REVIEW ARTICLEPEDIATRICS Volume 137 , number 3 , March 2016 :e 20153501
Signs and Symptoms of Primary Tooth Eruption: A Meta-analysisCarla Massignan, DDS,a Mariane Cardoso, DDS, MsC, PhD,a André Luís Porporatti, DDS,b Secil Aydinoz, MD,c Graziela De Luca Canto, DDS, MsC, PhD,a,d,e Luis Andre Mendonça Mezzomo, DDS, MsC, PhD,a,d Michele Bolan, DDS, MsC, PhDa
abstractCONTEXT: Symptoms associated with the primary tooth eruption have been extensively studied
but it is still controversial.
OBJECTIVE: To assess the occurrence of local and systemic signs and symptoms during primary
tooth eruption.
DATA SOURCES: Latin American and Caribbean Health Sciences, PubMed, ProQuest, Scopus, and
Web of Science were searched. A partial gray literature search was taken by using Google
Scholar and the reference lists of the included studies were scanned.
STUDY SELECTION: Observational studies assessing the association of eruption of primary teeth
with local and systemic signs and symptoms in children aged 0 to 36 months were included.
DATA EXTRACTION: Two authors independently collected the information from the selected
articles. Information was crosschecked and confirmed for its accuracy.
RESULTS: A total of 1179 articles were identified, and after a 2-phase selection, 16 studies
were included. Overall prevalence of signs and symptoms occurring during primary tooth
eruption in children between 0 and 36 months was 70.5% (total sample = 3506). Gingival
irritation (86.81%), irritability (68.19%), and drooling (55.72%) were the most frequent
ones.
LIMITATIONS: Different general symptoms were considered among studies. Some studies
presented lack of confounding factors, no clear definition of the diagnostics methods, use of
subjective measures and long intervals between examinations.
CONCLUSIONS: There is evidence of the occurrence of signs and symptoms during primary tooth
eruption. For body temperature analyses, eruption could lead to a rise in temperature, but it
was not characterized as fever.
aDepartment of Dentistry, and dBrazilian Centre for Evidence-based Research, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil; bBauru School of Dentistry, Bauru,
São Paulo, Brazil; cGulhane Military Medical Academy, Istanbul, Turkey; and eDepartment of Dentistry, University of Alberta, Edmonton, Canada
Dr Massignan worked on study conceptualization, design, data collection, data analysis, drafted the initial manuscript, and critically reviewed manuscript; Drs
Cardoso and Porporatti worked on data analysis, and reviewed and revised the manuscript; Dr Aydinoz worked on data analysis and critically reviewed the
manuscript; Drs De Luca Canto and Mezzomo worked on study conceptualization, design, data analysis, and critically reviewed manuscript; Dr Bolan worked on study
conceptualization, design, data collection, data analysis, and critically reviewed manuscript; and all authors approved the fi nal manuscript as submitted and agree
to be accountable for all aspects of the work.
DOI: 10.1542/peds.2015-3501
Accepted for publication Nov 23, 2015
Address correspondence to Michele Bolan, DDS, PhD, Departamento de Odontologia, Universidade Federal de Santa Catarina, UFSC, Campus Universitário, CCS-ODT-
Trindade Florianópolis, Santa Catarina, Brasil 88040–900. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
To cite: Massignan C, Cardoso M, Porporatti AL, et al. Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis. Pediatrics. 2016;137(3):e20153501
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al
Tooth eruption is a physiologic
process in which teeth move
from their development position
within the alveolar bone to break
the gum toward the oral cavity.1
Nevertheless, this mechanism and
the source of the eruptive force has
not been established nor completely
understood.2
Despite being a natural process
of child development, the impacts
of primary tooth eruption on the
overall health of children are still
controversial. Recent studies have
suggested that tooth eruption
could be accompanied by different
benign symptoms, such as increased
salivation, irritability, loss of appetite
for solid foods, and rise in body
temperature.3–11
Moreover, the eruption of
primary teeth has been assumed
among parents to be associated
with behavioral and systemic
changes.12–17 The period of time
that tooth eruption occurs can be
very frustrating and stressful for
parents, especially when it happens
to their first offspring. Many parents
do not know how to identify the
signs of tooth eruption in their
children and, therefore, do not feel
confident to relieve the discomfort
of the child.18,19 Likewise, many
health professionals also believe
that there is an association between
some signs and symptoms and the
eruption of primary teeth. Surveys
with pediatricians and other child
health professionals showed that
these beliefs are common.3,20,21
The use of this diagnostic label may
lead to either parents not managing
a likely illness10 or the doctors to
ignore significant symptoms and fail
in diagnoses.22
Nevertheless, consistent evidence
on the association of tooth eruption
and general signs and symptoms
are rather low and out of date. In a
review conducted by Tighe et al23
in 2007 to identify the existence
of any pathognomonic sign and
symptom of dental eruption, a
variety of symptoms that may occur
simultaneously with the tooth
eruption was demonstrated and no
evidence suggested the existence of
any signs or symptoms that could
predict the tooth eruption.
Thus, the purpose of this systematic
review was to answer the following
focused question: “In children aged
0 up to 36 months, are there local or
systemic signs and symptoms during
the eruption of the primary teeth?”
METHODS
This systematic review was oriented
following the Preferred Reporting
Items for Systematic Reviews and
Meta-Analyses protocol.24
Protocol Registration
The systematic review protocol
was recorded at the International
Prospective Register of Systematic
Reviews25 under number CRD
42015020822.
Eligibility Criteria
Inclusion Criteria
Observational studies assessing the
occurrence of local and systemic
signs and symptoms during the
spontaneous eruption of primary
teeth in healthy children aged
between 0 and 36 months, by means
of either clinical examination or a
questionnaire directed to the parents
or health care professionals, were
included. The local and systemic
signs and symptoms evaluated were
all reported complications related
to teething described in the studies
(eg, decreased appetite, diarrhea,
drooling, fever, inflammation,
swelling, vesicles or ulceration of the
gum, irritability, rash, rhinorrhea,
sleeping disturbances, vomiting).
Exclusion Criteria
Exclusion of the studies was
performed in 2 phases. In phase 1
(titles and abstracts), the exclusion
criteria were as follows: (1) studies
conducted in children aged >36
months old; (2) reviews, letters,
conference abstracts; (3) studies in
which the sample included patients
with genetic syndromes (eg, Down
syndrome, craniofacial anomalies,
neuromuscular disorders); (4)
studies in which the sample included
malignancies, malnutrition, and
chronic diseases; (5) studies in which
the sample included nonspontaneous
eruption of primary teeth; and (6)
studies in which the eruption of
primary teeth was not the primary
outcome. Besides the 6 cited criteria,
in phase 2 (full-test) the following
exclusion criteria were added: (7)
studies in which clinical examination
was not performed by a health care
professional, and (8) articles that
evaluated the same sample.
Information Sources and Search Strategies
A systematic search was conducted
on the following electronic databases:
Latin American and Caribbean Health
Sciences (LILACS), PubMed, ProQuest
Dissertations and Theses Database,
Scopus, and Web of Science, for
titles and abstracts relevant to the
research question. The syntax has
been adapted to each database
(Supplemental Appendix 1). A partial
gray literature search was taken
using Google Scholar limited to
the first 100 most relevant articles
published in the past 5 years. The
reference lists of the included articles
were scanned to identify additional
studies of relevance. All references
were managed by reference manager
software EndNote Basic (Thomson
Reuters, New York, NY) and duplicate
hits were removed. The end search
date was May 6, 2015. No language or
date restrictions were applied.
Study Selection
The selection occurred in a 2-phase
process to minimize bias. In phase 1,
studies were independently screened
by 2 reviewers (CM, MB) based
on the titles and, if available, the
abstracts derived from the search.
Any study that clearly did not fulfill
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PEDIATRICS Volume 137 , number 3 , March 2016
the inclusion criteria was discarded.
In phase 2, the full text of relevant
papers was retrieved for further
analysis by the same 2 reviewers
(CM, MB) and was either included or
excluded for review on the basis of
the eligibility criteria. Disagreements
of inclusion/exclusion were handled
through discussion, and the third
reviewer (MC) was consulted to
make a final decision.
Data Collection Process
Two authors (CM, MB) independently
collected the required information
from the selected articles. After that,
all the collected information was
crosschecked and confirmed for its
accuracy. Again, any disagreement
was resolved by discussion and
mutual agreement between the
authors. The third author (MC) was
involved, when required, to make a
final decision.
