Accepted Manuscript Higher vitamin D intake during pregnancy is associated with reduced risk of dental caries in young Japanese children Keiko Tanaka, DDS, PhD, Shinichi Hitsumoto, MD, PhD, Yoshihiro Miyake, MD, PhD, Hitomi Okubo, PhD, Satoshi Sasaki, MD, PhD, Nobuyuki Miyatake, MD, PhD, Masashi Arakawa, PhD PII:
S1047-2797(15)00134-9
DOI:
10.1016/j.annepidem.2015.03.020
Reference:
AEP 7811
To appear in:
Annals of Epidemiology
Received Date: 23 July 2014 Revised Date:
30 March 2015
Accepted Date: 30 March 2015
Please cite this article as: Tanaka K, Hitsumoto S, Miyake Y, Okubo H, Sasaki S, Miyatake N, Arakawa M, Higher vitamin D intake during pregnancy is associated with reduced risk of dental caries in young Japanese children, Annals of Epidemiology (2015), doi: 10.1016/j.annepidem.2015.03.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Higher vitamin D intake during pregnancy is associated with reduced risk of dental caries in young Japanese children
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Keiko Tanaka DDS, PhD1*, Shinichi Hitsumoto MD, PhD2, Yoshihiro Miyake MD, PhD1, Hitomi Okubo PhD3, Satoshi Sasaki MD, PhD4, Nobuyuki Miyatake MD, PhD5, Masashi Arakawa PhD6
Department of Epidemiology and Preventive Medicine, Ehime University Graduate
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1
School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
Total Medical Support Center, Ehime University Hospital, Ehime, Japan
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Department of Health Promotion, National Institute of Public Health, Saitama, Japan
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Department of Social and Preventive Epidemiology, School of Public Health, The
University of Tokyo, Japan
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Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan
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Health Tourism Research Center, Graduate School of Tourism Sciences, University of
the Ryukyus, Okinawa, Japan
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*Corresponding: Keiko Tanaka, DDS, PhD, Department of Epidemiology and Preventive Medicine, Ehime University Graduate School of Medicine, Shitsukawa,
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Toon, Ehime, 791-0295, Japan Phone: +81-89-960-5283 Fax: +81-89-960-5284
E-mail: [email protected]
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Abstract Purpose: The intrauterine environment, including maternal nutrition status, may affect
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the development, formation, and mineralization of children’s teeth. We assessed the relationship between self-reported maternal dietary vitamin D intake during pregnancy and the risk of dental caries among young Japanese children.
Methods: This study is based on a prospective analysis of 1210 Japanese mother-child
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pairs. Information on maternal intake during pregnancy was collected using a validated diet history questionnaire. Data on oral examination at 36–46 months of age were
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obtained from the mothers, who transcribed the information from their maternal and child health handbooks to our self-administered questionnaire. Children were classified as having dental caries if one or more primary teeth had decayed or had been filled. Results: Compared with the lowest quartile of maternal vitamin D intake during
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pregnancy, adjusted odds ratios (95% confidence intervals) for quartiles 2, 3, and 4, were 1.06 (0.72–1.56), 0.53 (0.34–0.81), and 0.67 (0.44–1.02), respectively (P for trend = 0.01). When maternal vitamin D intake was treated as a continuous variable, the adjusted odds ratio (95% confidence interval) was 0.94 (0.89–0.995).
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Conclusions: Higher maternal vitamin D intake during pregnancy may be associated
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with a lower risk of dental caries in children.
Keywords
Caries; diet; prospective studies; vitamin D
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List of abbreviations CI: confidence interval DHQ: diet history questionnaire
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KOMCHS: Kyushu Okinawa Maternal and Child Health Study
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OR: odds ratio
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.
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Introduction Dental caries is a chronic disease that can cause pain, chewing difficulty, and discomfort, thereby impacting the quality of life of the affected individuals [1, 2]. Although its
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prevalence has declined, dental caries is still the most prevalent childhood disease worldwide. Dental caries is a multifactorial disease. Various etiological factors,
including physical, biological, environmental, and behavioral factors, are involved in dental caries [1].
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Human teeth are unique in that they are formed during a limited time period [3]. After mineralization, teeth are structurally and metabolically relatively stable [3].
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Primary tooth formation and mineralization starts during the fetal period [4]. Therefore the intrauterine environment, which is affected by factors such as smoking and maternal nutrition during pregnancy, might influence the development, formation, and mineralization of children’s teeth [5, 6].
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Vitamin D plays an essential role in the mineralization of bones and teeth: it maintains the appropriate concentrations of calcium and phosphorus ions in the blood, which ensures the normal mineralization of bones and teeth [7]. Previous studies on the association between vitamin D intake and dental caries have focused mainly on vitamin
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D deficiency and the protective effects of vitamin D supplementation against dental caries [8]. Additionally, these studies were carried out between the First and Second
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World Wars, and health, nutrition, and lifestyle have undergone significant changes since that time [8]. Recent observational epidemiological studies on the association between vitamin D and dental caries are limited [9-12]. It is therefore necessary to accumulate additional evidence to clarify the effect of vitamin D on dental caries. During prenatal development, vitamin D reaches the fetus through the placenta alone [13]. Maternal vitamin D status might affect primary tooth mineralization, and eventually caries susceptibility, in the child. Therefore, the relationship between maternal vitamin D intake during pregnancy and dental caries is worth investigating. In
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the present prospective study, we assessed the relationship between maternal dietary vitamin D intake during pregnancy and the risk of dental caries among young Japanese children, using the data set of the Kyushu Okinawa Maternal and Child Health Study
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(KOMCHS).
