Effectiveness of interventions on improving early-life dental care utilization: A Systematic Review and Meta-Analysis

Abstract

Objectives:

Although early-life dental care is crucial for preventing early childhood caries and has numerous benefits, the utilization rate of such care remains remarkably low worldwide, especially in families of low socioeconomic status. The aim of this study was to systematically review the scientific evidence relating to the effectiveness of interventions on improving early-life dental care utilization of very young children.

Method and materials:

We reviewed scientific evidence relating to these positive changes, with 7 randomized controlled trials after qualitative evaluation. Interventions assessed included prenatal oral health promotion, motivational interviewing, intraoral camera use alongside social work consultations to aid in decreasing barriers to care, monetary incentives for tooth brushing, fluoride varnish applications, and probiotic usage.

Results:

The intervention was significantly effective in reducing the incidence of dental caries among children, especially in caries risk. Caries reduction was significant when oral health information was provided at frequent intervals prenatally. Caries increment was also reduced when probiotics were introduced when administered daily. Interventions that attempted to increase parental involvement in oral health care by increasing motivation and decreasing barriers had inconclusive results within the study groups.

Conclusions:

Considering high rates ECC, early establishment and preservation of a dental home should be a focus in public health measures. Continuous monitoring and parental involvement are key components to maintaining healthy oral conditions. Future studies could explore and test various innovative strategies that utilize technological platforms to engage with parents and promote early-life dental care utilization among the underserved population.

Introduction

Dental caries is the localized destruction of dental hard tissues (enamel & dentin) by acidic by-products from the microbial fermentation of carbohydrates¹. Caries can progress quickly from the very early (subclinical) stages, typified by white spot lesions on the tooth enamel surface, to an irreversible cavity. This process, when detected early, can be reversed with preventive measures, e.g., fluoride treatment, diet modification, and oral hygiene practice.

Despite being largely preventable, early childhood caries (ECC) is by far the most common chronic childhood disease, with nearly 1.8 billion new cases per year globally^2–4. In the US only, ECC disproportionately affects up to 55% of preschool children from low-income marginalized populations^2–4. This inequity requires a focused approach to disease prevention and early screening within low-income communities. The current biomedical approach to controlling the dental caries pandemic has had limited success because it focuses primarily on individual-level treatment rather than population-wide early prevention.

Early-life dental care not only enables timely identification of ECC, but also encourages caregiver participation in oral health-promoting activities like proper child feeding habits and routine oral hygiene practice that can promote long-term dental health. According to the American Academy of Pediatric Dentistry (AAPD)^{5, 6}, American Dental Association (ADA)⁷, American Public Health Association (APHA)⁸, and American Academy of Pediatrics (AAP)⁹, all children should have their first dental appointment before 12 months. For underserved children in North America, this aim is rarely realized; only 1% or fewer have had a dental visit by 12 months, and <10% between 1-2 years^10–14. Many low-income families experience challenges accessing dental treatments, either because they have no insurance, cannot determine which pediatric dentistry clinic accepts their insurance^{10, 12}, or there is limited availability of providers that accept their insurance in their locales. As a result, tooth decay is often diagnosed at later stages requiring more extensive restorative treatments¹¹, and also often requiring advanced behavior management techniques to safely render such treatments¹⁵.

Improving early dental utilization is vital to oral health care among young children. Anticipatory guidance measures, the process of providing practical and developmentally appropriate information about children’s health to prepare parents for significant milestones¹⁶, are only effective if the health provider can assess the child and have a dialogue with the caregiver ahead of potential problems. Multiple community-centered motivational strategies have shown promise in improving dental care utilization among preschool children and adolescents^17–20; however, efforts geared toward young, underserved children under three years of age are limited.

In theory, early-life dental care utilization is highly advised to reduce the prevalence of ECC. Although some studies tried to prove the effectiveness of early-life dental care, there is no systematic review to quantitively and qualitatively emphasize the necessity of early-life dental care utilization in any medium in our knowledge. Questions remain in the relevance and effectiveness of oral health care interventions that target the very young population in the uptake of early-life dental care and the overall effect on ECC.

