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Comunidad Dent Oral Epidemiol 2010; 38: 145-151

2009 John Wiley & Sons A/S

Todos los derechos reservados

Asociacin entre el uso de


medicamentos para el asma y la
prevalencia de opacidades en
demarcados primeros molares
permanentes en 6-a-8- aos de
edad, los nios daneses.

P. Wogelius1,2, D. Haubek1, A. Nechifor3,


2
4,5
M. Nrgaard , T. Tvedebrink and
1
S. Poulsen
1

Departamento de pediatra dentista, Escuela


de dentista,facultad de ciencias de la salud,
Universidad de Aarhus, Dinamarca, 2
Departamento de Epidemiologa Clnica,
Hospital de Aalborg Hospital de la
Universidad de Aarhus, Dinamarca,
Universidad de Medicina y Farmacia, Targu

Mures, Rumania, Centro de Investigacin


Cardiovascular, Hospital de Aalborg, Aarhus
University Hospital, Dinamarca,
Departamento de Ciencias Matemticas,
Universidad de Aalborg, Dinamarca

Wogelius P, D Haubek, Nechifor A, NOERGARD M, Tvedebrink T, S. Poulsen asociacin


entre el uso de medicamentos para el asma y la prevalencia de opacidades demarcadas de
los primeros molares permanentes en 6 a 8 aos de edad, los nios daneses. Comunidad
Dent Oral Epidemiol 2010. 2009 John Wiley & Sons A / S
Extracto - Objetivos: opacidades demarcadas de los primeros molares permanentes son
defectos dentales comunes de desarrollo, caracterizadas por zonas con insuficiente
mineralizacin del esmalte. Los defectos se presentan clnicamente como un continuo que
va desde blanco-cremoso opacidades delimitadas, de color amarillo-marrn opacidades
demarcadas a la prdida macroscpica de la sustancia dental. La etiologa se aclara poco,
pero los medicamentos para el asma se ha sospechado de aumentar la prevalencia. El
objetivo de este estudio fue examinar la prevalencia de opacidades demarcadas de los
primeros molares permanentes entre los nios de 6 a 8 aos de edad, con recetas y sin
recetas de medicamentos para el asma. Mtodos: En un estudio transversal en dos
municipios daneses, todos los nios de 6-8 aos (n = 891) fueron incluidos.
Un total de 745 (83,6%) fue a travs de un examen dental durante el cual
opacidades demarcadas y prdida de sustancia dental debido a estos se registraron. Los
anlisis se limita a 647 nios en los cuales los cuatro primeros molares permanentes haban
estallado. Los datos sobre el uso de medicamentos para el asma desde su nacimiento hasta
el momento de la exploracin dental se obtuvieron de una base de datos de prescripcin
farmacolgica epidemiolgico basado en la poblacin. Resultados: Entre 47 nios con
recetas para ambos inhalados b2-agonistas y corticosteroides inhalados antes de la edad de
3 aos, 15 (31,9%) haban demarcadas opacidades de cualquier tipo, y seis nios (12,8%)
tuvieron prdida de opacidad relacionada con la sustancia dental . Los 264 nios que no
tienen recetas para cualquiera de medicamentos para el asma inhalados u orales, desde el
nacimiento hasta la fecha del examen dental, 96 (36,4%) haba demarcado opacidades de
cualquier tipo, y 13 (4,9%) tuvieron prdida de opacidad relacionada con la sustancia
dental. El odds ratio (OR) de cualquier opacidad delimitada, y de la prdida relacionada con
la opacidad de la sustancia dental en nios con recetas para ambos inhalados b2-agonistas y
los corticosteroides inhalados antes de la edad de 3 aos (IC del 95%: 0,39 a 1,65) 0,82 y
(IC del 95%: 0,70 a 7,43) 2,42. Conclusiones: Los nios con las recetas de medicamentos
inhalados para el asma antes de la edad de 3 aos no tienen un mayor riesgo global de
opacidades demarcadas de primer molar permanente, pero parece que tienen un mayor
riesgo de los graves opacidades delimitadas, es decir, opacidades provocando la prdida
macroscpica de la sustancia dental, y, posiblemente, una necesidad de atencin de
restauracin.