Data Items
For all of the included studies, the
following structured information
was recorded: study characteristics
(authors, year of publication, country,
study design, setting), population
characteristics (sample size, age
of participants), intervention
characteristics (type of diagnostic
approach: clinical examination,
body temperature, questionnaire)
and, finally, outcome characteristics
(assessed teeth, symptoms, mean
temperature in noneruption days,
mean temperature in eruption
days, and conclusions pertaining
to the occurrence of local and
systemic signs and symptoms during
the eruption of primary teeth).
Authors were contacted for further
details when relevant information
was not reported or there was
doubt remaining about duplicate
publication.
Risk of Bias in Individual Studies
Two reviewers (CM, MB)
independently assessed the
methodological quality of the
included studies, using the “Quality
in Prognosis Studies Tool” (QUIPS).26
The QUIPS tool comprises 6 domains:
study participation, study attrition,
prognostic factors measurement,
outcome measurement, study
confounding and statistical analysis
and reporting to guide ratings of
high, moderate, or low risk of bias.
Disagreements were resolved
through consensus when possible, or
a third reviewer (MC) made the final
decision.
Summary Measures
Presence of local and systemic signs
and symptoms and differences
in body temperature during the
eruption of primary teeth were
considered the main outcomes. For
body temperature, the threshold
point was considered according to a
recent meta-analysis on accuracy of
infrared tympanic thermometry,27
between 37.4°C and 37.8°C for
tympanic temperature and 38.0°C
for rectal temperature. Any type of
related outcome measurement was
computed (categorical variables and
continuous variables).
Synthesis of Results
A meta-analysis was planned within
the studies presenting enough
data. The occurrence of signs and
symptoms of the eruption of primary
teeth was analyzed by 2 types of
meta-analysis, for fixed and random
effects following the appropriate
Cochrane Guidelines.28 Meta-
analysis was performed with the
aid of MedCalc Statistical Software
version 14.8.1 (MedCalc Software,
Ostend, Belgium). Heterogeneity
was calculated by inconsistency
indexes (I2), and a value >50% was
considered an indicator of substantial
heterogeneity between studies.29 The
significance level was set at 5%.
Risk of Bias Across Studies
Clinical heterogeneity (differences
in participants, interventions, and
outcomes) and methodological
heterogeneity (study design, risk of
bias) were explored.
RESULTS
Study Selection
The search identified 1318 citations
across 5 databases. After duplicates
removal, 1179 articles were screened
in phase 1. A total of 65 articles
met criteria for full-text screening.
Additionally, 100 citations from
Google Scholar were considered.
From these, 4 further studies
met the inclusion criteria. A hand
search on the reference lists was
performed for any study that might
have been inadvertently missed by
the electronic search procedures
and 6 additional references were
identified. Based on exclusion criteria
for phase 2 (full-text screening), 59
articles were excluded. Two articles
evaluated the same sample and 1 was
not found. The reasons for exclusion
are compiled in a comprehensive
list (Supplemental Appendix 2).
Therefore, 16 articles were selected
for data collection with the aim of
answering the review question.
A flowchart of the process of
identification and selection of studies
is shown in Fig 1.
Study Characteristics
Research was conducted in 8
different countries: Australia,10,30
Brazil,31–33 Colombia,34 Finland,35
India,36–38 Israel,11,39,40 Senegal,41
and United States.42,43 The sample
size ranged widely from 1640 to
116532 children. The search involved
papers published between 196935,39
and 2012.38 A summary of the study
descriptive characteristics can be
found in Table 1.
Risk of Bias Within Studies
The reported methodological
quality of the included studies
ranged between low and high risk
of bias following QUIPS26 domains.
Studies selected have shown to be
heterogeneous considering bias, 7
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MASSIGNAN et al
presented high11,31,32, 36,37,41,43 risk
of bias, 4 moderate,34,38,39,42 and 5
low.10,30,33,35,40 None of them fulfill
all the methodological criteria.
Summarized assessment considering
risk of bias can be found in Table 2.
Detailed results on the use of QUIPS26
tool in selected studies can be found
in Supplemental Appendix 3.
Results of Individual Studies
There were 2 studies that
investigated exclusively local
modifications.30,36 Other studies
evaluated, besides general problems,
local disturbances that could
be involved on primary tooth
eruption.32,35,37,41 Hulland et al30
observed that 85% of 128 teeth
in 21 children presented gingival
hyperemia in the early stages
of eruption. Chakraborty et al36
reported that anterior teeth erupted
with fewer local signs than posterior.
King et al43 suggested that local signs
could be confound with oral herpetic
infection.
Shapira et al40 observed an increase
in inflammatory cytokine levels in the
gingival crevicular fluid surrounding
erupting teeth, whereas Galili et
al39 found that multiple eruptions
occurring at the same time were
associated with diseases. Bengtson et
al,31 Carpenter,42 Cunha et al,32 and
Yam et al41 observed that eruption
of primary teeth was associated
with symptoms. Kiran et al,37
Noor-Mohammed and Basha,38 and
Peretz et al34 found more symptoms
associated with the eruption of
the incisors. Tasanen35 evaluated
that mild symptoms like sucking
fingers, rubbing gums, and drooling
increased during teething, whereas
Wake et al10 reported that primary
tooth eruption was not associated
with symptoms. Jaber et al11 found
that tooth eruption in children was
associated with fever and Ramos-
Jorge et al33 found that there was a
slight rise in body temperature.
The frequency of body temperature
measurement varied between
studies. In some of them
daily registration could be
assessed,11,31,33,35,39 whereas in
others every week day,10 twice
a week,40 or monthly.42 From
the studies in which type of
thermometer and measurement
were informed, 4 studies used
rectal temperature11,35,39,42 and
2 tympanic.10,33 In studies that
presented these data, the cutoff
point to consider a child with high
temperature ranged from 37.5°C
over a period of 2 days (rectal)39
to 39°C in a single assessment (not
informed).34 A summary of body
temperature assessment can be
found in Table 3.
In relation to individual signs and
symptoms, some investigations
demonstrated that fever,11,31,32, 34,37–42 drooling,31,33–35,37 ,38,42 diarrhea,31–34,37, 38,41,42
irritability,31–33,37,40,42 loss of
appetite,31,33,35,37,42 sleeping
problems,31–33,35,37 and
rhinorrhea31–33,37,42 were associated
with primary teeth eruption. In the
opposite site, other studies exposed
that the same symptoms (fever,10,35
irritability,10 sleep disturbances,10,39
and loose stools10,39) had no
association with the eruption.
Synthesis of Results
To easily interpret the results, the
studies were clustered into overall
4
FIGURE 1Flow diagram of literature search and selection criteria. Adapted from Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
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PEDIATRICS Volume 137 , number 3 , March 2016 5
TABL
E 1
Su
mm
ary
of D
escr
ipti
ve C
har
acte
rist
ics
of In
clu
ded
Art
icle
s (n
= 1
6)
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Ben
gtso
n et
al
1988
Bra
zil31
PS
Inst
itu
tion
aliz
ed
child
ren
livi
ng
in a
sh
elte
r
365–
11C
hild
ren
wer
e
exam
ined
for
adm
issi
on t
o
the
rese
arch
.
Exam
iner
NI.
Nur
ses/
Dai
ly. T
ype
of t
herm
omet
er,
mea
sure
men
t N
I.
Nu
rses
dai
ly
regi
ster
ed
saliv
atio
n, d
iarr
hea
,
slee
pin
g tr
oub
le,
irri
tab
ility
, ru
nn
y
nos
e, r
ash
, fev
er,
dec
reas
ed a
pp
etit
e,
vom
itin
g, s
tron
g
uri
ne,
itch
ing
hea
rin
g, p
hys
ical
dif
fi cu
lty.
7288
.88%
had
saliv
atio
n,
87.5
0% d
iarr
hea
,
72.2
2% s
leep
ing
trou
ble
, 69.
44%
irri
tab
ility
,
68.0
5% r
un
ny
nos
e, 6
1.11
%
rash
, 58.
33%
feve
r, 5
0.00
%
dec
reas
ed
app
etit
e, 1
1.40
%
no
sym
pto
ms.
4 m
oN
I/N
IC
hild
ren
had
th
eir
teet
h e
rup
ted
wit
h s
ymp
tom
s.
Carp
ente
r
1978
, Uni
ted
Stat
es42
RS
Wel
l-in
fan
t cl
inic
of a
med
ical
un
iver
sity
hos
pit
al (
Sou
th
Car
olin
a)
120 re
cord
s
4–10
Med
ical
stu
den
t
and
a b
oard
-
cert
ifi ed
ped
iatr
icia
n.