Methods Study Population
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The KOMCHS is an ongoing prospective prebirth cohort study that investigates risk and preventive factors for maternal and child health problems such as oral health and
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allergic disorders. Eligible subjects were those women who became pregnant in one of seven prefectures on Kyushu Island in southern Japan or Okinawa Prefecture, an island chain in the southwest of Japan, between April 2007 and March 2008. At 423 obstetric hospitals, a set of leaflets explaining the KOMCHS, an application form to participate in
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the study, and a self-addressed and stamped return envelope were distributed to pregnant women, insofar as this was possible. Pregnant women who intended to participate in the KOMCHS returned the application form to the data management center. In the end, a total of 1757 pregnant women between the 5th and 39th week of
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pregnancy gave their written informed consent to participate in the KOMCHS and also completed the baseline survey. Of these 1757 women, 1590 (90.5%), 1527 (86.9%),
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1430 (81.4%), 1362 (77.5%), and 1306 (74.3%) mother-child pairs participated in the second survey (after birth), third (around 4 months postpartum), fourth (around 12 months postpartum), fifth (around 24 months postpartum), and sixth (around 36 months postpartum) surveys, respectively. In Japan, as a provision of the Maternal and Child Health Law, the municipality in which a child lives sponsors a physical examination at a public health center when the child is between 36 and 47 months of age. This examination includes an oral examination, anthropometric measurements of height and weight, and an interview with
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parents or guardians concerning the child’s health condition. Data on the physical examination are recorded by the medical or dental staff of the public health center in the family’s maternal and child health handbook, which was provided by the municipality
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during the pregnancy and which includes information on prenatal checkups as well as the postnatal health condition of both mother and baby, along with data on the growth of the child. To participate in this study, each child’s mother was required to transcribe the data collected during the physical examination from the maternal and child health
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handbook to our form and then mail the completed form to the data management center. To facilitate the transcription of the data on the physical examination to our form, we
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used exactly the same format as that used for the records in the maternal and child health handbook, and asked the mothers to transcribe all of the information, including symbols. Out of the 1306 mother-child pairs who took part in the sixth survey, 1210 participants provided the data on the oral examination of the child, meaning that, in the
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end, data on 1210 mother-child pairs were available for analysis. The ethics committee of the Faculty of Medicine, Fukuoka University and Ehime University Graduate School of Medicine approved the KOMCHS.
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Outcome variable
At the time of the physical examination at a public health center, the presence of dental
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caries was assessed by visual examination without the use of radiographs. Our study subjects received their oral examinations at 36–46 months of age. Children were classified as having dental caries if one or more primary teeth had decayed or had been filled.
Exposure variables and covariates In each survey, a self-administered questionnaire was used. Participants filled out the questionnaires and then mailed them to the data management center at the time of each
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survey. Research technicians completed missing or illogical data by telephone interview. In the baseline survey, each participant filled out a two-part questionnaire; all data were derived from this questionnaire which was mailed directly to the participants.
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The first part of the questionnaire elicited information on maternal age, region of residence, household income, and maternal and paternal education levels. The second part of the questionnaire was a semi-quantitative, comprehensive diet history
questionnaire (DHQ) that assessed dietary habits during the preceding month [14, 15].
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Estimates of daily intake of foods (total of 150 foods), energy, and selected nutrients were calculated using an ad hoc computer algorithm for the DHQ based on the Standard
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Tables of Food Composition in Japan [16]. Information on dietary supplements was not used due to the lack of a reliable composition table for dietary supplements in Japan. Also, only a small number of participants (6.0%) used supplemental multivitamins at least once per week. According to a validation study of 92 females aged 31 to 69 years,
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the Pearson’s correlation coefficient between the DHQ and 16-day weighted dietary records was 0.54 for vitamin D (S. Sasaki, unpublished observation, 2006). Energy-adjusted intake by the residual methods was used for the analyses [17]. The second survey included questions about the baby’s sex and maternal
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smoking during pregnancy. The third survey asked about household smoking. The fourth survey inquired about household smoking, age in months at first tooth eruption,
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tooth-brushing frequency, and use of fluoride. Information on breastfeeding duration was obtained from questions in the fourth and fifth surveys. In the fifth survey, a brief diet history questionnaire that assessed the dietary habits of the child over the previous month was obtained. Mothers of children were asked to state how frequently their children consumed each of 51 selected food and beverage items. Children’s total dairy products intake was defined as the sum of milk, yogurt, and cheese intake. Children’s total sweetened foods intake was defined as the sum of cookies, Japanese cakes, snacks, and chocolate intake. The fifth and sixth surveys included questions about
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tooth-brushing frequency and the use of fluoride. In the sixth survey, information on between-meal snack frequency was also obtained. Use of fluoride was defined as positive if mothers reported that their children used fluoride agents, such as toothpaste
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or gel, at any point during the time period covered by the survey.
Statistical analysis
Intake of vitamin D was categorized into quartiles on the basis of its distribution in the
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1210 subjects. Maternal age, region of residence, household income, maternal and paternal educational levels, maternal intake of calcium during pregnancy, child’s sex,
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maternal smoking during pregnancy, household smoking during the first year of life, age at first tooth eruption, age at which daily toothbrushing was started, use of fluoride, breastfeeding duration, between-meal snack frequency at the sixth survey, and age at oral examination were a priori selected as potential confounding factors. In the
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sensitivity analyses among 1205 mother-child pairs for whom information on children’s diet at the fifth survey was available, we additionally adjusted for children’s intake of total dairy products and fish and shellfish or total sweetened foods; such intake was categorized into four levels in order to represent the quartiles as closely as possible.
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Logistic regression analysis was performed to estimate crude odds ratios (ORs) and 95% confidence intervals (CIs) for dental caries according to the quartiles of
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maternal vitamin D intake, with the lowest quartile serving as the reference. Multiple logistic regression analysis was employed to adjust for potential confounding factors. The trend of association was assessed by a logistic regression model in which the median value in each quartile of maternal vitamin D intake was assigned as the representative score. Two-sided P values less than 0.05 were considered statistically significant. Using STATA/SE software version 13 (Stata Corp, College Station, TX), the authors employed a restricted cubic spline model to calculate a P value for non-linearity by testing the null hypothesis that the log-odds of the binary outcome under study is a
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linear function of maternal vitamin D. A linear relationship is indicated when the P value for non-linearity is ≥ 0.05. Excluding the restricted cubic spline model, all statistical analyses were performed using the SAS software package version 9.3 (SAS
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Institute, Inc., Cary, NC, USA).
Results
Of the 1210 children, 267 (22.1%) had experienced dental caries, and 943 (77.9%) were
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caries-free. The mean numbers of teeth with dental caries for all subjects and for subjects who had experienced caries were 0.71 and 3.2, respectively. Characteristics of
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the study population are presented in Table 1. The mean maternal age at baseline was 31.6 years. Approximately 46% of mothers and 57% of fathers had received at least 15 years of education. Maternal mean daily total energy intake was 7414.8 kJ, and mean energy-adjusted intakes of vitamin D and calcium were 5.8 µg and 508.6 mg,
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respectively. The mothers of 7% of the children had smoked during pregnancy. At least one smoker had lived in the household during the child’s first year of life in about 43% of the families. Nearly 52% of mothers reported that they had started daily toothbrushing of their children prior to 12 months of age. Fluoride agents were used by
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approximately 88% of children. Compared with children who were caries-free, children who experienced dental caries were more likely to have parents with low educational
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levels, to live in families with low family income, to be boys, to live with a smoker during the first year of life, to have had early eruption of the first tooth, to have breastfed for a relatively long time, and to have received an oral examination at a later month of age. There were no differences in maternal age, total energy intake, maternal calcium intake during pregnancy, maternal smoking during pregnancy, use of fluoride, or between-meal snack frequency between the two groups. Table 2 presents the distributions of confounding factors according to maternal dietary vitamin D intake during pregnancy. Maternal dietary vitamin D intake was
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positively associated with age, household income, maternal educational level, and maternal calcium intake during pregnancy, and inversely associated with maternal smoking during pregnancy, living with a smoker during the first year of life, and age at
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oral examination. There was a linear relationship between the intake of vitamin D and the log-odds of dental caries (P for non-linearity = 0.09) among the 1210 mother-child pairs.
