PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

SYSTEMATIC REVIEW AND META-ANALYSIS O

Risk Factors for Early Childhood Caries: A Systematic Review and Meta-Analysis of Case
Control and Cohort Studies
Kirthiga M, MDS1 • Muthu Murugan, MDS, PhD2 • Ankita Saikia, MDS3 • Richard Kirubakaran, MSc4

Abstract: Purpose: The purpose of this study was to perform a systematic review to assess current evidence for association between various
risk factors and the prevalence or incidence of early childhood caries (ECC). Methods: Two reviewers searched various databases until January
2019. The Newcastle-Ottawa scale was used to perform risk of bias assessment.The included studies were categorized according to the World
Bank classification. Data were summarized in a meta-analysis using fixed and random effects inverse-generic meta-analyses. Results: A total of
7,034 records involving 89 studies that evaluated 1,352,097 individuals were included; 23 were high, 46 were moderate, and 20 were of low
quality. A total of 123 risk factors were found. Meta-analysis revealed that the strongest risk factors found in the high-income countries were
presence of dentinal caries (dmft greater than zero; odds ratio [OR] equals 4.21 [2.18 to 8.16]) and high levels of mutans streptococci (OR equals
3.83 [1.81 to 8.09]). In upper-middle-income countries, presence of enamel defects (OR equals 14.62 [6.10 to 35.03]) was found to be the
strongest risk factor. Conclusion: The strongest risk factors associated with early childhood caries was the presence of enamel defects, presence
of dentinal caries and high levels of mutans streptococci. (Pediatr Dent 2019;41(2):95-106.E18-E23) Received September 11, 2018 | Last Revision
January 31, 2019 | Accepted February 4, 2019
KEYWORDS: DENTAL CARIES, RISK FACTORS, INFANT, CHILD, COHORT STUDIES, CASE CONTROL STUDIES

Early Childhood Caries (ECC) remains the most prevalent percent of the included studies were cross-sectional, thereby
chronic disease in children, with significant impact on society.1,2 lacking robustness for the evaluation of risk factors and for
Numerous studies have observed the increasingly skewed conclusions to be drawn. In addition, there were few studies of
distribution of carious lesions.3-6 Most carious lesions or restora- a high quality, defined as those using validated and standard-
tions are found in a small number of disadvantaged individuals. ized measures for oral hygiene and dietary habits. The other
ECC is disproportionately found in certain segments of the systematic review 10 studied risk factors for ECC only in the
childhood population.7,8 Although the key factors causing dental first year of life and suggested further clarification to identify
caries in adults and children are similar, there are certain unique and quantify the main risk factors. Neither of the two system-
risk factors present in young children, probably because oral atic reviews presented a quantitative analysis. Furthermore,
microbial flora and host defense mechanisms are in the devel- recently reported risk factors—namely, increased body mass
oping stage. Also, newly erupted tooth surfaces may have index, maternal cognitive disorders, increased enamel perme-
hypoplastic defects associated with higher risk for caries. In ability, enamel composition, and the influence of parental
addition, parents must understand the dietary changes from attitudes, were not included. Finally, the search for the review
liquids to solids through breastfeeding/bottle feeding. by Harris8 was conducted over a decade ago, in 2004; hence, an
Several studies have evaluated and categorized the risk update is indicated.
factors of ECC, such as sociodemographic factors, dietary Therefore, the purpose of this study was to conduct a
factors, oral hygiene factors, and factors related to oral bac- systematic review and a meta-analysis of cohort and case control
terial flora and breastfeeding/bottle feeding. 1,2,6,8,9 However, studies for possible associations between various risk factors
the degree to which different risk factors are associated with and early childhood caries.
ECC remains unclear.
Significant gaps have been observed in the collective Methods
evidence on risk factors known to cause ECC. Until now, Guidelines from PRISMA (Preferred Reporting Items for
only two systematic reviews have examined the evidence on Systematic Reviews and Meta-analyses) were followed in the
multiple risk factors associated with ECC. Harris et al. in present review, which was registered at PROSPERO before the
20049 systematically reviewed the literature and identified 106 initial screening stage. We deviated from the original protocol
risk factors associated with ECC. Nevertheless, more than 50 by adding a category of included studies based on the World
Bank Classification. In addition, we also searched for another
database—LILACS—which was not mentioned in the original
Dr. 1M is an Early Career Research fellow (Wellcome Trust DBT India Alliance) and protocol.
2Dr. Murugan is Head of Center for Early Childhood Caries Research (CECCRe), De-
partment of Pedodontics and Preventive Dentistry, Faculty of Dental Sciences, Sri Rama-
Search strategy. The identification of included studies,
chandra Institute of Higher Education and Research, Chennai, Tamil Nadu; 3Dr. Saikia which began on July 1, 2016 and was updated until January
is a pediatric dental surgeon, Pedo Planet — Children’s Dental Centre, Chennai; and 2019, was based on a search strategy performed for each elec-

e
4
Dr. Kirubakaran is a biostatistician, South Asian Cochrane Network and Centre, Chris- tronic database: MEDLINE; EMBASE; Cochrane Central
tian Medical College, Vellore, Database; Cochrane Oral Health Group’s Specialised Register;
Tamil Nadu, all in India. CINAHL via EBSCO; LILACS; and IndMED. The MeSH
Supplemental material available
Correspond with Dr. Murugan
at muthumurugan@gmail.com
xtra in the online version. terms used were “dental caries,” “preschool child,” “infant,”