Therefore, this systematic review aims to assess the impact of interventions on improving early-life dental care utilization among children under age three, and give scientific evidence on the effectiveness of these interventions. The analysis on the evidence of interventions may promote oral health care strategies and policies at both community and individual levels to improve oral health outcomes, especially in reducing ECC, for children.

Methods

This systematic review followed PRISMA guidelines²¹, the protocol was registered in the PROSPERO (CRD42024533065) (https://www.crd.york.ac.uk/prospero/).

Search Strategy

Database searches were conducted in January 2023 to identify published studies on interventions used to improve early-life dental care utilization (infants and their families receiving interventions to improve dental care utilization prior to age 3). A medical reference librarian developed individual search strategies and retrieved citations from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. A combination of text words and controlled vocabulary terms were used (infant, preschool, dental care, pediatric dentistry, office visit).

Eligible criteria

This systematic review included randomized controlled trials that examined the effect of interventions aimed at improving early-life dental care utilization, with outcomes of increased access to dental care, improved oral health knowledge, or reduction of early-life dental caries in children. Three independent reviewers were trained in one synchronous session on the specific and clear inclusion/exclusion criteria. Each reviewer was assigned a subset of the total dataset, and completed the article selection in accordance with the clear inclusion/exclusion criteria. A structured spreadsheet was used to standardize their input and maintain uniformity of how the data was organized. Disagreements were resolved by consensus between the three reviewers. A fourth reviewer was tasked with ensuring the final selection of articles met all the defined inclusion/exclusion criteria. All four reviewers were involved in the qualitative analysis of the articles. The following inclusion and exclusion criteria were used for literature selection.

Inclusion Criteria

• Types of participants (P): parents or caregivers and their children under the age of three years.

• Types of interventions of interest (I): caries risk reduction and behavioral strategies aimed at improving early-life dental care utilization.

• Types of comparisons (C): infant and their families who received and did not receive interventions to improve early-life dental care utilization.

• Types of outcomes (O): improved early-life dental care utilization (before 3 years of age); improved oral health knowledge of parents or caregivers; reduced dental caries in children. Types of studies: randomized controlled trials.

• Types of statistical data: odds ratio (OR); relative risk; confidence intervals (CI); p-values, and frequency of an absolute number of events versus total number of individuals per group.

Exclusion Criteria

The exclusion criteria were the followings: in vitro studies; animal studies; papers with abstract only; literature reviews; letters to the editor; editorials; patient handouts; case report or case series; case-control studies; cross-sectional studies; retrospective cohort studies; and non-randomized controlled trials.

Data Extraction

Descriptive data, including clinical and methodological factors such as year and author, country of origin, study design, study site, child age at exam, total subjects, type of intervention, outcome measures, as well as results from statistical analyses were obtained using an extraction form.

Qualitative Assessment and Quantitative Analysis

Four trained independent reviewers were involved in the qualitative assessment process. The quality of the selected articles was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) Checklist for Randomized Controlled Trials as well as the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials^{22, 23} (Table 1). Articles were scaled for the following bias categories: selection bias, performance bias, detection bias, attrition bias, reporting bias, and other bias.

Table 1.

Randomized controlled Trial Modified SIGN (Scottish Intercollegiate Guideline Network) Checklist.

Item	Yes/Noa
1. Study addresses an appropriate and clearly focused question
2. Group assignment was randomized
3. Sample size was justified by a power calculation
4. Investigators were blinded to patients’ group assignment
5. Patients were blinded to group assignment
6. Groups were similar at the start of the trial
7. The only difference between groups was the treatment of interest
8. Outcomes were measured in a standard, valid and reliable way
9. A power calculation was used and required sample size attained
10. An intention-to-treat analysis was performed
Total scoreb

^aRating: “Yes”=1; “No” or “Unable to tell ftom the article”=0

^bScoring: 9-10= high quality, low risk of bias; 6-8= acceptable quality, moderate risk of bias; <6= low quality, high risk of bias.

