√
√
√
√
√
√
√
√
√
√

√
√

obtained (data not shown). When

data from prospective studies
were analyzed, similar results
Ascertainment of

were obtained (data not shown).

Exposure

Additionally, the authors of 1 study

—
—
√
√
√
√
√
√
√
√
√
√
√

reported that in children with

CHD, having DS was not associated
Selection

with a higher need for mechanical

Selection of the

ventilation (OR: 1.34; 95% CI:

Nonexposed

0.90–1.98).‍14
Cohort

—
√
√
√

√
√
√
√
√
√
√

√
√
TABLE 2 Risk of Bias of the Included Prospective and C-C Studies

Additional Medication Use

The authors of 1 study‍17 reported
Representativeness
of the Exposed

a higher chance of prescription of

Cohort

bronchodilators in patients with DS

—
√
√
√

√
√
√
√
√
√
√

√
√

with no additional risk factors than

in controls (OR: 5.16; 95% CI: 1.31–
20.34). The authors of 2 studies‍17,​20
‍
reported a higher use of antibiotics
Megged and Schlesinger,​‍15 2010

and a higher use of systemic

Medrano López et al,​‍14 2009

corticosteroids in children with DS

Sánchez-Luna et al,​‍22 2017
Galleguillos et al,​‍20 2016
Kristensen et al,​‍16 2012
Zachariah et al,​‍17 2012

Zachariah et al,​‍17 2012

compared with controls (pooled OR:

Bloemers et al,​‍13 2007

Stagliano et al,​‍19 2015

2.65 [95% CI: 1.38–5.08; I2 = 0%] and

Fjaerli et al,​‍12 2004

Zhang et al,​‍18 2013

Study Type, Author, y

Grut et al,​‍23 2017

Lee et al,​‍21 2016

pooled OR: 5.82 [95% CI; 2.66–12.69;

—, not applicable.

I2 = 0%], respectively). The single

Prospective

study that only included individuals

with DS without additional risk
C-C

factors revealed similar results.‍17

6 BECKHAUS and CASTRO-RODRIGUEZ

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 FIGURE 2
Pooled ORs and 95% CIs for the number of hospital admissions because of RSV infection between children with DS and children without DS. df, degrees
of freedom; M-H, Mantel-Haenszel test.

FIGURE 3
Pooled ORs and 95% CIs for mortality because of RSV infection between children with DS and children without DS. df, degrees of freedom; M-H, Mantel-
Haenszel test.

FIGURE 4
A, Pooled ORs and 95% CIs for oxygen requirement because of RSV infection between children with DS and children without DS. B, Pooled ORs and 95%
CIs for mechanical ventilation support because of RSV infection between children with DS and children without DS. df, degrees of freedom; M-H, Mantel-
Haenszel test.

