Scholarly article on topic 'Breastfeeding and the risk of dental caries: a systematic review and meta-analysis'

Breastfeeding and the risk of dental caries: a systematic review and meta-analysis Academic research paper on "Health sciences"

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Academic research paper on topic "Breastfeeding and the risk of dental caries: a systematic review and meta-analysis"

ACTA P/EDIATRICA

NURTURING THE CHILD

Acta Pœdiatrica ISSN 0803-5253

REVIEW ARTICLE

Breastfeeding and the risk of dental caries: a systematic review and meta-analysis

R Tham1, G Bowatte1, SC Dharmage12, DJ Tan1'3, MXZ Lau1, X Dai1, KJ Allen2'4, CJ Lodge (clodge@unimelb.edu.au)1'2

1.Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Vic., Australia

2.Murdoch Childrens Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Parkville, Vic., Australia

3.NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, TAS, Australia 4.Institute of Inflammation and Repair, University of Manchester, UK

Keywords

Breastfeeding, Child, Dental caries, Meta-analysis, Systematic review

Correspondence

Caroline Lodge MBBS Grad Di Epi PhD, Allergy and Lung Health Unit (ALHU), Centre for Epidemiology and Biostatistics, School of Population & Global Health, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Level 3, 207 Bouverie Street, Melbourne, Vic. 3010, Australia. Tel: +61 3 83440848 | Fax: +61 3 93495815 | Email: clodge@unimelb.edu.au

Received

18 May 2015; revised 10 June 2015; accepted 7 July 2015.

D0I:10.1111/apa.13118

ABSTRACT

Aim: To synthesise the current evidence for the associations between breastfeeding and dental caries, with respect to specific windows of early childhood caries risk. Methods: Systematic review, meta-analyses and narrative synthesis following searches of PubMed, CINAHL and EMBASE databases.

Results: Sixty-three papers included. Children exposed to longer versus shorter duration of breastfeeding up to age 12 months (more versus less breastfeeding), had a reduced risk of caries (OR 0.50; 95%CI 0.25, 0.99, I2 86.8%). Children breastfed >12 months had an increased risk of caries when compared with children breastfed <12 months (seven studies (OR 1.99; 1.35, 2.95, I2 69.3%). Amongst children breastfed >12 months, those fed nocturnally or more frequently had a further increased caries risk (five studies, OR 7.14; 3.14, 16.23, I2 77.1 %). There was a lack of studies on children aged >12 months simultaneously assessing caries risk in breastfed, bottle-fed and children not bottle or breastfed, alongside specific breastfeeding practices, consuming sweet drinks and foods, and oral hygiene practices limiting our ability to tease out the risks attributable to each. Conclusion: Breastfeeding in infancy may protect against dental caries. Further research needed to understand the increased risk of caries in children breastfed after 12 months.

INTRODUCTION

Dental caries (tooth decay) is a major public health problem affecting 60-90% of school-aged children (1), with increased prevalence in children from lower socio-economic groups (2). It is caused by multi-factorial and complex interactions between cariogenic bacteria in the mouth with dietary carbohydrates that produce acids and demineralise the teeth (2). The pain and infection caused by dental caries can be extremely distressing and can impact on quality of life and ability to function (3), lead to lost productivity and involve high health care costs (4) including general anaesthesia for treatment of severe cases. This accounts for one of the most common causes of child hospitalisation in industrialised countries (5) and is among the most common causes of avoidable child hospitalisations (6). Early loss of deciduous dentition can lead to ongoing dental problems in the permanent dentition.

The evidence concerning infant feeding as a risk factor for dental caries is inconsistent. Dental caries risk is related

to the carbohydrate content of breast milk or formula along with factors which determine the length of contact between breast milk or formula and the erupted dentition (i.e. frequency of feeding, and feeding practices which result in pooling of breast milk or formula around the teeth surfaces, such as feeding babies to sleep). The central determinant of caries risk, however, is the age of colonisation and levels of cariogenic bacteria (e.g. Streptococcus mutans) (7) in an infant's mouth. Earlier and denser oral colonization by cariogenic bacteria are related to increased caries risk (8). Breast milk, in contrast to formula, contains breast-specific

Abbreviations

95%CI, 95% Confidence Intervals; NOS, Newcastle Ottawa Scale; OR, Odds ratio; RCT, Randomized controlled trials; RR, Relative risk; WHO, World Health Organization.

Key notes

• Children exposed to more versus less breastfeeding up to 12 months had reduced risk of dental caries.

• Increased risk of dental caries in children breastfed >12 months, especially if frequent or nocturnal, may be due to unmeasured confounders including dietary sugars and oral hygiene practices.

• Research should simultaneously investigate breastfeeding practices including frequency and nocturnal routines, along with dietary and oral hygiene practices to more accurately determine specific risks.

©2015 The Authors. Acta P^diatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta P^diatrica 2015 104, pp. 62-84 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,

provided the original work is properly cited.

Lactobacilli and substances, including human casein and secretory IgA, which inhibit the growth and adhesion of cariogenic bacteria, particularly oral Streptococci (9,10). The risk of dental caries is also dependent on the presence of teeth and rises with increasing number of teeth. Risk also changes as the infant's diet starts to include foods and drinks other than breast milk or formula, depending on the carbohydrate content, acidity and consumption frequency of the introduced diet.

The important aspect of timing of tooth eruption for our systematic review is that the deciduous teeth most at risk of early childhood caries (eight upper and lower central and lateral incisors) start to erupt at 6 months and are fully erupted by 12 months. The next most vulnerable deciduous teeth (four upper and lower first molars) erupt between 13 and 19 months, the remainder are erupted by 33 months (11).

Current WHO breastfeeding guidelines recommend exclusive feeding for the first 6 months of life and complementary breastfeeding up to 2 years (12). Although the UNICEF calculated global prevalence of breastfeeding at 12 months from 62 countries is 74%, this figure hides the underlying heterogeneity between countries (13). As opposed to low income countries, the duration of total breastfeeding in high/middle income countries is shorter with only 21% of US mothers breastfeeding at 12 months (14) and similar rates in the UK (13), Canada (5) and Australia (15). National guidelines in high/middle income countries, where the risk of infant morbidity and mortality from gastrointestinal disease is relatively low, recommend breastfeeding for at least 12 months (16). Thus, investigating windows of exposure before and after 12 months of age is relevant to breastfeeding guidelines and practices as well as timing of tooth eruption.

The relationship between breastfeeding and dental caries has been systematically (17) and narratively reviewed (1820) with conflicting results between studies. There is controversy about what constitutes the best form of infant feeding to prevent dental caries and promote optimal dental health (21). Consequently no definitive optimal weaning times or breastfeeding practices have been determined to specifically address the risk of dental caries.

To summarise the current evidence for the association between breastfeeding and dental caries with specific reference to exposure windows and breastfeeding practices.

METHODS

Search strategy

We identified human English language studies through systematically searching electronic databases: PubMed Central, CINAHL and EMBASE from inception to the present. Our exposure of interest was breastfeeding as compared to formula or other feeding. Our outcome of

Table 1 Search terms used for the three databases electronically searched

[PUBMED]

#1 "Breast Feeding"[Mesh]

#2 "Milk, Human"[Mesh]

#3 Breast[All Fields] AND Feed*[All Fields]

#4 Breast-fe*[All Fields]

#5 Infant fe* [All Fields]

#6 Infant nutrition* [All Fields]

#7 #1 OR #2 OR #3 OR #4 OR #5 OR 6

#8 Dental caries (MeSH)

#9 Tooth decay

#10 "Early childhood caries"

#11 "Nursing bottle caries"

#12 #8 OR #9 OR #10 OR #11

#13 animals [mh] NOT humans [mh]

#14 #7 AND #12

#15 #14 NOT #13

[EMBASE]

#1 'breast feeding'/exp #2 'breast milk'/exp #3 Breast AND Feed* #4 Breast-fe* #5 Infant fe* #6 Infant nutrition*

#7 #1 OR #2 OR #3 OR #4 OR #5 OR 6

#8 'dental caries'/exp

#9 Tooth decay

#10 "Early childhood caries"

#11 "Nursing bottle caries"

#12 #8 OR #9 OR #10 OR #11

#13 [animals]/lim NOT [humans]/lim

#14 #7 AND #12

#15 #14 NOT #13

[CINAHL]

#1 "Breast Feeding" #2 "Milk, Human" #3 Breast AND Feed* #4 Breast-fe* #5 Infant fe* #6 Infant nutrition*

#7 S1 OR S2 OR S3 OR S4 OR S5 OR S6

#8 dental caries

#9 tooth decay

#10 early childhood caries

#11 nursing bottle caries

#12 S8 OR S9 ORS10 OR S11

#13 S7 AND S12

**For #13 limit to 'Human'

interest was the development of dental caries in deciduous or permanent teeth. An extensive list of search terms was used and is reported in Table 1.

We checked reference lists of all primary studies and review articles for additional references. The titles and abstracts were independently reviewed for initial inclusion by two researchers (RT and GB). Disagreement was resolved by discussion and if consensus could not be reached, a third author (CL) made the final decision.