Table 3 shows crude and adjusted ORs and their 95% CIs for dental caries in
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relation to maternal vitamin D intake. Compared with the lowest quartile of maternal intake of vitamin D during pregnancy, both the third and fourth quartiles were
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significantly associated with a reduced risk of dental caries in the children, showing a clear inverse exposure-response relationship. After adjustment for the confounding factors under study, the inverse association remained statistically significant only in the third quartile. Compared with the lowest quartile of maternal vitamin D intake, adjusted
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ORs (95% CIs) for quartiles 2, 3, and 4 were 1.06 (0.72–1.56), 0.53 (0.34–0.81), and 0.67 (0.44–1.02), respectively. A significant inverse trend was observed between maternal intake of vitamin D and dental caries in children, even after controlling for the confounding factors under study (P for trend = 0.01). When maternal vitamin D intake
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was treated as a continuous variable, the adjusted OR (95% CI) was 0.94 (0.89–0.995), which means that the risk reduction of dental caries for every microgram increase of
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maternal daily vitamin D intake during pregnancy is 6%. When children were classified according to whether their mothers had
participated in the baseline survey by 13 weeks of gestation (n = 233) or after 14 weeks of gestation (n = 977), the adjusted ORs (95% CIs) for quartiles 2, 3, and 4 and P for trend were 0.60 (0.22–1.56), 0.14 (0.04–0.42), 0.50 (0.18–1.33) and 0.03, respectively, for those participating at 13 or fewer weeks of gestation; and 1.23 (0.79–1.90), 0.64 (0.40–1.03), 0.68 (0.42–1.09) and 0.02, respectively, for those participating at more than 14 weeks of gestation. No significant differences were observed between those
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participating at 13 or fewer weeks and those participating at more than 14 weeks with regard to the association of maternal vitamin D intake with the risk of dental caries (P = 0.25, 0.10, and 0.83 for homogeneity of OR in quartiles 2, 3, and 4, respectively).
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We also conducted a sensitivity analysis in which we additionally adjusted for children’s intake of total dairy products and fish and shellfish at the fifth survey among 1205 mother-child pairs for whom information on children’s diet was available; the inverse association of maternal vitamin D intake with the risk of dental caries was
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essentially unaltered: the additional adjusted ORs (95% CIs) for quartiles 2, 3, and 4 were 1.08 (0.73–1.60), 0.51 (0.33–0.78), and 0.69 (0.44–1.06), respectively (P for trend
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= 0.02).
Results of another sensitivity analysis in which further adjustment was made for children’s intake of total sweetened foods at the fifth survey were similar to those of the overall analysis: the additional adjusted ORs (95% CIs) for quartiles 2, 3, and 4 were
Discussion
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0.02).
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1.07 (0.73–1.59), 0.52 (0.34–0.81), and 0.69 (0.45–1.06), respectively (P for trend =
In this prospective study in Japan, we found that higher maternal vitamin D intake
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during pregnancy was associated with a reduced risk of dental caries in children. Recent studies on the relationship between vitamin D intake or serum levels of 25-hydroxyvitamin D (25[OH]D) and dental caries are scarce [9-12]. In a case-control study of Canadian preschool children, the subjects with severe early childhood caries were significantly more likely to have low serum levels of 25(OH)D compared to the caries-free controls [9]. A longitudinal study in the US observed that inadequate intake of vitamin D at three years of age was significantly associated with an increased risk of dental caries at four to seven years of age [11]. In a prospective cohort study in Canada,
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maternal 25(OH)D level during pregnancy was inversely associated with the risk of dental caries in children during the first year of life [12]. These previous studies are not directly comparable to our study because of differences in the study designs and
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populations, exposure assessment methods and timing, and confounding factors. In addition, the main sources of vitamin D intake are different in different countries. For
example, among adults in the US, milk is the highest ranked food source of vitamin D (45.1%) [18]; among Japanese, fish and shellfish are the main source of vitamin D
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(78.4%) [19]. In addition, vitamin D can be synthesized in the skin through sunlight exposure as well as obtained through dietary intake. In fact, sunlight exposure is the
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major influence on vitamin D status, and it is influenced by skin color, latitude, season, and life-style and cultural practices [20]. Thus many confounding and unidentified factors are likely to be present in the current study as well as existing studies. The biological mechanism by which higher maternal vitamin D intake during
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pregnancy may reduce the risk of dental caries in children is not known. The classical function of vitamin D is related to calcium and phosphate homeostasis and bone health. Deficiency of vitamin D leads to inadequate levels of calcium in circulating plasma [21]. Formation and mineralization of deciduous teeth usually begin at 13 weeks of gestation.
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Because the fetus is entirely dependent on the mother for its supply of vitamin D metabolites [13], maternal vitamin D deficiency during pregnancy may have a negative
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impact on tooth mineralization in the fetus. Another possible explanation is that vitamin D might directly affect tooth mineralization [22]. Ameloblasts and odontoblasts are target cells for vitamin D [23]. An animal study demonstrated that vitamin D appeared to indirectly regulate dentin mineralization by controlling the Ca/P ratio, while enamel mineralization might be directly regulated through genomic and non-genomic pathways [22]. Alternatively, higher maternal intake of vitamin D may simply reflect a healthier diet and/or lifestyle. In the current study, the risk reduction associated with maternal vitamin D intake
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did not appear to be confounded by child’s dietary intake such as dairy products and fish and shellfish; those foods, in Japan, are the main sources of calcium and vitamin D. The caries resistance of teeth might be more influenced by the vitamin D status in the fetal
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period rather than that in early childhood. Our study has certain methodological strengths. We evaluated the association in a prospective cohort study which is free from recall bias, and we were able to control
confounded by unknown or residual factors.