The methodological quality of randomized controlled trials was assessed using modified SIGN scoring tool. The aim of SIGN scoring is to improve the quality of health care for patients by developing evidence-based guidelines.

For the selection of articles subjected to quantitative analysis, the OpenMeta[Analyst] software (available at http://cebm.brown.edu/openmeta/) was employed to conduct the meta-analysis. Given the significant heterogeneity (p=0.02) observed among the studies, the estimation of 95% Confidence Intervals (CIs) and p-values was performed utilizing a random-effects model. To visually summarize the outcomes of the meta-analysis on changes in the prevalence of dental caries among children, forest plots were generated. The analysis included both the assessment of risk differences and the calculation of odds ratios.

Results

The literature analyses identified a total of 971 papers from the database search. A total of 21 duplicate references were removed. The remaining 950 studies were imported into an Endnote Library for further review. From those, 586 studies were excluded after title screening and 331 studies were further excluded after abstract screening. The remaining 33 articles were selected for a full text review. After the full text analysis, 26 were eliminated based on the exclusion criteria. The remaining 7 studies were subjected to an intense qualitative assessment (Figure 1). The full list of excluded articles after the full text review is shown in Appendix.

Figure 1.

Flow diagram of study identification.

The 4-phase Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was used to determine the number of studies identified, screened, eligible, and included in the systematic review and meta-analysis (http://www.prisma-statement.org).

Study Characteristics

The characteristics of studies included in the qualitative review are summarized in Table 2. All 7 studies were published between 2008 and 2020. Two studies^{24, 25} were conducted in the USA, two studies in Sweden^{26, 27}, one study in Australia²⁸, one in Brazil²⁹, and one in Chile ³⁰. Quality and risk of bias for randomized controlled trials was assessed and are shown in Figure 2.

Table 2A.

Characteristics of studies assessed early-life dental care utilization as the outcomes.

Author, year	City, country	Study site	Age of child at exam (mean)	Total subjects	Intervention	Control	Outcome measurement	Statistical analysis	Study findings	Limitations
Seirawan, 2020	Los Angeles, USA	2 Women, Infants, and Children (WIC) centers	2.2 years (SD 1.4)	418 children	(1) Intraoral Camera to demonstrate to guardians the healthy/diseased areas in child’s mouth; (2) Social Work Intern consultation to provide personalized support for each family; (3) IOC +SWI	Standard baseline protocol of oral health screening and oral + written instructions for guardian on OHI and referral to community clinical site if needed	Reported scheduled or completed dental appointment for the screened child after field encounter (follow-up done by phone using standard script)	Descriptive statistics, chi-squared tests and multivariate logistical models were used to compare groups	Participants experiencing both interventions were more likely to schedule appointments by second follow-up than controls. The best predictor of scheduling a dental visit was having had a dental visit in the last six months.	Small sample size per intervention arm; statistically significant independent variable of having had a recent dental visit at baseline; self-reported data at follow-up.
White, 2020	Los Angeles, USA	2 Early Head Start centers	0-3 years old	36 parent-child dyads	Digital (Bluetooth) monitoring of toothbrushing with: (1) fixed monetary incentive package; (2) lottery monetary incentive package	Delayed monetary incentive (“waitlist”)	Toothbrushing performance-mean number of BT recorded toothbrushing half-day episodes per week; and dental visit by 2-month follow-up among children with no prior dental visit.	Descriptive statistics, linear mixed-effects models, validity measured by pairwise correlations; McNemar’s x2 test to compare paired camera feasibility	Digital monitoring was feasible. Lottery monetary incentives produced the greatest increase in toothbrush frequency. Effects were concentrated among children ≤ 24 months.	Inadequate power (pilot trial); novelty and Hawthorne effects for powered brushes seem to halt by 12 weeks; no direct observation of BT syncing; regular feedback reminders may have muted the effects of the incentives alone.