Rec
ord
s u
sed
in t
he
stu
dy
ind
icat
ed
teet
h w
ere
eru
pti
ng
that
tim
e or
in
pre
viou
s vi
sit
one
mon
th
bef
ore.
Med
ical
stu
dent
and
a bo
ard-
cert
ifi ed
pedi
atri
cian
/
mon
thly
rec
tal
tem
pera
ture
s
<37
.77a
wer
e
not
reco
rded
as
feve
r.
NN
um
ber
of
teet
h N
I.
Infe
rior
pri
mar
y
cen
tral
inci
sors
.
39.1
6% h
ad 1
dis
turb
ance
an
d
22.5
0% h
ad ≥
2
dis
turb
ance
s
(fev
er, v
omit
ing,
dia
rrh
ea,
dro
olin
g,
irri
tab
ility
,
faci
al r
ash
an
d
rhin
orrh
ea)
con
curr
ent
wit
h t
eeth
ing;
17 p
atie
nts
had
feve
r.
NI
NI/
NI
Ther
e is
a
corr
elat
ion
bet
wee
n
teet
hin
g
pro
cess
an
d
the
occu
rren
ce
of s
yste
mic
dis
turb
ance
s.
Chak
rabo
rty
et a
l 199
4,
Indi
a36
PS
Ped
iatr
ic
dep
artm
ents
of d
iffe
ren
t
hos
pit
als
of
Cal
cutt
a an
d
ped
odon
tic
dep
artm
ent
Dr.
R. A
hm
ed
Den
tal C
olle
ge
201
6–12
Den
tist
/2-m
o
inte
rval
.
NA
Par
ents
wer
e as
ked
dir
ect
qu
esti
ons
on
the
app
oin
tmen
t
day
on
ext
ent
and
nat
ure
of
loca
l
dis
turb
ance
s
(in
fl am
mat
ion
of t
he
gum
,
non
spec
ifi c
oral
ulc
ers,
ch
eek
fl u
sh, c
hee
k ra
sh,
eru
pti
on c
yst)
,
wit
hin
2-m
o p
erio
d.
NI
80.0
8% s
uff
ered
from
at
leas
t 1
com
plic
atio
n
in r
elat
ion
to
ante
rior
tee
th
and
92.
53%
fro
m
pos
teri
or t
eeth
.
Infl
amm
atio
n o
f
the
gum
was
th
e
mos
t co
mm
on
com
plic
atio
n.
NI
NA
Eru
pti
on o
f
ante
rior
tee
th
was
ass
ocia
ted
wit
h f
ewer
com
plic
atio
ns
than
pos
teri
or
teet
h.
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MASSIGNAN et al 6
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Cu
nh
a, e
t
al 2
004,
Bra
zil32
RS
Infa
nt
clin
ic o
f
Araç
atu
ba
Den
tal S
choo
l
1165
reco
rds
0–36
Exam
iner
NI/
2-m
o
inte
rval
s.
Par
ents
wer
e as
ked
rega
rdin
g th
e
occu
rren
ce o
f
feve
r, t
ype
of
ther
mom
eter
,
mea
sure
men
t N
I.
Par
ents
wer
e as
ked
rega
rdin
g th
e
occu
rren
ce o
f
dis
turb
ance
s
du
rin
g er
up
tion
.
Gin
giva
l irr
itat
ion
,
run
ny
nos
e,
dia
rrh
ea, f
ever
,
gen
eral
agi
tati
on,
incr
ease
d
saliv
atio
n, a
gita
ted
slee
p w
ere
anal
yzed
.
889b
95%
of
the
reco
rds
rep
orte
d
som
e ty
pe
of
man
ifes
tati
on,
85%
gin
giva
l
irri
tati
on, 7
4%
agit
atio
n, 7
0%
incr
ease
d
saliv
atio
n,
46%
fev
er,
39%
agi
tate
d
slee
p, 3
5%
dia
rrh
ea, 2
6%
run
ny
nos
e. T
he
mos
t fr
equ
ent
teet
h in
volv
ed
wer
e th
e lo
wer
cen
tral
inci
sors
52%
, max
illar
y
cen
tral
inci
sors
20%
.
Rec
ord
s fr
om
Jan
199
6
to D
ec
2001
wer
e
anal
yzed
.
NI/
NI
Ch
ildre
n s
how
ed
som
e ty
pe
of
dis
turb
ance
du
rin
g er
up
tion
of t
eeth
.
Gal
ili e
t al
1969
,
Isra
el39
PS
Inst
itu
tion
aliz
ed
child
ren
resi
den
ts
of a
Wiz
o
Bab
y H
ome,
Jeru
sale
m
435–
23 M
ean
11.0
7 (±
0.8)
Auth
or/W
eekl
y.
Eru
pti
on w
as
regi
ster
ed if
any
por
tion
of
the
occl
usa
l
surf
ace
had
pen
etra
ted
the
gin
giva
.
Nu
rses
/Dai
ly/R
ecta
l
tem
per
atu
re o
f
at le
ast
37.5
°C
over
a p
erio
d
of 2
d w
as
des
ign
ated
as
feve
r.
Nu
rses
dai
ly
regi
ster
ed s
tool
,
con
sist
ence
an
d
nu
mb
er, v
omit
ing,
sick
nes
s, d
rool
ing
and
res
tles
snes
s.
They
ref
erre
d
the
child
to
the
resi
den
t
ped
iatr
icia
n in
case
of
any
sign
of
dis
turb
ance
.
93Th
e d
iffe
ren
ce
bet
wee
n
eru
pti
ons
in p
erio
ds
wit
h f
ever
of
un
know
n o
rigi
n
and
th
ose
in
per
iod
of
hea
lth
is s
ign
ifi ca
nt.
The
asso
ciat
ion
bet
wee
n
eru
pti
on a
nd
feve
r w
ith
out
app
aren
t ca
use
is s
ign
ifi ca
nt.
Mu
ltip
le
eru
pti
ons
asso
ciat
ed w
ith
feve
r an
d il
lnes
s
was
sig
nifi
can
t.
4 m
oN
I/ N
ITh
ere
was
no
asso
ciat
ion
betw
een
toot
h
erup
tion
and
syst
emic
dist
urba
nces
.
Erup
tion
and
feve
r w
itho
ut
reco
gniz
able
caus
e w
as
asso
ciat
ed.
Mul
tipl
e
erup
tion
and
dise
ase
(res
pira
tory
and
alim
enta
ry)
was
asso
ciat
ed.
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 3 , March 2016 7
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Hul
land
et
al 2
000,
Aust
ralia
30
PS
3 d
ay c
are
cen
ters
216–
24 M
ean
14.4
(±
4.9)
Den
tal h
ygie
nis
t
exam
ined
(tac
tile
an
d
visu
al)
the
alve
olar
rid
ges
to
iden
tify
red
nes
s or
swel
ling
and
stag
e of
too
th
eru
pti
on/e
very
wee
kday
, mid
-
mor
nin
g,
NA
NA
128
On
ly 1
6
obse
rvat
ion
s
of s
wel
ling.
Red
nes
s
occu
rred
in 8
5%
of t
eeth
in t
he
earl
y st
ages
of
eru
pti
on.
7 m
oN
A/ N
AD
uri
ng
eru
pti
on
mos
t of
tee
th
show
ed s
ign
s
of g
ingi
val
red
den
ing
(hyp
erem
ia)
and
sof
t ti
ssu
e
swel
ling
is
un
com
mon
.
Jab
er e
t
al 1
992,
Isra
el11
PS
Auth
or’s
pri
vate
clin
ic t
o
con
fi rm
too
th
eru
pti
on
466–
18m
othe
rs
exam
ined
gum
s da
ily.
Prof
essi
onal
confi
rm
atio
n of
toot
h er
upti
on.
Mot
her
s/D
aily
/
Rec
tal
Mot
her
s, d
aily
not
ed
if t
her
e w
as
any
dia
rrh
ea,
con
vuls
ion
s,
bro
nch
ial
sym
pto
ms,
or
any
oth
er d
isea
ses;
med
icat
ion
s
and
med
ical
exam
inat
ion
s. A
ll
dat
a re
fer
to t
he
pre
viou
s 20
d.
Num
ber
of t
eeth
NI.
Onl
y da
ta
colle
cted
up t
o th
e
erup
tion
of t
he
fi rst
too
th
(inc
isor
s)
wer
e
anal
yzed
.