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for relevant confounding factors. It is possible, however, that our results remain
Our study has several limitations. First, selection bias could have affected our
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results. Of the 1757 participants at baseline, 1210 children (68.9%) were ultimately evaluated in this analysis. Compared with children who were excluded due to incomplete information or nonparticipation in follow-up surveys, study subjects were more likely to live in families with relatively high incomes, and to have parents with
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relatively high educational levels, while they were less likely to have been exposed to maternal smoking during pregnancy. Moreover, at baseline, we could not estimate the participation rate because the exact number of eligible pregnant women who were provided with a set of leaflets explaining the KOMCHS, an application form, and a
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self-addressed and stamped return envelope by the 423 collaborating obstetric hospitals was not available. Our subjects were also probably not a representative sample of
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Japanese women in the general population: it is known, in fact, that educational levels were higher in the parents in our study than in the general population [24]. However, it has been shown that selection bias in cohort studies primarily arises from loss to follow-up rather than to non-response at baseline [25]. With regard to dietary intake, vitamin D intake in this population (5.8µg/day) is similar to that in the general population. According to the National Health and Nutrition Survey in Japan, for women aged 30 to 39 years, the average daily per capita intake of vitamin D is 5.7µg/day [18]. On the other hand, our children appeared to have a lower incidence of dental caries
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(22.1%) compared to the sample of three-year-old Japanese children in the Survey of Dental Diseases conducted in 2011 (25.0%) [26]. In the present study, we were not able to include vitamin supplements in our calculation of maternal vitamin D intake. Only
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6.0% (73 women) used supplemental multivitamins at least once per week, however. The results of a sensitivity analysis which excluded these 73 women were similar to
those of the overall analysis: the adjusted ORs from the lowest to highest category of
intake by quartiles were 1.00, 1.10 (95% CI: 0.74–1.66), 0.60 (95% CI: 0.38–0.92), and
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0.71 (95% CI: 0.47–1.09), respectively (P for trend = 0.04).
Second, our DHQ could only approximate consumption and was designed to
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assess dietary intake for one month prior to completing the questionnaire. We believe that the possibility of non-differential exposure misclassification would introduce a bias toward the null. In the present study, assessment of diet was performed during pregnancy. Substantial changes in diet in the previous month were experienced by 358
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pregnant women because of nausea gravidarum (341 women), maternal and fetal health (15 women), and other reasons (two women). The results of a sensitivity analysis excluding these 358 women were similar to those of the overall analysis: the adjusted ORs from the lowest to highest category of intake by quartile were 1.00, 1.08 (95% CI:
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0.68‒1.71), 0.53 (95% CI: 0.32‒0.88), and 0.69 (95% CI: 0.43‒1.12), respectively (P for trend = 0.05).
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Third, the data on dental caries used in the current study were gathered during
routine examinations by dentists at public health centers. The dentists were given detailed criteria for performing the examinations, but they received no specific training aimed at standardizing the procedures. Therefore, it is unknown whether intra- and interexaminer consistency was established. Moreover, because the mothers of the children transcribed the oral examination data from their maternal and child health handbooks to our form, we cannot exclude the possibility that transcription errors occurred, which could have driven the results.
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Fourth, the present study did not take sunlight exposure status into consideration. Our study population lived in southern Japan, in latitudes ranging from 26° to 33° N. UVB radiation at this latitude is sufficient for vitamin D synthesis for about 11 months
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each year [27]. In a sensitivity analysis, additional adjustment for birth season did not materially change the inverse association between maternal vitamin D intake and caries: the further adjusted ORs (95% CIs) from the lowest to highest category of intake by quartile were 1.00, 1.06 (0.72‒1.56), 0.53 (0.34‒0.81), and 0.68 (0.44‒1.04),
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respectively (P for trend = 0.02). Finally, data on serum 25(OH)D concentrations were
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not available.
Conclusions
Our results indicate an association between higher maternal vitamin D intake during pregnancy and a reduced risk of dental caries in young Japanese children. Because of
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the numerous limitations, these results should be interpreted cautiously and subsequently confirmed in other populations. Further studies are needed to clarify both the mechanisms underlying the association and the long-term consequences.
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Acknowledgements
The authors would like to acknowledge the Kyushu Branch of the Japan Allergy
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Foundation, the Fukuoka Association of Obstetricians & Gynecologists, the Okinawa Association of Obstetricians & Gynecologists, the Miyazaki Association of Obstetricians & Gynecologists, the Oita Association of Obstetricians & Gynecologists, the Kumamoto Association of Obstetricians & Gynecologists, the Nagasaki Association of Obstetricians & Gynecologists, the Kagoshima Association of Obstetricians & Gynecologists, the Saga Association of Obstetricians & Gynecologists, the Fukuoka Society of Obstetrics and Gynecology, the Okinawa Society of Obstetrics and Gynecology, the Fukuoka City Government, and the Fukuoka City Medical Association
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for their valuable support. This study was supported by JSPS KAKENHI (Grant numbers 19590606, 20791654, 21590673, 22592355, 22119507, 24390158, 25463275, and 25670305);
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Health and Labour Sciences Research Grants for Research on Allergic Disease and Immunology; Health Research on Children, Youth and Families from the Ministry of Health, Labour and Welfare, Japan; Meiji Co. Ltd.; the Food Science Institute
Foundation; and the Danone Institute of Japan Foundation. These organizations did not
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have any influence on the study design; the collection, analysis, or interpretation of
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data; the writing of the report; or the decision to submit the article for publication.
Conflict of interest
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The authors have no conflict of interest to disclose.
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[20] Thorne-Lyman A, Fawzi WW. Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis. Paediatr Perinat
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Epidemiol 2012; 26 Suppl 1:75-90.
[21] Nikiforuk G, Fraser D. The etiology of enamel hypoplasia: a unifying concept. J Pediatr 1981; 98: 888-93.
[22] Zhang X, Rahemtulla F, Zhang P, Beck P, Thomas HF. Different enamel and dentin mineralization observed in VDR deficient mouse model. Arch Oral Biol 2009; 54: 299-305. [23] Berdal A, Papagerakis P, Hotton D, Bailleul-Forestier I, Davideau JL. Ameloblasts and odontoblasts, target-cells for 1,25-dihydroxyvitamin D3: a review. Int J Dev
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Biol 1995; 39: 257-62. [24] Statistics Bureau, Ministry of Public Management, Home Affairs, Post and Telecommunications, Japan: 2000 population census of Japan, Vol. 3-2-27, labour
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force status of population, industry (major groups) of employed persons, and education. Osaka-fu. Tokyo: Japan Statistical Association; 2002.
[25] Nohr EA, Frydenberg M, Henriksen TB, Olsen J. Does low participation in cohort studies induce bias? Epidemiology 2006; 17: 413-8.
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[26] Japanese Society for Dental Health: Report on the Survey of Dental Diseases (2011). Tokyo: Japanese Society for Oral Health; 2013.
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2007; 297: 62-5, 68-70, 72.
