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\begin{document}

\title{Clinical severity of atopic dermatitis is associated with dental caries
risk in 3-year old children}



\author[1]{Tosha Ashish Kalhan}%
\author[2]{Evelyn Loo}%
\author[1]{Lynette Shek}%
\author[3]{Michael Kramer}%
\author[4]{Carolina Un Lam}%
\author[1]{Bindu Karunakaran}%
\author[1]{Hugo Van Bever}%
\author[5]{Anne Goh}%
\author[6]{Yap Chong}%
\author[1]{bee wah lee}%
\author[7]{Kok Hian Tan}%
\author[6]{Seang Saw}%
\author[8]{Keith Godfrey}%
\author[1]{Chin-Ying Hsu}%
\affil[1]{National University of Singapore}%
\affil[2]{Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR),Singapore}%
\affil[3]{McGill University Faculty of Medicine}%
\affil[4]{Ministry of Health Holdings Pte Ltd}%
\affil[5]{KK Women's and Children's Hospital}%
\affil[6]{NUHS}%
\affil[7]{Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital (KKH)}%
\affil[8]{University of Southampton}%


\vspace{-1em}



  
  \date{June 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Infants with atopic dermatitis (AD) are reported to be at
higher risk of early childhood caries (ECC) at 3-years, but the clinical
validity of the reported link remains unknown. We investigated if
clinical severity of AD in young children is associated with increased
ECC risk at 3-years. Methods: In Growing Up in Singapore Towards healthy
Outcomes (GUSTO) mother-offspring cohort, AD was diagnosed by trained
physicians using Hanifin and Rajka criteria at 18-month and 3-year
clinic visits (n=837). Of the children diagnosed with AD, disease
severity was assessed using SCORAD (SCORing Atopic Dermatitis) index and
categorized into moderate-to-severe AD (SCORAD[?]25), and mild AD
(SCORAD\textless{}25), with children without AD (non-AD) as a reference
group. Oral examinations for ECC detection was performed by calibrated
dentists in 656 children at age 3-years. Negative binomial regression
was used to calculate the adjusted incidence risk ratio (aIRR; adjusted
for socio-demographic factors and prenatal tobacco smoke exposure).
Results: Atopic dermatitis was diagnosed in 7.3\% (61/837) children;
amongst which 23\% had moderate-to-severe AD and 77\% had mild AD. ECC
was observed in 85.7\%, 36.8\% and 42.8\% of the children in
moderate-to-severe, mild and non-AD groups, respectively. Children with
moderate-to-severe AD were at higher risk of ECC (aIRR 2.30 {[}95\%
confidence interval (CI) 1.04-5.06{]}; p=0.03) at 3 years compared to
non-AD, while no association was seen between mild AD and ECC.
Conclusions: Children with moderate-to-severe atopic dermatitis were at
higher risk of ECC compared to those without AD and may benefit from
early dental referral.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease
with peak incidence in the first 2 years of life \textsuperscript{1}. It
affects approximately 8.4 million children (\textless{}18 years) in the
US , with 1 in 3 AD cases exhibiting moderate to severe forms of
disease\textsuperscript{2}. Moreover, children with severe AD exhibit
lower quality of life \textsuperscript{3} and higher risk of comorbid
chronic health conditions, such as asthma and allergic rhinitis,
compared to mild AD, in addition to a two-fold higher healthcare
utilization\textsuperscript{4}. Early childhood caries (ECC), a chronic
diet-mediated oral infectious disease, affecting approximately 12.4
million children (\textless{}18 years) \textsuperscript{5}, is ranked
fifth amongst the top 30 global health conditions in terms of incidence
rates \textsuperscript{6}. Although two large-scale cross-sectional
studies in 0-17 year old American (N=79,667) \textsuperscript{4} and
6-15 year old Japanese children (N=21,792) \textsuperscript{7} reported
no association between allergic diseases (including AD) and dental
caries, our previous study using a longitudinal study design revealed a
potential link with higher ECC risk at 2- and 3-years in infants with
atopic dermatitis \textsuperscript{8}. However, validity of the
diagnostic criteria employed previously and effect of clinical severity
on the AD-ECC link remains unknown.

