The relationship between maternal nutrition in pregnancy and early childhood caries – a systematic literature review

analysis:


Introduction
Deciduous odontogenesis begins already during foetal life. Once the deciduous crowns are fully developed in the first year of life and the mineralisation process is completed at the time of tooth eruption, the enamel shows structural stability and is not subject to metabolic processes. Therefore, the intrauterine environment, which is shaped, among other things, by prenatal maternal nutrition, is a key factor determining proper development of deciduous dentition, formation and mineralisation of the enamel and dentin, and thus susceptibility to cariogenic factors (1). The current knowledge of the effects of prenatal nutrition and supplementation on the risk of early childhood caries (ECC) is unknown. Low vitamin D levels in pregnancy were considered to be associated with reduced foetal weight (< 10 percentile), preterm birth, adverse effects on the development of the child's skeletal system and dental tissues as well as an increased risk of infectious diseases (2). Maternal hypovitaminosis (25(OH)D < 20 ng/mL or < 50 nmol/L) is an important risk factor for abnormalities in the newborn. The levels of 1,25-dihydroxyvitamin D (1,25[OH] 2 D) increase in early pregnancy and are doubled in the third trimester to cover the calcium needs of the foetus during skeletal development. Karras et al. suggest that this is also associated with the physiological adaptation of the immune system to maintain the pregnancy (3). Vitamin D supplementation in pregnancy increases both umbilical cord and neonatal blood levels of this vitamin (4,5). However, Galthen-Sørensen et al. found no evidence to support the relationship between maternal 25(OH)D levels and szkliwa i zębiny zależy podatność na czynniki próchnicotwórcze. Obecny stan wiedzy dotyczącej wpływu odżywiania i suplementacji w ciąży na ryzyko wystąpienia próchnicy wczesnego okresu dzieciństwa (ang. early childhood caries -ECC) pozostaje niejasny. Cel pracy. Ocena związku między odżywianiem w ciąży a ryzykiem wystąpienia próchnicy wczesnego okresu dzieciństwa. Materiał i metody. Przeprowadzono systematyczny przegląd literatury dotyczącej związku między odżywianiem w czasie ciąży a próchnicą wczesnego okresu dzieciństwa w oparciu zarówno o elektroniczne, jak i manualne przeszukiwanie medycznych baz danych, takich jak: PubMed, EMBASE i MEDLINE, co pozwoliło zidentyfikować 6 badań spełniających kryteria włączenia. Do oceny ryzyka wystąpienia błędów systematycznych wykorzystano kwestionariusz ROBINS-I, natomiast do oceny jakości prac oryginalnych wykorzystano skalę Newcastle-Ottawa (Newcastle-Ottawa Scale -NOS). Wyniki. Wszystkie analizowane prace były obarczone ryzykiem błędu wynikającym z obecności czynników zakłócających, wpływających na interwencję i interpretację wyników. Jakość czterech badań oceniono jako dobrą (NOS > 6), natomiast dwóch pozostałych jako średnią. Wnioski. Zwiększone spożycie witaminy D, wapnia, produktów mlecznych, jogurtów i serów przez kobietę w trakcie ciąży stanowi istotny czynnik obniżający ryzyko wystąpienia próchnicy u dziecka. Niedobór witaminy D, niskie spożycie wapnia oraz dieta bogata w kwasy tłuszczowe i węglowodany zwiększają ryzyko wystąpienia próchnicy wczesnego okresu dzieciństwa. New Medicine 4/2019 "pregnant women" OR "pregnant", and the development of ECC as an effect (O) (searched terms: "early childhood caries" OR "dental caries"), in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol (17), which allowed to identify 5 studies meeting the inclusion criteria. A total of 6 studies were included in the review following an additional, manual search through the cited literature. The search strategy and the inclusion/exclusion criteria are presented in table 1 and figure 1.

Search strategy
Medical databases, i.e. PubMed, MEDLINE and EM-BASE, were searched through for prenatal nutrition and supplementation as an exposure (I), using the following key terms: "prenatal vitamin" OR "dairy products" OR "protein deficiency" OR "calcium" OR "nutrition status" OR "intake of sugar" OR "sugar consumption" OR "vitamin" combined with: "prenatal*" OR "pregnancy" OR PUBMED, EMBASE, MEDLINE "Prenatal vitamin" OR "dairy products" OR "protein deficiency" OR "calcium" OR "nutrition status" OR "intake of sugar" OR "sugar consumption" OR "vitamin" combined with: "prenatal*" OR "pregnancy" OR "pregnant women" OR "pregnant", and the development of ECC as an effect (O) (searched terms: "early childhood caries" OR "dental caries") N = 132 Searched key terms "Prenatal vitamin" OR "dairy products" OR "protein deficiency" OR "calcium" OR "nutrition status" OR "intake of sugar" OR "sugar consumption" OR "vitamin" combined with: "prenatal" OR "pregnancy" OR "pregnant women" OR "pregnant" AND "early childhood caries" OR "dental caries"

Database search findings
The electronic search through databases and the manual search through literature allowed to identify 6 studies meeting the inclusion criteria.