RISK FACTORS FOR ECC 95

PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

and “risk factors.” The following strategy was used to search included. Children with special health care needs were excluded.
MEDLINE: (“dental caries”[MeSH terms] OR (“dental”[all Exposure included socio demographic factors, dietary factors,
fields] AND “caries”[all fields]) OR “dental caries”[all fields]) factors related to oral hygiene, factors related to breastfeeding
AND ((“infant”[MeSH terms] OR “infant”[all fields]) OR and bottle feeding, and other factors. In case control studies,
((“child”[MeSH terms] OR “child”[all fields]) AND preschool individuals without ECC are the matched control group.
[all fields]) OR (“child”[MeSH terms] OR “child”[all fields] Presence of ECC was the outcome. However, any method of
OR “children”[all fields])) AND (“risk factors”[MeSH terms] assessment of the outcome (ECC) was considered.
OR (“risk”[all fields] AND “factors”[all fields]) OR “risk Data extraction and quality assessment. For all studies
factors”[all fields] OR (“risk”[all fields] AND “factor”[all that met the inclusion criteria, data extraction was performed
fields]) OR “risk factor”[all fields]). The search strategies for independently by two reviewers using piloted electronic Excel
CENTRAL (Cochrane Central Register of Controlled Trials), 10 spreadsheets. Wherever possible, appropriate translators were
EMBASE, EBSCO, LILACS, and IndMED were comparable used for data extraction from papers in languages not known
to those used in the MEDLINE search. We identified and syn- by the review authors. Review authors discussed disagreements
thesized all relevant studies, up to June 2016, to reduce selection in data extraction. A third review author resolved discrepan-
bias. In addition, the reference lists of existing systematic and cies, and lead authors of the respective studies were contacted
narrative reviews and of all included studies were reviewed for to obtain missing data, if necessary. Data were recorded in
studies that might have been missed. We hand searched some accordance with the guidelines outlined by the Cochrane Col-
key journals in this field (from 2005)—such as Community laboration and categorized as study characteristics, participant
Dental Health, International Journal of Paediatric Dentistry, characteristics, adjusted effects, and absolute effects estimates.
Journal of Public Health Dentistry, Community Dentistry and The Newcastle-Ottawa scale (NOS), modified for obser-
Oral Epidemiology, Pediatrics, Pediatric Dentistry, European vational studies,12 was used to perform the risk of bias assess-
Archives of Pediatric Dentistry, European Journal of Pediatric ment of the included studies. The domains of the scale include
Dentistry, Pediatric Dental Journal, Journal of Dentistry for selection of cases and controls, comparability of the groups,
Children, Journal of Clinical Pediatric Dentistry, and Interna- and measurement of exposure and outcomes. The scale has two
tional Journal of Clinical Pediatric Dentistry—to identify those parts, one pertinent to case control studies and one for cohort
publications that could have been missed from the electronic studies. Studies were categorized as having low, moderate, and
database and searches of the reference lists.10 Hand searches were high methodological quality, according to NOS scores under
performed from 2005 to June 2016. This was because there five, from five to seven, and above seven, respectively. This
was already an update on hand searches by Harris et al.9 until quality assessment was used only for the descriptive part and
2004. This has further been updated to January 2019. This also not for statistical evaluation.
helped us identify very recent articles. Attempts to obtain grey Data synthesis and analysis. Although there is a need for
literature were performed by screening a national database for controlling confounders in observational studies, we used un-
dissertation abstracts (i.e., SHODHGANGA). adjusted measures as the primary effect estimates when they
Selection of studies. A reference management system were provided. Odds ratio (OR) is considered an appropriate
(Mendeley Desktop 1.17.13, Elsevier, Atlanta, Ga., USA) was
used to upload all the potentially eligible studies and remove
duplicate studies. Two trained reviewers independently assessed
for inclusion of all the eligible studies on the basis of the title,
abstract, and keywords. Full texts of papers or reports, for those
studies that required more information to determine relevance or
in cases where abstracts were unclear/unavailable, were obtained
through electronic mail or communication through Research
Gate. In addition, the full text of each study considered
for inclusion was also obtained. Blinding of the articles was
not performed regarding the journals published, authors, or
institutions. Disagreements among the reviewers were resolved
by discussion. Where agreement could not be reached, a third
reviewer arbitrated to reach consensus. All excluded studies at
this stage were documented in an Excel spreadsheet (Excel 10,
Microsoft Corp., Redwood City, Calif., USA), along with the
reasons for exclusion.
Selection criteria. We included prospective cohort, retro-
spective cohort, and case control studies that investigated the
association between risk factors and ECC prevalence, experience,
or incidence. Case series, case reports, and cross-sectional
studies were excluded. Randomized controlled trials (RCTs)
were also excluded because an interventional study is not the
ideal study design in which to evaluate the association be-
tween the risk factor and disease occurrence. Our study followed
the PECO format.
All preschool children, regardless of gender, race, health
status, geographical location, or socioeconomic status (SES), Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and
from birth until six years of age (less than 72 months old) were Meta-analyses) flow diagram.

96 RISK FACTORS FOR ECC

 PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

effect estimate for cohort and case control studies. Only those We assessed clinical heterogeneity (e.g., participant charac-
studies that reported or allowed the calculation of OR and error teristics, risk factors, and study settings) by investigating the
estimates (P-values, confidence intervals [CIs], and standard pertinent criteria. The chi-square and I-square tests were used
deviation) were used for quantitative data synthesis. When for the assessment of heterogeneity.13 An I-square value between
investigators used multivariate models to adjust for potential 50 percent and 100 percent was considered for statistical
confounders, we did not consider the measures, since they heterogeneity to be present. A random-effects model for meta-
would usually involve adjusted ORs. If unadjusted measures analysis was used if there was evidence of substantial or con-
were not given as a part of the primary analysis, we calculated siderable heterogeneity. To estimate effect sizes and their 95%
the same wherever possible. CIs, both random and fixed-effects generalized linear models
The results of the included studies were evaluated Review were used.
Manager 2012 statistical software (Revman 5.3, The Cochrane
Collaboration, London, UK). Forest plots were used to visualize Results
the estimate effect sizes and 95 percent (95%) CIs of indiv- Study selection and characteristics. The search revealed that
idual studies. Inverse-variance weighted averages and 95% CIs 7,034 studies were relevant to the present systematic review.
were used to represent the summary estimates for the entire Following the removal of 1,215 duplicates, 5,819 records were
sample. Data were summarized in a meta-analysis when they screened based on the title, abstract, and keywords. Of these,
were sufficiently homogeneous. We combined data from studies 5,610 records were eliminated based on improper study design
if they had comparable risk factors, follow-ups, and outcome or outcome. The remaining 209 papers were assessed for com-
measures and organized the results by the particular type of plete examination. The reason for exclusion of the 120 articles
exposure examined in the study. For ease of categorization, at this stage was different study design— including review,
the studies retrieved were categorized according to the World cross sectional or interventional-based studies, outcomes other
Bank classification into lower-income (LI), lower-middle- than dental caries, or the absence of follow-up, as described
income (LMI), upper-middle-income (UMI), and high-income in Figure 1. After a full text review, 89 studies 1,2,14-101 with a
(HI) countries. 1,352,097 total participants, were included in the present