Large-scale population studies often employ caregiver-reported 1-year
history of a doctor-diagnosed AD as a proxy measure to estimate AD
prevalence in children \textsuperscript{9}, which has been reported to
render low sensitivity (70\%) in identifying AD in 0-17 year old
children \textsuperscript{10}. As more than two-thirds of infants with
moderate-to-severe forms of AD demonstrate allergic sensitization in the
first 2 years of life \textsuperscript{11}, our previous study
supplemented the caregiver-reported history with a positive skin prick
test (SPT) for identification of AD \textsuperscript{8}. Nevertheless,
use of SPT in AD diagnosis has not been validated yet. Furthermore,
children with severe AD have been associated with poor oral
hygiene/dietary control possibly due to a distraction by symptoms and
management of AD \textsuperscript{12}; however the regression model
testing the previous AD-ECC link did not account for these behavioural
factors. Hence, the current study aimed to investigate if clinical
severity of AD by 3 years is associated with increased ECC risk among
3-year old children with/without control of potential
dietary/behavioural confounders. Additionally, diagnostic accuracy of
caregiver-reported history of doctor-diagnosed AD, with/without SPT, was
evaluated using physician diagnosis as the gold standard.

\textbf{Methods}

Study design and data collection

A schematic illustration of study design is presented in Figure 1.
Ethical approval was obtained from Centralized Institutional Review
Board (CIRB) of SingHealth (reference 2009/280/D) and Domain Specific
Review Board (DSRB) of Singapore National Healthcare Group (reference
D/09/021). The Growing Up in Singapore Towards healthy Outcomes (GUSTO)
cohort is a mother-offspring birth cohort where only Singapore citizens
or permanent residents of Chinese, Malay and Indian ethnicity with
homogenous ethnic background were approached for participation
\textsuperscript{13}. A total of 1247 healthy pregnant women, aged 18
years and above, were recruited during their first trimester
(\textless{}14 weeks' gestation) at two major public maternity hospitals
in Singapore. Interviewer-administered questionnaires were used at 26-28
weeks of gestation to collect data on a) demographic/socioeconomic
characteristics (ethnicity, mother's educational status, monthly
household income, child's gender), and b) history of prenatal tobacco
smoke exposure (active and/or passive). Information on current feeding
practices was periodically collected at 3-month intervals using a
separate interviewer-administered questionnaire provided to the mothers
and cumulatively used to derive ``duration of total breastfeeding''.
Additionally, child's frequencies of daily toothbrushing and sweet snack
intake were recorded using a separate oral health questionnaire provided
to primary caregivers at the 24-month dental visit.

Skin and oral examination

Skin examinations for AD diagnosis was performed by physicians/clinical
residents at the clinic visits using Hanifin and Rajka
criteria\textsuperscript{14}. Of the children diagnosed with AD, the
disease severity was assessed using the SCORAD (SCORing Atopic
Dermatitis) index\textsuperscript{15}. Trained clinical residents
performed the SCORAD assessments in children at 18- and 36-month clinic
visits. If a child had SCORAD scores at both the 18- and 36-month clinic
visits, the higher of the two SCORAD scores was used in the analysis.
Additionally, caregiver-reported history of doctor-diagnosed AD in the
first year and findings from skin prick test at 18 months were recorded
as described previously \textsuperscript{8}.

Dental examinations in children were carried out at 3-year clinic visit
by three dentists, who were trained and calibrated to standardize ECC
scoring. Examinations were conducted with the knee-to-knee position,
using plane surface mouth mirrors aided by tactile inspection, when
deemed necessary. Caries detection was performed using modified
International Caries Detection and Assessment System (ICDAS) diagnostic
criteria \textsuperscript{16}, with ICDAS code 1 not recorded due to
logistical constraints. No additional detection methods or radiographs
were used. Inter- and intra-examiner reliability were assessed during
the training phase and quantified using the Intraclass Correlation
Coefficient (ICC).