Sin
ce t
he
day
th
at
toot
h e
rup
tion
was
reg
iste
red
was
ref
erre
d t
o
day
0, a
nd
all
dat
a re
fer
to
the
pre
viou
s 20
d, t
he
resu
lts
of c
omp
aris
on
of d
ays
0 to
9
and
10
to 1
9
show
ed 4
7 vs
67 d
of
otit
is
med
ia, 8
5 vs
72
d o
f d
iarr
hea
,
and
52
vs 5
8
d w
ith
cou
gh;
no
con
vuls
ion
s
occu
rred
.
NI
MTN
ED M
DT
36.9
an
d
37.1
fro
m
day
19
to
day
4. T
hre
e
day
s b
efor
e
the
toot
h
eru
pti
on
occu
rred
the
MD
T
incr
ease
d
to 3
7.14
(0.6
6) o
n
day
3, 3
7.2
(0.6
8) o
n
day
2, 3
7.4
(0.7
6) o
n
day
1.
Infa
nts
cu
t th
eir
teet
h w
ith
feve
r.
MTE
D 3
7.6
(0.8
5) o
n
the
day
the
toot
h
eru
pte
d
(95%
CI
37.3
3–
37.8
6).
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al 8
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Kin
g et
al 1
999,
Un
ited
Sta
tes43
CS
SG
pat
ien
t at
a
den
tal s
choo
l
ped
iatr
ic
den
tist
ry c
linic
,
a co
mm
un
ity
hos
pit
al, a
nd
the
pri
vate
offi
ces
of
a p
edia
tric
den
tist
an
d a
ped
iatr
icia
n;
CG
sel
ecte
d b
y
age-
mat
chin
g
to S
G, a
t lo
cal
chu
rch
’s in
fan
t
care
fac
ility
40 T
otal
20 S
G
dist
ress
from
toot
h
erup
tion
20 C
G
no
dist
ress
7–30
Res
pons
ible
pers
onne
l
at e
ach
loca
tion
mad
e
exam
inat
ion
and
vira
l
sam
plin
g
prot
ocol
for
HVS
, for
SG
and
one
of t
he
auth
ors
for
CG s
ubje
cts.
Sam
ples
for
vira
l cul
ture
wer
e ob
tain
ed
from
sub
ject
’s
ging
iva
in b
oth
grou
ps.
Exam
iner
NI/
Type
of t
herm
omet
er,
mea
sure
men
t
and
freq
uenc
y
NI.
Whe
n
tem
pera
ture
s
wer
e ob
tain
ed
by o
ther
tha
n th
e
oral
met
hod
(ski
n
tape
, rec
tal)
, the
y
wer
e ad
just
ed
to o
ral v
alue
s
for
com
pari
son
purp
oses
.
N, o
nly
th
at
info
rmat
ion
obta
ined
on
eac
h
sub
ject
was
reco
rded
on
a
pre
par
ed f
orm
and
incl
ud
ed
nam
e, a
ge, g
end
er,
tem
per
atu
re, a
nd
oral
fi n
din
gs.
NI
SG P
osit
ive
cult
ures
for
HVS
in 9
infa
nts,
the
y
pres
ente
d
infl
amm
atio
n,
swel
ling,
ves
icle
s,
ulce
rati
on)
limit
ed t
o ar
ea
adja
cent
/ be
yond
to e
rupt
ing
toot
h
(tee
th).
CG
all
nega
tive
for
HVS
and
norm
al o
ral
fi ndi
ngs
NA,
Sin
gle
clin
ical
asse
ssm
ent
MTN
ED N
ACh
ildre
n ha
d
elev
ated
tem
pera
ture
that
cou
ld n
ot
be e
xpla
ined
by
othe
r di
seas
es
duri
ng t
eeth
ing
peri
od.
MTE
D S
G 7
from
9 po
sitiv
e
for
HVS
had
tem
pera
ture
>37
.77a f
rom
11 n
egat
ive
5 pr
esen
ted
elev
ated
tem
pera
ture
CG a
ll
nega
tive
for
HVS
nor
mal
tem
pera
ture
.
Kira
n e
t al
2011
, In
dia
37
PS
Dep
artm
ent
of
Ped
iatr
ic a
nd
Pre
ven
tive
Den
tist
ry,
Inst
itu
te
of D
enta
l
Sci
ence
s, a
nd
the
Dep
artm
ent
of P
edia
tric
s,
Roh
ilkh
and
Med
ical
Col
lege
894
6–36
Exam
iner
NI/
3-m
onth
inte
rval
s.
Eru
pti
on w
as
defi
ned
as
visi
ble
clin
ical
crow
n o
f th
e
toot
h, b
ut
not
exce
edin
g
3 m
m o
f
exp
osu
re in
the
oral
cav
ity.
Nu
rse/
Afte
r d
enta
l
exam
inat
ion
.
Typ
e of
ther
mom
eter
,
mea
sure
men
t N
I.
Pare
nts
wer
e
aske
d ab
out
the
occu
rren
ce o
f
loca
l and
sys
tem
ic
dist
urba
nces
.
Anal
ysis
of t
he
reco
rds
show
ed
the
pres
ence
of t
he
follo
win
g sy
mpt
oms:
ging
ival
irri
tati
ons;
diar
rhea
; fev
er;
loss
of a
ppet
ite;
irri
tabi
lity;
incr
ease
d
saliv
atio
n; r
unni
ng
nose
; agi
tate
d sl
eep;
feve
r w
ith
diar
rhea
;
feve
r w
ith
incr
ease
d
saliv
atio
n; d
iarr
hea
wit
h in
crea
sed
saliv
atio
n; fe
ver
wit
h di
arrh
ea a
nd
incr
ease
d sa
livat
ion.
Nu
mb
er o
f
teet
h N
I.
Inci
sors
,
can
ines
, an
d
mol
ars.
95.7
% r
epor
ted
som
e ty
pe o
f
man
ifest
atio
ns,
ging
ival
irri
tatio
n
was
obs
erve
d in
95.9
%, i
rrita
bilit
y
in 9
2.1%
, fev
er
in 7
8.0%
. In
the
cont
rol g
roup
92.1
% o
f inf
ants
did
not m
anife
st
any
sym
ptom
.
11 m
oN
I/N
ILo
cal a
nd s
yste
mic
man
ifest
atio
ns
wer
e m
ore
pron
ounc
ed
duri
ng e
rupt
ion
of p
rim
ary
inci
sors
.
Ther
e w
as
asso
ciat
ion
bet
wee
n
pri
mar
y to
oth
eru
pti
on a
nd
inci
den
ce o
f
sign
s an
d
sym
pto
ms.
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 3 , March 2016 9
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Noo
r- Moh
amm
ed
and
Bas
ha
2012
, In
dia
38
CS
Ch
ild h
ealt
h
inst
itu
te a
nd
rese
arch
cen
ter
1100
4–36
On
e of
th
e
auth
ors.
Eru
pti
on w
as
det
erm
ined
if t
he
clin
ical
crow
n o
f th
e
toot
h w
as
visi
ble
, bu
t
not
exc
eed
ing
3-m
m
exp
osu
re
abov
e th
e
gin
giva
.
Mot
her
s co
mp
lete
a
shor
t an
d s
imp
le
qu
esti
onn
aire
in
a ye
s/n
o m
ann
er
incl
ud
ing
feve
r.
Pare
nts
com
plet
ed a
ques
tion
nair
e in
a ye
s/no
man
ner
abou
t 3
obje
ctiv
e
man
ifes
tati
ons
note
d du
ring
the
erup
tion
of
the
prim
ary
teet
h
incl
udin
g dr
oolin
g,
diar
rhea
, fev
er, a
nd
the
com
bina
tion
of
thes
e sy
mpt
oms.
Nu
mb
er o
f
teet
h N
I.
The
mos
t fr
eque
nt
clin
ical
man
ifes
tati
ons
wer
e fe
ver
(16%
), d
rool
ing
(12%
), d
iarr
hea
(8%
), f
ever
-
droo
ling
(15%
),
feve
r-di
arrh
ea
(8%
), d
rool
ing-
diar
rhea
(6%
), a
nd t
he
com
bina
tion
of
feve
r-dr
oolin
g-
diar
rhea
(3%
).
NA,
Sin
gle
clin
ical
asse
ssm
ent
NI
Ther
e w
as
asso
ciat
ion
betw
een
gene
ral
obje
ctiv
e si
gns
(dro
olin
g,
feve
r, an
d
diar
rhea
) an
d
the
erup
tion
of p
rim
ary
teet
h. M
ost
sign
s ap
pear
ed
duri
ng t
he
erup
tion
of
the
prim
ary
inci
sors
.
