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 13. A total of 1247
healthy pregnant women, aged 18 years and above, were recruited during
their first trimester (<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 criteria14. Of the children diagnosed with AD, the disease
severity was assessed using the SCORAD (SCORing Atopic Dermatitis) index15. 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 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 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 (dmfs ). The SCORAD criteria was used to categorize AD
severity into: i) moderate-to-severe AD (SCORAD≥25) and ii) mild AD
(SCORAD<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).