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 DISCUSSION
This systematic review with a meta-
analysis of 12 studies that were
conducted in 10 different countries
around the world revealed that
children with DS are at a significantly
higher risk of having severe RSV
infection (higher hospital admission,
mortality, LOS, oxygen requirement,
ICU admission, need for ventilator
support, and additional medication
use) than children without DS
with the absence of bias in the vast
majority these outcomes.
Because DS is the most common
chromosomal disorder worldwide
and given that RSV is associated with
∼28% of all acute LRTI episodes
and 13% to 22% of all acute LRTI
mortality in young children,​‍24 the
results of the current study carry
high importance and consequences
for public health. Therefore, any
potential strategy to reduce RSV
infection (eg, prophylaxis with
monoclonal antibodies or new
vaccines‍25) in children with DS
could decrease their morbidity
and mortality.
Palivizumab, a humanized
monoclonal antibody, is used
for prophylaxis against RSV and
reduces hospitalizations in children
at high risk (eg, those with chronic
lung disease, hemodynamically
significant CHD, neuromuscular
disease, immunodeficiency, and/or
prematurity) <2 years of age.‍26–30
‍‍‍
Currently, the American Academy of
Pediatrics does not recommend the
routine use of palivizumab to prevent
RSV infection in patients with DS who
do not qualify for other reasons (eg,
CHD, chronic lung disease, airway
clearance issues, or prematurity)
because insufficient data are
available to recommend palivizumab
prophylaxis routinely for children
with Down syndrome.‍31,​32‍
However, according to the present
systematic review and the results
of our meta-analysis, children with
DS have a 9 times higher mortality
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risk and an 8.7 times higher risk
of hospitalization because of RSV
than children without DS. There
is also a high economic burden on
families and health care systems.
They have a 6.5-fold higher risk of a
supplemental oxygen requirement,
a 2.7-fold increased risk of ICU
admission, and a 4.7-fold higher risk
of need for ventilator support and on
average spend 4.7 days longer in the
hospital. Our analysis also revealed
that even in children with DS without
additional risk factors (eg, CHD or
prematurity), they had significantly
more risk.
A recent report revealed a decrease
in hospitalization rates because of
RSV in the United States (between
1997 and 2012) in non–high-risk
infants as well as among those with
chronic lung disease and high-risk
CHD but not among those with DS
without CHD.‍33 Indeed, this latter
group had the highest hospitalization
rate trend in this period.‍33 In 2015,
the total charges for infants with
DS who were hospitalized for RSV
increased from $10 141 (US dollars)
to $18 217 (from 1997 to 2012,
respectively); in contrast, charges
for non–high-risk infants increased
from $6983 to $11 273.‍33 The authors
of a recent prospective study of
532 Canadian children with DS who
received palivizumab reported a 3.6-
fold reduction in the incidence rate
ratio of RSV-related hospitalizations
during the first 2 years of life.‍34
A recent Japanese multicenter
postmarketing surveillance study
about palivizumab prophylaxis
against RSV infection in 138 children
with DS without hemodynamically
significant CHD revealed palivizumab
prophylaxis to be safe and effective
for the prevention of LRTI caused
by RSV. Only 2 (0.7%) children
were hospitalized.35 However, it is
important to note that hospitalization
might be a weak proxy outcome
because the threshold to admit a
patient with DS might be lower.
More cost-utility studies used
to determine the efficacy of RSV
immunoprophylaxis in this specific
high-risk patient population need to
be done.
A limitation of the present systemic
review is that not all of the studies
had a subgroup of participants with
DS with CHD and without CHD or
other additional risk factors, but
almost all results were similar when
only studies with data of participants
with DS without other risk factors
were considered. However, the
present review had strengths. In
regard to methodology, according
to the Newcastle–Ottawa scale, the
risk of bias of the 12 included studies
was reasonably low, the total number
of participants was considerably
high (n = 3662 children with DS
and 1 145 509 children without DS;
1 149 171 children in total), and the
outcomes selected had importance
for the patients and also public
health implications. It is important to
remark that the vast majority of the
outcomes that were analyzed had no
or unimportant bias.
CONCLUSIONS
This systematic review reveals that
children with DS are at a significantly
higher risk of having severe RSV
infections (higher hospital admission,
mortality, LOS, oxygen requirement,
ICU admission, need for respiratory
support, and additional medication
use) than children without DS.
ABBREVIATIONS
C-C: c ase-control
CG: c ontrol group
CHD: c ongenital heart disease
CI: c onfidence interval
DS: D  own syndrome
LOS: length of hospital stay
LRTI: lower respiratory tract
infection
OR: odds ratio
RSV: r espiratory syncytial virus
 Accepted for publication May 29, 2018
Address correspondence to Jose A. Castro-Rodriguez, MD, PhD, Division of Pediatrics, School of Medicine, Pontificia Universidad Católica de Chile, Lira 44, 1er
Piso, Casilla 114-D, Santiago, Chile. E-mail: jacastro17@hotmail.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2018 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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