Opacidades demarcadas son defectos en el esmalte de los dientes


cualitativos (1, 2). En el momento de erupcin de los dientes, los defectos
presentan clnicamente como un continuo desde
doi: 10.1111/j.1600-0528.2009.00510.x

Palabras claves: agentes anti-asmaticos,


esmalte dental, epidemiologia, odontologa,
pediatra, diente.
Pia Wogelius, Aalborg Municipal de
odontologia,Filstedvejen
10,
DK-9000
Aalborg, Dinamarca Tel.: +45 9932 2858
e-mail: wog-fb@aalborg.dk
Enviado 25 de febrero de 2009, 9 de
septiembre de 2009 aceptada

Opacidades demarcadas color blanco-crema a amarillo-marrn opacidades.


Dependiendo del tamao y la profundidad del defecto, el ms grave de
color marrn amarillento

145

Wogelius et al.
opacidades pueden romperse debido a las fuerzas de la
masticacin, lo que resultar en la prdida macroscpica
de la sustancia dental (1-3).
La condicin es comn y estudios previos han reportado
tasas de prevalencia del 3-37% en perma- nente primer
molar (4-11). La mayor parte de los defectos son
opacidades demarcadas de color blanco cremoso, pero
opacity- relacionados con la prdida macroscpica de la
sustancia dental en primeros molares permanentes se han
notificado a ocurrir hasta en un 8% de los nios (7).
Los sntomas frecuentes despus de la prdida de esmalte
macroscpica incluyen la sensibilidad de los dientes
afectados aumentaron, el rpido desarrollo de la caries en
los dientes afectados y la ruptura repetida de las
restauraciones que ya estn incluidas (1, 12). Por lo tanto,
el manejo clnico de la enfermedad se ve obstaculizada.
A pesar de su alta prevalencia y complicaciones clnicas
integrales, la etiologa de esta condicin requiere
aclaracin. Estudios anteriores han indicado que los
factores sistmicos, tales como las infecciones del tracto
urinario maternas durante el ltimo perodo del embarazo,
parto prematuro, la ingesta prolongada de la leche
materna, con especial referencia a la dioxinacontaminacin, la mala salud general en los primeros 3
aos, o la falta de calcio fosfato puede causar opacidades
demarcadas (1).
Otra causa sistmica se sospecha es el asma y su
tratamiento (13, 14). Esta cuestin se examin en un
estudio poblacional, transversal que incluy 696 nios de
9 aos de edad, de Nueva Zelanda que tenan un examen
mdico y dental (13). Entre los 121 nios con asma en el
momento del examen, se ha demostrado un aumento del
riesgo de opacidades CATed demarcacin. La formacin
del esmalte de los primeros molares se lleva a cabo
durante la ltima parte del embarazo y el primer
3 aos despus del nacimiento, lo que nos hizo considerar
este perodo sera el momento en el que el esmalte del
primer molar permanente era ms vulnerables a la
exposicin sistmica. Tomarse el tiempo correspondiente
ventana en consideracin, Jalevik et al. realizado un
estudio transversal basado en la poblacin de 516
8 aos de edad. Utilizaron informaron sus padres en la
informacin sobre los factores de embarazo y la salud del
nio durante los 3 primeros aos de vida (14). Entre cinco
nios con asma durante el primer ao de vida, cuatro
haban demarcado opacidades en primer molar
permanente en comparacin con 73 entre los 511 nios
sin asma, lo que result en un odds ratio de (IC del 95%:
5,2 a 110,0) 24.
Los dos estudios que examinaron la asociacin entre el
asma y opacidades delimitadas en los dientes permanente
no incluan informacin sobre los medicamentos para el
asma. Por lo tanto, se realiz un estudio
para comparar la prevalencia de opacidades demarcadas
de los primeros molares permanentes entre los nios con y
sin la informacin del registro en el consumo de drogas
asma desde su nacimiento.