Table 1. QUALITY OF EVIDENCE OF INCLUDED STUDIES BASED ON THE NEWCASTLE-OTTAWA SCALE

Studies graded with high Studies graded with moderate methodological quality Studies graded with low
methodological quality methodological quality

Peltzer and Mongkochali (2015)51 Ostberg et al. (2016)2 Nelson et al. (2005)84 Ghazal et al. (2015)29
Yokomichi H et al. (2015)52 Shantinath et al. (1996)86 Warren et al. (2016)1 Zaror et al. (2014)14
Winter et al. (2015)53 Mahesh et al. (2013)28 Tanaka et al. (2015)40 Gao et al. (2014)55
Peltzer et al. (2014) 27
Tanaka et al. (2015) 88
Watanabe et al. (2014) 54
Almeida et al. (2012)60
Majorana et al. (2014)15 Campus et al. (2007)85 Hong et al. (2014)56 Mattila et al. (1998)70
Zhou et al. (2012) 31
Schroth et al. (2014) 76
Moimaz et al. (2014) 57
Sanders and Slade (2010)33
Kay et al. (2010)17 Law and Seow (2006)39 Tanaka et al. (2013)58 Ismail et al. (2009)23
Hong et al. (2009)47 Wigen and Wang (2011)77 Kato et al. (2015)34 Yonezu and Yakushiji (2008)21
Teanpaisan et al. (2007) 18
Peretz and Kafka (1997) 78
Tanaka et al. (2013) 59
Lim et al. (2008)66
Oliveira et al. (2006)19 Slade et al. (2006)83 Chankanka et al. (2015)25 Yonezu et al. (2006)67
Van Palenstein Henderman et al. (2006) 41
Nunes et al. (2012) 16
Tanaka et al. (2012) 32
Yonezu et al. (2006)46
Ansai et al. (2000)45 Grytten et al. (1988)75 Grindefjord et al. (1996)73 Tada et al. (1999)35
Lai et al. (1997)20 Levy et al. (2003)68 Bankel et al. (2011)61 O’ Sullivan et al. (1996)44
Wendt et al. (1996) 72
Rodrigues and Sheiham (2000) 69
Parisoto et al. (2011) 62
Al Mendalwi and Karam (2014)24
Wendt et al. (1995)74 Ollila et al. (1998)37 Targino et al. (2011)49 Seow et al. (2009)48
Aaltonen et al. (1994) 43
Thibodeau and O’ Sullivan (1996) 71
Wigen et al. (2011) 63
Yu et al. (2015)79
Menon et al. (2013)26 Meruman and Pienihakkihen (2010)30 Ismail et al. (2008)65 Evans et al. (2013)81
Dantas Cabral de Melo et al. (2015)80 Warren et al. (2009)42 Feldens et al. (2010)64 Del Rosario Garcia et al. (2011)82
Melo et al. (2011) 22
Nishide et al. (2018) 89
Peres et al. (2017) 94
Lulic Dukic et al. (2001)38
Qin et al. (2008)87 Cabral et al. (2017)91 Bernabe et al. (2017) Marino et al. (1989)36
Boustedt et al. (2018) 90
Jean et al. (2018)92
Fan et al. (2016)98

Birungi et al. (2017) 95

Feldens et al. (2018) 93
Paglia et al. (2016)99
Nirunsittirat (2016)97 Dabawala et al. (2017)100 Roberts et al. (1994)101