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[27] Tavera-Mendoza LE, White JH. Cell defenses and the sunshine vitamin. Sci Am
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Number (%) or mean ± SD
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Baseline characteristics Maternal age, years, mean ± SD
31.6 ± 4.0
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Region of residence Fukuoka Prefecture Other than Fukuoka Prefecture in Kyushu
≥ 6,000,000 Maternal educational level, years < 13 13–14 ≥ 15 Paternal educational level, years
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4,000,000–5,999,999
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< 4,000,000
31.9 ± 4.0
31.5 ± 4.0
P value
0.14 0.0004
693 (57.3)
127 (47.6)
566 (60.0)
403 (33.3)
110 (41.2)
293 (31.1))
114 (9.4)
30 (11.2)
84 (8.9)
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Okinawa Prefecture Household income, yen/year
Caries status Caries (n =267) Caries free (n = Number (%) or 943) Number (%) mean ± SD or mean ± SD
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Table 1 Distribution of characteristics in 1210 mother-child pairs, KOMCHS, Japan Variable Overall
0.03
387 (32.0)
96 (36.0)
291 (30.9)
457 (37.8)
104 (39.0)
353 (37.4)
366 (30.3)
67 (25.1)
299 (31.7)
S1047-2797(15)00134-9
DOI:
10.1016/j.annepidem.2015.03.020
Reference:
AEP 7811
To appear in:
Annals of Epidemiology
Received Date: 23 July 2014 Revised Date:
30 March 2015
Accepted Date: 30 March 2015
Please cite this article as: Tanaka K, Hitsumoto S, Miyake Y, Okubo H, Sasaki S, Miyatake N, Arakawa M, Higher vitamin D intake during pregnancy is associated with reduced risk of dental caries in young Japanese children, Annals of Epidemiology (2015), doi: 10.1016/j.annepidem.2015.03.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Higher vitamin D intake during pregnancy is associated with reduced risk of dental caries in young Japanese children
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Keiko Tanaka DDS, PhD1*, Shinichi Hitsumoto MD, PhD2, Yoshihiro Miyake MD, PhD1, Hitomi Okubo PhD3, Satoshi Sasaki MD, PhD4, Nobuyuki Miyatake MD, PhD5, Masashi Arakawa PhD6
Department of Epidemiology and Preventive Medicine, Ehime University Graduate
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1
School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
Total Medical Support Center, Ehime University Hospital, Ehime, Japan
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2 3
Department of Health Promotion, National Institute of Public Health, Saitama, Japan
4
Department of Social and Preventive Epidemiology, School of Public Health, The
University of Tokyo, Japan
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Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan
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5
Health Tourism Research Center, Graduate School of Tourism Sciences, University of
the Ryukyus, Okinawa, Japan
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*Corresponding: Keiko Tanaka, DDS, PhD, Department of Epidemiology and Preventive Medicine, Ehime University Graduate School of Medicine, Shitsukawa,
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Toon, Ehime, 791-0295, Japan Phone: +81-89-960-5283 Fax: +81-89-960-5284
E-mail: [email protected]
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Abstract Purpose: The intrauterine environment, including maternal nutrition status, may affect
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the development, formation, and mineralization of children’s teeth. We assessed the relationship between self-reported maternal dietary vitamin D intake during pregnancy and the risk of dental caries among young Japanese children.
Methods: This study is based on a prospective analysis of 1210 Japanese mother-child
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pairs. Information on maternal intake during pregnancy was collected using a validated diet history questionnaire. Data on oral examination at 36–46 months of age were
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obtained from the mothers, who transcribed the information from their maternal and child health handbooks to our self-administered questionnaire. Children were classified as having dental caries if one or more primary teeth had decayed or had been filled. Results: Compared with the lowest quartile of maternal vitamin D intake during
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pregnancy, adjusted odds ratios (95% confidence intervals) for quartiles 2, 3, and 4, were 1.06 (0.72–1.56), 0.53 (0.34–0.81), and 0.67 (0.44–1.02), respectively (P for trend = 0.01). When maternal vitamin D intake was treated as a continuous variable, the adjusted odds ratio (95% confidence interval) was 0.94 (0.89–0.995).
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Conclusions: Higher maternal vitamin D intake during pregnancy may be associated
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with a lower risk of dental caries in children.
Keywords
Caries; diet; prospective studies; vitamin D
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List of abbreviations CI: confidence interval DHQ: diet history questionnaire
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KOMCHS: Kyushu Okinawa Maternal and Child Health Study
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OR: odds ratio
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.
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Introduction Dental caries is a chronic disease that can cause pain, chewing difficulty, and discomfort, thereby impacting the quality of life of the affected individuals [1, 2]. Although its
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prevalence has declined, dental caries is still the most prevalent childhood disease worldwide. Dental caries is a multifactorial disease. Various etiological factors,
including physical, biological, environmental, and behavioral factors, are involved in dental caries [1].
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Human teeth are unique in that they are formed during a limited time period [3]. After mineralization, teeth are structurally and metabolically relatively stable [3].
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Primary tooth formation and mineralization starts during the fetal period [4]. Therefore the intrauterine environment, which is affected by factors such as smoking and maternal nutrition during pregnancy, might influence the development, formation, and mineralization of children’s teeth [5, 6].
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Vitamin D plays an essential role in the mineralization of bones and teeth: it maintains the appropriate concentrations of calcium and phosphorus ions in the blood, which ensures the normal mineralization of bones and teeth [7]. Previous studies on the association between vitamin D intake and dental caries have focused mainly on vitamin
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D deficiency and the protective effects of vitamin D supplementation against dental caries [8]. Additionally, these studies were carried out between the First and Second
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World Wars, and health, nutrition, and lifestyle have undergone significant changes since that time [8]. Recent observational epidemiological studies on the association between vitamin D and dental caries are limited [9-12]. It is therefore necessary to accumulate additional evidence to clarify the effect of vitamin D on dental caries. During prenatal development, vitamin D reaches the fetus through the placenta alone [13]. Maternal vitamin D status might affect primary tooth mineralization, and eventually caries susceptibility, in the child. Therefore, the relationship between maternal vitamin D intake during pregnancy and dental caries is worth investigating. In
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the present prospective study, we assessed the relationship between maternal dietary vitamin D intake during pregnancy and the risk of dental caries among young Japanese children, using the data set of the Kyushu Okinawa Maternal and Child Health Study
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(KOMCHS).