Typ
e of
ther
mom
eter
,
mea
sure
men
t N
I.
Inci
sors
,
can
ines
, an
d
mol
ars.
Freq
uen
cy N
A.
Per
etz
et
al 2
003,
Col
omb
ia34
CS
Pu
blic
ch
ild c
ente
r58
54–
36D
enti
st/S
ingl
e
asse
ssm
ent.
Nu
rse/
Freq
uen
cy
NA/
Typ
e of
ther
mom
eter
,
mea
sure
men
t
NI.
Feve
r w
as
reco
rded
wh
en
exce
eded
39°
C.
Par
ents
acc
omp
anyi
ng
the
child
com
ple
ted
a q
ues
tion
nai
re.
Info
rmat
ion
was
rel
ayed
in a
yes/
no
man
ner
abou
t 3
obje
ctiv
e
man
ifes
tati
ons
not
ed d
uri
ng
the
eru
pti
on o
f th
e
pri
mar
y te
eth
,
incl
ud
ing
dro
olin
g,
dia
rrh
ea, f
ever
, an
d
the
com
bin
atio
n o
f
thes
e sy
mp
tom
s.
The
den
tist
an
d t
he
nu
rse
con
fi rm
ed
dro
olin
g an
d f
ever
du
rin
g th
e cl
inic
al
chec
kup
.
Nu
mb
er o
f
teet
h N
I.
Inci
sors
,
can
ines
, an
d
mol
ars.
CG 9
3% o
f th
e
child
ren
did
not
pres
ent
any
clin
ical
man
ifes
tati
on.
In t
he S
G, o
nly
39%
. The
mos
t
freq
uent
clin
ical
man
ifes
tati
ons
wer
e dr
oolin
g
(15%
), d
iarr
hea
(13%
), a
nd
droo
ling-
diar
rhea
(8%
),
feve
r an
d fe
ver-
diar
rhea
(8%
).
NA,
Sin
gle
clin
ical
asse
ssm
ent
NI
An a
ssoc
iati
on
has
bee
n
show
n b
etw
een
gen
eral
obje
ctiv
e si
gns
(dro
olin
g, f
ever
,
dia
rrh
ea)
and
the
eru
pti
on o
f
pri
mar
y te
eth
wit
h d
rool
ing
bei
ng
the
mos
t
pre
vale
nt
sign
.
145
SG
Eru
pti
on w
as
det
erm
ined
if t
he
clin
ical
crow
n o
f th
e
toot
h w
as
visi
ble
, bu
t n
ot
exce
edin
g 3
mm
exp
osu
re
abov
e th
e
gin
giva
.
Mos
t si
gns
app
eare
d
du
rin
g th
e
eru
pti
on o
f
the
pri
mar
y
inci
sors
.
340
CG
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al 10
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Ram
os-J
orge
et a
l 201
1,
Bra
zil33
PS
/RS
Res
iden
ces
of t
he
infa
nts
475–
1511
val
idat
ed
trai
ned
den
tist
s/
dai
ly.
11 v
alid
ated
tra
ined
den
tist
s/D
aily
.
Mot
hers
wer
e
inte
rvie
wed
to
inve
stig
ate
the
occu
rren
ce o
f sig
ns
and
sym
ptom
s
such
as
incr
ease
d
saliv
atio
n, r
ash,
runn
y no
se,
diar
rhea
, los
s of
appe
tite
, col
d,
irri
tabi
lity,
feve
r,
smel
ly u
rine
,
cons
tipa
tion
,
vom
itin
g, c
olic
,
and
seiz
ure,
in t
he
prev
ious
24
h an
d 1
wee
k af
ter
the
end
of d
ata
colle
ctio
n,
the
mot
hers
answ
ered
the
sam
e
ques
tion
nair
e.
231
(inc
isor
s).
Mea
n
num
ber
of
teet
h pe
r
infa
nt w
as
near
ly 5
(ran
ge=
2–8)
.
The
asso
ciat
ions
betw
een
sign
s
and
sym
ptom
s
repo
rted
by
mot
hers
and
toot
h er
upti
on
wer
e st
atis
tica
lly
sign
ifi ca
nt.
8 m
oM
TNED
Tym
pan
ic
36.3
9 (0
.26)
Ther
e ar
e
asso
ciat
ions
betw
een
teet
hing
and
slee
p
dist
urba
nce,
incr
ease
d
saliv
atio
n, r
ash,
runn
y no
se,
diar
rhea
, los
s
of a
ppet
ite,
irri
tabi
lity,
and
a sl
ight
ris
e in
tem
pera
ture
.
Feve
r w
as m
ore
freq
uent
ly
repo
rted
in
the
RS.
Non
inst
itutio
naliz
edM
ean
8.9
(± 2
.7)
The
day
of
eru
pti
on w
as
defi
ned
as
the
fi rs
t d
ay
on w
hic
h t
he
inci
sor
edge
emer
ged
in
the
oral
cav
ity
wit
hou
t b
ein
g
com
ple
tely
cove
red
by
gin
giva
l
tiss
ue.
Infr
ared
au
ricu
lar
ther
mom
eter
and
a d
igit
al
axill
ary
ther
mom
eter
.
The
mos
t co
mm
on
sym
ptom
s on
days
of e
rupt
ion
wer
e ir
rita
bilit
y,
incr
ease
d
saliv
atio
n, r
unny
nose
, and
loss
of
appe
tite
. Fev
er
was
rep
orte
d %
tim
es m
ore
ofte
n
in t
he R
S.
Axill
ary
35.9
8
(0.3
6)
MTE
D
Tym
pan
ic
36.5
1 (0
.20)
Axill
ary
35.9
9
(0.4
6)
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 3 , March 2016 11
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Sh
apir
a et
al 2
003,
Isra
el40
PS
Day
car
e ce
nte
r16
5–14
Ped
iatr
ic d
enti
st/
Twic
e w
eekl
y.
Eru
pti
on o
f
the
teet
h w
as
refe
rred
to
the
act
of
teet
h b
reak
ing
out
the
gum
.
Info
rmat
ion
pro
vid
ed
by
par
ents
/
care
give
rs.
Twic
e w
eekl
y.
The
child
ren
’s s
ign
s
and
sym
pto
ms
for
each
day
wer
e
reco
rded
by
the
exam
inin
g d
enti
st
on t
he
bas
is o
f
the
info
rmat
ion
pro
vid
ed b
y
par
ents
as
wel
l as
care
give
rs a
t th
e
day
car
e ce
nte
r.
The
follo
win
g si
gns
and
sym
pto
ms
wer
e re
cord
ed:
feve
r; v
omit
ing;
gast
roin
test
inal
dis
turb
ance
s;
dro
olin
g; b
ehav
iora
l
pro
ble
ms;
sle
ep
dis
turb
ance
s;
cou
ghin
g; a
pp
etit
e
dis
turb
ance
s; a
nd
bit
ing;
su
ckin
g.
50 t
eeth
(an
teri
or),
eval
uat
ed
and
sam
ple
s
from
21
of
them
for
the
test
an
d
the
con
trol
grou
p (
fl u
id
from
th
e
sulc
us)
.
Du
rin
g th
e
teet
hin
g p
erio
d,
beh
avio
ral
pro
ble
ms
wer
e
obse
rved
in 5
0%
of t
he
infa
nts
,
com
par
ed w
ith
16%
in t
he
con
trol
per
iod
(P <
.01)
; fev
er
was
ob
serv
ed
in 2
4% o
f th
e
infa
nts
du
rin
g
toot
h e
rup
tion
and
in 8
% o
f th
e
infa
nts
du
rin
g
the
con
trol
per
iod
(P
= .0
4);
and
cou
ghin
g
was
ob
serv
ed
in 1
2% d
uri
ng
toot
h e
rup
tion
com
par
ed
wit
h 2
% (
P
= .0
6) o
f th
e
infa
nts
du
rin
g
the
con
trol
per
iod
. In
teet
hin
g p
erio
d
vom
itin
g (2
%),
dro
olin
g (1
2%),
and
ap
pet
ite
dis
turb
ance
s
(12%
), b
ut
wer
e
abse
nce
du
rin
g
the
con
trol
per
iod
.
5 m
oM
TNED
Du
rin
g
the
con
trol
per
iod
,
8% o
f th
e
child
ren
exh
ibit
ed
low
/
mod
erat
e
feve
r, n
o
epis
odes
of h
igh
feve
r w
ere
fou
nd
.