Figure 2. Summary of quality and risk of bias assessment using the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials and the modified SIGN scoring tool.

The quality of the selected articles was assessed using two methodological validities: 1) Cochrane Collaboration’s tool for assessing risk of bias in randomized trials²³. 2) Modified SIGN score scoring²² that assess the methodological quality of randomized controlled trials. A total score of 10 represents the highest study quality.

Caries Reduction

With interventions, four studies showed significant reduction in caries between intervention and control groups. These four studies had different interventions, showing that any medium of early-life dental care, not limited to a certain method, may be effective. Plutzer and Spencer²⁸ had oral health promotion information given to the mothers in three rounds; Hedayati-Hajikand et al.²⁷ had distributed chewing tablet with live probiotic bacteria; Rodríquez et al.³⁰ supplemented milk with probiotic strain; Faustiono-Silva et al.²⁹ only had motivational interviewing as an intervention. Although two studies did not measure the prevalence of caries, the groups with intervention showed results with dental visits and increase in toothbrush frequency. Anderson et al.²⁶ applied topical fluoride varnish in the intervention group, which did not observe significant difference in caries development. However, it is noticeable that the reference group also received a standardized oral health program, including toothbrushing instructions, emphasis on toothbrushing twice daily with fluoride toothpaste, and dietary counseling. Therefore, in other words, this standardized oral health program was effective to prevent early childhood caries.

Improving Knowledge and Decreasing Barriers

Three studies^{24, 28, 29} assessed improving parental oral health knowledge and confidence and decreasing perceived barriers to care. Plutzer and Spencer²⁸ demonstrated a statistically significant reduction in development of S-ECC when first-time mothers were provided with oral health care information via printed oral health promotion materials prenatally, and at six-month intervals after birth of their child. Seirawan et al.²⁴ and Faustino-Silva et al.²⁹ both took approaches geared at motivating parents to improve oral hygiene and accessing dental care for their children. Seirawan et al.²⁴ evaluated the internal motivation provided with the use of an intraoral camera versus, or combined with, the aid of a social work intern to decrease perceived barriers to care. Faustino-Silva et al. ²⁹ evaluated the approach of motivational interviewing to explore a parent’s self-efficacy, as compared to conventional provision of oral health education. It was demonstrated that motivational interviewing was associated with a statistically significant reduction of caries only amongst lower income groups. While no statistically significant differences were found between intervention groups in the Seirawan study²⁴, positive data trends were supportive of the employments of intraoral cameras and social worker involvement to encourage parents to schedule dental appointments and establish dental homes.

Early Application of Fluoride

One large, stratified cluster-randomized controlled trial conducted by Anderson et al.²⁶ found that the early initiation and biannual application of topical fluoride treatments did not significantly lower the caries prevalence in children between 1 and 3 years of age. Of interest, despite planned baseline dental visits in approximation of the eruption of the first primary teeth, 5% of the 1-year-old children in the study had already developed early stages of dental caries by their initial study visit. Frequency in toothbrushing with fluoridated toothpaste increased with age in both conventional and intervention group, indicating that the conventional group, which did not receive the fluoride varnish treatments, was still exposed to fluoride which is a cost-effective method to prevent dental caries³¹

Incentivization

White et al. looked at whether oral hygiene in young children ages 0-3 could be improved if the use an electric toothbrush and smartphone application was tied into a monetary reward system²⁵. This BEECON pilot trial demonstrated that it was possible to increase tooth brushing frequency in the short term; however, a decline in all study groups was noticed so ecological validity of the trial is questionable. The authors noted that while a substantial increase in tooth brushing frequency was observed, many participants still failed to brush twice daily, which has been the long-standing recommendation by the American Academy of Pediatric Dentistry. Also, the incentive packages produced the largest gains in toothbrushing among parents whose child was ≤ 24 months, while this group also showed less cooperative behavior with the powered toothbrush.