Eligibility criteria

We included observational and experimental studies published in full text. We included children and adolescents from both general and high-risk populations (e.g. low socioeconomic communities). Dental caries as reported by appropriately qualified practitioner/researchers, a parent or through health records databases were included. We excluded participants who were born prematurely (<36 weeks gestation) because these infants are often fed by other sources and can have complicated medical interventions.

Assessment of quality and risk of bias

Two researchers (RT and GB) independently conducted a quality assessment of each study using the Newcastle-Ottawa Scale (NOS) (22). Study quality was graded on a scoring system (see Tables 2-5 for key criteria). Differences in assessment and grading were resolved by discussion with a third researcher (CL).

The assessment of risk of bias was guided by the GRADE system for rating the quality of the evidence of observational studies (23).

Literature review identified key confounders that should be controlled for in breastfeeding and dental caries studies: socio-economic status, age, mother's educational level,

number of teeth, and exposure to sugar in the diet (food or other liquid).

Data extraction

We extracted: study design; study country; age range of children; number of children; exposure and outcome definitions; how the outcome data were measured; effect estimates; confounders included in analysis; sub-group analysis; interactions; and findings.

Assessment for meta-analysis

Exposure and outcome definitions and effect estimates (odds ratios (OR), relative risks, prevalence ratios) with 95% Confidence Interval (95%CI) were abstracted where available for inclusion in a meta-analysis. Given the biological plausibility of the potential associations, we aimed to assess exposure to breastfeeding in two specific time windows: (i) Up to 12 months of age (upper and lower incisors present) and (ii) Beyond 12 months of age (other teeth erupting up to 33 months- increased risk of caries). As there were very few mothers who exclusively breastfed infants until 12 months or beyond, within these time windows we categorized studies into: (i) Never breastfed compared to any breastfeeding and (ii) More versus less breastfeeding. This category was created to include all

Table 2 Newcastle-Ottawa Quality Assessment score for Cohort studies nested in Randomized Controlled Trials

Selection of Outcome of Adequate

non- exposed Ascertainment interest not Assessment Adequate follow up

RCT Representativeness cohort of exposure present at start Comparability of outcome follow up time of cohorts Score/10

Feldens et al. (30) * * * * ** * * 8

Feldens et al. (27) * * * * ** * * 8

Table 3 Newcastle-Ottawa Scale Quality Assessment score for Cohort Studies

Selection of Outcome of Adequate

non-exposed Ascertainment interest not Assessment follow Adequate follow

Cohort studies Representativeness cohort of exposure present at start Comparability of outcome up time up of cohorts Score/10

Feldens et al. (25) * * * * ** ** * * 10

Chaffee et al. (26) * * * * * * * * 8

Hong et al. (31) * * * ** ** * 8

Kramer et al. (29) * * * * ** * * 8

Kramer et al. (28) * * * * ** * * 8

Ollila (38) * * * ** * * 7

Silver (32) * * * * * 5

Tada et al. (33) * * * * 5

Tanaka et al. (34) * * * ** ** * 8

Thitasomakul et al. (35) * * * * ** * 7

van Palenstein * * ** * * 6

Helderman et al. (36)

Yonezu et al. (37) * ** * * 5

Table 4 Newcastle-Ottawa Scale Quality Assessment score for Case-Control Studies

Adequate Representativeness Selection of Definition of Ascertainment Method of Nonresponse

Case control case definition of cases controls controls Comparability of exposure ascertainment rate Score/10

Bahuguna et al. (39) * * * * * 5

Matee et al. (40) * * * * 4

Roberts et al. (41) * * ** * 5

studies, which compared groups with relatively more (longer duration of breastfeeding) and relatively less breast milk exposure (shorter duration). To choose between multiple reported ORs for a single study we preferentially selected: estimates for exclusive breastfeeding or, if not available, any breastfeeding; then the longest duration compared with the shortest. If there were multiple ages of outcome within the particular group then we chose the oldest age reported.

We performed meta-analysis if there were three or more studies in each time window and category of breastfeeding. Random effects meta-analyses were performed if the heterogeneity (I2) was >25%. Heterogeneity was considered to be high, and results unreliable if I2 values were >75%. We were unable to quantitatively assess for publication bias as no group contained more than 10 studies. Studies not meeting these criteria were qualitatively assessed.

Statistical analysis was performed using Stata IC 13 (StataCorp., LP Texas, USA).

RESULTS

Search results

Electronic literature search (2 October 2014) and manual search found 480 peer-reviewed scientific articles after duplicate papers were removed. Of these, 366 were excluded after abstract review for failing to meet the eligibility criteria. A large number of these papers were not related to breastfeeding or dental caries, were not in English or were not original research. Of the remaining 114 full text articles, 51 were excluded as: (i) they did not assess the relevant exposure (breastfeeding) and outcome (dental caries) or (ii) all feeding types were analysed together or (iii) data were duplicated in more than one paper or (iv) no analysis was reported or studies lacked control or comparator groups [Fig. 1 (24)]. In total 63 papers were included.

Characteristics of included studies

Although the 63 papers did not include randomised controlled trials (RCT) of breastfeeding, six cohort studies (25-30) were nested within RCTs of breastfeeding promotion interventions. There were eight additional cohort studies (31-38) and three case-control studies (39-41). The remaining 46 studies were cross-sectional in design (42-86). The studies were predominantly conducted in high and middle income countries with only eight studies from low income countries (87). All caries outcomes were

assessed by dental professionals through oral examination. Key characteristics are summarised in the Appendix.

Quality assessment

Tables 2 3, 4, and 5 detail the NOS score assigned to each included study. The cohort and cross-sectional studies that were embedded in RCTs of a range of breastfeeding promotion interventions (25-30) scored highly as the study designs overcame many sources of bias and reporting limitations that were apparent in the other cohort, case-control and cross-sectional studies. Other cohort studies were weakened by the method used to ascertain infant feeding practices (self-report) which subjected them to recall bias, recruitment of children through oral health services (selection bias), lack of reporting of the absence of caries at the commencement of the study (ascertainment bias), loss to follow -up and accounting for these participants (attrition bias), and lack of controlling for confounders. Case-control study designs were inherently subject to recall bias when ascertaining infant feeding practices. Furthermore, cases and controls were not representative of the broader population as they were recruited in settings where children were likely to have caries. Selection bias was also a problem as the selection of controls was not clearly described. Cross-sectional studies were the weakest but most common study design. The studies which scored <4 were classified as unsatisfactory due to major limitations in study design and reporting. Studies that scored 4 were classified as satisfactory, however, all of these studies lacked consideration of key confounders. In the higher quality studies (>5) there were limitations in how exposure was ascertained as many studies used self-report questionnaires (recall bias).

Meta-analysis

We meta-analysed the small number of studies which included statistical effect measures.

Breastfeeding up to 12 months of age

One prospective cohort (34) and four cross-sectional studies (48,52,59,70) reported odds ratios for the association between children who were exposed to more versus less breastfeeding up to 12 months (OR 0.50; 0.25-0.99, I2 86.8%) (Fig. 2). There were not enough studies to perform metaregression for formal investigation of this heterogeneity. There appeared to be differences, however, based on the comparison groups of the included studies. The two studies

Table 5 Newcastle-Ottawa Scale Quality Assessment score for Cross-sectional Studies

Selection of non- Ascertainment Assessment

Cross-sectional Representativeness exposed cohort of exposure Comparability of outcome Score/7

Alaluusua et al. (42) * * * 3

al-Dashti et al. (43) * * ** 4

Azevedo et al. (44) * * * ** 5

Campus et al. (45) * * ** * 5

Carino et al. (46) * ** 3

Dini (47) * * * * 4

Du et al. (48) * ** * 4

Dye et al. (49) * * ** ** 6

Folayan et al.(50) * * * 3

Folayan et al. (87) * * * 3

Forsman et al. (51) * * * 3

Hallett et al. (52) * * ** ** 6

Hallonsten et al. (53) * * * 3

Haq et al. (54) * * 2

Hardy (55) * 1

Harrison et al. (56) * * ** 4

Holt et al. (57) * * * 3

Hong et al. (58) * * ** * 5

lida et al. (59) * * * * * 5

Johansson et al. (60) * * * 3

Livny et al. (61) * * * 3

Majorana et al. (62) * * ** 4

Masumo et al. (63) * * * ** 5

Mattos-Graner et al. (64) * * ** 4

Nobile et al. (65) * * * 3

Nunes et al. (66) * ** ** 5

Perera et al. (67) * * * 3

Prakash et al. (68) * * * * 4

Prakasha Shrutha et al. (69) * * 2

Qadri et al. (70) * * * * 4

Retnakumari (71) * * * 3

Rosenblatt (72) * * * 3

Sankeshwari et al. (73) * * * 3

Santos (74) * * 2

Sayegh et al. (75) * * ** 4

Sayegh et al. (76) * * * ** 5

Serwint et al. (77) * * * 3

Slabsinskiene et al. (78) * * * 3

Songo et al. (79) * * 2

Tanaka, (80) * * ** * 5

Tiano et al. (81) * * * 3

Tyagi, (82) * 1

Vachirarojpisan et al. (83) * * * * * 5

Vazquez-Nava et al. (84) * * ** * 5

Wendt (85) * * * * 4

Yonezu et al. (86) * 1

which compared ever breastfeeding in the first 12 months with never breastfeeding (48,70), both showed a marked protective effect of breastfeeding on dental caries compared with other feeding. Whereas the three studies which compared a longer duration of breastfeeding in the first 12 months to a comparison group which included children who had had some exposure to breastfeeding did not (34,52,59). A meta-analysis on this three study subgroup found an OR of 0.92; 0.69-1.23, I2 0% (Fig. 3).