Teet
hin
g w
as
asso
ciat
ed
wit
h f
ever
,
beh
avio
ral
pro
ble
ms,
cou
ghin
g, a
nd
the
cyto
kin
e
tum
or n
ecro
sis
fact
or-α
leve
ls.
Flu
id f
rom
th
e
sulc
us
was
colle
cted
on
the
day
of
eru
pti
on o
r
on 1
of
the
follo
win
g 3
d,
and
was
aga
in
colle
cted
for
the
con
trol
grou
p f
rom
the
sam
e
toot
h 1
mo
late
r.
Typ
e of
ther
mom
eter
,
mea
sure
men
t N
I.
MD
T N
I
A ch
ild w
ith
a
tem
per
atu
re
<37
.5°C
was
clas
sifi
ed
as h
avin
g
“no
feve
r.”
A
tem
per
atu
re o
f
37.6
°C t
o 38
.5°C
was
reg
ard
ed a
s
low
/mod
erat
e
feve
r, a
nd
a
tem
per
atu
re
>38
.5°C
was
clas
sifi
ed a
s
hig
h f
ever
.
MTE
D In
th
e
teet
hin
g
per
iod
,
14%
of
the
child
ren
exh
ibit
ed
low
/
mod
erat
e
feve
r
and
10%
exh
ibit
ed
hig
h f
ever
MD
T N
I
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al 12
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Tasa
nen
, 196
9,
Fin
lan
d35
PS
/CS
Nu
rser
y, d
ay-
nu
rser
y,
wel
fare
cen
ter
SG
: PS
:
42 n
urs
ery
GI
43 d
ay-n
urs
ery
GII
41 w
elfa
re
cen
ter
GIII
CG
: CS
:
107
the
sam
e
loca
ls
126
SG
107
CG
+50
new
born
and
50 te
ethi
ng
child
ren
for
eval
uatio
n
of th
e gu
m
colo
r
+17
mu
cosa
l
spec
imen
s
0–30
1 in
vest
igat
or w
ith
both
med
ical
and
dent
al
qual
ifi ca
tions
,
daily
, gro
ups
I /II
and
sum
mon
ed
whe
n er
uptio
n
occu
rred
,
grou
p III
.
Erup
tion:
fi rs
t
time
the
edge
of in
ciso
r/
cusp
of m
olar
emer
ges
thro
ugh
ging
iva
and
is
palp
able
with
the
fi nge
rnai
l.
Coin
cide
ntal
infe
ctio
n: if
feve
r or
oth
er
sign
of i
nfec
tion
was
not
ed 1
wk
befo
re o
r 5
d
afte
r er
uptio
n,
child
was
pla
ce
in th
e in
fect
ed
grou
p. B
lood
inve
stig
atio
n:
sedi
men
tatio
n
rate
per
hou
r
and
tota
l whi
te
bloo
d ce
ll
coun
t. Lo
cal
inve
stig
atio
ns:
cond
ition
of
Sam
e in
vest
igat
or:
rect
al
tem
pera
ture
,
twic
e da
ily
(mor
ning
/
afte
rnoo
n),
1-m
inut
e
ther
mom
eter
°C.
a
Beh
avio
r di
stur
banc
es:
nurs
ing
staf
f/
mot
hers
. Sym
ptom
s:
slee
p, d
ayti
me
rest
less
ness
,
rubb
ing
the
chee
k
and
ear,
rubb
ing
gum
and
suc
king
the
fi nge
r, dr
oolin
g,
appe
tite
and
loos
e
stoo
ls.
Qu
esti
onn
aire
mat
ern
al o
pin
ion
:
200
mot
her
,
100
>40
y o
ld.
Sym
pto
ms:
fev
er,
slee
p d
istu
rban
ces,
rest
less
nes
s
du
rin
g th
e d
ay,
gum
ru
bb
ing
and
fi n
ger
suck
ing,
chee
k an
d e
ar
rub
bin
g, a
pp
etit
e,
dro
olin
g, d
iarr
hea
,
con
vuls
ion
.
192
(in
cisi
ve,
can
ine,
mol
ar).
Infe
ctio
n d
uri
ng
eru
pti
on: 2
6%
SG
, 15%
CG
.
Tem
per
atu
re:
NoI
was
in
aver
age
of
0.1°
C lo
wer
in
pre
- an
d p
ost-
eru
pti
ve p
has
e.
Sed
imen
tati
on
rate
: du
rin
g an
d
afte
r er
up
tion
not
sig
nifi
can
t.
Wh
ite
blo
od c
ells
du
rin
g er
up
tion
:
sign
ifi ca
nt
only
for
lym
ph
ocyt
e
rati
o in
SG
com
par
ed C
G.
Dis
turb
ance
s
in b
ehav
ior:
stat
isti
cal
dif
fere
nce
on
ly
for
rest
less
nes
s
and
dro
olin
g in
SG
an
d a
pp
etit
e
show
ed li
ttle
dec
reas
e
for
SG
. Loc
al
obse
rvat
ion
:
Aver
age
per
iod
of 1
3.3
d
MTP
E
NoI
37.
0
I 37.
2
MTE
D
NoI
36.
9
I 37.
3
MTP
NoI
37.
0
I 37.
3
Erup
tion
did
not
infl
uenc
e
the
body
tem
pera
ture
or in
crea
se
the
poss
ibili
ty
of in
fect
ion.
Suck
ing
fi nge
r,
rubb
ing
gum
,
droo
ling,
dayt
ime
rest
less
ness
,
loss
of a
ppet
ite
incr
ease
d
duri
ng t
eeth
ing.
Ther
e w
as n
o
chan
ge in
the
colo
r of
muc
osa
in o
ne-t
hird
of
the
erup
ting
teet
h. T
here
wer
e so
me
loca
l
com
plic
atio
ns
duri
ng t
eeth
ing.
Mot
her
attr
ibut
ed s
ome
dise
ase
to
teet
hing
.
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 3 , March 2016 13
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
the
muc
osa:
norm
al, s
light
redn
ess
and
deep
red
.
Sens
itivi
ty o
f
ging
iva:
fi ng
er
palp
atio
n,
mod
erat
e
pres
sure
.
Sens
itivi
ty
of to
oth
to
pres
sure
:
with
spe
cial
equi
pmen
t 800
g. H
isto
logi
c
inve
stig
atio
n:
gum
at t
he
erup
tion
site
.
gum
col
or
chan
ge: i
n
40%
was
dee
p
red
. Ch
ange
s
in m
uco
sa: 2
8
in 1
26 c
ases
show
ed s
ligh
t
hem
orrh
ages
,
mod
erat
e
per
icor
onor
ite,
fi st
ula
s,
swel
ling,
or
eru
pti
on c
yst.
No
dif
fere
nce
cou
ld b
e fo
un
d
in r
elat
ion
to t
he
oth
er
fi n
din
gs. P
ain
was
not
fou
nd
in
pre
ssu
re t
o th
e
gin
giva
or
to t
he
eru
pti
ng
teet
h.
No
inve
stig
atio
n
was
mad
e
con
cern
ing
corr
elat
ion
bet
wee
n c
linic
al
and
his
tolo
gic
fi n
din
gs. A
t le
ast
20%
of
mot
her
s
bel
ieve
d t
hei
r
child
ren
cou
ld
pre
sen
t so
me
of
the
inve
stig
ated
sym
pto
ms.
TABL
E 1
Con
tin
ued
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al 14
Stu
dy
Pop
ula
tion
Inte
rven
tion
Ou
tcom
e
Auth
or, Y
ear,
Cou
ntr
ya
Stud
y
Des
ign
Set
tin
gTo
tal n
Age,
Mea
n
or R
ange
,
mo
Clin
ical
Asse
ssm
ent
Bod
y Te
mp
erat
ure
°C (
Wh
o/H
ow)
Qu
esti
onn
aire
Asse
ssed
Tee
thS
ymp
tom
sFo
llow
-Up
Per
iod
MTN
ED/
MTE
D
(°C
)
Mai
n C
oncl
usi
on
Wak
e et
al
2000
,
Aust
ralia
10
PS
/RS
3 ch
ild c
are
cen
ters
216
– 2
4D
enta
l th
erap
ist
exam
ined
for
toot
h e
rup
tion
ever
y w
eekd
ay
(mid
mor
nin
g).
An e
rup
tion
day
was
defi
ned
as
the
fi rs
t d
ay
that
th
e ed
ge
of a
n in
ciso
r
or c
usp
of
a
mol
ar c
row
n
cou
ld b
e
seen
or
felt
emer
gin
g
thro
ugh
th
e
gum
.