Probiotics

Two studies (Hedayati-Hajikand et al. and Rodriguez et al.) looked at the effect of probiotics on young preschool aged children’s caries increment, with very promising results^{27, 30}. Both studies targeted children of vulnerability in low socioeconomic regions representing children of high dental caries risk. Hedayati-Hejikand et al., provided chewing tablets containing a blend of three strains of probiotic bacteria (S. uberis KJ2^™, S. oralis KJ3^™, S. rattus JH145^™), with an interesting limitation in enrolment noted that many parents were reluctant to give their child a “pill” on a daily basis for a prolonged period of time (in this case, one year)²⁷. Rodgriguez et al., chose one probiotic, L. rhamnosus, lyophilized and packed in a sachet as the intervention required it be mixed to reconstituted powdered milk³⁰. Both studies found a statistically significant difference in new caries development between the intervention and control groups, with the probiotic groups having lower new caries lesions. It has been previously studied that L. rhamnosus is only transiently observed in the saliva and rapidly cleared from the mouth after discontinuation, so there is a reliance on daily intake to achieve an anticipated reduction in caries. Nonetheless, neither study observed any participant adverse effects because of the interventions.

Meta-Analysis

The scope of studies included in the meta-analysis was constrained due to the necessity for uniform comparisons and outcome metrics. This analysis aimed to assess the variation in dental caries prevalence among children from baseline (at 12 months old) to follow-up (at 24 months old) across both the intervention and control groups, as depicted in Figure 3.

Figure 3.

Forest plot of odds ratio of the caries changes

Analysis of the forest plots indicated that the intervention was effective in reducing the incidence of dental caries among children. Specifically, the intervention was associated with a statistically significant 6.7% reduction in caries risk. Furthermore, the odds of developing caries in the intervention group were 0.656 times those in the non-intervention group, underscoring that the intervention mitigated the risk of early childhood caries. Additionally, the relatively high p-value suggests the necessity for additional data to achieve a result with greater statistical significance.”

The intervention was effective in decreasing the incidence of early childhood caries among children. It was found to significantly reduce the risk by 6.7%. Moreover, the odds ratio for the occurrence of caries in the intervention group was 0.656 times that of the control group.

Discussion

This systematic review demonstrates that there is focus on addressing caries from a preventive standpoint and targeting young age. The notion of anticipatory guidance is to provide parents and caregivers with practical, timely and developmentally-appropriate information on a continuous basis¹⁶. The American Academy of Pediatric Dentistry (AAPD) recommends that establishment of a dental home happens no later than 12 months of age. Utilization of dental services at such a young age allows parents to connect with oral health providers that can provide preventive strategies and have family-centered conversations about oral hygiene, orofacial growth and development, dietary counselling, fluoride exposure, nonnutritive habits, and injury prevention³². Seirawan et al. noted that, although many outreach programs have been developed to improve oral health and reduce related disparities, it has been difficult to study and document the impact of these models on establishing dental homes in these communities²⁴.

Prevention for early childhood caries (ECC) needs to begin in infancy³³. ECC is defined as the presence of one or more decayed (non-cavitated or cavitated lesions), missing or filled (due to caries) surfaces, in any primary tooth of a child under six years of age³⁴. It has been well established that dental caries in primary teeth may lead to chronic pain, infections, and other morbidities, and yet many caregivers still have difficulty accessing preventive dental care. ECC has major impact on the quality of life of children and their families³⁵. ECC reduction strategies are of individual and societal interest to decrease the health and financial burden of this preventable disease. It has been demonstrated that for the oral health education and preventive interventions to have positive impact, oral health promotion by printed materials should occur often, and as early as prenatally when motivation for behavior change is heightened²⁸.

Previous studies emphasize the oral health care of expectant mothers, since maternal oral health is closely related to children’s oral health³⁶. Vertical transmission of oral pathogens, such as cariogenic bacteria and fungi, from mothers to infants have been observed³⁷. It requires a lot of attention for pregnant women to take care of their oral health as they are more prone to periodontal disease along with high level of certain oral microorganisms, which has been studied to be associated with adverse pregnancy outcomes^{38, 39}.