Statistical analyses

Statistical analyses were performed using STATA (Version 12). Continuous
variables are presented as mean (standard deviation) and median
(interquartile range), while categorical variables are presented as N
(\%). The outcome of interest was number of decayed, missing, or filled
surfaces (\emph{dmfs} ). The SCORAD criteria was used to categorize AD
severity into: i) moderate-to-severe AD (SCORAD[?]25) and ii) mild AD
(SCORAD\textless{}25) cases. A third group comprising children without
AD diagnosis at both clinic visits was used as the reference group
(non-AD). Comparison of caries rates across the three groups was done
using Kruskal-Wallis analysis, followed by Mann-Whitney test with
Bonferroni correction. The distribution of caries was skewed with
overdispersion, making negative binomial regression the appropriate
statistical technique for multivariable analysis. The estimates were
exponentiated to obtain adjusted incidence risk ratios (aIRR) to
estimate caries risk in 3-year old children. Potential confounding
factors, including ethnicity, maternal education, household income,
child's gender, and prenatal tobacco smoke exposure (active/passive)
were adjusted for in the analysis. Additionally, robustness of
association was further assessed by controlling for postnatal diet (such
as duration of breastfeeding, child's daily frequency of sweet snack
intake) and oral hygiene factors (such as child's daily frequency of
toothbrushing).

\textbf{Results}

Participant characteristics

Participants' characteristics are presented in Table 1. Out of 837
children who underwent skin examinations, 7.3\% (61/837) presented with
AD lesions at the time of clinic visits. Amongst 61 children diagnosed
with AD, 23\% (14/61) presented with moderate-to-severe AD lesions while
77\% (47/61) had mild AD lesions. The mean (SD) SCORAD scores for mild
and moderate-to-severe AD cases were 17.2 (4.6) and 37.86 (12.7),
respectively.

Of these 837 participants, 181 children (21.6\%) did not undergo oral
examination at 3-years due to logistic/manpower constraints, with no
significant differences in socio-demographic characteristics, except for
monthly household income, between those who received oral examination vs
those who did not (Appendix Table 1). Although the AD severity profile
of children who underwent oral examination significantly differed from
those who did not, no differences in SCORAD scores were observed for
both moderate-to-severe AD and mild AD groups (p\textgreater{}0.05).
Oral examinations for ECC detection were performed in 656 participants
at the 3-year visit. ECC lesions were observed in 85.7\% (6/7), 36.8\%
(14/38) and 42.8\% (262/611) children in moderate-to-severe AD, mild AD
and non-AD groups, respectively. Furthermore, the mean (SD) decayed
surfaces in moderate-to-severe, mild and non-AD groups were 5.4 (4.6),
2.2 (4.1) and 2.4 (5.1), respectively. Three examiners performed oral
examinations, with mean inter- and intra-examiner reliability scores of
0.80 and 0.80, respectively (for ICDAS code 2) and 0.80 and 0.90,
respectively (for ICDAS codes 3-6).

AD severity and early childhood caries

A significant difference in number of decayed surfaces across the AD
severity groups was observed (P=0.04). On subgroup analysis after
Bonferroni correction, significantly higher decayed surfaces were found
in moderate-to-severe AD group compared to those without AD (p=0.03),
while no difference was found between mild AD and the reference group
(p=0.62) (Table 1). After adjusting for potential confounders (Model-1),
children in the moderate-to-severe AD group were at higher risk of ECC
(aIRR 2.30 {[}95\% confidence interval (CI) 1.04-5.06{]}; p=0.03),
compared to non-AD group. However, no differences in ECC risk was
observed between mild AD and reference group (aIRR 0.89 {[}95\% CI
0.47-1.70{]}; p=0.74) (Table 2). Other significant risk factors for ECC
included Chinese ethnicity (aIRR 2.91 {[}95\%CI 1.82-4.66{]};
p\textless{}0.001), Malay ethnicity (aIRR 2.31 {[}95\%CI 1.37-3.89{]};
p=0.002) and lower household income level (aIRR 1.94 {[}95\%CI
1.15-3.26{]}; p=0.01), detailed in Table 2.