146

Material y mtodos
poblacin de estudio
El estudio se realiz en los municipios anteriores Stovring
y Nibe en la Regin Norte (ex Jutlandia del Norte del
Condado), Dinamarca. El grupo de estudio consisti de
todos los nios en los dos municipios (n = 891) que
estaban 6-8 aos de edad durante el perodo de estudio
desde enero 1, 2005 hasta diciembre 31, 2005.
En Dinamarca, el cuidado dental es gratis para los nios
hasta la edad de 18 aos. Todos los nios se ofrecen
regularmente examen dental, y la mayora de los nios son
examinados rutinariamente cada ao. En los dos
municipios de estudio, el servicio dental fue ofrecida por
tres clnicas dentales infantiles municipales que decidieron
realizar la grabacin de las opacidades CATed
demarcacin una parte del examen clnico regular. Para
ms detalles, vase Wogelius et al. (11). El estudio fue
aprobado por la Agencia de Proteccin de Datos de
Dinamarca (File # 2007-41-0178). Ing de acuerdo a la
legislacin danesa el consentimiento informado de los
padres no es necesario cuando la aprobacin de la
se obtiene Agencia Danesa de Proteccin de Datos.
Los datos sobre los medicamentos para el asma
Todas las farmacias de la Regin Norte estn equipadas
con un sistema de contabilidad computarizado mediante el
cual los datos se envan al Servicio de Salud Nacional de
Dinamarca como parte de un programa de salud apoyado
impuesto nacional. La parte del programa de reembolsos
de los costos asociados con la compra de los
medicamentos recetados, incluyendo medicamentos para
el asma. En la Regin Norte, el sistema de contabilidad
tambin proporciona datos clave sobre las recetas de
medicamentos reembolsables a la base de datos de la
prescripcin farmacolgica (15). Esta base de datos
incluye informacin sobre: (i) el tipo de frmaco de
acuerdo con el sistema anatmico-teraputica-qumica
clasificacin cin (16), (ii) dispersin al del frmaco, (iii)
los cdigos municipio, (iv) la fecha de compra de la
prescripcin drogas y (v) y nmero de registro civil del
paciente, un nmero que se ha asignado a todos los
residentes en Dinamarca desde 1968 y que codifica sexo y
fecha de nacimiento. medicamentos para el asma se
clasifican en: (a) inhalados b2-agonistas, (b) los agonistas
b2 orales y (c) los corticosteroides inhalados. Un historial
de recetas com- pleta se puede establecer para todos los
nios nacidos durante el ao 1996 y en adelante.

Gestational age
To elucidate whether preterm birth is a confounder
we included information on gestational age from
the Danish Medical Birth Registry (17).

Data on demarcated opacities


The permanent first molar was chosen as the index
tooth in this study because severe demarcated
opacities resulting in loss of tooth substance are
often seen in this tooth type and rarely in other
tooth types in affected children (11). By choosing
this tooth type, it was possible to categorize the
demarcated opacities according to severity.
The following conditions were recorded as previously described (11) and according to the criteria
developed by Weerheijm et al. (18).
eruption stage of the tooth; the tooth was
recorded as fully erupted if more than half of
the crown was visible; otherwise it was recorded
as unerupted;
demarcated opacities; the color of the opacities
was recorded as creamy-white or yellowishbrown;
posteruptive enamel breakdown characterized by
irregular and sharp edges (18);
atypical restorations. The extension of restorations in teeth with demarcated opacities is
usually atypical and not similar to that seen in
teeth with caries (18). (The examiner confirmed
the diagnosis of demarcated opacities as the
underlying reason for making the fillings by
checking notes in the dental records);
extraction due to demarcated opacities as confirmed from notes in the childrens dental records.
The training of the examiners and the reliability
of the clinical recordings have been described
previously (11). Examiners were calibrated during
clinical photos of different manifestations of the
demarcated opacities. Additionally, seven patients
were examined three times each; once by one of the
authors and twice by two different examiners; thus,
each examiner had two examinations compared
twice. The overall proportion of identical diagnoses
were 75.6% for demarcated creamy-white or yellowish-brown opacities, 93.9% for posteruptive
breakdown, and 97.5% for atypical restorations.

Data analysis
The unit of analysis is individuals, and the analysis
was restricted to children with four fully erupted
permanent molars in order to avoid misclassification of individuals.

Extracted teeth, posteruptive breakdown and


atypical restorations were combined into one category, named opacity-related loss of tooth substance. Individuals with one or more molar(s) with
any type of lesion related to demarcated opacity
were classified as any demarcated opacity. Individuals with one or more molars with yellowishbrown opacity were classified as yellowish-brown
opacity if they were free of more severe demarcated opacities (i.e. opacity-related loss of tooth
substance), even though they may also have
molar(s) with creamy-white opacity. Individuals
with one or more molar(s) with opacity-related loss
of tooth substance were classified as having opacity-related loss of tooth substance even they may
also have molar(s) with creamy-white opacity or
yellowish-brown opacity.
We obtained contingency tables from which we
calculated the prevalence ORs (with 95% CIs) of
demarcated opacities in children with prescriptions
for both inhaled b2-agonists and inhaled corticosteroids during the first 3 years of life compared with
children with no prescriptions for any asthma drugs
from birth until the time of the dental examination.
All analyses were performed using the STATA
version 9.0; STATA, Texas, USA.