Breastfeeding after 12 months of age

Two cohort studies (33,34), one case control study (40) and four cross-sectional studies (52,65,75,78) reported odds ratios for the association between more or less breastfeeding after the age of 12 months and dental caries. The comparison groups for these studies included both those who had never been breastfed and those who had been breastfed for shorter durations. The pooled estimate was OR 1.99; 1.35-2.95, I2 69.3% (Fig. 4).

Records identified through database searching PubMed, Embase, CINAHL, Medline = 817

Additional records identified through other sources and hand searching = 10

Records after duplicates removed (n=347) = 480

Records screened = 480

Full text articles assessed for eligibility = 114

Articles included in synthesis = 63

Articles assessed for meta-analyses = Breastfeeding at 12 months: n=5 Breastfeeding beyond 12 months: n=6 Breastfeeding on demand or nocturnally: n=6

Title and abstract review - exclude n= 366

Not breastfeeding = 170

Not dental caries = 54

Not English = 30

Not research = 75

Pre-term babies = 3

Review papers = 32

Study protocols = 2

Full paper reviews - exclude BF not exposure or DC not outcome = 7 Breast & bottle feeding grouped together = 3 Data duplicated in other paper = 1 No analysis of BF and DC = 29 No control/comparator group = 12

Figure 1 PRISMA Flow diagram of review.

Only two studies (26,80) reported prevalence ratios so these could not be meta-analysed.

Nocturnal breastfeeding in those breastfed longer than 12 months

One cohort (36), one case-control (40) and three cross-sectional studies (67,84,86) reported odds ratios for the association between more versus less nocturnal breastfeeding and the risk of dental caries amongst the subgroup of children breastfed longer than 12 months. The pooled estimate was OR 7.14; 3.14-16.23, I2 77.1% (Fig. 5).

Narrative synthesis

The majority of studies (n = 46) were not included in the meta-analyses due to methodological differences in the measures of exposure and outcomes, or reporting of correlational analyses only.

Studies embedded in randomised controlled trials (RCTs)

It is not ethical to conduct randomized trials assigning participants to breastfeeding and non-breastfeeding groups in order to more definitively assess the association between breastfeeding and dental caries. However, a number of RCTs have been conducted that investigated the impact of breastfeeding promotion programmes (25-30). In a RCT of an intervention that provided monthly advice on healthy feeding practices over 12 months via home visits in Brazil

(25,27,30) the intervention group demonstrated a lower incidence of caries at 12 months (OR = 0.52, 0.27-0.97, p = 0.03) and 4 years (RR = 0.78, 0.65-0.93, p = 0.004). Investigating breastfeeding frequency at 12 months, the study also found a doubled risk of caries when feeding frequency was 3-6 times/day (RR = 2.04, 1.22-3.39, p = 0.000) and >7 times/day (RR = 1.97, 95%CI 1.452.68, p = 0.000) compared to 0-2 times/day. Analyses were adjusted for maternal schooling level, daily meals, bottle use for fruit juice/soft drinks, consumption of high density sugar and number of teeth. Another birth cohort study nested in an intervention conducted through maternal health centres in Brazil (26) found that, in adjusted regression models, as breastfeeding continued beyond 6 months the prevalence ratio of caries in breastfed children increased (compared to breastfeeding <6 months) but was only significant when still breastfeeding at >24 months: 6-11 months (PR = 1.45, 95% CI 0.83-2.53); 12-23 months (PR = 1.39, 95%CI 0.732.64); >24 months (PR = 1.85, 95%CI 1.11-3.08). A birth cohort study nested in a breastfeeding promotion intervention in Belarus found no significant difference in caries incidence or prevalence in the intervention group when children were aged 6.5 years (28,29).

Breastfed versus formula fed

Studies that examined ever versus never breastfed children reported a range of findings. Six cross-sectional studies

Study ID

Cohort study Tanaka (2013)

Cross-sectional study Du (2000) Hallett (2003) Iida (2007) Qadri (2012)

More vs Less Breastfeeding up to 12 months and risk of caries

Overall (I-squared = 86.8%, p = 0.000) NOTE: Weights are from random effects analysis

Ratio (95% CI)

0.67 (0.27, 1.65)

0.19 (0.08, 0.46) 1.00 (0.71, 1.41) 0.80 (0.42, 1.53) 0.27 (0.18, 0.41)

0.50 (0.25, 0.99)

Odds Ratio

Figure 2 More versus Less breastfeeding (including never breastfed) up to 12 months of age and the risk of dental caries

More vs Less Breastfeeding up to 12 months and the risk of caries

Study Odds %

ID Ratio (95% CI) Weight

Cohort study Tanaka

Cross-sectional study

Hallett

Overall (I-squared = 0.0%, p = 0.645)

NOTE: Weights are from random effects analysis

~~i— .05

~~i— .25

0.67 (0.27, 1.64) 10.47

1.00 (0.71, 1.41) 69.99

0.80 (0.42, 1.54) 19.53

0.92 (0.69, 1.23) 100.00

—I-T

1 1.5 2

Odds Ratio

Figure 3 More versus Less Breastfeeding (excluding never breastfed) up to 12 months of age and the risk of dental caries.

reported no significant difference in the prevalence of caries between the two groups (49,61,72-74,83); one cohort and one cross-sectional study reported significantly lower caries in breastfed children (32,57); one cross-sectional study found a lower adjusted caries risk in breastfed versus bottle-fed children (OR = 0.61, 95%CI 0.39-0.97, p = 0.038) (70); one cohort study reported higher caries increment in breastfed children between 12 to 18 months but the association disappeared in the multivariate analysis (35);

one cross-sectional study reported an increased risk of dental caries in ever breastfed children of borderline significance (p = 0.08) (77); and one cross-sectional study found a lower adjusted caries risk in breastfed versus bottle-fed children.

Breastfeeding duration

Three of four cohort studies found that breastfeeding beyond 12 months was correlated or associated with increased caries

Breastfeeding beyond 12 months and risk of caries

Study ID

Cohort study

Tanaka(2013)[=18 mth]

Tada (1999) [=18 mth]

Case-Control

Matee (1994) [1yr vs 3yr]

Cross-sectional study Hallett (2003) [>13mth] Nobile (2014) [= 20mth] Sayegh (2002) [>18mth] Slabsinskiene (2010) [>13mth]

Overall (I-squared = 69.3%, p = 0.003) NOTE: Weights are from random effects analysis

Odds Ratio (95% CI)

2.47 (0.94, 6.51) 6.65 (2.90, 15.25)

2.40 (0.67, 8.65)

1.50 (0.94, 2.40) 1.26 (1.01,1.57) 1.50 (1.09, 2.07) 10.00 (1.28, 78.12)

1.99 (1.35, 2.95)

Odds Ratio

Figure 4 Breastfeeding beyond 12 months and the risk of dental caries.

Study ID

Nocturnal breastfeeding beyond 12 months and risk of dental caries

Odds Ratio (95% CI)

Cohort study van Palenstein (2006)

Case-Control Matee (1994)

Cross-sectional study Perera (2014) Vazquez-Nava (2008) Yonezu (2007)

Overall (I-squared = 77.1%, p = 0.002)

NOTE: Weights are from random effect ~T

> 35.00 (6.29, 194.87)

•> 17.80 (6.30, 50.30)

2.54 (1.29, 5.01) 3.60 (2.51, 5.16) 10.66 (2.23, 50.96)

7.14 (3.14, 16.23)

~l-1—T

10 15 20

Odds Ratio

Figure 5 More versus Less nocturnal breastfeeding and the risk of dental caries in those breastfed longer than 12 months.

prevalence compared with shorter durations of breastfeeding. Chaffee et al. (26) found that the adjusted prevalence ratio of caries in children breastfed >24 months was 2.1 (95%CI 1.5-3.25) compared to children breastfed <6 months. Yonezu et al. (37) found significantly more caries in children breastfed >18 months than those weaned <18 months. Feldens et al. (25) found the risk of caries

rose in children breastfed beyond 12 months. Ollila et al.'s (38) survival analysis found no difference between children breastfed >12 months and those not. Cross-sectional studies reported variable findings: increased caries prevalence in children breastfed longer than those breastfed for shorter times (44,45,53,54,63,65,71,75,78,81,85); and no difference in caries prevalence between duration groups (66,82).

The few studies that controlled for confounding factors found decreased caries risk with shorter breastfeeding duration (6-12 months) compared to longer duration (>13 months) (26,34,45,76,80) and increased risk of caries if breastfed <6 months (31,48).

Breastfeeding on demand and nocturnally

In addition to the meta-analysed studies, a number of cross-sectional studies reported significant correlations between infants/children breastfed during the night (44,67), on demand (68) or sleeping with a nipple in the mouth (60,71,76) and increased prevalence of dental caries. One cohort study found an increased adjusted risk of dental caries with increased daily breastfeeding frequency including nocturnal feeding (25).