RISK FACTORS FOR ECC 97

PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

review. Of these, five articles were translated to English by Assessment of the outcome. Most studies evaluated dental
Google Translate. Further, six authors were contacted requesting caries using the decayed, filled, and missing primary teeth
full texts through Research G or electronic mail. Figure 1 sum- (dmft) index and decayed, filled, and missing primary surfaces
marizes the study identification process in the form of PRISMA (dmfs) index, according to the World Health Organization 23;
flow diagram. The study participants’ ages ranged from birth a few studies determined both noncavitated and cavitated teeth
to six years. Publication years of included studies ranged from and surfaces, according to the International Caries Detection
1981 to Jan 2019. Among the included studies, 64 were pro- and Assessment System (ICDAS). Only one study used a five-
spective cohort,1,2,17-21,23,25,27,29-35,37,39-47,49,51-77,89-91,93-97 four were grade caries diagnostic system, from the most superficial (grade
retrospective cohort,14,15,16,92 and 21 were case control.22,24,26,28,36, one) to the most profound (grade five). Grades one and two
38,48,78-87,98-101
Among the 68 cohort studies, 50 studies1,2,14,15,17, constituted enamel carious lesions (initial caries), and grades
20,21,23,25,29,30,32-35,37,40,42-47,52-56,58,59,61,63,65-77,88-90,92,97
belonged to the three to five were diagnosed when the carious lesions had
HI category, 1616,18,19,27,31,49,51,57,60,62,64,69,91,93,94,96 studies belonged reached the dentin (manifest caries). Initial and/or manifest
to the UMI category, one study41 belonged to the LMI category, carious lesions (grades one to five) constituted all carious lesions
and one study95 belonged to the LI category. Among the 21 of different depths.2
case control studies, 10 studies 36,38,48,78,81,83-86,99 belonged to Narrative review. Most of the included studies examined
the HI category, eight studies22,24,79,80,82,87,98,101 belonged to the a wide range of exposures. Information about these exposures
UMI category, three belonged to the LMI category26,28,100 and was obtained predominantly from parents through interviews,28,30
no studies were present in the LI category.
Risk of bias in included studies.
The NOS was used for the quality assess- Table 2. FACTORS RELATED TO THE PREVALENCE AND/OR INCIDENCE OF PRIMARY
ment of included studies (Table 1). This TEETH CARIES IN CHILDREN AGE 6 YEARS AND YOUNGER
is a star rating system, with eight ques-
tions, that assigns a maximum of nine Sociodemographic factors Dietary factors Oral hygiene
stars within three domains: selection
Gender (male)27,51,52,81 Daily sweet snacks17,54 Daily frequency of toothbrushing
(four stars); comparability (two stars); Residence (urban) 24 High sugar foods >1x/day15,29,74,101 at <1 year old24,27,33,53,87
and measurement of exposure (risk Age65,79,81 Cariostat 3 or more54 No daily toothbrushing by
factor) in case control studies or outcome Non-Hispanic Caucasian81 Daily consumption of fruit juice79 parents2,54
(dental caries) in cohort studies (three Low socioeconomic status2,26,85,101 Added sugar beverage intake1,42 Age brushing started >12,33,38,53
stars). A high risk of bias was considered Low education of the caregiver22 Consumption of beverages/ Visible plaque31,39,42,48,89
for those studies with less than five stars. Low parental education24,81,56 carbonated drinks daily54 Parental indulgence while
Quality varied greatly among studies, No schooling of mother51 Sweet food index >2453 toothbrushing2
with 20 studies of low quality, 46 stud- Low maternal education1,22 Presweetened cereal consumption Lack of fluoride toothpaste28,49,53,101
ies showing moderate quality, and 23 Greater household size 1,22,81 at meals 25 Poor oral hygiene exam at 18
studies demonstrating high quality. Young maternal age1,63
No milk consumption at meals 25 months26,46
Overall, five studies were rated with low Birth order (3 or more)33,54,80,101 Use of thirst quenchers other Low Oral Hygiene Index score84
risk of bias and high methodological Drinking water in household1,33 than water30 Trouble with toothbrushing48
quality in all three NOS risk of bias Ethnicity 30,33,84
Added sugar 22,30
Visible plaque index79
categories (i.e., four prospective cohort Mother unemployed 28,48
High density of sugar at 12
studies and one case control study. All Single mother27 months64
Low household income 27,33,40,48,51 Very frequent sugar consumption75
four cohort studies studied different risk
Single parenting household36 Cariogenic food consumption82
factors and were conducted in various
First born child28 Sweet drinks1,87,100
parts of the world, including England Regular exposure to sweet drinks
(HI),17 Brazil (UMI),18 Thailand (UMI),19 in the first 6 months83
and the United States (HI). The study 20
Nighttime consumption of sweet
by Lai et al.20 was a case-controlled pro- beverages after 24 months38
spective study conducted in the United Eating sweets several times a day87
States (HI) to learn if the enamel hypo- Added sugar at snacks25
plasia seen in very low birthweight Pre-chewed food87
children predisposed them to increased Juice in bottle during day-time86
dental caries risk; it concluded that no Snack more than 3x/day28
significant association existed. Studies Solid sugar consumption79
with a high risk of bias and low method- Consumption of sweets between
ological quality in all three NOS risk of meals80
bias categories included one case control 82 Low levels of Vitamin D during
and three cohort studies,21,46,67 as seen in pregnancy32,76
Low levels of calcium during
Table 1. Three of the four studies were
pregnancy32
based on the same cohort in Japanese pre-
Low levels of dairy products
school children (HI country), with data during pregnancy32
collected prospectively.21,46,67 The fourth Low levels of curd during
study was a retrospective study in which pregnancy32
risk factors—namely consumption of Low levels of cheese during
cariogenic food, oral hygiene habits, pregnancy32
topical application of fluoride, and annual
oral evaluation—were studied.82

98 RISK FACTORS FOR ECC

 PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

self-reports,14,24,52 or questionnaires.1,2,15,22,27,29,40,51,53-55-60 In total, in different studies, based either on only household income24
the number of risk factors found to be associated with ECC or mother’s education at recruitment and family income,25 per
among the 76 included studies were 123. These could be capita monthly income,26 or based on the parent’s occupation
grouped as 19 sociodemographic factors, 28 factors related to status, with social class level based on the higher occupation
diet, 10 factors related to oral hygiene habits, 10 factors related status of the father or mother85. The factors studied in a single
to breastfeeding, 15 related to bottle feeding, three related study were residence of the child (urban/rural),24 low education
to oral bacteria flora, and 38 related to other factors such as of the caregiver,22 presence of a single mother,27 and the child
genetic mutation and parental smoking (Table 2). The results being firstborn.28
of the studies, according to each category (sociodemographic Dietary factors. There were many dietary factors associated
factors, dietary factors, factors related to oral hygiene, factors with ECC. Most of these factors were related either to the fre-
related to breastfeeding and bottle feeding, and other factors), quency, amount, or timing of sugar consumption.17,29,30 Among
are summarized next. all the dietary factors, the most commonly investigated risk
Sociodemographic factors. Of the 19 sociodemographic factor was frequency of eating foods high in sugar more than
factors, gender (male) and low household income were found once per day. Although this factor was found to have a signi-
to be frequently implicated in most studies.27,33,40,48,51,52,81 Factors ficant association in some studies,5,29,74 one study reported31
such as low SES, low maternal education, and unemployed that this association was not significant when adjusted for
mother have been investigated and were found to be significant confounders (unadjusted OR equals 2.5; 95% CI equals 1.2
in only a few studies.1,2,26-28,48 The reason for the inconsistent to 5.2; adjusted ORs not provided). Another study32 was con-
results with the SES factor could be the different scales used ducted on the association between calcium intake and dairy

Table 2. CONTINUED
Factors related to breastfeeding/bottle feeding Oral bacterial flora Other factors*
Breastfeeding Bottle feeding