Potential confounding effect of postnatal dietary and oral hygiene
factors

On adjusting for additional postnatal dietary factors such as duration
of breastfeeding and frequency of child's daily sweet snack intake
(Model-2), children with moderate-to-severe AD also showed a 2-fold
increase in ECC risk (aIRR 2.41 {[}95\%CI 1.08-5.37{]}; p=0.03) compared
to non-AD, similar to Model-1 (Table 3). On further inclusion of oral
hygiene factors such as child's daily tooth-brushing frequency
(Model-3), strength of the association remained robust (aIRR 2.31
{[}95\%CI 1.06-5.03{]}; p=0.03). For both Models-2 and 3, no association
was seen between mild AD and ECC, similar to Model 1 where no
dietary/oral hygiene factors were controlled in the regression model.

Comparative evaluation of different diagnostic systems for AD estimation

Using physician diagnosis as the gold standard, caregiver-report of
doctor-diagnosed AD demonstrated high specificity (86.6\%) and negative
predictive value (NPV=95.5\%), but low sensitivity (51.9\%) and positive
predictive value (PPV=24.8\%), in identifying true AD cases (Table 4).
Single use of SPT performed similar to the caregiver-report of
doctor-diagnosed AD with sensitivity, specificity, PPV and NPV of
40.3\%, 88.2\%, 22.6\% and 94.6\%, respectively. In contrast, combined
criteria of caregiver-reported doctor-diagnosed AD and a positive SPT
demonstrated 2-fold higher PPV values (45.4\%), compared to individual
criteria, although other parameters such as sensitivity (44.1\%),
specificity (96.3\%) and NPV (96.2\%) remained similar.

\textbf{Discussion}

The present study findings demonstrated that children with
moderate-to-severe AD, but not mild AD, to be more susceptible to ECC
development, compared to those without the disease. Although complex
pathogenic mechanisms of AD are still evolving, current concepts suggest
that defective skin barrier may be a potential driving factor in AD
pathogenesis and not a consequence of the disease \textsuperscript{17}.
As skin/hair and dental enamel originate from ectoderm, we proposed a
sub-clinical structural hypothesis to explain this link based on
presence of hair keratin proteins in the mature enamel organic matrix
\textsuperscript{18} and association of its mutations with increased
caries risk \textsuperscript{19}. This was substantiated in a
prospective twin study reporting children with infantile eczema to be at
2 times higher risk of developmental enamel defects
\textsuperscript{20}, which is a well-established risk factor for ECC
susceptibility \textsuperscript{21}.

Degree/type of skin barrier dysfunction may be one of the major
differences between mild and severe forms of the disease, as evidenced
by, a) a two-fold increased risk of genetic defects in skin proteins
(filaggrin, \emph{FLG} ) in severe AD individuals compared to mild
AD\textsuperscript{22}, and b) an increased skin permeability
dysfunction (transepidermal water loss, TEWL) in severe AD individuals,
compared to milder forms of the disease \textsuperscript{23}.
Furthermore, polymorphisms in genes regulating skin barrier
function/homeostasis have been linked with tooth developmental
anomalies. First, defects in desmosomal proteins such as desmoplakin
have been associated with severe AD \textsuperscript{24} and enamel
dysplasia \textsuperscript{25}, respectively. Second, defects in genes
encoding for laminin-332 and type XVII collagen have not only been
associated with AD\textsuperscript{26}, but also play a critical role in
differentiation of enamel-forming (ameloblasts) cells
\textsuperscript{27}. Hence, it may be plausible that severity of AD
(with corresponding skin barrier defects) may parallel degree of enamel
defects and hence risk of caries. Further characterization of enamel
proteins in exfoliated deciduous teeth from children with
moderate-to-severe AD and non-AD are ongoing and may elucidate or even
confirm the pathogenic pathway proposed in the study.