Results
Among the 891 children included, 745 (83.6%) were
examined. The remaining 146 children were not
examined for various reasons: withdrawn from the
municipal clinic (n = 4), moved outside the municipality (n = 28), missed the appointment (n = 13),
not invited because the individual interval between
two routine examinations was longer than 1 year
(n = 3) and, finally, the staff forgot to examine
some children for opacities during the routine
examinations (n = 98).
The proportions of children with fully erupted
permanent first molars were 90.9% among girls,
83.2% among boys, 89.2% among individuals
without asthma drug prescriptions, 79.3% among
individuals with prescriptions for both inhaled
b2-agonists and inhaled corticosteroids anytime,
and 79.7% among individuals with prescriptions
for both inhaled b2-agonists and inhaled corticosteroids during the first 3 years of life.
Among the 647 children with fully erupted
permanent first molars, 264 (40.8%) received no
asthma drug prescriptions from birth until the time
of the dental examination (Table 1). The remaining

Table 1. Distribution of children according to type of demarcated opacities and prescriptions of asthma drugs (inhaled
b2-agonists, inhaled corticosteroids, and oral b2-agonists)
Inhaled b2agonists and
steroids

Inhaled
b2-agonists

Before
Before
Anytime third year Anytime third year Anytime
N (%)
N (%)
N (%)
N (%)
N (%)
Number of children
65
47
Category of opacity Creamy-white
16 (24.6) 11 (23.4)
Yellowish-brown 5 (7.7)
5 (10.6)
Opacity-related
5 (7.7)
6 (12.9)
loss of tooth
substance
Any
20 (30.8) 15 (31.9)

No asthma
drug
prescriptions

Oral
b2-agonists

Before
third year Anytime
N (%)
N (%)

50
34
14 (28.0) 10 (29.4)
3 (6.0)
2 (5.9)
3 (6.0)
3 (8.8)

254
257
264
98 (38.6) 95 (37.0) 83 (31.4)
25 (9.8)
23 (8.9)
26 (9.8)
19 (7.5)
18 (7.0)
13 (4.9)

15 (30.0) 10 (29.4)

105 (41.3) 101 (39.3)

96 (36.4)

Some children who used oral b2-agonists during the first three years were prescribed inhaled asthma drugs later in life.

Table 2. Distribution of children according to demarcated opacities in permanent first molars and use of asthma drugs
(both inhaled b2-agonists and inhaled corticosteroids) the first 3 years of life compared with children with no
prescriptions of asthma drugs
Type of demarcated opacity
Number of children

Creamy-white

Yellowish-brown

Opacity-related
loss of tooth substance

Any

None

With asthma drug


Without asthma drug
OR
95% CI

11
83
0.70
(0.301.50)

5
24
1.09
(0.303.23)

6
13
2.42
(0.707.43)

15
96
0.82
(0.391.65)

32
168

Prevalence odds ratio (OR) with 95% confidence interval (95% CI).

383 children received one or more asthma drug


prescription of which the major part received
prescriptions for oral b2-agonists. During the first
3 years of life, 257 (39.7%) children received
prescriptions for oral b2-agonists only, 34 (5.3%)
for inhaled b2-agonists but no inhaled corticosteroids and 47 (7.3%) for both inhaled b2-agonists and
inhaled corticosteroids. The proportion of children
with no asthma drug prescriptions was 36.6%
among the 6-year-olds, 40.4% among the 7-yearolds, and 44.4% among the 8-year-olds.
We found that 241 children (37.3%) had demarcated creamy-white yellowish-brown opacities or
opacity-related loss of tooth substance. A total of
164 children (25.3%) had only creamy-white opacities, while 77 (11.9%) had yellowish-brown opacities or opacity-related loss of tooth substance.
Information on gestational age was available for
718 children of the 745 children examined in our
study. Among the 622 children with fully erupted
permanent first molars and information on gestational age, 28 children were born before 37 weeks
of gestation. Nine of these (32.1%) had demarcated