Methods Study Population
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The KOMCHS is an ongoing prospective prebirth cohort study that investigates risk and preventive factors for maternal and child health problems such as oral health and
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allergic disorders. Eligible subjects were those women who became pregnant in one of seven prefectures on Kyushu Island in southern Japan or Okinawa Prefecture, an island chain in the southwest of Japan, between April 2007 and March 2008. At 423 obstetric hospitals, a set of leaflets explaining the KOMCHS, an application form to participate in
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the study, and a self-addressed and stamped return envelope were distributed to pregnant women, insofar as this was possible. Pregnant women who intended to participate in the KOMCHS returned the application form to the data management center. In the end, a total of 1757 pregnant women between the 5th and 39th week of
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pregnancy gave their written informed consent to participate in the KOMCHS and also completed the baseline survey. Of these 1757 women, 1590 (90.5%), 1527 (86.9%),
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1430 (81.4%), 1362 (77.5%), and 1306 (74.3%) mother-child pairs participated in the second survey (after birth), third (around 4 months postpartum), fourth (around 12 months postpartum), fifth (around 24 months postpartum), and sixth (around 36 months postpartum) surveys, respectively. In Japan, as a provision of the Maternal and Child Health Law, the municipality in which a child lives sponsors a physical examination at a public health center when the child is between 36 and 47 months of age. This examination includes an oral examination, anthropometric measurements of height and weight, and an interview with
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parents or guardians concerning the child’s health condition. Data on the physical examination are recorded by the medical or dental staff of the public health center in the family’s maternal and child health handbook, which was provided by the municipality
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during the pregnancy and which includes information on prenatal checkups as well as the postnatal health condition of both mother and baby, along with data on the growth of the child. To participate in this study, each child’s mother was required to transcribe the data collected during the physical examination from the maternal and child health
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handbook to our form and then mail the completed form to the data management center. To facilitate the transcription of the data on the physical examination to our form, we
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used exactly the same format as that used for the records in the maternal and child health handbook, and asked the mothers to transcribe all of the information, including symbols. Out of the 1306 mother-child pairs who took part in the sixth survey, 1210 participants provided the data on the oral examination of the child, meaning that, in the
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end, data on 1210 mother-child pairs were available for analysis. The ethics committee of the Faculty of Medicine, Fukuoka University and Ehime University Graduate School of Medicine approved the KOMCHS.
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Outcome variable
At the time of the physical examination at a public health center, the presence of dental
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caries was assessed by visual examination without the use of radiographs. Our study subjects received their oral examinations at 36–46 months of age. Children were classified as having dental caries if one or more primary teeth had decayed or had been filled.
Exposure variables and covariates In each survey, a self-administered questionnaire was used. Participants filled out the questionnaires and then mailed them to the data management center at the time of each
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survey. Research technicians completed missing or illogical data by telephone interview. In the baseline survey, each participant filled out a two-part questionnaire; all data were derived from this questionnaire which was mailed directly to the participants.
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The first part of the questionnaire elicited information on maternal age, region of residence, household income, and maternal and paternal education levels. The second part of the questionnaire was a semi-quantitative, comprehensive diet history
questionnaire (DHQ) that assessed dietary habits during the preceding month [14, 15].
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Estimates of daily intake of foods (total of 150 foods), energy, and selected nutrients were calculated using an ad hoc computer algorithm for the DHQ based on the Standard
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Tables of Food Composition in Japan [16]. Information on dietary supplements was not used due to the lack of a reliable composition table for dietary supplements in Japan. Also, only a small number of participants (6.0%) used supplemental multivitamins at least once per week. According to a validation study of 92 females aged 31 to 69 years,
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the Pearson’s correlation coefficient between the DHQ and 16-day weighted dietary records was 0.54 for vitamin D (S. Sasaki, unpublished observation, 2006). Energy-adjusted intake by the residual methods was used for the analyses [17]. The second survey included questions about the baby’s sex and maternal
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smoking during pregnancy. The third survey asked about household smoking. The fourth survey inquired about household smoking, age in months at first tooth eruption,
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tooth-brushing frequency, and use of fluoride. Information on breastfeeding duration was obtained from questions in the fourth and fifth surveys. In the fifth survey, a brief diet history questionnaire that assessed the dietary habits of the child over the previous month was obtained. Mothers of children were asked to state how frequently their children consumed each of 51 selected food and beverage items. Children’s total dairy products intake was defined as the sum of milk, yogurt, and cheese intake. Children’s total sweetened foods intake was defined as the sum of cookies, Japanese cakes, snacks, and chocolate intake. The fifth and sixth surveys included questions about
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tooth-brushing frequency and the use of fluoride. In the sixth survey, information on between-meal snack frequency was also obtained. Use of fluoride was defined as positive if mothers reported that their children used fluoride agents, such as toothpaste
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or gel, at any point during the time period covered by the survey.
Statistical analysis
Intake of vitamin D was categorized into quartiles on the basis of its distribution in the
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1210 subjects. Maternal age, region of residence, household income, maternal and paternal educational levels, maternal intake of calcium during pregnancy, child’s sex,
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maternal smoking during pregnancy, household smoking during the first year of life, age at first tooth eruption, age at which daily toothbrushing was started, use of fluoride, breastfeeding duration, between-meal snack frequency at the sixth survey, and age at oral examination were a priori selected as potential confounding factors. In the
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sensitivity analyses among 1205 mother-child pairs for whom information on children’s diet at the fifth survey was available, we additionally adjusted for children’s intake of total dairy products and fish and shellfish or total sweetened foods; such intake was categorized into four levels in order to represent the quartiles as closely as possible.
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Logistic regression analysis was performed to estimate crude odds ratios (ORs) and 95% confidence intervals (CIs) for dental caries according to the quartiles of
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maternal vitamin D intake, with the lowest quartile serving as the reference. Multiple logistic regression analysis was employed to adjust for potential confounding factors. The trend of association was assessed by a logistic regression model in which the median value in each quartile of maternal vitamin D intake was assigned as the representative score. Two-sided P values less than 0.05 were considered statistically significant. Using STATA/SE software version 13 (Stata Corp, College Station, TX), the authors employed a restricted cubic spline model to calculate a P value for non-linearity by testing the null hypothesis that the log-odds of the binary outcome under study is a
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linear function of maternal vitamin D. A linear relationship is indicated when the P value for non-linearity is ≥ 0.05. Excluding the restricted cubic spline model, all statistical analyses were performed using the SAS software package version 9.3 (SAS
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Institute, Inc., Cary, NC, USA).