It can be argued that children with exacerbated AD symptoms, especially
in moderate-to-severe AD, may exhibit compromised compliance and/or
attention towards oral hygiene \textsuperscript{4} and thus lead to
increased caries susceptibility. Hence, the association between AD
severity and ECC was further tested controlling for post-natal dietary
(such as duration of breastfeeding, child's daily frequency of sweet
snacks) and oral hygiene factors (such as child's brushing frequency)
(Table 3). Consistently, similar findings were revealed, with
moderate-to-severe AD cases to be at 2-fold higher ECC risk compared to
those without AD, substantiating an underlying biological link
independent of the dietary-behavioural effect, between
moderate-to-severe AD and ECC.

Diagnosis of AD, especially in epidemiological studies, may be subject
to potential errors especially in in young children. Conventionally,
caregiver-reported history of doctor-diagnosed AD is employed in
epidemiological studies \textsuperscript{9}, with a reported sensitivity
of 70\% and a positive predictive value (PPV) of 87\% in
children/adolescents (\textless{}18 years) in a referral dermatological
care setting with high prevalence rates (~29.5\%) \textsuperscript{10}.
However, in the present study when the true disease outcome was low
(7.3\%), our results showed lower sensitivity (51.9\%) and PPV (24.8\%)
in identifying true AD cases (Table 4). These findings indicate that
although caregiver-reported criteria may be useful in estimating AD
burden in populations with high prevalence rates, its utility in very
young children and/or cohorts with low prevalence rates may be
compromised. Furthermore, although more than two-thirds of
moderate-to-severe AD children in the first 2 years of life demonstrate
sensitization to food allergens \textsuperscript{11}, low PPV (22.6\%)
and sensitivity (40.3\%) of a positive skin prick test suggested that
allergic sensitization alone may not be sufficient for AD diagnosis in
early-life. In contrast, combining a positive SPT with a
caregiver-reported history of doctor-diagnosed AD, as employed in our
previous work \textsuperscript{8}, resulted in a \textasciitilde{}2-fold
higher PPV (45.4\%) compared to single use of SPT or caregiver-report
alone. However, since overall PPV values still remained low (inflated
Type I error), its utility in epidemiological studies needs to weighed
against the more established diagnostic systems such as Hanifin and
Rajka criteria and UK Working Party criteria \textsuperscript{28}.

The strengths of this study include the longitudinal study design, use
of physician diagnosis in AD estimation, and enumeration of caries at
the surface-level (number of surfaces affected), instead of
individual-level outcome (yes/no) reported
previously\textsuperscript{8}. Study limitations include few moderate
(N=12) and severe AD (N=2) cases available in the cohort. Second,
missing data seen due to multiple time-points of data collection reduced
the sample size (N=581). Nevertheless, post-imputation results using
multiple imputation by chained equation (creating 40 imputed datasets),
demonstrated that exclusion of few missing cases did not affect the
results of the study (Appendix Table 2). Third, it was logistically
impossible to obtain inter- and intra-examiner reliability among
physicians for AD assessment, although both Hanifin-Rajka criteria
\textsuperscript{29}and SCORAD scores \textsuperscript{30} have been
shown to exhibit high inter-rater agreement (ICC\textgreater{}0.80)
among physicians/dermatologists. Fourth, severity of AD cases may be
underestimated in the current study owing to possible regression of skin
lesions before the time of clinic visits and the logistic inability to
obtain SCORAD in the first year when the prevalence of the disease is at
its peak \textsuperscript{1}. Lastly, there may be potential residual
confounding as not all confounding factors could be accounted in the
analysis due to constraints of sample size.

In conclusion, children with moderate-to-severe atopic dermatitis
demonstrated a two-fold increased caries risk at 3 years compared to
those without the disease, and early dental referral may be beneficial.
Furthermore, diagnostic accuracy of caregiver-reported history of
doctor-diagnosed AD, skin prick test, and the combined criteria may be
compromised in identifying true AD cases in certain populations with low
AD prevalence rates.