The cruciality of good oral health care is reported again in a recent systematic review on changes in microbiota during pregnancy. This review reported that pregnancy influences the oral microflora and oral and systemic disease status accordingly⁴⁰. Prenatal Total Oral Rehabilitation (PTOR) has been suggested as a new treatment regimen, targeting the critical prenatal period and total oral rehabilitation to a “disease free status” before the delivery, which showed a positive oral health conditions and perinatal oral health literacy with reduction in Streptococcus mutans⁴¹. This innovative regimen may help to reduce ECC via lowering the vertical transfer of carious oral microbiome to the infants from mothers.

With ECC remaining a highly prevalent chronic childhood disease, and early establishment of a dental home having enormous potential to employ preventive strategies in an empowering, family-centered manner, it is of vital importance to uncover new, effective mechanisms of accessing and maintaining dental care as early as infancy. Innovative approaches, such as the use of an intraoral camera and, more recently, smartphone cameras and smartphone applications^{24, 42} have shown promise in improving parental dental education and involvement in their children’s dental care. Motivational interviewing in a dental setting has the ability to help parents explore their own efficacy and resources²⁹.

Today’s parents are more technologically savvy, with most US parents and women of childbearing age engaging with applications such as YouTube, Facebook, and Instagram daily⁴³, including for accessing health-care related information. Engaging with parents in these non-invasive platforms to provide evidence-based information and promote early dental care use may be an area of impressive value to explore.

Other pioneering approaches explored in this systematic review were: a) the use of incentivization to promote tooth brushing, which seemed to hold promise for those families whose children were of particularly young age²⁵; and b) the use of probiotics for caries control^{27, 30}, which showed significant potential. More research is needed in both arenas, but there is excitement in what the future holds. Of particular interest in the study by Rodriguez et al.³⁰ was that the probiotic intervention was easily and non-invasively administered by day care providers of socially vulnerable families. For parents that have difficulty accessing or attending routine dental care visits, the involvement of other trusting adults in the children’s dental care regimen may be a source of relief.

Even if it is not easy to generalize, we recognize that the results from these studies with similar intervention and similar outcome, we were able to generate the meta-analysis from these data. Although the outcome is improved as seen in meta-analysis, it is too early to generalize that all the interventions are effective and that all the population will get benefits from all the interventions. Unfortunately, one absolute intervention to solve ECC does not exist; this research, however, showed that the healthcare providers are combining the interventions in various approaches, such as biochemical, knowledge, and behavior aspects. Continuous effort of healthcare providers, especially education on prevention for caregivers is advised.

The impact of Early Childhood Caries is widespread globally and economically. Interventions that can be easily accessed by families with limited resources or access to care, or interventions that can be easily implemented by general practitioners with limited resources or training, will have profound transformative potential in the reduction of disparities and improvement of early-life dental care utilization (with the ultimate goal of improving oral health of very young children globally).

While this systematic review aimed to assess the evidence on interventions that have been utilized to improve early-life dental care utilization among children under age three, the following limitations should be cautiously considered when interpreting the results: (1) we found that many randomized controlled trials (RCTs) had difficulty separating cohorts of children in the preschool ages, and as such, we included studies that looked at children even in age 3; (2) the included studies had inconsistent and heterogeneous approaches in reporting findings, in terms of measurement and follow-up; and (3) the included studies had varying outcome measurements, thus making it difficult to reach one defined conclusion. Additionally, small sample sizes and high attrition rate plagued the majority of the studies. We found three RCTs dedicated to interventions of improving dental care utilization, one RCT on incentivizing tooth brushing, and three RCTs evaluating caries reduction strategies.