DISCUSSION

Qualitative assessment of studies investigating breastfeeding up to 12 months of age suggested that children who were exposed to more breastfeeding (longer duration) compared to less or no breastfeeding were protected from dental caries. Meta-analysis of five studies also found reduced risk of dental caries in children breastfed more versus less up to 12 months, however, the heterogeneity between studies was too high to make the estimate reliable. In contrast, children who were breastfed beyond 12 months had an increased prevalence of dental caries. Amongst those who continued to be breastfed after 12 months, there was a further increased risk of caries in children who were breastfed nocturnally.

Three elements are essential for dental caries to occur: a tooth, cariogenic bacteria (e.g. Streptococcus mutans) and substrate for the bacteria (sugar) (2). The risk of developing dental caries changes as factors associated with each element change. The first tooth usually erupts in an infant's mouth between 6 and 12 months of age. As each tooth erupts the risk of developing dental caries increases, hence age and number of teeth increases risk. Cariogenic bacteria are transmitted to the child via close contact with the mother's saliva (88) but their levels and cariogenicity vary between individuals (2) depending on maternal bacterial levels, maternal caries prevalence, oral hygiene practices and exposure to dietary sugars (21). Breast milk is known to contain immunomodulatory factors along with a rich microbiome which is responsible for establishing normal intestinal flora (89). Initial protection from dental caries may be mediated through establishment of a healthy oral microbiome in infants through exposure to breastfeeding and contact with skin and breast milk microbiomes. Additionally, the child's oral microbiome changes over time with the emergence of new teeth. The essential substrates for cariogenic bacteria are simple carbohydrates (sugars) which can be in a range of forms (e.g. lactose, sucrose, glucose). The longer these sugars are in contact with teeth, the higher the risk of dental caries. The amount of carbohydrate (cariogenicity) contained in the different milks and formulas may also help to explain the different

results we found before and after 12 months of age. The cariogenicity of human breast milk has not been extensively examined under in vivo conditions, however animal studies suggest that at high frequency exposures, human breast milk has greater cariogenicity compared to bovine milk but less than infant formula (90,91). Relative cariogenicity of breast milk will also depend on the comparison group. Below 12 months it is usual to feed infants either breast milk or formula which have around the same carbohydrate content. After 12 months, however, children in high income countries are often weaned onto cow's milk which has half the carbohydrate content of human milk. However, each element is subject to modification by risk factors such as socio-economic status, maternal educational level, maternal oral health, maternal smoking status, position in birth order, sugars in diet, oral hygiene and exposure to fluoride (2).

Breastfeeding duration, frequency of breastfeeding and nocturnal breastfeeding during sleep are most often analysed as separate breastfeeding behaviours, however they are inter-related. Nocturnal breastfeeding is often used to comfort an infant or child who may then fall asleep with the nipple in their mouth. In this position, the tongue fills the mouth and holds the breast milk against the surfaces of the teeth, thereby prolonging the exposure of the substrate to the cariogenic bacteria that are attached to the teeth surfaces and hence increasing the risk of dental caries. It is possible that children breastfed beyond 12 months are also engaging in nocturnal breastfeeding but the modification of dental caries risk by infant feeding practices has not been examined in depth in any of the studies included in this review. In addition, children >12 months are no longer being exclusively breast or bottle fed and the diet is expanding to include other fluids and solids. It has been reported that children who are breastfed for longer durations also have more frequent cariogenic food intakes (25,53,58). Oral hygiene practices to remove bacterial plaque are important as more teeth erupt to reduce the risk of dental caries. Only a few studies included in this review controlled for key confounding factors and this may have resulted in an over-estimation of the role of prolonged, frequent and nocturnal breastfeeding in the development of dental caries. Until the dietary and oral hygiene details of these children are controlled for we cannot be certain whether prolonged, frequent or nocturnal breastfeeding can be principally associated with early childhood caries.

This is the first systematic review of breastfeeding and dental caries that includes critical exposure windows, limited meta-analyses and a range of study types. We provide quantitative evidence that is suggestive of the potentially protective effects of breastfeeding from dental caries up to 12 months, but higher risk of dental caries in children breastfed beyond 12 months, frequently, and/or nocturnally. However, there is high heterogeneity between the studies included in the meta-analyses (possibly due to differing comparison groups) and lack of controlling for key confounders (e.g. other foods/drinks in the diet, oral

hygiene, maternal oral health status) which limits the reliability of the results.

CONCLUSION

Breastfeeding up to 12 months of age is not associated with an increased risk of dental caries and in fact may offer some protection compared with formula. However, children breastfed beyond 12 months, a time during which all deciduous teeth erupt, had an increased risk of dental caries. This may be due to other factors which are linked with prolonged breastfeeding including nocturnal feeding during sleep, cariogenic foods/drinks in the diet, or inadequate oral hygiene practices. Further research with careful control of pertinent confounding factors is needed to elucidate this issue and better inform infant feeding guidelines. As per recommendations from previous reviews (17,19), the introduction of food sources to infants should be low in simple carbohydrates (sugars) and oral hygiene practices should start with the eruption of the first tooth so that bacterial plaque is removed from tooth surfaces to reduce the risk of dental caries.

CONFLICT OF INTEREST STATEMENT

Preparation of the manuscript was assisted by funding from the WHO, which had no part in determining the outcomes or presentation of findings. None of the authors has any conflicts of interest to declare.

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APPENDIX Study characteristics and summary of NOS QA

References [NOS QA Type of study/brief Sample size (gender

score] description Study population/Country °/o given if reported)

Randomised controlled trial (RCT) Feldens et al. (30) [8* Good]

Feldens et al. (27) [8* Good]

RCT of an intervention that provided monthly advice on healthy feeding practices (exclusive breastfeeding up to 6 months. >6 months encouraged to continue breastfeeding and introduce foods) up to 12 months via home visits

As for Feldens et al. (2007)

Mothers who gave birth in public health system; Sao Leopoldi, Brazil; October 2001 - June 2002

Mothers who gave birth in public health system; Sao Leopoldi, Brazil; October 2001 - June 2002

N = 500 Intervention n = 200 Control n = 300

N = 340 Boys =195 (57.4%) Intervention n = 141 Control n = 199

Cohort

Chaffee et al. (26) [8* Good]

Birth cohort study nested in a cluster RCT of an intervention in maternal health centres, 2008-2011

Birth to 38 months years; Porto Alegre, Brazil; Low income families

715 pregnant women

Feldens et al., (25) [10* Very good]

Birth cohort study (nested in an RCT of an intervention in a birth cohort)

Cohort of children aged 4 years; Sao Leopoldo, Brazil

340 children (baseline = 500); Boys =195 (57.4%)

Hong et al. (31) [8* Good]

Longitudinal birth cohort Iowa, USA study

N = 509

Questionnaires: 3-6 months from birth Dental exams: 5 years and 9 years

Exposure definition

Outcome definition and age

Exposure estimate (95% CI)

Other variables included in the models as confounders

Interactions

(Q Q Q.

Intervention group received advice at home

Age 12 months Early Childhood Caries (ECC) -decayed surfaces >1 in any primary tooth (decay)

Intervention group risk of caries: OR = 0.52 (0.27-0.97) p = 0.03 cf control group

Number of teeth

Intervention group received advice at home

Age 4 years

1. ECC -dmfs >1 in any primary tooth (decay)

2. Severe-ECC (S-ECC) - dmfs >5 or one or more cavitated, missing, filled smooth surface of anterior teeth.

3. Affected teeth (decayed or cavitated) - dmft

Ref group = control with RR = 1.0 None reported

ECC: Interv RR = 0.78 (0.65-0.93)

p = 0.004

NNT = 7 (4-20)

S-ECC: Interv RR = 0.68 (0.5-

0.92) p = 0.01

NNT = 8 (5-30)

Affected teeth: Mean

Interv = 3.25 (4.25) cf

Control = 4.15 (4.57) p = 0.023

Breastfeeding duration: <6 months 6-11 months 12-23 months 24 months+

Breastfeeding: Frequency

Breastfeeding duration <6 months >6 months

Dental status evaluated at 38 months

Severe-ECC - 1 or more affected maxillary teeth or 4 or more decayed, missing due to caries or filled tooth surfaces (dmfs >4)

Age 4 years Severe ECC

>1 cavitated, missing or filled smooth surfaces in primary maxillary anterior teeth, or dmfs values >5

Age 5 years and 9 years Dental caries in:

(a) All primary teeth

(b) 2nd deciduous molars (e)

Fully adjusted regression models Breastfeeding at stages and S-ECC: Prevalence ratio <6 = 1

6-11 = 1.45 (0.83-2.53) 12-23 = 1.39 (0.73-2.64) >24 = 1.85 (1.1 1-3.08)

Adjusted model: RR of S-ECC associated with daily breastfeeding frequency at 12 months: 0-2 RR = 1.0

3-6 RR = 2.04 (1.22-3.39) >7 RR = 1.97 (1.45-2.68) p = 0.000 Tooth level: Caries in (e) at 5 years Mean dfs

BF <6 months = 0.55 BF >6 months = 0.33 p = 0.02

Person level: caries in (e) at 5 years Breastfeeding <6 months OR = 15.58 [no 95% CI reported] (p = 0.005)