Results
Of the 1210 children, 267 (22.1%) had experienced dental caries, and 943 (77.9%) were
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caries-free. The mean numbers of teeth with dental caries for all subjects and for subjects who had experienced caries were 0.71 and 3.2, respectively. Characteristics of
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the study population are presented in Table 1. The mean maternal age at baseline was 31.6 years. Approximately 46% of mothers and 57% of fathers had received at least 15 years of education. Maternal mean daily total energy intake was 7414.8 kJ, and mean energy-adjusted intakes of vitamin D and calcium were 5.8 µg and 508.6 mg,
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respectively. The mothers of 7% of the children had smoked during pregnancy. At least one smoker had lived in the household during the child’s first year of life in about 43% of the families. Nearly 52% of mothers reported that they had started daily toothbrushing of their children prior to 12 months of age. Fluoride agents were used by
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approximately 88% of children. Compared with children who were caries-free, children who experienced dental caries were more likely to have parents with low educational
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levels, to live in families with low family income, to be boys, to live with a smoker during the first year of life, to have had early eruption of the first tooth, to have breastfed for a relatively long time, and to have received an oral examination at a later month of age. There were no differences in maternal age, total energy intake, maternal calcium intake during pregnancy, maternal smoking during pregnancy, use of fluoride, or between-meal snack frequency between the two groups. Table 2 presents the distributions of confounding factors according to maternal dietary vitamin D intake during pregnancy. Maternal dietary vitamin D intake was
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positively associated with age, household income, maternal educational level, and maternal calcium intake during pregnancy, and inversely associated with maternal smoking during pregnancy, living with a smoker during the first year of life, and age at
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oral examination. There was a linear relationship between the intake of vitamin D and the log-odds of dental caries (P for non-linearity = 0.09) among the 1210 mother-child pairs.
Table 3 shows crude and adjusted ORs and their 95% CIs for dental caries in
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relation to maternal vitamin D intake. Compared with the lowest quartile of maternal intake of vitamin D during pregnancy, both the third and fourth quartiles were
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significantly associated with a reduced risk of dental caries in the children, showing a clear inverse exposure-response relationship. After adjustment for the confounding factors under study, the inverse association remained statistically significant only in the third quartile. Compared with the lowest quartile of maternal vitamin D intake, adjusted
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ORs (95% CIs) for quartiles 2, 3, and 4 were 1.06 (0.72–1.56), 0.53 (0.34–0.81), and 0.67 (0.44–1.02), respectively. A significant inverse trend was observed between maternal intake of vitamin D and dental caries in children, even after controlling for the confounding factors under study (P for trend = 0.01). When maternal vitamin D intake
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was treated as a continuous variable, the adjusted OR (95% CI) was 0.94 (0.89–0.995), which means that the risk reduction of dental caries for every microgram increase of
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maternal daily vitamin D intake during pregnancy is 6%. When children were classified according to whether their mothers had
participated in the baseline survey by 13 weeks of gestation (n = 233) or after 14 weeks of gestation (n = 977), the adjusted ORs (95% CIs) for quartiles 2, 3, and 4 and P for trend were 0.60 (0.22–1.56), 0.14 (0.04–0.42), 0.50 (0.18–1.33) and 0.03, respectively, for those participating at 13 or fewer weeks of gestation; and 1.23 (0.79–1.90), 0.64 (0.40–1.03), 0.68 (0.42–1.09) and 0.02, respectively, for those participating at more than 14 weeks of gestation. No significant differences were observed between those
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participating at 13 or fewer weeks and those participating at more than 14 weeks with regard to the association of maternal vitamin D intake with the risk of dental caries (P = 0.25, 0.10, and 0.83 for homogeneity of OR in quartiles 2, 3, and 4, respectively).
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We also conducted a sensitivity analysis in which we additionally adjusted for children’s intake of total dairy products and fish and shellfish at the fifth survey among 1205 mother-child pairs for whom information on children’s diet was available; the inverse association of maternal vitamin D intake with the risk of dental caries was
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essentially unaltered: the additional adjusted ORs (95% CIs) for quartiles 2, 3, and 4 were 1.08 (0.73–1.60), 0.51 (0.33–0.78), and 0.69 (0.44–1.06), respectively (P for trend
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= 0.02).
Results of another sensitivity analysis in which further adjustment was made for children’s intake of total sweetened foods at the fifth survey were similar to those of the overall analysis: the additional adjusted ORs (95% CIs) for quartiles 2, 3, and 4 were
Discussion
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0.02).
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1.07 (0.73–1.59), 0.52 (0.34–0.81), and 0.69 (0.45–1.06), respectively (P for trend =
In this prospective study in Japan, we found that higher maternal vitamin D intake
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during pregnancy was associated with a reduced risk of dental caries in children. Recent studies on the relationship between vitamin D intake or serum levels of 25-hydroxyvitamin D (25[OH]D) and dental caries are scarce [9-12]. In a case-control study of Canadian preschool children, the subjects with severe early childhood caries were significantly more likely to have low serum levels of 25(OH)D compared to the caries-free controls [9]. A longitudinal study in the US observed that inadequate intake of vitamin D at three years of age was significantly associated with an increased risk of dental caries at four to seven years of age [11]. In a prospective cohort study in Canada,
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maternal 25(OH)D level during pregnancy was inversely associated with the risk of dental caries in children during the first year of life [12]. These previous studies are not directly comparable to our study because of differences in the study designs and
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populations, exposure assessment methods and timing, and confounding factors. In addition, the main sources of vitamin D intake are different in different countries. For
example, among adults in the US, milk is the highest ranked food source of vitamin D (45.1%) [18]; among Japanese, fish and shellfish are the main source of vitamin D
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(78.4%) [19]. In addition, vitamin D can be synthesized in the skin through sunlight exposure as well as obtained through dietary intake. In fact, sunlight exposure is the
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major influence on vitamin D status, and it is influenced by skin color, latitude, season, and life-style and cultural practices [20]. Thus many confounding and unidentified factors are likely to be present in the current study as well as existing studies. The biological mechanism by which higher maternal vitamin D intake during
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pregnancy may reduce the risk of dental caries in children is not known. The classical function of vitamin D is related to calcium and phosphate homeostasis and bone health. Deficiency of vitamin D leads to inadequate levels of calcium in circulating plasma [21]. Formation and mineralization of deciduous teeth usually begin at 13 weeks of gestation.
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Because the fetus is entirely dependent on the mother for its supply of vitamin D metabolites [13], maternal vitamin D deficiency during pregnancy may have a negative
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impact on tooth mineralization in the fetus. Another possible explanation is that vitamin D might directly affect tooth mineralization [22]. Ameloblasts and odontoblasts are target cells for vitamin D [23]. An animal study demonstrated that vitamin D appeared to indirectly regulate dentin mineralization by controlling the Ca/P ratio, while enamel mineralization might be directly regulated through genomic and non-genomic pathways [22]. Alternatively, higher maternal intake of vitamin D may simply reflect a healthier diet and/or lifestyle. In the current study, the risk reduction associated with maternal vitamin D intake
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did not appear to be confounded by child’s dietary intake such as dairy products and fish and shellfish; those foods, in Japan, are the main sources of calcium and vitamin D. The caries resistance of teeth might be more influenced by the vitamin D status in the fetal
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period rather than that in early childhood. Our study has certain methodological strengths. We evaluated the association in a prospective cohort study which is free from recall bias, and we were able to control
confounded by unknown or residual factors.