Characteristics of the works
Four prospective cohort studies, a longitudinal observational study and a retrospective cohort study were included in the analysis. The discussed works are summarised in table 2.
Three studies evaluated prenatal vitamin D levels and the risk of ECC. Schroth et al. demonstrated a statistically significant negative correlation between serum maternal

The quality and risk of bias assessment
The qualified studies were assessed independently by two investigators using the The Risk Of Bias In Non-randomized Studies -of Interventions (ROBINS-I) assessment tool ver. 1.08.2016 (18). Also, the quality was evaluated based on the Newcastle Ottawa Scale (19). Contentious issues were discussed. Final assessment was performed jointly by all investigators involved. Key factors potentially disturbing study results, i.e. the socioeconomic status, age, maternal education, the course of pregnancy (maternal comorbidities, preterm birth, low birth weight), the number of teeth in a child, dietary exposure to sugars, the lack of calibration of the investigators, dental assessment in daylight with no previous dental surface cleaning, the lack of radiological assessment, were identified based on the literature. Each study was briefly characterised (country, type of study, age and number of participants, definition of intervention/exposure and final result, findings, conclusions and confounders). with high prenatal consumption of cheese. It was observed that the risk of ECC in children decreased with higher consumption of cheese, whereas the negative correlation between consumption of dairy products, calcium and yoghurts was at the limit of statistical significance. No correlation was found between maternal intake of milk and ECC in the child. One study determined the relationship between ECC and maternal obesity, combined with high dietary intake of sugar and fat. Wigen et al. demonstrated a higher risk of ECC in children from families of non-Western origin (OR 5.0), children of mothers with overweight (OR 2.4) or obesity (OR 1.5), low education (OR 2.0), smoking habits (OR 1.9), higher sugar (OR 1.6) and fat (OR 1.6) intake, as well as asthma or allergy (OR 1.4), based on a prospective cohort study in 1348 mother-child pairs in Norway, which involved a questionnaire (eating habits, lifestyle, habits) for pregnancy and 18-month-year-old child and dental evaluation in 5-year-old children (25).

Bias and quality assessment
Bias evaluation is presented in table 3. Four works were considered to be of good quality (NOS > 6) and two other of medium quality (tab. 4). The analysed studies had a risk of data distortion due to methodological limitations and confounders.

Discussion
D-hypovitaminosis is associated with an increased risk of mineralisation disorders and enamel hypoplasia, which are well documented risk factors for ECC (26)(27)(28).  The authors observed a 6% reduction in the risk of ECC with increased maternal vitamin D intake per every microgram per day. Singleton et al. used prenatal blood samples drawn at 16 week of gestation or later and cord blood drawn at birth for the analysis of vitamin D levels and electronic dental records to calculate dmft scores in children aged 12-35 months and 36-59 months in Alaska (22). They observed a 2-fold higher dmft scores at 12 to 35 months in children with deficient vitamin D levels in cord blood (22). Two studies evaluated calcium supplementation and dietary intake and ECC (23,24). Thitasomakul et al. examined 495 children aged 9, 12 and 18 months and observed increased caries between 9 and 12 months of age in children whose mothers reported lack of calcium supplementation and non-daily milk consumption during pregnancy (23). Tanaka et al. assessed prenatal dietary intake of dairy and calcium products in 315 Japanese mother-child pairs based on a dietary questionnaire including the total intake of dairy products (milk, yoghurts and cheese) (24). A statistically significant negative correlation with the risk of ECC at an average age of 41-50 months was reported in children of

Study
Bias due to confounding Studies exploring the correlation between maternal vitamin D level and ECC demonstrated that ECC incidence is greater in children of mothers with low level of vitamin D and low dairy intake, but due to methodological aspects (evaluation of serum maternal vitamin D level or vitamin D level in cord blood v. dietary questionnaire), they cannot be compared (20)(21)(22). Moreover, Schroth et al. (20) conducted their among Aboriginal women with low socioeconomic status, therefore the results cannot be extrapolated to the entire population. The questionnaire did not include all risk factors for ECC, thus an assessment of confounders was not possible. Singleton et al. we were not able to adjust for key confounding factors such as dental hygiene, sugar-sweetened beverage use, or access to running water, which affect dental caries (22).