opacities of any type, and none (0%) had opacityrelated loss of tooth substance. The remaining 594
children were at term and among these 220 (37.0%)
had demarcated opacities of any type and 41 (6.9%)
children had opacity-related loss of tooth substance.
Among children with prescriptions for both
inhaled b2-agonists and inhaled corticosteroids
during the first 3 years of life, the proportion with
yellowish-brown opacities or opacity-related loss
of tooth substance was higher than in children
without asthma drug prescriptions and in children
with prescriptions of only inhaled or oral
b2-agonists (Table 1).
The ORs of demarcated opacities are presented
in Table 2, which compares children with prescriptions for both inhaled b2-agonists and inhaled
corticosteroids during the first 3 years of life with
children without prescriptions for asthma drugs.
Overall, we found no increased risk of demarcated
opacities in children with use of asthma drugs.
However, the risk of opacity-related loss of tooth
substance may show a tendency to be increased.

Discussion
This population-based study among 6-to-8-year-old
Danish children showed no association between use
of inhaled asthma drugs during the first 3 years of
life and an increased risk of demarcated opacities.
However, our data indicated a tendency of an
association between use of inhaled asthma drugs
during the first 3 years of life and the more severe
types of lesions (opacity-related loss of tooth substance). Demarcated opacities in permanent teeth
are commonly considered to be caused by local
trauma and infection during the period of tooth
development. However, in a previous detailed
description of the present study-population (11),
children with permanent first molars with demarcated opacities were shown to have affected permanent incisors 2.5 times more frequently than children
without affected permanent first molars, thus indicating a systemic origin. Furthermore, our analyses
were based on permanent first molars in which local
infection or traumatic damage is unlikely to occur.
The classification of demarcated opacities was
done using the criteria recommended for epidemiological studies of this condition (1820). We did
not register hypoplasia and the examiners were
carefully trained in the difference between hypoplasia and demarcated opacities with loss of tooth
substance. Among the strengths of the diagnostic
criteria used are their simplicity and the classification of the demarcated opacities according to
severity, which includes sequelae of demarcated
opacities. The creamy-white demarcated opacities
represent defects with less mineral deficiency than
the yellowish-brown ones (3). Thereby, the recording of the color of the opacities is a reflection of the
severity of the enamel lesions.
The data were collected by the dental staff in three
municipal clinics in connection with routine dental
examinations. All of the examiners were exclusively
treating children, which has given all of them
comprehensive clinical experience with pediatric
dentistry. The registrations were considered to be
valid, especially with regards to the yellowishbrown opacities or opacity-related loss of tooth
substance (11). Any misclassification of children
according to demarcated opacities will most likely
occur with equal frequency among children with use
of asthma drugs and healthy children and thus
cause bias toward no difference between children
with use of asthma drugs and healthy children. A
considerable proportion of the included children
were not examined for different reasons, which

included ignored registration of demarcated opacities during the routine dental examination. The
prevalence of demarcated opacities recorded may
have been affected by a potential higher propensity
of dental staff to overlook children without demarcated opacities than children with such opacities.
The relative estimates will, however, hardly be
influenced by this drop-out, since the drop-out very
unlikely was associated with the use of asthma
drugs. The examiners were not aware of the purpose
of the present study, nor were they aware of the
childrens history of asthma drug use (11), and thus
bias of the relative estimates was avoided.
We used registry data on asthma drug use from
the time of tooth formation. In the present study,
we were unable to establish precise measures of the
compliance. However, a previous validation study
on a population similar to the present study
population showed that more than 90% of children
with parentally reported asthma drug use had
received asthma drug prescriptions according to
registry information. Therefore, we believe that the
compliance was high (21).
Childhood asthma is, among other factors, associated with preterm birth (22,23). Aine et al. compared the prevalence of enamel defects in 32
preterm and 64 full-term born children and found
that demarcated opacities occurred in 47% of the
preterm and 25% of the full-term born children
(24). We retrieved information on preterm birth
from the Danish Medical Birth Registry (17) and
found that demarcated opacity was not associated
with gestational age.
The availability of information about the exact
date of drug prescription allowed us to study
specific time windows and hence allowed evaluation of the drug use effect during the period most
vulnerable with regards to enamel developmental
disturbances. In the present study, 65 children had
prescriptions for both inhaled corticosteroids and
inhaled b2-agonists some time from birth until the
date of dental examination, while a smaller group
received their asthma drug prescriptions during
the first 3 years after birth. In the latter group, we
found a tendency of an increased prevalence of
opacity-related loss of tooth substance, which may
be consistent with a causal effect. On the other
hand, posteruptive breakdown of the enamel may
be accelerated or complicated in an acidic environment caused by the use of asthma drugs, some of
which have low pH-values (25). If such an effect,
the vulnerable period for opacity-related loss of
tooth substance may be after tooth eruption.