\textbf{Acknowledgements}

We thank Dr Chng Chai Kiat for his assistance in securing funding for
this study, Dr Pui Ling Chay and Dr Rahul Nair for their help in oral
examination and Dr Nisha Subash Chandran Suyien for providing useful
comments to revise the manuscript draft. The continuous and skilful help
of the home visitors and the clinical team from the National University
Hospital and the K.K Women's and Children's Hospital, as well as the
database and biostatistics teams, is deeply appreciated.

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27. Asaka T, Akiyama M, Domon T, et al. Type XVII collagen is a key
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28. De D, Kanwar AJ, Handa S. Comparative efficacy of Hanifin and
Rajka's criteria and the UK working party's diagnostic criteria in
diagnosis of atopic dermatitis in a hospital setting in North
India.\emph{J Eur Acad Dermatol Venereol.} 2006;20(7):853-859.

29. Jøhnke H, Vach W, Norberg LA, Bindslev-Jensen C, Høst A, Andersen
KE. A comparison between criteria for diagnosing atopic eczema in
infants. \emph{Br J Dermatol.} 2005;153(2):352-358.

30. Bo\selectlanguage{polish}ż\selectlanguage{english}ek A, Reich A. Assessment of Intra- and Inter-Rater Reliability
of Three Methods for Measuring Atopic Dermatitis Severity: EASI,
Objective SCORAD, and IGA. \emph{Dermatology.} 2017;233(1):16-22.

Table 1. Participants' characteristics\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Risk Predictors\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
AD groups N (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
AD groups N (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
AD groups N (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Caries (dmfs) at 3-years (N=656)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Caries (dmfs) at 3-years (N=656)\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Moderate-to-severe AD (SCORAD[?]25) {[}N=14{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Mild AD (0\textless{}SCORAD\textless{}25) {[}N=47{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Non-AD {[}N=776{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Median (IQR)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Ethnicity}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Chinese\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11 (79)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30 (64)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
441 (56.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.5 \selectlanguage{ngerman}± 5.0\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Malay\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14 (30)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
197 (25.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.3 \selectlanguage{ngerman}± 9.0\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Indian\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
137 (17.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.0 \selectlanguage{ngerman}± 1.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,1.7)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Mother's education}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Pre-university \& above\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13 (93)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
35 (74)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
457 (59.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.9 \selectlanguage{ngerman}± 3.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Secondary \& below\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12 (26)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
312 (40.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.4 \selectlanguage{ngerman}± 8.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Monthly household income}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0-1999 SGD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8 (18)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
108 (14.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.5 \selectlanguage{ngerman}± 6.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1 (0,5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2000-3999 SGD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
213 (29.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.8 \selectlanguage{ngerman}± 6.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4000-5999 SGD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (30)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 (14)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
188 (25.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.0 \selectlanguage{ngerman}± 3.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textgreater{}6000 SGD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7 (54)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
15 (35)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
222 (30.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.8 \selectlanguage{ngerman}± 3.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Prenatal tobacco smoke exposure}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13 (29)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
277 (37.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.0 \selectlanguage{ngerman}± 8.0\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11 (79)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
32 (71)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
463 (62.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.1 \selectlanguage{ngerman}± 4.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's gender}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8 (57)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27 (57)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
363 (46.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.6 \selectlanguage{ngerman}± 7.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
413 (53.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.3 \selectlanguage{ngerman}± 4.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of sweet snack intake by 2-years}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Twice or more\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11 (78.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
298 (43.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.0 \selectlanguage{ngerman}± 7.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Once or none\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 (21.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
384 (56.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.2 \selectlanguage{ngerman}± 4.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Child's daily frequency of tooth brushing by 2-years}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Twice or more\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8 (57.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (57.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
359 (52.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.8 \selectlanguage{ngerman}± 7.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Once or none\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 (42.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17 (42.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
324 (47.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.3 \selectlanguage{ngerman}± 4.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0,3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Duration of breastfeeding (in months)}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Duration of breastfeeding (in months)}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Duration of breastfeeding (in months)}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Duration of breastfeeding (in months)}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8.6 \selectlanguage{ngerman}± 10.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7.1 \selectlanguage{ngerman}± 8.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.9 \selectlanguage{ngerman}± 7.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{SCORAD scores\textsuperscript{a}}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{SCORAD scores\textsuperscript{a}}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{SCORAD scores\textsuperscript{a}}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{SCORAD scores\textsuperscript{a}}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
37.8 \selectlanguage{ngerman}± 12.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17.2 \selectlanguage{ngerman}± 4.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
N.A.\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Caries (dmfs) at 3-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Caries (dmfs) at 3-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Caries (dmfs) at 3-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\emph{Caries (dmfs) at 3-years}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Mean \selectlanguage{ngerman}± SD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.4 \selectlanguage{ngerman}± 4.6 \emph{\textsuperscript{b}}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.2 \selectlanguage{ngerman}± 4.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.4 \selectlanguage{ngerman}± 5.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7 (1 to 10)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0 to 3.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0 to 2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{AD, atopic dermatitis; SCORAD,} \emph{SCORing Atopic Dermatitis;
dmfs, decayed missing and filled surfaces; SGD, Singapore dollars; SD,
standard deviation; IQR, interquartile range.}