Maternal age; Education; Parity; Pre-pregnancy BM1; Smoking status; Social class; Child age; gender; Time varying bottle use; Feeding habits; Length-for-age z scores

Maternal schooling; Daily meals and snacks; Bottle use for fruit juice/soft drinks at 12 months; High density sugar at 12 months; Teeth at 12 months

Gender, hypoplasia, parental education level, family income level, gestational weeks, birth weight, age at time of dental exam, average daily fluoride intake (mg), home tap water fluoride level(ppm), average daily soda pop intake, daily tooth-brushing frequency

High frequency day time breastfeeding Long duration, high frequency

Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender °/o given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Kramer et al. (29) Prospective cohort study Children aged 6.5 years Total n = 13,883 Experimental vs control Age 6.5 years The experimental intervention had None reported

[8* Good] nested in RCT of BF Belarus Experimental n = 7108 groups Dental caries no significant effect on the DMFT/

promotion intervention Control n = 6781 DMFT/dmft dmft numbers or proportions (both

(PRO BIT) all teeth and incisors only)

Kramer et al. (28) Prospective cohort study Children aged 6.5 years Exclusive BF at 3 months: Children aged 6.5 years No significant difference in dmft in None reported

[8* Good] nested in RCT of BF Belarus EBF3 n = 2862 Dental caries EBF3 and EBF6 groups

promotion intervention Exclusive BF at 6 months dmft

(PRO BIT) EBF6 n = 621

Ollila and Larmas (38) Cohort study 11 day care centres N = 183 (baseline) Breastfeeding Baseline 2.5 years Prolonged breastfeeding (> None reported

[7* Good] Time points: Oulu, Finland N = 175 (follow up) <12 months Follow up 9.6 years 12 months) had no effect on caries

Baseline = mean age > 12 months Restoration due to caries in a onset in terms of survival estimates

2.5 years (0.7- primary 2nd molar and first in either the deciduous molars or

4.3 years) permanent molar on upper permanent molars.

Follow up 7 years right and lower left (teeth id

later = mean age numbers: 55 and 75; 16 and

9.6 years (3.1- 36)

12.7 years)

Survival analysis

Silver, (32) Longitudinal cohort study Town north of London 3 years olds n = 161 Questionnaire at age 3: 3 years & 8-10 years Babies that were breast fed only had None reported

[5* Satisfl Baseline 3 years (1973) Boys = 84 (52%) Breast fed Dental caries significantly lower dmft cf children

Follow up 8-10 years 8-10 years olds Bottle fed dmft bottle fed, especially those with

(1979) Kendall's Tau n = 161 (unsweetened/ sweetened bottle content.

instead of X2 Boys = 85 (53%) sweetened) p < 0.01

Tada et al. (33) Cohort Infants N = 392 Breast feeding (yes/no) 18 months & 3 years Breast feeding at 18 months of age None reported

[5* Satisfl Examination at Chiba city, Japan Boys = 215 (54.8%) Dental caries significantly associated with caries

18 months and 3 years dmft increment increase in caries in

of age - increment All upper anterior teeth OR = 6.65

change was analysed. Upper anterior (2.89-15.2, p = <0.05)

Tanaka et al. (34) Prospective cohort study Pregnant women and their N = 315 Breast feeding duration: Aged 41-50 months Adjusted OR Adjusted for: Maternal age

[8* Good] 5 surveys at baseline, 2- infants <6 months; 6- Dental caries dft (missing Risk of breastfeeding duration and at baseline; Maternal

9 months, 16- Neyagawa City, Japan 11 months; 12- teeth excluded) ECC: smoking during

24 months, 29- 17 months; Moderate ECC = 1-4 teeth <6 months OR = 1 pregnancy; Family

39 months, 41- >18 months with caries not involving 6-11 months OR = 0.67 (0.27- income; Parental

49 months. maxillary anterior teeth 1.62) education level; Child's

Dental exam at 41- Severe ECC = >1 caries in 12-17 months OR = 1.09 (0.45- gender; Birth weight; Age

50 months maxillary anterior teeth or >5 2.71) at first tooth eruption;

caries in all teeth >18 months OR = 2.47 (0.95- Tooth brushing

6.59) frequency at 4th and 5th

Quadratic trend p < 0.05 surveys; Use of fluoride;

Statistical significance was lost Regular dental check-

when comparing risk for M-ECC ups; Household smoking

with caries free and S-ECC and at 5th survey; Age at oral

caries free - but the trend was examination

towards positive associations with

increased BF duration

m S-a' (Q Q Q.

Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender °/o given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Thitasomakul et al. (35) Longitudinal observational All women in district who gave N = 495 Type of milk feeding: Age 9-12 months & 12- Bivariate analysis: crude caries None reported

[7* Good] community based study birth November 2000 to Boys = 254 (51.3%) Breast feeding 18 months increment between 9-12 months

- birth cohort. October 2001 Bottle feeding Dental caries and 12-18 months was

Followed up at 9,12 and Thepa district Thailand Mixed breast- and bottle Crude caries significantly higher among children

18 months feeding increment = from 9- who were breast fed cf bottle fed or

12 months and 12- mixed feeding.

18 months Negative binomial analysis - no

Incidence density = tooth association between increased

surface developing caries; incident density and breastfeeding

Incidence density ratio = ratio reported.

of incidence density of those

exposed to those not exposed

to the particular independent

variable concerned.

van Palenstein Helderman Retrospective cohort Children aged 25-30 months - N = 163 breastfed Breastfeeding: Children aged 25-30 months Significant associations: None reported

et al. (36) recruited through children (children Total number Dental caries >2 nocturnal breast feedings and

[6* Satisfl immunization records at excluded who Of feeds (low/high) ECC - presence of caries in >1 ECC OR = 35 (p < 0.0001)

health centres consumed 'jaggery; and Total exposure time to tooth >15 min feeding per night

Daik-U, Burma those who were bottle breastfeeding (low/high) OR = 100 (p < 0.0002)

fed and breastfed from Median value sets low/

5 months) high

Prolonged breastfeeding

beyond 12 months age

Yonezu et al. (37) Prospective cohort Infants attending preventive N = 922 at 18 months Prolonged breastfeeding Aged 18 months, 24 months Mean dft of children being breastfed None reported

[5* Satisfl Control sample = 205 dental care programs at public N = 742 at 24 months or bottle feeding at and 36 months at 18 months (0.36) was

children weaned off health centres N = 910 at 36 months 18 months Dental caries dft significantly higher than the control

breast or bottle feeding Japan N = 592 followed group (0.06) p < 0.05

<18 months longitudinally Mean dft of children being

breastfed at 24 months (0.51) was

significantly higher than the control

group (0.11) p < 0.05

Cose control

Bahuguna et al. (39) Case control Outpatient department of Case n = 400 Breast feeding duration Children aged 1-18 years Significantly higher proportion of None reported

[5* Satisfl Cases had caries paedodontics and preventive Control n = 400 <6 months Dental caries case subjects were breastfed for

Control were caries free dental clinic > 6 months DMFT/deft longer than 6 months compared to

Lucknow, India Bottle feeding (no detail control (p < 0.001)

reported) Significantly higher proportion of

cases had been bottle fed

(p = 0.017)

Matee et al. (40) Case control Children aged ]-4 years Case n = 116 Breastfeeding duration Case mean age = 1.6 years Duration of breastfeeding (1 yearvs None reported

[4* Unsatisf] Cases = rampant caries attending maternal and child Control n = 243 Night feeding (duration Control mean 3 years) OR = 2.4 (0.7-9.1)

Controls = no caries health centres in 9 out of 25 of nipple in the mouth: age = 2.1 years p = 0.18

regions in Tanzania 0 h, y2 h, 1 h, >1 h) Dental caries Night breast feeding habits

Bottle feeding and Rampant caries (>2 caries OR = 17.8 (6.3-50.3) p < 0.0001

content in bottle lesions in maxillary incisors) Linear hypoplasia OR = 15.6 (8.0-

30.5) p = <0.0001

Roberts et al., (41) Case control 1 -4 year old children Case n = 109 Breast feeding frequency Aged 1 -4 years Dental caries No significant association between None reported

[5* Satisfl Cases = caries South Africa Control n = 109 Breast feeding duration dmft frequency and duration of breast

Controls = caries free Bottle feeding dmfs feeding and dental caries

prevalence

S-«s Q 3 Q.