Conclusion

This review reports on a caries reduction when children are involved in early introduction of dental care, whether through frequent prenatal oral health promotion, strategies that reduce barriers to care and enhance parental involvement in monitoring the oral conditions, or exposure to probiotics that interact with the oral microbiome. Caries risk was significantly reduced in children with intervention, such as topical application of fluoride and probiotics. Early establishment and preservation of a dental home should be a focus in public health measures, given that rates of ECC remain high and focused anticipatory guidance along with diligent monitoring and parental involvement are key components to maintaining healthy oral conditions. Further studies should consider testing strategies that engage with parents in technological platforms and encourage early dental care use to build a foundation to lower the prevalence of ECC.

Table 2B.

Characteristics of studies assessed dental caries as the outcomes.

Author, year	City, country	Study site	Age of child at exam (mean)	Total subjects	Intervention	Control	Outcome measurement	Statistical analysis	Study findings	Limitations
Plutzer, 2008	Adelaide, Australia	Five Adelaide Public Hospitals	20 ± 2.5 months	Test: 327 pregnant mothers, 232 children Control: 322 pregnant women, 209 children	Oral health promotion information was given to mothers in a total of 3 rounds (1 during pregnancy and 2 between 6-12 months after birth)	Oral health information was NOT given.	Incidence of S-ECC (AAPD definition)	Fisher’s exact test	Caries reduction was significant between the intervention and control groups.	Dental examiners were blinded, but the subjects were randomized without blinding.
Hedayati-Hajikand, 2015	Malmö, Sweden	Rosengård, a multi-cultural low socio-economic suburban area	2-3 years	138 children	Chewing tablet containing three strains of live probiotic bacteria taken once a day for 12 months	Identical tablets without bacteria	Caries increment (Δds), presence of plaque, bleeding-on-brushing	Nonparametric Wilcoxon signed rank test for continuous variables, chi-square test for categorical data	Caries reduction was significant between intervention and control groups. No differences between groups for plaque or bleeding-on-brushing.	Subject recruitment goal per initial power calculation was not reached. Parental hesitation to give daily “pills” for one year developed.
Anderson, 2016	Stockholm, Sweden	23 dental clinics in multicultural areas of medium or low socio-economic status	12, 24 and 36 months	3,403 children	Standard preventive program + topical application of fluoride varnish on the buccal surfaces of teeth every 6 months	Standard preventive program only, NO fluoride varnish	Prevalence of dental caries and number of surfaces affected by caries (ICDAS II)	Multiple logistic regression analyses for dichotomous variables, multiple linear regression analyses for numerical variables	Neither prevalence nor caries increment differed between intervention and control groups.	Lack of blinding. Twenty-five percent drop-out rate at 2-year follow-up.
Rodríguez, 2016	Metropolitan region, Chile	16 nursery schools in a metropolitan region in Chile	2-3 years	261 children	150 mL of milk supplemented with Lactobacillus rhamnosus SP1 (107 CFU/mL)	Standard medium-fat milk	Caries increment (Δdmft) using ICDAS	Pearson X2 test for dichotomous variables, analysis of variance for interval-level variables	Caries reduction was significant between intervention and control groups.	High attrition rate (21%).
Faustino-Silva, 2019	Porto Alegre, Rio Grande do Sul, Brazil	12 healthcare clinics	27.8 months	1441 children	Motivational interviewing (MI)	Conventional education (CE)	Caries increment (Δdmfs) using ICDAS	Chi-square test with Pearson’s correlation for categorical variables, analysis of variance for continuous variables	Significant difference between CE and MI among lower-income children, but not for those of higher income in terms of ECC rates.	High attrition rate.

Appendix 1. List of studies excluded after full text review.

1. Bagattoni S, Nascimben F, Biondi E, Fitzgibbon R, Lardani L, Gatto MR, Piana G, Mattarozzi K. Preparing Children for Their First Dental Visit: A Guide for Parents. Healthcare (Basel). 2022 Nov 19;10(11):2321. doi: 10.3390/healthcare10112321. PMID: 36421645; PMCID: PMC9690852.