Duration of breastfeeding Sleep with bottle at 30 months Presence of Streptococcus Presence of enamel defects19,31,48,47,49
<6 months56 1-6x/week51 mutans48 Smoking by family members27,54
No breastfeeding15,54 Nocturnal bottle feeding64 Increased baseline salivary 1 parent born abroad2
Prolonged breastfeeding Nighttime bottle use at 2 months64 S. mutans levels30,31,42-45,71 2 parents born abroad2,73
>12 months14,46,64,101 Bottle feeding38,84,85 Presence of LB37,55 Parent’s dental attendance2
Breastfeeding at least 6 months34 Slept at night with bottle Parent’s negative attitude2
Nocturnal breastfeeding30,31,46 containing sweet drink33,101 High chance locus of control2
Breastfeeding35 Feeding to help them sleep86 Drinking water in household/home water
Daily breastfeeding On-demand feeding86 fluoride level27,28,56
frequency at 12 months64 Feeding associated with nap time86 Low birthweight56,96
>15 minutes/feeding at night41 Age of weaning from bottle36,86 History of previous dental visit at age 3 years29
>2 nocturnal breastfeeding41 Formula in bottle at night86 Previous dental experience14
Breastfeeding ≥24 months94 Child held bottle while falling asleep Regular dental check ups <553
(propping)86 Late bedtime36,54
Prolonged bottle feeding, Low body mass index31
especially at night36,93 One or both parents of non-western origin63
Added sugar in bottle48 Blue collar occupation of caretaker30
Sleeping while feeding after Reported poor oral health of father30,33
12 months87 Teeth erupted at 18 months >633
Feeding habits before 6 months87 Low Apgar score33
High density of lipids at 12 months64
Soda consumption 2-6x/day65
Mother missing teeth75
Incidence of caries (DMFT>0)48,70
Parental stress26
Reason for dental visits84,101
Complication during pregnancy78
Delivery (instrument/Caesarean)78,90
Tantrums/strong temper36
Parental smoking24,96
Ear infection84
No previous dental visit28
Day care person28
Visible abscess48
Mutation in the locus79
Inappropriate fluoride supplementation36
Mothers knowledge of when to clean the
child’s mouth and brush the child’s teeth48
Oral thrush92

* DMFT= decayed, filled, and missing permanent teeth.

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PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

products during pregnancy and dental caries

Table 3. OVERVIEW OF THE META-ANALYSIS OF THE INCLUDED COHORT
in children; it concluded that the increased
STUDIES CATEGORIZED AS UPPER-MIDDLE-INCOME AND UPPER-
maternal intake of cheese during pregnancy may
INCOME COUNTRIES*
significantly decrease the risk of developing
Risk factor n K Pooled odds ratio Chi-square2 I2 value dental caries in children (P=0.001). Weaning
(95% Cl) value after 18 months as a risk factor was assessed in
another study33 and found to be not significant
Upper-middle-income countries (P=0.291).
Low birthweight31,51 822 2 0.83 (0.49, 1.41) 1.83 45 Factors related to breastfeeding/bottle
Increased baseline salivary levels 394 2 9.21 (4.97, 17.07) 0.22 0 feeding. The number of included studies that
of Streptococcus mutans18,31 investigated breastfeeding and bottle feeding as
Presence of enamel defects19,31 453 2 14.62 (6.10, 35.03) 0.00 0
a risk factor are 15 and 13, respectively. Accord-
ing to Kato et al. in 2015, 34 breastfeeding for
Night bottle feeding49,64 564 2 0.62 (0.49, 0.78) 1.91 48
six to seven months or more might increase
Night breastfeeding31,49 449 2 1.28 (1.11, 1.47) 1.54 35 dental caries risk due to simultaneous events
Gender (male)51,64 937 2 1.26 (0.85, 1.88) 3.45 71 that occur during the same period, such as the
Toothbrushing at least once 449 2 1.36 (1.08, 1.72) 0.60 0 eruption of primary teeth. The same study re-
a day31,49 ported breastfeeding and bottle feeding as
Brushing with fluoride 937 2 1.03 (0.75, 1.42) 0.47 0 risk factors for ECC; in that study, breastfeed-
toothpaste51,64 ing was specifically associated with caries in
Sugar snacks at least once a 449 2 0.69 (0.16, 3.00) 0.95 84 maxillary anterior teeth and bottle feeding was
day31,49 associated with caries in molars.34 That study
Low maternal age (<25 years)31,51 822 2 0.65 (0.45, 0.94) 1.75 43 also mentioned that this association became
attenuated through the follow-up period and
High-income countries was no longer statistically significant beyond
Low maternal education 5,885 8 1.84 (1.14, 2.08) 31.49 78 the age of 42 months for the partially breastfed
(≤9 years)2,17,56,63,66,70,75 group and beyond the age of 54 months for the
Low birthweight 1,857 2 1.70 (0.89, 3.23) 0.00 0 exclusively breastfed group. Another case con-
(<2,500 g)56,63 trol study involving South African children
Smoking during pregnancy1,63 1,580 2 1.33 (0.74, 2.39) 2.53 60 compared a group with nursing caries to those
without it. They found no statistically signifi-
Increased baseline salivary 2,812 5 3.83 (1.81, 8.09) 47.96 92
cant differences for feeding patterns between the
levels of S. mutans30,42,45,55,73
groups in relation to the prevalence of nursing
Increased consumption of 886 2 1.12 (1.03, 1.23) 0.18 0 caries.101 Most studies counted on parental recall
soda pop25,56
in the form of questionnaires or interviews,14,23,
Maternal age (<25 years)1,17,63 2,565 3 1.26 (0.65, 2.45) 17.43 89 31,35-40
and very few studies used standardized
Toothbrushing at least once 2,328 4 0.91 (0.55, 1.51) 6.69 55 validated questions or previous dental records,
a day2,25,66,67 which are more reliable.14,41
Visible plaque present42,70,72 1,106 3 3.1 (2.00, 4.80) 0.52 0 Factors related to oral hygiene. Past
Poor oral hygiene67,72 394 2 3.12 (1.77, 5.49) 0.28 0 studies collected data by means of self-reports
Night bottle feeding37,42,58 592 3 1.15 (0.44, 3.04) 14.91 87 or more directly via the use of a plaque or oral
hygiene index for oral hygiene habits. It is
Age at dental exam 2,328 2 1.68(1.06, 2.66) 0.78 0
>1 year2,25,66,67
interesting to note that, in one of the included
studies, parental indulgence (when parents ne-
Liquids in bottle other than 421 2 1.27 (0.83, 1.94) 2.04 51
glected to help the child brush twice daily or
milk58,68
when they did not have the time to brush) was
Presence of lactobacilli37,55 1,728 2 2.18 (2.03, 2.34) 1.13 11
reported as one of the most important risk
Gestational age <37 weeks 29,63
1,445 2 0.67 (0.14, 3.12) 3.50 71 factors for ECC.2 Among all the factors studied,
Gender (males)17,30,39,63 2,727 4 0.98 (0.80, 1.19) 2.01 0 visible plaque42,48 and toothbrushing less than
Age started brushing ≥12,53 836 2 2.12 (1.49, 3.01) 0.00 0 once daily 24,27,33,53,87 were the two most im-
Brushing <1x/day17,53,54,75 32,984 4 1.08 (0.61, 1.92) 12.39 76 portant oral hygiene factors related to ECC.
The other less important factors are age at
Dentinal caries (dmft >0)66,70 2,268 2 4.21 (2.18, 8.16) 0.42 0
which toothbrushing was started,3,38 not having
No topical fluoride 31,768 2 1.50 (1.39, 1.63) 1.22 18 teeth brushed at bedtime, using nonfluor-
application53,54 idated toothpaste,28,49 and parental supervision
Frequent consumption of 31,472 2 3.14 (0.89, 11.04) 3.01 67 of toothbrushing.2
sweetened foods2,54 Factors related to oral bacteria flora.
Intake of sugar snacks daily2,30,54 31,831 3 1.56 (1.42, 1.71) 0.68 0 Streptococcus mutans is known to be the main
Intake of sugar beverages2,42,67,68,73 1,298 5 1.67 (0.25, 3.92) 46.18 91 bacterium in the aetiology of dental caries. An
Socioeconomic status25,39 412 2 0.46 (0.28, 0.74) 0.05 0 association between ECC and the colonization of
mutans streptococci (MS) in saliva or plaque
* n=number of participants; K=number of studies; dmft=decayed, filled, and missing primary has been demonstrated. The age at which MS
teeth. is detectable in a child’s oral cavity is said to be