Risk of bias judgement
The mechanism of action of low vitamin D precursor level in the period of deciduous mineralisation has not been explained. The authors suggest that enamel developing in such an environment is less resistant to acids. In analysed studies the influence of vitamin D was considered only in relation to mineralised tooth tissue (prenatal mineralisation). However, low level of (25(OH)D) is associated with immunodeficiency (29,30), which may affect the environment of maternal oral cavity in favour of cariogenic micro-flora. High maternal levels of oral bacteria is a risk factor of early transmission of cariopathogens to oral cavity of a child and ECC (31,32). The impact of vitamin D level and oral bacterial load of pregnant women and ECC has not yet been investigated.
The normal level of calcium in blood plasma and Ca/P ratio is particularly important during odontogenesis and skeletal development. Calcium deficiency impedes mineralisation of forming hard tissues of the teeth. Mineralisation of primary dentition begins ca. 13 weeks of gestation, permanent teeth -perinatally. The mature enamel in erupted teeth is not remodelled during an individual's life. Hypocalcaemia during pregnancy and in the first years of a child's life may be the cause of developmental defecthypomineralisation of enamel and dentin (27,30,(33)(34)(35)(36)(37)(38). Studies of enamel of hypomineralised teeth showed a higher content of carbon and a lower content of calcium and phosphorus in comparison with normal enamel (38). Calcium deficiency is also conducive to reducing the size of the teeth, shortening their roots as well as delaying tooth eruption and premature exfoliation of milk teeth (33)(34)(35)(36). In addition, hypocalcaemia at the time of odontogenesis promotes the accumulation of lead in the tissues of the teeth, which is the cause of their greater susceptibility to decay (39). The degree of mineralisation of dental tissues determines their sensitivity to bacterial and non-bacterial acids as well as mechanical factors. Teeth containing insufficient amount of minerals are more susceptible to decay, erosion and mechanical wear (27,30).
The studies assessing calcium supplementation and dairy intake in pregnancy and ECC demonstrated a decreased risk of ECC with higher dairy consumption (23,24). The mechanism underlying the effects of dairy intake on child's dentition remains unexplained; it has been suggested that an increased intake of dairy products increases total level of body calcium. However, the lack of calcium supplementation during pregnancy does not necessarily mean that serum calcium levels are low. The presented studies are also affected by multiple confounders and thus should be interpreted with caution. In the study of Thitasomakul et al. a high proportion of mothers (35%) admitted that they did not brush their children's teeth until participation in the study at the age of 9 months; no information was provided on the use of toothpaste or other fluorine-containing products (23). Tanaka et al. collected questionnaires via e-mail and the results might prove to be false due to the tendency to respond in line with the expectations of researchers as they determined the frequency of consumption of dairy products only in the preceding month, which does not reflect the nutritional pattern throughout pregnancy (24). Dental evaluation was performed by hygienists trained in the detection of caries, however, with no calibration or an assessment of the Kappa (compatibility) factor or an X-ray evaluation of caries on interproximal surfaces -therefore the rates of caries could be underestimated. The study group was characterised by a higher education level compared to the general Japanese population, which could have influenced the level of health awareness and may account for the 50% lower percentage of children with ECC compared to population data.
Apart from changes in appetite control, neuroendocrine function and metabolism, consuming a large amount of sugars during pregnancy promotes the child's preference for sweet taste by stimulating taste buds in the developing fetus (40,41). Frequent and high carbohydrate intake may increase cariogenic bacteria counts in maternal oral cavity and increase the risk of early transmission of Streptococcus mutans. Wigen et al. demonstrated a higher risk of ECC in children of obese mothers, and those who reported higher sugar and fat intake (25). Limitations of the study are as follows: dental status assessment by hygienists with no calibration. Tooth decay was diagnosed when a cavity was identified, therefore the percentage (11%) of children with caries (d > 0) may be underestimated. The dietary questionnaire data may also be underestimated.

Conclusions
It was found, based on the review, that increased maternal intake of vitamin D, dairy products, yoghurts and cheese during pregnancy as well as calcium supplementation are important factors reducing the risk of caries in children. The risk of ECC is increased in the case of maternal vitamin D deficiency and the lack of calcium supplementation as well as diet rich in fatty acids and carbohydrates.