2. Cahuana, A., et al. (2016). “Maternal and infant oral health care. how do we improve it?” Matronas Profesion 17(1): 12-19.

3. Chile, U. o. (2012). Effect of the Consumption of Probiotics in the Reduction of Incidence of Carious Lesions in Preschool Children, https://ClinicalTrials.gov/show/NCT01648075.

4. Copenhagen, U. o. (2013). Preventive Effect of a Probiotic Tablet on Oral Health in Preschool Children, https://ClinicalTrials.gov/show/NCT01720771.

5. de Oliveira BH, Dos Santos AP. Semiannual Fluoride Applications in Low-Risk Toddlers May Not Be More Effective Than Toothbrushing Instruction and Dietary Counseling in Controlling Dental Caries. J Evid Based Dent Pract. 2016 Dec;16(4):246-248. doi: 10.1016/j.jebdp.2016.11.006. Epub 2016 Nov 12. PMID: 27938699.

6. Genova, U. o. (2012). GENOA ORAL GROWTH LONGITUDINAL STUDY (GeOrGS), https://ClinicalTrials.gov/show/NCT02798809.

7. Güdük, Ö. F., et al. (2022). “Comparative Analyses of the Computer Aided Presentation and Brochure Based Information on the Knowledge of Mothers Regarding the Oral Health Status of Their 0-3 Years Old Children.” Meandros Medical and Dental Journal 23(3): 259-268.

8. Holland ML, Yoo BK, Kitzman H, Chaudron L, Szilagyi PG, Temkin-Greener H. Mother-child interactions and the associations with child healthcare utilization in low-income urban families. Matern Child Health J. 2012 Jan;16(1):83-91. doi: 10.1007/s10995-010-0719-z. PMID: 21127953.

9. Karjalainen S, Sewón L, Söderling E, Lapinleimu H, Seppänen R, Simell O. Oral health of 3-year-old children and their parents after 29 months of child-focused antiatherosclerotic dietary intervention in a prospective randomized trial. Caries Res. 1997;31(3):180-5. doi: 10.1159/000262395. PMID: 9165187.

10. Lave JR, Keane CR, Lin CJ, Ricci EM, Amersbach G, LaVallee CP. Impact of a children’s health insurance program on newly enrolled children. JAMA. 1998 Jun 10;279(22):1820-5. doi: 10.1001/jama.279.22.1820. PMID: 9628715.

11. Lee JY, Bouwens TJ, Savage MF, Vann WF Jr. Examining the cost-effectiveness of early dental visits. Pediatr Dent. 2006 Mar-Apr;28(2):102-5; discussion 192-8. PMID: 16708783.

12. Milgrom P, Riedy CA, Weinstein P, Mancl LA, Garson G, Huebner CE, Smolen D, Sutherland M. Design of a community-based intergenerational oral health study: “Baby Smiles”. BMC Oral Health. 2013 Aug 6;13:38. doi: 10.1186/1472-6831-13-38. PMID: 23914908; PMCID: PMC3751087.

13. Nct (2011). “Evaluation of a Bright Futures Oral Health Intervention.” https://clinicaltrials.gov/show/NCT01406366.

14. Nelson TM, Huebner CE, Kim A, Scott JM, Pickrell JE. Parent-reported distress in children under 3 years old during preventive medical and dental care. Eur Arch Paediatr Dent. 2015 Jun;16(3):283-90. doi: 10.1007/s40368-014-0161-9. Epub 2014 Dec 17. PMID: 25514877; PMCID: PMC4470890.

15. Ng MW, Chase I. Early childhood caries: risk-based disease prevention and management. Dent Clin North Am. 2013 Jan;57(1):1-16. doi: 10.1016/j.cden.2012.09.002. Epub 2012 Oct 22. PMID: 23174607.

16. Parker, M. (2011). “Promoting children’s oral health in Shelton, Washington.” Journal of Investigative Medicine 59(1): 142-143.

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