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Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Cross-sectional

Alaluusua et al. (42) Cross-sectional Children aged 5 who N = 144 Duration of exclusive Aged 5 years Distribution of dmfs among children None reported

[3* Unsatisf] participated in a longitudinal Boys = 59 (41 %) breastfeeding: Dental caries with longer or shorter duration of

nutrition and health study that <2 months dmfs breastfeeding was equal

promoted breast feeding up <2-6 months

to 12 months; Finland >6-9 months

>9-12 months

>12 months

al-Dashti et al., (43) Cross-sectional Children aged 18-48 months N = 227 Infant feeding practices Aged 18-48 months Children breast fed at birth None reported

[4* Satisf] bom and continuously Boys =101 (44.5%) Breast fed Dental caries - no detail significantly more likely to be caries-

resident in Kuwait. Bottle fed provided re how this is free than those breast and bottle

Recruited through hospital Breast and bottle fed assessed fed or bottle fed only

and health centre

Azevedo et al. (44) Cross-sectional Preschool children; age 36- N = 369 Infant feeding practices Age 36-71 months Breastfeeding during night None included as None

[5* Good] 71 months; Brazil public Boys = 188 (51%) including patterns and S-ECC - >1 dmfs in primary time = 265 (72%) - statistically confounders

health centres duration of bottle maxillary anterior teeth associated with SECC (p = 0.02);

feeding and Breastfeeding after 12 months of

breastfeeding age = 70% of SECC children and

50% of non-SECC children -

significant association b/w

breastfeeding children >12 months

and presence of SECC (p = 0.004)

Campus et al. (45) National cross-sectional 4 years old children, Italy N = 5538 (aged 47.2 monthDuration of breastfeeding Age 4 years Children BFfor>13 months had Gender; Parent nationality;

[5* Good] survey; March 2004- +/- 3.5 months) (<13 months or Dental caries dmfs significantly higher dmfs than those Parent education; Pre-

April 2005 Boys = 2518 (45.5%) >13 months) BF <13 months (p < 0.05) term births; Age of tooth

Association between prolonged BF eruption; Tooth brushing

and dental caries only seen in habits; Disease or

bivariate analysis and no conclusion medication during

about harmful consequences can pregnancy

be drawn from multivariate

modelling

Cariño et al. (46) Cross sectional survey; Children aged 2-6 years; n = 452 Feeding Aged 2-6 years Bivariate analysis Child's primary caregiver;

[3* Unsatisf] October - November Northern Philipines - 3 areas Aged 3-6 years Breastfed only Dental caries No significant difference in Feeding practices;

1999 in 2 regions Stratified 3-A and 5- Mixed breastfed and ECC associations between Toothbrushing; Snaeking

6 years bottle fed dmft breastfeeding bottle feeding and frequency; Type of

Bottle fed only weaning age and ECC snacks eaten; Last dental

No answer visit; Reason for last visit

Weaning age

<2 years old

>2 years

Still breast or bottle

feeding

No answer

Dini et al. (47) Cross-sectional survey; Children enrolled in municipal N = 245 Breast feeding and/or Aged 3-4 years Statistically significant: None reported

[4* Satisf] 1998 nurseries; 3-4 years; Boys =137 (56%) bottle feeding Dental caries dmfs or dmft Caries in molars and incisors and

Araraquara, Sao Paolo, Brazil Duration of children who were never breast fed

breastfeeding: or those who were breast fed

Never beyond 24 months age OR = 3.1

<24 months (1.1-8.4) p = 0.03

>24 months

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Appendix (Continued) Type of study/brief References [NOS QA score] description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Du et al. (48) Cross sectional survey Children in kindergartens; N = 426 Infant feeding - breast Aged 24^17 months; Mean Bottle fed only children had Stepwise logistic

[4* Satisf] urban Hanchuan, China Boys = 250 (59%) and /or bottle age = 40 months statistically significant higher regression: Gender

Duration of breast Dental caries (dmfs or dmft) prevalence of incisor caries (male/female); Age

feeding Rampant caries = 2 or more (p < 0.05) and rampant caries (24-35 months /36-

teeth with caries affecting (p < 0.01) cf with partially or fully 47 months); Education

palatal and /or labial surfaces breast fed children. (low/high); Income

of primary incisors Children who had been wholly (low/high); Feeding

bottle fed had higher risk of caries (bottle/breast)

cf children partially or wholly

breastfed:

rampant caries OR = 5.27 (2.16-

12.89) p = 0.003

incisor caries OR = 2.38 (1.03-

4.76) p = 0.042

Dye et al. (49) Cross sectional National Children aged 2-5 years; N = 4236 History of breast feeding - Aged 2-5 years In models adjusted for poverty, Poverty Poverty and

[6* Very good] Health and Nutrition USA Boys = 2081 (49.1%) yes or no Dental caries - decayed or education and race/ethnicity the Education of parent educational

Examination Survey III - filled primary dental surfaces findings indicate that there is no Race/ethnicity attainment

1988-1994 (dfs) relationship between caries and a

history of ever breastfeeding

Folayan et al. (50) Cross-sectional Children aged 6-71 months; N = 396 -Exclusive breastfeeding Aged 6-71 months Significant predictors of dmft: None reported

[3* Unsatisf] 3 randomly selected LGAs in Boys = 217 (54.8%) Almost exclusive: breast dmft Duration of breastfeeding

Lagos State, Nigeria milk with water Rampant caries = caries (p = 0.002) & form of

supplement affecting 1 or more maxillary breastfeeding [exclusive

Partial/mixed incisors with or without breastfeeding] (p = 0.03)

breastfeeding involvement of primary molars No significant association b/w form

Caries = caries affecting of breast feeding and rampant

tooth/teeth exclusive of caries or caries.

maxillary anterior tooth/teeth No sig association b/w duration of

No caries breastfeeding and caries or no

caries - however significant

association between duration of

breastfeeding and rampant caries

(p = 0.02)

Folayan et al. (87) Cross-sectional Children attending the Child N = 205 Duration of breastfeeding Aged 1 -16 years No association found between None reported

[3* Un satisf] Dental Health Clinic of 2 Boys = 108 (52.7%) Breastfeeding on Rampant caries rampant caries, duration of breast

hospitals in Nigeria 1-5 years n = 91 demand or leaving the feeding (p = 0.13), form of

6-10 years n = 88 nipple in mouth breastfeeding (p = 0.84) or

11-16 years n = 26 overnight during night duration of bottle feeding

feeding. (p = 0.07) in children aged 1-

Duration of bottle 5 years

feeding

Forsman et al. (51) Cross-sectional study; 2 (1) Vaxjo, Sweden; Vaxjo -Exclusive breastfeeding Aged 4 years Results reported in frequencies and None reported

[3* Un satisf] sites Children born 1962 and n = 726 for first 5 months (B) Dental caries t-tests

1963; Gothenburg n = 115 -Exclusive water diluted defs and deft No significant differences in caries

Data on infant feeding infant dry milk formula between the B and F groups in both

extracted from records in for first 5 months of life sites.

Children's Welfare Centre, (F)

(2) Gothenburg, Sweden

Children born in 1964

Questionnaire

(Q Q 3 Q.

Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Hallett et al. (52) Cross-sectional; Preschool s; N = 2515 Duration of breastfeeding: Aged 4-5 years Multivariate analysis Sleep with bottle (y/n);

[6* Very good] Self administered North Brisbane, Australia Boys = 1307 (52%) None; <3 months; 3- ECC- dmfs and dmft > 1 Ref = no breastfeeding Sip from bottle (y/n);

questionnaire 6 months; 7- <3 months OR = 1.0 (0.7-1.3) Ethnicity; Family income

12 months; (P = 0.9)

>13 months 3-6 months OR = 0.7 (0.5-1.0)

(p = 0.05)

7-12 months OR = 1.0 (0.7-1.4)

(P = 0.9)

>13 months OR = 1.5 (0.9-2.3)

(p = 0.09)

Hallonsten et al. (53) Cross-sectional survey; Child welfare centres (n = 48 N = 200 Breastfeeding Aged 18 months No significant difference in defs of None reported

[3* Unsatisf] 1981-1982 centres); 3 counties in Duration of Dental caries children with caries being breastfed

Comparative study of 4 Sweden breastfeeding defs and children with caries not being

groups (± breastfeed in g breastfed

and ± dental caries) No analysis of association between

defs and breastfeeding duration

Haq et al. (54) Cross-sectional Recruited from hospitals, N = 530 Feeding: Aged 5 months - 6 years No significant difference in caries Sweet drink intake

[2* Unsatisf] private dental clinics and Breast fed Dental caries between those breast fed, bottle analysed with each

public dental clinic, Dhaka, Bottle fed dmft fed or mixed fed. exposure

Bangladesh Mixed fed Longer duration of feeding (either

Breastfeeding duration: breast, bottle or mixed fed)

6 months - 1 year significantly associated with

1-2 years prevalence of caries.

2-3 years

Hardy (55) Cross-sectional Village communities in Greece N = 225 Breast fed Aged 2-6 years No significant difference in caries None reported

[1* Unsatisf] Wholly breast fed = 159 Bottle fed Dental caries dmft between the two groups.