\emph{\textsuperscript{a}recorded at 18 mo and/or 36 mo clinic
visit;\textsuperscript{b}P\textless{}0.05, Mann-Whitney test followed by
Bonferroni correction.}

Table 2. Association between AD severity (by 3 years) and caries risk
(at 3 years)\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\textbf{CHARACTERISTICS} & \textbf{CHARACTERISTICS} & \textbf{Outcome:
Caries risk at 3 years (dmfs)} & \textbf{Outcome: Caries risk at 3 years
(dmfs)} & \textbf{Outcome: Caries risk at 3 years (dmfs)} &
\textbf{Outcome: Caries risk at 3 years (dmfs)} & \textbf{Outcome:
Caries risk at 3 years (dmfs)} & \textbf{Outcome: Caries risk at 3 years
(dmfs)}\tabularnewline
\midrule
\endhead
& & \textbf{N} & \textbf{Crude IRR (95\%CI)} & \textbf{P value} &
\textbf{N} & \textbf{aIRR\textsuperscript{a} (95\%CI)} & \textbf{P
value}\tabularnewline
AD severity & Moderate-to-Severe AD & 7 & \textbf{2.22 (1.20-4.09)} &
\textbf{0.01} & 6 & \textbf{2.30 (1.04-5.06)} &
\textbf{0.03}\tabularnewline
& Mild AD & 38 & 0.91 (0.49-1.67) & 0.77 & 33 & 0.89 (0.47-1.70) &
0.74\tabularnewline
& Non-AD & 611 & 1 & & 542 & 1 &\tabularnewline
Ethnicity & Chinese & 408 & 2.48 (1.69-3.64) & \textless{}0.001 & 321 &
2.91 (1.82-4.66) & \textless{}0.001\tabularnewline
& Malay & 193 & 3.21 (1.93-5.33) & \textless{}0.001 & 166 & 2.31
(1.37-3.89) & 0.002\tabularnewline
& Indian & 120 & 1 & & 94 & 1 &\tabularnewline
Gender & Female & 347 & 1.12 (0.79-1.60) & 0.50 & 278 & 0.94 (0.69-1.28)
& 0.71\tabularnewline
& Male & 374 & 1 & & 303 & 1 &\tabularnewline
Maternal educational levels & Secondary \& below & 289 & 1.76
(1.26-2.47) & 0.001 & 238 & 1.29 (0.90-1.86) & 0.17\tabularnewline
& Pre-university \& above & 426 & 1 & & 343 & 1 &\tabularnewline
Monthly household income & 0-1999 SGD & 108 & 1.86 (1.21-2.84) & 0.004 &
89 & 1.94 (1.15-3.26) & 0.01\tabularnewline
& 2000-3999 SGD & 201 & 1.49 (0.98-2.25) & 0.06 & 175 & 1.51 (0.95-2.40)
& 0.08\tabularnewline
& 4000-5999 SGD & 169 & 1.06 (0.73-1.55) & 0.75 & 151 & 1.06 (0.68-1.64)
& 0.79\tabularnewline
& [?]6000 SGD & 194 & 1 & & 166 & 1 &\tabularnewline
Prenatal tobacco smoke exposure & Yes & 261 & 1.41 (0.97-2.06) & 0.07 &
219 & 0.95 (0.67-1.35) & 0.80\tabularnewline
& No & 423 & 1 & & 362 & 1 &\tabularnewline
\bottomrule
\end{longtable}