100 RISK FACTORS FOR ECC

 PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

an important indicator of caries risk, although it may

not be detectable in the infant’s mouth prior to tooth
eruption (Table 2). One study31 suggested that the
earlier S. mutans colonizes in a child, the greater the
risk of developing caries. Another study18 observed
MS in 1.78 percent of predentate infants as young
as three months and studied the presence of dental
caries in nine- and 24-month-old children. Most
studies assessed how the individual’s baseline caries
risk influenced the development of caries in children
aged six months to six years. Almost all the studies in
this area observed an increase in the caries experience,
with increased salivary MS levels at baseline.30,42-46
However, whatever the ethnic group may be, if MS
is present in the oral cavity, it appears to be an im-
portant indicator of caries risk. Ethnic differences in
the prevalence of dental caries can, to an extent, be
explained by differences in the acquisition of cario-
genic bacteria.
Other factors. There were 38 factors which
belonged to this category. Among them, enamel hypo-
plasia was the most commonly studied. All studies
that included the presence of enamel hypoplasia as
a potential risk factor for ECC concluded that the
risk of developing dental caries was significantly
increased.19,31,47-49 One study19 observed a total of 224
children, with enamel defects from the age of 12 to
54 months, for the presence of ECC. At 12 months,
none of the infants showed the presence of dental
caries. At 42 months, 9.2 percent of children pre-
sented with carious teeth; at 54 months, 48.4 percent
of the children with dental caries showed the presence
of enamel defects. The study also concluded that
enamel hypoplasia was the most common category
of enamel defect associated with dental caries. On
the contrary, another study47 concluded that the type
of enamel defect with the most frequently associated
risk factor with dental caries in children aged 36
Figure 2. Risk factors found in the high-income category. (a) Forest plot showing presence of months was opacity with enamel hypoplasia (42.7
dentinal caries (decayed, filled, and missing primary teeth [dmft] index score greater than zero) percent), followed by hypoplasia (42.7 percent) and
as a risk factor for early childhood caries. (b) Forest plot showing presence of mutans strepto- diffuse opacity (6.4 percent).
cocci as a risk factor for ECC. (c) Forest plot showing frequent consumption of sweetened foods A recent study assessed whether there is an
as a risk factor for ECC. (d) Forest plot showing poor oral hygiene as a risk factor for ECC.
association between oral thrush or other Candida-
(e) Forest plot showing visible plaque present as a risk factor for ECC.
related conditions in infancy and ECC diagnosed by
pediatricians. The study design was a retrospective
cohort using electronic health records from six na-
tional children’s hospitals. There were 1,012,668 chil-
dren included in the study, with one visit at ages
one to 12 months and another visit at ages 13 to 71
months. This study concluded that oral thrush may
be a risk factor for ECC.92
Quantitative analysis. Among the 89 included
studies, 68 are cohort studies and 21 are case control
studies. Of the 68 cohort studies 50 studies1,2,14,15,17,
20,21,23,25,29,30,32-35,37,40,42-47,52-56,58,59,61,63,65-77,88-90,92,97
be-
longed to the HI category, 16 studies16,18,19,27,31,49,51,57,
60,62,64,69,91,93,94,96
fit in the UMI category, one study41
was categorized as LMI, one study95 belonged to the
LI category. From the 68 cohort studies, only 29
studies contributed for quantitative analysis. Among
these 29 studies, 23 studies1,2,17,25,29,30,37,39,42,45,53-56,58,63,
Figure 3. Risk factors found in the upper-middle-income category. (a) Forest plot showing
presence of enamel defects as a risk factor for ECC. (b) Forest plot showing presence of mutans
66-68,70,72,73,75
fit within the HI category and six stud-
streptococci as a risk factor for ECC. ies 18,19,31,49,51,64 belonged to the UMI category. No