Den
tal t
hera
pist
Ever
y w
eekd
ay
(mid
mor
ning
)/
Infr
ared
tym
pani
c
ther
mom
eter
Two
qu
esti
onn
aire
s:
to s
taff
(af
tern
oon
)
and
par
ents
(mor
nin
g) in
qu
ired
abou
t th
e ch
ild’s
moo
d, w
elln
ess/
illn
ess,
dro
olin
g/
dri
bb
ling,
sle
ep,
stoo
ls, w
et d
iap
ers,
and
ras
hes
/
fl u
shin
g ov
er t
he
pre
ced
ing
24 h
wer
e an
swer
ed
ever
y w
eekd
ay.
At t
he
end
of
the
stu
dy,
par
ents
com
ple
ted
a
qu
esti
onn
aire
abou
t th
eir
bel
iefs
and
exp
erie
nce
s
rela
ted
to
teet
hin
g.
90 (
inci
sive
,
can
ine,
mol
ar).
Anal
ysis
did
not
ind
icat
e a
rela
tion
ship
bet
wee
n t
ooth
eru
pti
on a
nd
feve
r. A
ll p
aren
ts
retr
osp
ecti
vely
rep
orte
d t
hat
thei
r ow
n c
hild
had
su
ffer
ed
teet
hin
g
sym
pto
ms.
7 m
oM
TNED
36.
18To
oth
eru
pti
on is
not
ass
ocia
ted
wit
h f
ever
,
moo
d
dis
turb
ance
,
illn
ess,
sle
ep
dis
turb
ance
,
dro
olin
g,
dia
rrh
ea,
stro
ng
uri
ne,
red
ch
eeks
,
or r
ash
es/
fl u
shin
g on
th
e
face
or
bod
y.
Mea
n 1
4.4
(± 4
.9)
MTE
D 3
6.21
Yam
et
al 2
002,
Sen
egal
41
PS
Ch
ild h
ealt
h
inst
itu
te C
entr
e
de
Pro
tect
ion
Mat
ern
elle
et In
fan
tile
in
Dak
ar-M
édin
a
499
5–30
Med
ical
ser
vice
Mon
thly
.
Info
rmat
ion
pro
vid
ed b
y
par
ents
.
NI
Nu
mb
er o
f
teet
h N
I.
Inci
sors
,
can
ines
, an
d
mol
ars.
Loca
l ob
serv
atio
n:
7 h
emat
oma
of e
rup
tion
, 5
wid
esp
read
gin
givi
tis,
297
loca
l gin
givi
tis.
At le
ast
60%
of t
he
child
ren
had
≥1
of t
he
sym
pto
ms:
hyp
erth
erm
ia,
vom
itin
g,
dia
rrh
ea
and
ap
pet
ite
pro
ble
ms.
NI
NI/
NI
Ch
ildre
n c
ut
thei
r
teet
h w
ith
loca
l
and
sys
tem
ic
dis
turb
ance
s.M
oth
ers
shou
ld
bri
ng
the
child
ren
if
ther
e w
ere
any
sign
s or
sym
pto
ms
in
this
per
iod
.
Typ
e of
ther
mom
eter
,
mea
sure
men
t N
I
HS
V, h
erp
es s
imp
lex
viru
s; I,
infe
cted
; MD
T, m
ean
dai
ly t
emp
erat
ure
; MTE
D, m
ean
tem
per
atu
re in
eru
pti
on d
ays;
MTN
ED, m
ean
tem
per
atu
re in
non
eru
pti
on d
ays;
MTP
E, m
ean
tem
per
atu
re b
efor
e er
up
tion
; MTP
; mea
n t
emp
erat
ure
aft
er e
rup
tion
; NA,
not
ap
plic
able
; NI,
not
info
rmed
; N, n
o; N
oI, n
onin
fect
ed; P
S, p
rosp
ecti
ve s
tud
y; R
S, r
etro
spec
tive
stu
dy;
SG
, stu
dy
grou
p.
a D
ata
wer
e m
odifi
ed b
y au
thor
s (°
F to
°C
).b D
ata
calc
ula
ted
by
auth
ors.
TABL
E 1
Con
tin
ued
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PEDIATRICS Volume 137 , number 3 , March 2016
prevalence of signs and symptoms
(Fig 2) and separately prevalence
for each individual sign or symptom
(Fig 3). A total of 10 studies were
included in the meta-analysis. Eight
studies had data enough to conduct
15
TABL
E 2
Ris
k of
Bia
s S
um
mar
ized
Ass
essm
ent
(QU
IPS
26)
Bia
ses
Ben
gtso
n
et a
l
1988
31
Car
pen
ter
1978
42
Ch
akra
bor
ty
et a
l 199
436
Cu
nh
a
et a
l
2004
32
Gal
ili
et a
l
1969
39
Hu
llan
d
et a
l
2000
30
Jab
er e
t
al 1
99211
Kin
g et
al
1999
43
Kira
n e
t
al 2
01137
Noo
r-
Moh
amm
ed
and
Bas
ha
2012
38
Per
etz
et a
l
2003
34
Ram
os-
Jorg
e et
al 2
01133
Sh
apir
a
et a
l
2003
40
Tasa
nen
1969
35
Wak
e et
al 2
00010
Yam
et
al
2002
41
Stu
dy
par
tici
pat
ion
Hig
hM
odLo
wLo
wM
odLo
wM
odLo
wLo
wLo
wLo
wLo
wLo
wLo
wLo
wH
igh
Stu
dy
attr
itio
nH
igh
XM
odX
Hig
hH
igh
Hig
hX
Low
Low
Hig
hM
odH
igh
Mod
Mod
Hig
h
PF
mea
sure
men
tH
igh
Mod
Hig
hH
igh
Hig
hM
odH
igh
Hig
hH
igh
Hig
hLo
wLo
wM
odLo
wLo
wH
igh
Ou
tcom
e
Mea
sure
men
t
Hig
hLo
wH
igh
Hig
hLo
wLo
wH
igh
Hig
hH
igh
Hig
hM
odLo
wLo
wLo
wLo
wH
igh
stu
dy
con
fou
nd
ing
Hig
hLo
wH
igh
Hig
hLo
wLo
wH
igh
Hig
hH
igh
Hig
hH
igh
Low
Low
Low
Low
Hig
h
Sta
tist
ical
an
alys
is
and
pre
sen
tati
on
Hig
hH
igh
Low
Hig
hLo
wLo
wH
igh
Hig
hH
igh
Low
Low
Low
Low
Low
Low
Hig
h
Ove
rall
Hig
hM
odH
igh
Hig
hM
odLo
wH
igh
Hig
hH
igh
Mod
Mod
Low
Low
Low
Low
Hig
h
Rat
ings
: Hig
h, m
oder
ate,
an
d lo
w in
dic
ates
hig
h, m
oder
ate,
an
d lo
w r
isk
of b
ias,
res
pec
tive
ly. P
F, p
rogn
osti
c fa
ctor
.
TABLE 3 Summarized Body Temperature Assessment
Measurement MTNED MTDE Study Reference Association
Rectal42 NI NI 37.7°C Yes
Rectal39 NI NI 37.5°C Yes
Rectal11 36.9–37.1°C 37.6°C NI Yes
Rectal35 37.0°C 36.9°C 37.5°C No
Tympanic33 36.39°C 36.51°C NI Yes (slight rise)
Tympanic10 36.18°C 36.21°C NI No
It was not possible to calculate the weighted average because data were insuffi cient. MTED, Mean temperature in eruption
days; MTNED, Mean temperature in noneruption days.
FIGURE 2Forest plot for all signs and symptoms that occurred during the eruption of primary teeth. Sample = 3506.
FIGURE 3Pooled prevalence for each individual sign or symptom that occurred during the eruption of primary teeth.
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al
meta-analysis11,32,34,37, 38,40, 42,43
of general prevalence of signs and
symptoms. Another 2 studies were
included in the meta-analysis of
individual signs or symptoms.33,35
Because of the heterogeneity
between the studies, a random model
was chosen.44 All the information
about the meta-analysis of individual
studies is described in Fig 2 and
Supplemental Appendix 4. The
results from this meta-analysis
revealed that the overall prevalence
of signs and symptoms associated
with primary tooth eruption in
children between 0 and 36 months
was 70.5% (total sample = 3506;
Fig 2), where gingival irritation,
irritability, and drooling were the
most frequent ones with 86.81%,
68.19%, and 55.72%, respectively.