Wholly bottle fed = 66

Harrison et al. (56) Cross-sectional Vietnamese migrants; N = 60 Breastfed Mean age Correlational statistics. None reported

[4* Satisfl Vancouver, Canada Boys = 31 (52%) Breastfeeding duration 32.4 months ±21.3 No association between dental

Dental caries - defs caries and nursing caries and

Nursing caries (>2 maxillary breastfeeding.

teeth have decay)

Holt et al. (57) Cross-sectional Maternal and child welfare N = 555 Breast feeding Aged 12 - 60 months A significantly higher proportion of None reported

[3* Unsatisf] centres in Camden and Boys = 275 (49.5%) No breastfeeding for Caries - visible cavity involving children wholly breastfed (95%)

Islington Health Authority, >2 weeks = Wholly dentine were caries free compared with the

London, UK bottle fed Rampant caries - labial or proportion of children wholly bottle

palatal carious lesions fed (82%) (p <0.01)

involving >2 maxillary incisor

Hong et al. (58) Cross-sectional Singapore 190 children Breast feeding Mean Presence of dental decay: Child racial group,

[5* Good] Boys = 98 (51.6%) till 10 months; age = 36.3 months ± 6.9 Adjusted frequency of sweets,

Chinese = 60% > 10 months Dental caries Breastfeed <10 months (ref) importance of baby

Malay = 32% dmfs/dmft breastfeed >10 months: RR = not teeth, plaque on teeth

Other = 7% significant [Results not shown]

Risk for decayed and filled teeth

Adjusted

Breastfeed <10 months (ref)

breastfeed > 10 months: mean

ratio =1.85 (1.12-3.05)

p = 0.016

Risk for decayed and filled surfaces

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Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Adjusted

Breastfeed <10 months (ref)

breastfeed > 10 months: mean

ratio = 2.32 (1.44-3.70)

p = 0.001

lida et al. (59) Cross-sectional Children aged 2-5 years N = 1576 History of BF = ever BF; Aged 2-5 years ECC - Adjusted Birth weight; Age; Gender; Race/ethnicity

[5* Good] National Health and USA Boys = 793 (50.3%) Overall BF Dental caries Hx of BF: aOR = 0.97 (0.63-1.49) Race/ethnicity; Poverty Poverty status

Nutrition Examination duration = age when ECC = presence of any dfs on p = 0.89 status; Maternal age at

Survey child completely stopped any primary tooth S-ECC - Adjusted child's birth; Maternal

BF or being fed breast S-ECC = presence of any dfs Hx of BF: aOR = 0.83 (0.49-1.40) history of smoking during

milk; Exclusive BF on any maxillary incisor p = 0.47 pregnancy; History of

duration = Age when No statistically significant hospital admission; Time

child was first fed associations between of exclusive since last dental visit

something other than breastfeeding duration or full

breast milk or water; Full breastfeeding duration

BF duration = Age when

child was first fed

formula, milk or solid

foods on a daily basis

Johansson et al. (60) Cross-sectional Preschool children presenting N = 1206 Breastfeeding continues Aged 6 months - 5 years Children breast fed when sleeping None reported

[3* Unsatisf] for well children visits at Boys = 622 (51.6%) after falling asleep Dental caries had significantly higher deft (1.48)

paediatric clinic in Boston deft cf children who were not (0.61)

Medical Centre, USA p = 0.0003

Those bottle fed in bed or at nap

time did not have a significantly

higher deft (0.53) those who did

not (0.64) p = 0.233

Livny et al. (61) Cross-sectional Children in Jahalin Bedouin N = 102 Breastfeeding only Aged 12-36 months No significant associations between None reported

[3* Unsatisf] community, Jerusalem Boys = 56 (54.9%) Breastfeeding and bottle Dental caries dmft feeding practices and caries/no

feeding caries

Majorana et al. (62) Cross-sectional Children aged 24—30 months N = 2450 Exclusive breastfeeding Aged 24—30 months Moderate and high caries was not None reported

[4* Satisfl Questionnaire Brescia, Italy Males = 1181 (49.3%) Moderate-high mixed Caries - dmfs observed in subjects exclusively

feeding (58-99% breast ICDAS score for severity breast fed, whereas high caries

milk) severity level was predominant in

Low mixed feeding (1- children fed with formula

57% breast milk) OR = 6.75 (6.00-7.58) p < 0.01

Masumo et al. (63) Cross-sectional Manyara (high fluoride rural Child-caretaker pairs Current breastfeeding Aged 6-36 months Breast feeding status was not Age; Plaque score;

[5* Good] area) and Kampala (low Manyara n = 1221 (yes/no) Dental caries significantly associated with ECC in Enamel hypoplasia;

fluoride urban area), Uganda Boys = 616 (50.5%) Breastfeeding duration ECC = dmft multiple variable models Teeth present; Sugar

Kampala n = 816 Decayed (dt) - cavitated Manyara: consumption; Number

Boys = 414 (50.7%) dt = absent or present Currently breastfeeding a OR = 0.8 of teeth present

(0.30-2.17) p = NS

Kampala

Currently breastfeeding a OR = 1.4

(0.70-2.79) p = NS

Significantly higher prevalence of

caries in children breast fed 25-

36 months compared to those

breastfed 6-12 or 13-24 months

S-a' (Q Q 3 Q.

Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Mattos-Graner et al. (64) Cross sectional Children attending 9 public N = 142 Duration of breastfeeding Aged 1-2.5 years Children never breastfed or breastfed None reported

[4* Satisfl school nurseries, (0-3 months; 3- Dental caries to 3 months exhibited higher caries

Sao Paolo, Brazil 31 months); ds (no missing or filled teeth prevalence than children breastfed

Frequency of breast were found) for longer period (X2 = 4.11,

feeding p < 0.05)

Nobile et al. (65) Cross-sectional Children in kindergartens in N = 515 Occurrence and duration Aged 36-71 months Prevalence of ECC significantly Potential confounders

[3* Unsatisf] Southern Italy Boys = 262 (51 %) of breast feeding: History Dental caries increased with duration of breast included in the models

(yes/no); duration (<4; ECC: >1 decayed, missing of feeding OR = 1.26 (1.01-1.57) but these are not

5-10; 11-19; filled teeth (dmft) p = 0.039 specified.

>20 months) S-ECC: In children Prevalence of S-ECC significantly Possibly: Dental visit in

Bottle feeding - sleep <3 years = any sign of increased with breastfeeding previous year; Age;

with sweetened bottle or smooth surface caries; in OR = 2.06 (1.13-3.76) p = 0.019 Mother's education level;

pacifier children aged aged 3- Start using cup; Sleep

5 years = 1 or more with bottle or pacifier;

cavitated, missing or filled Start toothb rushing;

smooth surfaces in primary Maternal age at delivery;

maxillary anterior teeth; or Mother's age

dmft >4 at age 3; dmft >5 at

age 4; dmft >6 at age 5

Nunes et al. (66) Cross-sectional Preschool children; Low income N = 241 Non-exposed = those Aged 18 - 42 months Prolonged breastfeeding not Child age; Nocturnal bottle

[5* Good] families; Non exposed n = 192 breast fed for Mean age = 34.5 months associated with ECC in this model. feeding with infant

Sao Luis, Brazil Exposed n = 49 <12 months Dental caries [Data not shown] formula; Daily sucrose

Exposed = those still ECC, dmft consumption between

breastfeeding at time of main meals

examination

Perera et al. (67) Cross-sectional Children aged <60 months in a N = 285 Exclusive breastfeeding- Aged <60 months No significant difference in the deft None reported

[3* Unsatisf] pediatric ward of a teaching Boys = 138 (48.4%) breast milk up to Dental caries of children exclusively breast fed

Hospital; Sri Lanka 6 months deft and those not exclusively breastfed

Overnight feeding (bottle p = 0.28

or breast) Children fed overnight with breast

milk had caries prevalence of

51.4% cf children not fed overnight

(29%) OR = 2.54 (1.29-5.01)

along with higher mean deft

p = 0.001

Prakash et al. (68) Cross-sectional Playschools and private N = 1500 On-demand breastfeeding Age 8-48 months On demand breastfeeding and None reported

[4* Satisfl hospitals (not defined) Dental caries presence of caries X2 = 17.71

Children aged 8-48 months p = 0.001

Urban Bangalore, India

Prakasha Shrutha et al. (69) Cross-sectional Children aged 3-5 years - Play N = 2000 Breastfeeding frequency Age 3-5 years Prevalence of dental caries showed None reported

[2* Unsatisf] homes/preschools in Kanpur Boys = 974 (48.7%) 5 times Dental caries inverse relationship with frequency

District, India 5-10 times dmft of breastfeeding but not significant

>10 times Caries prevalence increased with

Duration of duration of breastfeeding and

breastfeeding p < 0.05

<6 months Caries prevalence higher in children

6 months-1 year who were introduced to the bottle

1-1.5 years around 2 years of age p < 0.001

1.5-2 years

Age bottle feeding

introduced

<6 months

6 months-1 year

1-2 years

Not introduced

—I zr

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Appendix (Continued) Type of study/brief Sample size (gender % given Other variables included in

References [NOS QA score] description Study population/Country if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) the models as confounders Interactions

Qadri et al. (70) Cross-sectional survey Children aged 3-5 years N = 400 Feeding practices during Aged 3-5 years Logistic regression: Models are adjusted but

[4* Satisfl 20 kindergartens in Syria Boys =191 (47.8%) infancy: predominately breastfed vs bottle fed. Dental caries dmft ECC Fully adjusted dietary practices (bottle vs breastfeeding) and (1) dmft OR = 0.61 (0.39-0.97) p = 0.038 (2) ECC OR = 0.27 (0.18-0.41) p < 0.001 Age was only significant factor associated with dmft and ECC confounders included are not reported (possibly age, gender and dietary practices are the covariates).