RISK FACTORS FOR ECC 101

PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

studies from the LMI and the LI category were included. The that the exposure has occurred prior to the outcome. Hence,
remaining 30 studies 14-16,20,21,23,27,32-35,40,41,43,44,46,47,52,57,59,60-62,65,69, longitudinal studies are needed to study risk factors. In a cross-
71,74,76,77,88-97
were excluded, either because the data were missing sectional study, an exposure associated with an outcome can
or heterogeneous. be considered a risk indicator only. Hence, we included only
None of the risk factors among the 21 case control cohort and case control studies in the present systematic review,
studies22,24,26,28,36,38,48,78,79,80-87,98-101 was eligible for quantitative which is the ideal study design to examine risk factors.50 This
analysis. Either the factors could not be combined, due to evidence can have key implications for the development of pre-
missing data, or they belonged to a different country classifica- vention strategies for common risk factors associated with ECC.
tion based on income. The present review used the NOS to assess risk of bias of
Figures 2 and 3 show the significant risk factors found in individual studies. Modification of this scale for two questions
the HI and UMI categories, respectively. The forest plots re- was needed to suit the present research question. First, in the
present only those with an OR greater than three (Figures 2 and rating system for ascertainment of exposure, one star was allo-
3). Figures 4 to 9 represent the re-maining risk factor forest plots cated not only for the structured interview (as in the original
(see Electronic Appendix). Table 3 shows an overview of the scale) but also for questionnaire or medical records. This item
meta-analysis of the included cohort studies, categorized as UMI was modified for both the cohort and case control studies.
and HI countries. Second, under the rating of comparability for cases and controls,
The important risk factors (OR greater than one) amid it was not possible to determine the main confounder, as the
HI countries were: low maternal education; low birth weight present systematic review studied the role of multiple etiological
(less than 2,500 g); smoking during pregnancy; the presence factors. Therefore, it was decided to give two stars if the study
of MS; increased daily soda pop intake; maternal age younger adjusted for confounders using multiple logistic regression anal-
than 25 years; visible plaque present; bad oral hygiene; night ysis and one star if the study controlled for at least one potential
bottle feeding; age at first dental examination younger than confounder (e.g., age, gender, income, or SES). In the present
one year; liquids other than milk in bottles; the presence of systematic review, 76 out of the 89 studies adjusted for at
lactobacilli; tooth brushing less than once daily; age when least one of the confounding variables, which can be considered
brushing began at one year of age or older; negative parental a major strength of the included studies.
attitudes; the presence of dentinal caries (dmft greater than zero); However, the present review used only the studies that
topical fluoride application; frequent consumption of sweetened provided unadjusted ORs for the meta-analysis, since there
foods; daily intake of sugary snacks; and intake of sugary was no standardization of confounders adjusted in various
beverages. The strongest risk factors associated were the: pre- studies. This probably led to the fewer number of studies in-
sence of dentinal caries (dmft greater than zero; OR equals cluded under each risk factor category.
4.21 [2.18 to 8.16]); high levels of MS (OR equals 3.83 [1.81 Limitations. Overall, there are three major limitations
to 8.09]); frequent consumption of sweetened foods (OR with the included studies of risk factors for ECC. The first is
equals 3.14 [0.89 to 11.04]); poor oral hygiene (OR equals the absence of adjustment for confounding factors. A known
3.12 [1.77 to 5.49]); and visible plaque present (OR equals constraint of observational studies is the ability of confound-
3.10 [2.0 to 4.80]; Figure 2). ing factors to exaggerate or diminish the significance of some
Among the studies grouped under UMI countries, the factors, since randomization is not possible. This is usually com-
factors found to have a positive association with ECC (OR pensated by using multiple logistic regression analysis, which is
greater than one) were high levels of MS counts, the presence almost compulsory in these studies. This analysis depends on
of enamel defects, nighttime breastfeeding, gender (male), the use of dichotomized data, which means that the categoriza-
brushing with fluoride toothpaste, and brushing at least once tions used in each study may be as significant as the numbers
a day. The strongest risk factors associated with ECC, among of exposures tested. For example, one study22 might investigate
the studies, were the presence of enamel defects (OR equals toothbrushing frequency by comparing once, twice, or thrice
14.62 [6.10 to 35.03]) and high levels of MS (OR equals 9.21 daily versus less than once daily, whereas another study might
[4.97 to 17.07]; Figure 3). compare one or more times daily53 and reach different conclu-
sions. Although most studies performed some form of adjust-
Discussion ment for confounders, this was often poorly reported or not
To the best of our knowledge, this study is the first systematic described. Moreover, the values—namely, adjusted or unad-
review and meta-analysis, including case control and cohort justed P-values and odds ratios were not provided. Further-
studies, examining possible associations between various risk more, 11 included studies in this review did not perform any
factors and ECC. The objective of a systematic review is to method to account for the confounding factors.
identify, evaluate, and synthesize evidence from previously The ideal selection of a confounder in the present study is
conducted studies to provide informative empirical answers to based on existing evidence of an accepted association with the
unanswered research questions. The key question of the present risk factor studied (exposure) and ECC (outcome). The second
review is, what are the main risk factors for early childhood is the lack of consistency and detail among the categories of
caries? risk factors studied, which restricts comparison between and
To answer this, we undertook a structured approach to among the studies. Also, it is possible that the mothers of the
identify pertinent literature and to minimize bias in the se- study participants, who completed questionnaires regarding
lected studies.9 The only way to understand the relationship their children’s various risk factors, were provided with some
between etiological factors and disease in the population is basic information regarding the same. Hence, the accuracy of
through observational studies, since randomization is impos- their answers could be questionable. This could be explained
sible. Nevertheless, the confounding factors may mask the exact by the wide range of risk factors evaluated across the included
association between a risk factor and ECC, in the absence of studies. However, specific definitions of risk factors studied are
randomization. The description of a risk factor clearly indicates necessary to ensure the accuracy of the data collected. Further

102 RISK FACTORS FOR ECC

 PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

Table 4. OVERVIEW OF THE SOCIOECONOMIC STATUS (SES) OF THE POPULATION STUDIED IN EACH STUDY IN THE META-ANALYSIS,
BASED ON WORLD BANK CLASSIFICATION
High-income countries Upper-middle-income Lower- Lower-
countries middle- income
income countries
Low SES High SES Not mentioned (n=18) All SES Low SES Not countries
(n=3) (n=1) profiles (n=4) mentioned
(n=1) (n=2) — —