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for relevant confounding factors. It is possible, however, that our results remain
Our study has several limitations. First, selection bias could have affected our
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results. Of the 1757 participants at baseline, 1210 children (68.9%) were ultimately evaluated in this analysis. Compared with children who were excluded due to incomplete information or nonparticipation in follow-up surveys, study subjects were more likely to live in families with relatively high incomes, and to have parents with
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relatively high educational levels, while they were less likely to have been exposed to maternal smoking during pregnancy. Moreover, at baseline, we could not estimate the participation rate because the exact number of eligible pregnant women who were provided with a set of leaflets explaining the KOMCHS, an application form, and a
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self-addressed and stamped return envelope by the 423 collaborating obstetric hospitals was not available. Our subjects were also probably not a representative sample of
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Japanese women in the general population: it is known, in fact, that educational levels were higher in the parents in our study than in the general population [24]. However, it has been shown that selection bias in cohort studies primarily arises from loss to follow-up rather than to non-response at baseline [25]. With regard to dietary intake, vitamin D intake in this population (5.8µg/day) is similar to that in the general population. According to the National Health and Nutrition Survey in Japan, for women aged 30 to 39 years, the average daily per capita intake of vitamin D is 5.7µg/day [18]. On the other hand, our children appeared to have a lower incidence of dental caries
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(22.1%) compared to the sample of three-year-old Japanese children in the Survey of Dental Diseases conducted in 2011 (25.0%) [26]. In the present study, we were not able to include vitamin supplements in our calculation of maternal vitamin D intake. Only
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6.0% (73 women) used supplemental multivitamins at least once per week, however. The results of a sensitivity analysis which excluded these 73 women were similar to
those of the overall analysis: the adjusted ORs from the lowest to highest category of
intake by quartiles were 1.00, 1.10 (95% CI: 0.74–1.66), 0.60 (95% CI: 0.38–0.92), and
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0.71 (95% CI: 0.47–1.09), respectively (P for trend = 0.04).
Second, our DHQ could only approximate consumption and was designed to
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assess dietary intake for one month prior to completing the questionnaire. We believe that the possibility of non-differential exposure misclassification would introduce a bias toward the null. In the present study, assessment of diet was performed during pregnancy. Substantial changes in diet in the previous month were experienced by 358
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pregnant women because of nausea gravidarum (341 women), maternal and fetal health (15 women), and other reasons (two women). The results of a sensitivity analysis excluding these 358 women were similar to those of the overall analysis: the adjusted ORs from the lowest to highest category of intake by quartile were 1.00, 1.08 (95% CI:
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0.68‒1.71), 0.53 (95% CI: 0.32‒0.88), and 0.69 (95% CI: 0.43‒1.12), respectively (P for trend = 0.05).
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Third, the data on dental caries used in the current study were gathered during
routine examinations by dentists at public health centers. The dentists were given detailed criteria for performing the examinations, but they received no specific training aimed at standardizing the procedures. Therefore, it is unknown whether intra- and interexaminer consistency was established. Moreover, because the mothers of the children transcribed the oral examination data from their maternal and child health handbooks to our form, we cannot exclude the possibility that transcription errors occurred, which could have driven the results.
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Fourth, the present study did not take sunlight exposure status into consideration. Our study population lived in southern Japan, in latitudes ranging from 26° to 33° N. UVB radiation at this latitude is sufficient for vitamin D synthesis for about 11 months
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each year [27]. In a sensitivity analysis, additional adjustment for birth season did not materially change the inverse association between maternal vitamin D intake and caries: the further adjusted ORs (95% CIs) from the lowest to highest category of intake by quartile were 1.00, 1.06 (0.72‒1.56), 0.53 (0.34‒0.81), and 0.68 (0.44‒1.04),
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respectively (P for trend = 0.02). Finally, data on serum 25(OH)D concentrations were
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not available.
Conclusions
Our results indicate an association between higher maternal vitamin D intake during pregnancy and a reduced risk of dental caries in young Japanese children. Because of
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the numerous limitations, these results should be interpreted cautiously and subsequently confirmed in other populations. Further studies are needed to clarify both the mechanisms underlying the association and the long-term consequences.
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Acknowledgements
The authors would like to acknowledge the Kyushu Branch of the Japan Allergy
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Foundation, the Fukuoka Association of Obstetricians & Gynecologists, the Okinawa Association of Obstetricians & Gynecologists, the Miyazaki Association of Obstetricians & Gynecologists, the Oita Association of Obstetricians & Gynecologists, the Kumamoto Association of Obstetricians & Gynecologists, the Nagasaki Association of Obstetricians & Gynecologists, the Kagoshima Association of Obstetricians & Gynecologists, the Saga Association of Obstetricians & Gynecologists, the Fukuoka Society of Obstetrics and Gynecology, the Okinawa Society of Obstetrics and Gynecology, the Fukuoka City Government, and the Fukuoka City Medical Association
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for their valuable support. This study was supported by JSPS KAKENHI (Grant numbers 19590606, 20791654, 21590673, 22592355, 22119507, 24390158, 25463275, and 25670305);
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Health and Labour Sciences Research Grants for Research on Allergic Disease and Immunology; Health Research on Children, Youth and Families from the Ministry of Health, Labour and Welfare, Japan; Meiji Co. Ltd.; the Food Science Institute
Foundation; and the Danone Institute of Japan Foundation. These organizations did not
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have any influence on the study design; the collection, analysis, or interpretation of
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data; the writing of the report; or the decision to submit the article for publication.
Conflict of interest
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The authors have no conflict of interest to disclose.
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Number (%) or mean ± SD
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Baseline characteristics Maternal age, years, mean ± SD
31.6 ± 4.0
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Region of residence Fukuoka Prefecture Other than Fukuoka Prefecture in Kyushu
≥ 6,000,000 Maternal educational level, years < 13 13–14 ≥ 15 Paternal educational level, years
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4,000,000–5,999,999
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< 4,000,000
31.9 ± 4.0
31.5 ± 4.0
P value
0.14 0.0004
693 (57.3)
127 (47.6)
566 (60.0)
403 (33.3)
110 (41.2)
293 (31.1))
114 (9.4)
30 (11.2)
84 (8.9)
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Okinawa Prefecture Household income, yen/year
Caries status Caries (n =267) Caries free (n = Number (%) or 943) Number (%) mean ± SD or mean ± SD
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Table 1 Distribution of characteristics in 1210 mother-child pairs, KOMCHS, Japan Variable Overall
0.03
387 (32.0)
96 (36.0)
291 (30.9)
457 (37.8)
104 (39.0)
353 (37.4)
366 (30.3)
67 (25.1)
299 (31.7)