Additional information regarding
the meta-analysis can be found in
Supplemental Appendices 4 and 5.
Risk of Bias Across Studies
The studies were heterogeneous
and had different designs. Analysis
revealed that the weakness in
methods was not considered an
important confounder capable
of masking possible signs and
symptoms related to other diseases
that could occur simultaneously with
primary tooth eruption.
DISCUSSION
This systematic review investigated
the available evidence about primary
tooth eruption and local and systemic
signs and symptoms. Currently,
the American Academy of Pediatric
Dentistry guidelines have indications
that eruption of primary teeth leads
to local discomfort, irritation, and
drooling.45
Parents follow the development of
children and witness any change
in behavior, mood, or health. Thus,
they can be helpful in assisting in
the detection of related problems.46
Although cooperative, parents
retrospectively reported symptoms
associated with primary tooth
eruption were memory biased. In a
retrospective study about parents’
beliefs related to primary tooth
eruption, the mean number of
symptoms reported per child was
11, whereas in the study sample the
mean number was 8.10 Similarly,
fever was reported 5 times more
often in the retrospective than
children experienced fever during
teething period in the prospective
study.33 Limitations of these studies
are represented by the subjectivity
of the parents’ observations. In
this context, a study that had the
collaboration of parents who daily
measured children’s temperature,
checked for tooth eruption, and kept
a daily log of symptoms, despite
presented adequate methods, was
excluded based on the criteria for this
systematic review because children
did not receive health professional
examination during the follow-up.
There was a significant association
to tooth emergence: biting, drooling,
gum rubbing, irritability, sucking,
sleep awakenings, ear rubbing, rash
on face, decreased appetite for solids,
and slight temperature elevation.6
Regarding the local signs, the most
frequent was inflammation of
the gum36 or gingival reddening
(hyperemia),30 mostly in posterior
teeth. The timing of eruption of the
primary teeth (6 months onward)
coincides with the age when infants
start to explore the environment. In
this phase, the introduction of the
hands and objects into the mouth
is normal; this, in turn, can bring
harmful microorganisms and cause
infection.47 Even sucking behavior,
nutritive and nonnutritive, may lead
to bruising or may traumatize the
gums causing inflammation.48
Regarding the most frequent general
symptoms during primary tooth
eruption, irritability and drooling
were the most observed followed
by decreased appetite, sleeping
problems, rhinorrhea, fever, diarrhea,
rash, and vomiting. Eruption was
associated with fever,40 did not
influence the body temperature,35
or leads to a slight rise in body
temperature.33 In contrast, symptoms
that were not related to primary
tooth eruption in the selected studies
were in this sequence: sickness,10,35,39
sleeping disturbances,10,39 loose
stools,10,39 drooling,10,39 vomiting,39
and fever.10,35 Three of most robust
studies in this systematic review
showed that sucking fingers, gum
rubbing, daytime restlessness, loss
of appetite,35 sleep disturbance,
increased salivation, rash,
rhinorrhea, diarrhea, irritability,33
and coughing40 increased during
teething.
Another robust study,10 which
accompanied 90 erupting teeth from
21 children every weekday, reported
that fever, mood disturbance, illness,
sleeping disturbance, drooling,
diarrhea, strong urine, red checks, or
rashes did not have association with
primary tooth eruption.
The stage of eruption considered
to represent the day of eruption
for the studies differed from the
first day the edge of an incisor or
a cusp of a molar could be seen or
felt emerging through the gum,10,33
palpable with the fingernail35;
clinical crown of the tooth visible
but not exceeding 3 mm of exposure
above the gingiva34,37,38 to any
portion of the occlusal surface
penetrated the gingiva.39 Besides
that, the frequency of clinical
examination varied from single in
cross-sectional (CS) studies to daily
assessment in some prospective
investigations. This is important
information, as Hulland et al30
found that the mean duration
of primary tooth eruption from
imminent eruption to completion
of the emergence phase was in an
average rate of 0.7 mm per month.
Those studies that evaluated
the eruption as the tooth crown
visible through gingiva but not
exceeding 3 mm or those in which
clinical examinations occurred in
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PEDIATRICS Volume 137 , number 3 , March 2016
monthly intervals may have lost
or overestimated some signs or
symptoms.
It seems that symptoms associated
with primary tooth eruption decrease
with age. Most manifestations were
observed during the eruption of
primary incisors32,34,37,38 or were
studied only in incisors.11,33,40 Also
there was a significant difference
between the mean age at which
eruptions were accompanied by
disturbances (11.8 months) and
the average age (14.8 months) at
which teeth erupted without general
disturbances. On the other hand,
there seems to be an association
between multiple eruption with
fever and respiratory and alimentary
illnesses that could be due to the
stress that led to the low resistance of
the body against infections.39
Accurate determination of body
temperature is essential to diagnose
fever.49 A recent systematic review
investigating the accuracy of infrared
tympanic thermometry used in
the diagnosis of fever in children,
disclosed that the accuracy of this
kind of thermometer is high, using
rectal measurement as the “gold
standard.” Besides, as temperature
measured by tympanic thermometry
was always 0.6°C to 0.2°C less than
rectal temperature, the threshold
of fever diagnosed by tympanic
thermometry can be decreased.
Therefore, if 38.0°C is the fever
diagnosed by rectal temperature,
the threshold of infrared tympanic
thermometry should be 37.4°C to
37.8°C.27 Under these circumstances,
in this systematic review, in 1 study
using rectal temperature, mothers
on a daily basis verified temperature
and the threshold point was not
informed. Fever was associated
with teething and the mean daily
temperature in days of noneruption
was between 36.90°C and 37.10°C,
and on the eruption day 37.60°C.11
Two studies with moderate risk
of bias used rectal temperatures
>37.77°C (100°F)42 and >37.50°C39;
these authors stated that fever was
associated with tooth eruption,
but mean daily temperature was
not informed. Analyzing the 3
most robust studies, 1 used rectal
temperature and detected that
eruption did not interfere in body
temperature with mean daily
temperature in noninfected children
(37.0°C in noneruption days and
36.9°C in eruption days) in twice-
daily examinations.35 The others
used tympanic measurements. One
study discovered a slight rise from
36.39°C in noneruption days to
36.51°C in eruption days in a daily
check by dentists,33 whereas the
other stated that children do not have
fever during the teething period,
with 36.18°C in noneruption days
and 36.21°C in eruption days every
weekday by the dental therapist.10
LIMITATIONS
Some methodological limitations of
this review should be considered.
Different general symptoms were
considered among studies and not all
studies related confounding factors,
such as other disease that might have
occurred with tooth eruption, or
several symptoms happening at the
same time. All of these may obscure
the actual findings.
Most studies failed to expose a clear
definition of the diagnostic methods.
Examinations were performed in
long intervals that could compromise
adequate data collection. Besides,
some symptoms did not use objective
measures, but parents’ observation,
such as irritability and loss of
appetite. In addition, some symptoms
need more specific examination,
such as diarrhea that may be caused
by infection and, without a virology
study the diagnostic is not conclusive.
Most of the selected studies
demonstrated a high risk of bias,
especially in relation to study design.
Articles with lower risk of bias had
small samples: 21 to 126 children
evaluated. The biggest samples were
found in studies with high risk of
bias, although a random effect for
meta-analysis was used, this might
have affected the results.
CONCLUSIONS
Based on the current limited
evidence, there are signs and
symptoms during primary tooth
eruption. Gingival irritation,
irritability, and drooling were
the most common. For body
temperature analyses, it was
possible to evaluate that eruption
of primary teeth is associated with
a rise in temperature, but it was not
characterized as fever.
17
ABBREVIATIONS
CG: control group
CI: confidence interval
CS: cross-sectional
LILACS: Latin American and
Caribbean Health
Sciences
QUIPS: Quality in Prognosis
Studies Tool
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.
FUNDING SOURCE: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.
by guest on April 27, 2020www.aappublications.org/newsDownloaded from
MASSIGNAN et al
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DOI: 10.1542/peds.2015-3501 originally published online February 18, 2016; 2016;137;Pediatrics
De Luca Canto, Luis Andre Mendonça Mezzomo and Michele BolanCarla Massignan, Mariane Cardoso, André Luís Porporatti, Secil Aydinoz, Graziela
Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis
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DOI: 10.1542/peds.2015-3501 originally published online February 18, 2016; 2016;137;Pediatrics
De Luca Canto, Luis Andre Mendonça Mezzomo and Michele BolanCarla Massignan, Mariane Cardoso, André Luís Porporatti, Secil Aydinoz, Graziela
Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis
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