The data showed that the combined use of


inhaled b2-agonists and inhaled corticosteroids
resulted in a higher prevalence of severe demarcated opacities compared with use of only oral
b2-agonists or only inhaled b2-agonist. This could
be associated with the asthma disease itself, the
severity of the asthma, or it could be an effect of
corticosteroids, or the combination of b2-agonists
and corticosteroids. We had no clinical data on the
severity of asthma in the children and were
therefore unable to evaluate the influence of the
asthma itself. Furthermore, the number of children
with prescription for only inhaled corticosteroids
was too low to allow drug-specific analyses.
Since demarcated yellowish-brown opacities
break down with time, one explanation of the
tendency of an aggravation of the demarcated
opacities associated with asthma drug use could be
that use of asthma drugs or asthma itself accelerates tooth eruption. Our data, however, showed
that a lower proportion of asthma drug users had
fully erupted first permanent molars compared
with nonusers. Thus, asthma or asthma drug use
more likely delays tooth eruption.
Corticosteroid therapy suppresses the osteoblast
formation and activity, resulting in a decreased bone
formation (26). A similar effect on the ameloblasts is
possible and may explain our findings regarding the
severe defects (27). While bone tissue is a dynamic
tissue that undergoes remodeling throughout life,
demarcated opacities are irreversible.
Using a different diagnostic system from us,
Suckling et al. found that the prevalence of white
or yellow demarcated opacities in permanent first
molars and incisors was 35% among 9-year-old
children irrespective of their asthma status (13).
These results agree with ours since we found no
increased prevalence of demarcated creamy-white
opacities associated with asthma drug use. But
because the registrations by Suckling et al. were
restricted to demarcated white or yellow opacities,
comparison with our prevalence figures on demarcated yellowish-brown opacities and opacityrelated tooth substance loss are impossible. In a
population-based study, Ja levik
et al. (14)
showed a 24-fold increased risk of having a
demarcated opacity of any type in five 8-year-old
children who had asthma in their first year of life
compared with children without asthma. Our
study found no increased risk of demarcated
opacity of any type and does thus disagree with
the study by Ja levik et al. The proportion of
Swedish children reported to have asthma during
the first year after birth was

unexpectedly low (1%), which may indicate that


the parents in the Jalevik et al. study have underreported their childrens asthma.
A previous study examined the prevalence of
caries in deciduous and permanent teeth in 4920 7year-old Danish children with and without asthma
drug use using registry data on asthma drugs and
caries (28). Among children with prescriptions for
both inhaled corticosteroids and inhaled b2-agonists between the ages of 3 and 7 years, the relative
risk of caries in first permanent molars was 1.62
(95% CI: 1.032.56), while the risk of caries in the
deciduous dentition in children with asthma was
not increased. Opacity-related loss of tooth substance is very often complicated with caries, which
is subsequently filled, or the lesion may itself result
in a filling being inserted (7). The present findings
of a tendency of an increased risk of opacity-related
loss of tooth substance in children with asthma
drug use is therefore in accordance with an
increased risk of caries in permanent first molars
affected by opacity-related loss of tooth substance.

Conclusion
In conclusion, children with prescriptions for
inhaled asthma drugs before the age of 3 years
did not have an overall increased risk of demarcated opacities in first permanent molar but they
seemed to have an increased risk of the more
severe demarcated opacities, i.e. opacities resulting
in macroscopic loss of tooth substance, and possibly a need for restorative care.

Acknowledgments
We wish to thank the Chief of the municipal dental
service in Stvring and Nibe, Gerd Bangsbo, and the
dental staff for permission and practical help with the
data collection. The study received financial support
from the Augustinus Foundation, The Western Danish
Research Forum for Health Sciences, The Danish Dental
Association, The New Dentists Association, The Research
Foundation of the University of Aarhus, Danish Lung
Association, and The Asthma and Allergy Association,
Denmark.

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2. Ja levik B, Nore n JG. Enamel hypomineralization


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