Lim et al. (2008)66; Hong et al. Gao et al. (2014)55; Warren et al. Feldens et al. (2010)64; Peltzer and
Warren et al.(2009)42; (2014)56 Watanabe et al. (2014)54; (2016)1 Oliveira et al. (2006)19; Mongkochali
Ghazal et al. (2015)29 Wigen and Wang (2011)77; Teanpaisan et al. (2007)18; (2015)51;
Tanaka et al. (2013)58; Targino et al. (2011)49 Zhou et al. (2012)31
Levy et al. (2003)68;
Kay et al. (2010)17;
Yonezu T et al. (2006)67;
Ansai et al. (2000)45;
Mattila et al. (1998)70;
Ollila et al. (1998)37;
Wendt et al. (1996)72;
Grindefjord et al. (1996)73;
Grytten et al. (1988)75;
Law and Seow (2006)39;
Gao et al. (2014)55;
Watanabe et al. (2014)54;
Wigen and Wang (2011)77;
Levy et al. (2003)68

standardization among the studies to measure oral health out- country category groups, using standardized data collection and
comes (dental caries) and the risk factors in children is required outcome measures with appropriate adjustment of potential
to facilitate a more accurate knowledge base of the risk factors confounders.
for ECC. In addition to the shortcomings of the included Meta-analysis of UI countries showed that presence of
studies, our statistical analysis has caveats, as we pooled estimates dentinal caries, high levels of MS, frequent consumption of
from various study designs, detection cutoffs, caries measures, sweetened foods, poor oral hygiene, and visible plaque present
and statistical models. The third limitation of the included are major risk factors (each with an OR above three) associated
studies was that, among the 89 included studies, quality varied with ECC. In UMI countries, high levels of MS and presence of
greatly among studies—with 20 studies of low quality, 46 enamel defects were the major risk factors. However, the readers
studies showing moderate quality, and 23 studies demon- are advised to interpret these findings with caution, because the
strating high quality. Overall, only five studies were rated high population studied might belong to a low, moderate, or high
in all three categories. These findings carry implications for SES in UI or UMI countries, as previously discussed (Table 4).
future research. Further studies in HI, UMI, LMI, and LI countries, includ-
Among the 89 included studies, using World Bank classi- ing all SES populations, are needed to better understand the
fication for categorizing the countries: 60 studies (10 case various risk factors associated with ECC in different countries
control studies, 50 cohort studies) were from the HI category; and among people from different SES.
24 studies (eight case control studies, 16 cohort studies) were Regardless of the heterogeneous nature of the included
categorized as UMI; four studies (three case control studies, studies, when it comes to study design and the statistical tests
one cohort study) fell into the LMI category; and one study used, the accuracy and magnitude of our estimates strongly sup-
was categorized as LI. Of the 76 studies only 29 cohort studies port the presence of an association between certain risk
contributed for quantitative analysis. Evaluation of the popula- factors and ECC. In the HI category, the presence of dentinal
tion studied in the 29 cohort studies (HI equals 23; UMI caries, high levels of MS, frequent consumption of sweetened
equals six; LMI equals zero; LI equals zero) showed that various foods, poor oral hygiene, and the presence of visible plaque were
SES children were included in each study. Among the 23 the significant risk factors. This can be attributed to the fact
studies in the HI category, SES profiles of the population that sugar consumption is usually higher and more equally
studied were low, high, all profiles, and not mentioned in three, distributed in HI countries versus LI countries. In UMI coun-
one, one, and 18 studies, respectively. In the six UMI categorized tries, the presence of enamel defects and high levels of MS were
studies, the SES profiles were low in four studies and not men- found to be significant. This may be because malnutrition and
tioned in two studies. As low SES is associated with greater increased rates of infection in early life are more prevalent in
risk of acquiring ECC, it is imperative that future studies these countries and are predisposing factors for enamel defects.
should mention the population studied for better understand- It is noteworthy that no longitudinal study was found that
ing of this association. The categorization further revealed that evaluated host factors, such as enamel permeability, enamel
only one study was performed in the LMI category (Myanmar)41 composition, contact areas, and types of pits and fissures, as
and one study was performed in the LI category (Uganda). 95 risk factors for ECC. Their role in the etiology of ECC remains
Therefore, future studies are required mainly in LMI and LI unclear and requires further investigation.

RISK FACTORS FOR ECC 103

PEDIATRIC DENTISTRY V 41 / NO 2 MAR / APR 19

Conclusions
Based on this study’s results, the following conclusions can
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Electronic Appendix

Figure 4. Risk factors found in the high-income category. (a) Forest plot showing low maternal
education as a risk factor for ECC. (b) Forest plot showing low birthweight (less than 2,500 g)
as a risk factor for early childhood caries. (c) Forest plot showing smoking during pregnancy
as a risk factor for ECC. (d) Forest plot showing increased consumption of soda pop as a risk
factor for ECC. (e) Forest plot showing maternal age (younger than 25 years) as a risk factor
for ECC.

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Figure 5. Risk factors found in the high-income category. (a) Forest plot showing presence of lactobacillus as
a risk factor for early childhood caries. (b) Forest plot showing age when brushing started at least by one year as a
risk factor for ECC. (c) Forest plot showing night bottle feeding as a risk factor for ECC. (d) Forest plot showing
age at dental exam older than one year of age as a risk factor for ECC. (e) Forest plot showing liquids in bottle
other than milk as a risk factor for ECC.

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Figure 6. Risk factors found in the high-income category. (a) Forest plot showing toothbrushing less than
once a day as a risk factor for early childhood caries. (b) Forest plot showing parental negative attitude as
a risk factor for ECC. (c) Forest plot showing topical fluoride application as a risk factor for ECC. (d) Forest
plot showing intake of sugary snacks daily as a risk factor for ECC.

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Figure 7. Risk factors found in the high-income category. (a) Forest plot showing intake of sugary beverages as
a risk factor for early childhood caries. (b) Forest plot showing gestational age as a risk factor for ECC. (c) Forest
plot showing gender (males) as a risk factor for ECC. (d) Forest plot showing brushing at least once a day as a
risk factor for ECC. (e) Forest plot showing socioeconomic status (SES) as a risk factor for ECC.

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Figure 8. Risk factors found in the upper-middle-income category. (a) Forest plot showing low birthweight as a risk factor
for early childhood caries. (b) Forest plot showing night bottle feeding as a risk factor for ECC. (c) Forest plot showing sugar
snacks at least once a day as a risk factor for ECC. (d) Forest plot showing maternal age as a risk factor for ECC.

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Figure 9. Risk factors found in the upper-middle-income category. (a) Forest plot showing night breastfeeding as a
risk factor for early childhood caries. (b) Forest plot showing gender (males) as a risk factor for ECC. (c) Forest plot
showing brushing at least once a day as a risk factor for ECC. (d) Forest plot showing brushing with fluoride tooth-
paste at 26 months as a risk factor for ECC.

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