\emph{IRR, incidence risk ratio; CI, confidence interval, AD, atopic
dermatitis; SGD, Singapore dollars; dmfs, decayed missing and filled
surfaces.}

\textsuperscript{\textbf{a}} \emph{aIRR, adjusted incidence risk ratio;
adjusted for ethnicity, gender, maternal educational levels, monthly
household income, prenatal tobacco smoke exposure.}

Table 3. Effect of postnatal dietary and oral hygiene factors on the
association between AD severity and caries risk\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{CHARACTERISTICS}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{CHARACTERISTICS}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Outcome: Caries risk at 3 years (dmfs)}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Outcome: Caries risk at 3 years (dmfs)}\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\textbf{Outcome: Caries risk at 3 years (dmfs)}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{N}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{aIRR\textsuperscript{a} (95\%CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{P value}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-1: Without postnatal dietary/oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-1: Without postnatal dietary/oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-1: Without postnatal dietary/oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-1: Without postnatal dietary/oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-1: Without postnatal dietary/oral hygiene factors}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Model-1\textsuperscript{a}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Moderate-to-Severe AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{2.30 (1.04-5.06)}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Mild AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
33\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.89 (0.47-1.70)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.74\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Non-AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
542\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-2: Addition of postnatal dietary factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-2: Addition of postnatal dietary factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-2: Addition of postnatal dietary factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-2: Addition of postnatal dietary factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-2: Addition of postnatal dietary factors}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Model-1\textsuperscript{a} + Duration of breastfeeding (in months) +
Frequency of daily sweet snacks at 2-years\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Moderate-to-Severe AD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{2.41 (1.08-5.37)}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Mild AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.99 (0.51-1.94)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.99\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Non-AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
503\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-3: Addition of postnatal oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-3: Addition of postnatal oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-3: Addition of postnatal oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-3: Addition of postnatal oral hygiene factors}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Model-3: Addition of postnatal oral hygiene factors}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Model-1\textsuperscript{a} + Duration of breastfeeding (in months) +
Frequency of daily sweet snacks at 2-years + Child's daily brushing
frequency at 2-years\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Moderate-to-Severe AD\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{2.31 (1.06-5.03)}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Mild AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.99 (0.51-1.92)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.99\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Non-AD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
503\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{IRR, incidence risk ratio; CI, confidence interval, AD, atopic
dermatitis; dmfs, decayed missing and filled surfaces.}

\textsuperscript{\textbf{a}} \emph{aIRR, adjusted incidence risk ratio;
adjusted for ethnicity, gender, maternal educational levels, monthly
household income, prenatal tobacco smoke exposure.}

Table 4. Internal validation of different diagnostic criteria in
identifying young children with atopic dermatitis\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Outcome: AD (Physician diagnosis)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Outcome: AD (Physician diagnosis)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Outcome: AD (Physician diagnosis)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Outcome: AD (Physician diagnosis)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Diagnostic criteria for AD\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
PPV (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
NPV (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Sensitivity (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Specificity (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Caregiver-reported doctor-diagnosed AD\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
24.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
95.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
51.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
86.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Positive SPT\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
94.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
40.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
88.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Caregiver-reported doctor-diagnosed AD + Positive SPT\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
96.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
44.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
96.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{AD, atopic dermatitis; SPT, skin prick test; PPV, positive
predictive value; NPV, negative predictive value}

Figure 1. Flowchart for the study design

Legend. Abbreviations: AD, atopic dermatitis; SCORAD, SCORing Atopic
Dermatitis

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