Retnakumari et al. (71) Cross-sectional Children attending N = 350 Duration of breastfeeding: Aged 12-36 months Significant association between None reported

[3* Unsatisf] immunisation clinic, day care centres - aged 12-36 months Kerala, India Male =171 (48.9%) Night feeding only Present now <1 year 1-2 years >2 years Falling asleep with nipple in the mouth Dental caries defs caries severity and duration of breastfeeding (analysis not shown) Severity of decay higher in children who fell asleep with nipple in the mouth (OR 2.92, p < 0.05) [95% CI not reported]

Rosenblatt et al. (72) Cross-sectional Pediatric clinic -two public N = 468 Feeding practices: Aged 12-36 months No significant association between None reported

[3* Unsatisf] maternity hospitals Recife, Brazil Boys = 222 (47.4%) Breast feeding Breast feeding + baby bottle sugared milk Baby bottle sugared milk Cup+ sugared milk Dental caries deft type of feeding and presence of caries

Sankeshwari, (73) Cross-sectional Children aged 3-5 years; 20 N = 1250 Breastfeeding: history, Aged 3-5 years Significant [unadjusted] associations None reported

[3* Unsatisf] preschool s in Bel gaum, India Boys = 663 (59.4%) duration, timing, frequency Bottle feeding: history, duration, timing frequency, contents Dental caries - dmft (ECC) (X2) between lower prevalence of ECC and history of breastfeeding (yes/no: p = 0.02), duration of breastfeeding (6-24 months/ <6 months or >24 months: p = 0.001).

Santos, (74) Cross-sectional Outpatients of the Pediatric N = 80 Breastfeeding Aged up to 36 months No significant associations were None reported

[2* Unsatisf] University Hospital, Brazil Boys = 45 (56.3%) Dental caries found between the prevalence of caries and nocturnal bottle- and breast-feeding.

Sayegh et al. (75) Cross-sectional Kindergartens in Amman, N = 1140 Infant feeding practice: Aged 4-5 years Breast feeding duration >18 months Characteristics included in

[4* Satisfl Jordan Boys = 582 (51.1 %) Breastfeeding Bottle feeding Both Duration Frequency (on demand) Dental caries Dmft Incisors; incisors and canines; molars; incisors, canines and molars or never (grouped together) - OR caries in any teeth = 1.5 (95% CI 1.1-2.1) p < 0.05 Breast feeding on demand cf not breast feeding on demand OR caries in any teeth = 1.8 (95% CI 1.3-2.5) p < 0.05 stepwise regression: Age; Social class; Sleep with mother; Bottle feeding time; Use of comforter; Confectionery at bed or night time

Sayegh et al. (76) Cross-sectional Kindergartens in Amman, N = 1075 Breastfeeding/ Bottle Aged 4-5 years Caries: Breastfeeding 18 months vs Characteristics included in

[5* Good] Jordan Boys = 553 (51.4%) feeding duration: <6-18 months >18 months Breastfeeding/ Bottle feeding frequency: Never; Not on demand; On demand Dental caries dmft Caries = dmft >1 Severe caries = dmft >4 never - not significant [data not shown] Severe caries: Breast feeding > 18 months vs never breastfeeding OR = 2.3 (95% CI 1.1-4.8) the stepwise multiple logistic regression model: Dental plaque; Sleeping beside mother; Use of comforters; Confectionery; Ma rma 1 a de/j a m/h oney/ halawi at breakfast or dinner

S-a' (Q Q 3 Q.

Appendix (Continued) References [NOS QA score] Type of study/brief description Study population/Country Sample size (gender % given if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) Other variables included in the models as confounders Interactions

Serwint et al. (77) Cross-sectional Hospital based pediatric clinic, N=110 Ever breast fed Aged 18-36 months Ever breast fed and caries OR = 2.9 Controlled for familial

[3* Unsatisf] California, USA Boys = 55 (50%) Bottle feeding was Dental caries: (95% CI 0.9-9.9) p = 0.08 - characteristics: Maternal

primary interest Caries borderline significance. cavities; Mother aims to

Non-caries keep teeth by age 65;

Child drank fluoride

water; fluoride

supplements; Brush

child's teeth

Slabsinskiene et al. (78) Cross-sectional Kindergartens in 10 counties in n = 80 Duration of breast Aged 2.5-3.5 years In children who breastfed beyond None reported

[3* Unsatisf] Subset questionnaire Lithuania feeding: Dental caries 13 months the risk of developing

Children with no caries <12 months dmft/dmfs S-ECC was high OR = 10.0 (95%

n = 40 Children with S- >13 months No caries CI 1.28-78.12)

ECC n = 40 S-ECC

Songo et al. (79) Cross-sectional Dental units of five hospitals or N = 158 Breast feeding: Aged 4-6 years Children being exclusively breast fed None reported

[2* Unsatisf] private clinics in Kinshasa, Boys = 79 (50%) Exclusive Dental caries - dmft or have both bottle and breast

Democratic Republic of Mixed with bottle presented with lower caries levels

Congo Bottle feeding only OR = 0.16 (95% CI 0.04-0.66)

Tanaka et al. (80) Cross-sectional Public health centre N = 2056 Breastfeeding duration Aged 3 years Adjusted Prevalence Ratios (95% CI) Adjusted for: gender;

[5* Good] Fukuoka City, Japan Boys = 1087 (52.9%) regardless of exclusivity: Dental caries Breastfeeding duration (months) Tooth brushing

<6 months dmft >1 <6 PR = 1 frequency; Use of

6-11 months 6-11 PR = 0.79 (0.6-1.05) Fluoride; Regular dental

12-17 months 12-17 PR 0.86 (0.66-1.13) check-ups; Between

>18 months >78 PR 1.66 (1.33-2.06) meal snack frequency;

Breastfeeding for 18 months or Maternal smoking during

longer significantly associated with pregnancy; Exposure to

higher prevalence of dental caries environmental tobacco

smoke at home; Parental

education levels

Tiano et al. (81) Cross-sectional Public day care centres in 2 N = 68 Breast feeding duration Aged 18-36 months CCL prevalence is significantly Not reported

[3* Unsatisf] municipalities in Brazil <12 months Dental caries associated with duration of

13 months + CCL = cavitated carious breastfeeding (p = 0.02)

lesions ECC prevalence is not associated

ECC = any stage of carious with duration of breastfeeding

lesion

Tyagi (82) Cross-sectional Kindergartens in Davangere, N = 813 Duration of breast Aged 2-6 years Mean dfs increases with duration of Not reported

[1 * Unsatisf] Karnataka, India Boys = 395 (48.6%) feeding: Dental caries breast feeding but not statistically

3-9 months dfs significant

10-12 months

13-24 months

25^12 months

Vachirarojpisan et al. (83) Cross-sectional Health centres, U-Thon District N = 520 Method of feeding: Aged 6-19 months Bivariate analysis of 15-19 month Multivariate models

[5* Good] in Suphan Buri Province, Boys = 272 (52.3%) Breast feeding Dental caries group: controlled for: Age;

Thailand Bottle feeding or mixed dmfs; dmft Significant association between Number of teeth present

feeding Intensity of ECC (l-ECC) = breastfeeding and l-ECC

ratio of affected teeth (non (p = 0.018). Significant association

cavitated + cavitated): erupted lost in multivariate models that

teeth include all age groups.

Vazquez-Nava et al. (84) Cross-sectional study Children aged 4-5 years who N = 1 160 Breast feeding Aged 4-5 years Significant association between Not reported

[5* Good] within prospective cohort had been longitudinally Boys = 585 (50.2%) Breast feeding Dental caries (assessed from breastfeeding beyond 12 months

study studied since 4 months of >12 months & at night 2 years of age) & at night and dental caries

2005 age. Bottle feeding deft and defs OR = 3.6 (2.51-5.16) p < 0.001

Not reported

m S-a' «s Q 3 Q.

Appendix (Continued) Type of study/brief Sample size (gender % given Other variables included in

References [NOS QA score] description Study population/Country if reported) Exposure definition Outcome definition and age Exposure estimate (95% CI) the models as confounders Interactions

Wendt & Birkhed (85) Cross-sectional study Preschool children in Baseline n = 671 Breast feeding: Examined at 1 year, 2 years Significantly more children with

[4* Satisfl within prospective Jonkoping, Sweden - 1 year n = 632 <2 months and 3 years of age caries than without caries at the age

longitudinal study comparison of Swedish 1 year caries free Still breast fed Dental caries of 3 had either been breast fed for

3 time points: 1 year, children and immigrant n = 629 dmfs <2 months or >12 months

2 years, 3 years children 2 years n = 298 2 years caries free n = 276 3 years n = 270 3 years caries free n = 210

Yonezu et al. (86) Cross-sectional Infants attending preventive N = 105 Bed time breast feeding Aged 18 months Odds of caries at 24 months was None reported

[1* Unsatisf] dental care programs at public health centres. Children have been or are being breastfed Dental caries dft significantly higher OR = 10.66 (2.23-50.96) for bedtime breast fed children than children not breast fed at bed time (p < 0.05)

ECC = Early childhood caries; S-ECC = Severe early childhood caries; dmfs/t = decayed, missing, filled and extracted deciduous surfaces/teeth; defs/t = decayed, extracted due to caries, filled deciduous surfaces/ teeth; DMFT = Decayed, Missing, Filled and Extracted permanent surfaces/teeth; ICDAS = International Caries Detection and Assessment System (Reference: ICDAS Foundation. What is ICDAS?. https:// www.icdas.org/what-is-icdas, 9 March 2015).