Association between duration of breastfeeding and malocclusions in primary and mixed dentition: a systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to examine the current evidence on the possible effects of breastfeeding on different malocclusion traits in primary and mixed dentition. A systematic search was made in three databases, using terms related to breastfeeding and malocclusion in primary and mixed dentition. Of the 31 articles that met the inclusion criteria and were included in the qualitative analysis, nine were included in the quantitative analysis. The quality of the 31 observational studies was moderate to high on the Newcastle-Ottawa Scale. It was found that the odds ratio for the risk of posterior crossbite was 3.76 (95% CI 2.01–7.03) on comparing children who had not been breastfed, with those breastfed for over six months, and rose to 8.78 (95% CI 1.67–46.1) when those not breastfed were compared to those breastfed for over twelve months. The odds ratio for class II malocclusion in children breastfed for up to six months compared to those breastfed for over six months was 1.25 (95% CI 1.01–1.55). Lastly, children who were breastfed for up to six months had an odds ratio of 1.73 (95% CI 1.35–2.22) for non-spaced dentition compared to those who were breastfed for over six months.


Results
Study selection and flow diagram. The protocol registered with PROSPERO stated that the search would be limited to the year 2000 or later, but during the search it was decided not to apply a time limit in order not to exclude any article that met the other inclusion criteria. The database searches identified 178 articles (146 in Pubmed, 21 in Embase and 11 in Scopus) and hand-searching found three more. The number of duplicates removed was 27. Initial screening of the titles and abstracts of the resulting 154 articles led to excluding 116. The full texts of the remaining 38 were then read. Finally, the 31 articles that met all the eligibility criteria were included in the qualitative synthesis. The inter-examiner agreement was greater than 0.9. Nine of the studies were included in the meta-analyses (Fig. 1).

Characteristics of the studies included.
Of the thirty-one articles included in the review, twenty were cross-sectional, three longitudinal, seven cross-sectional in a study cohort, and one was a case-control study. Four examined breastfeeding and malocclusion in mixed dentition and twenty-seven in primary dentition.
The sample sizes of the studies ranged between 80 and 2026. The mixed dentition ages ranged between 6 and 15 years and the primary dentition ages between 0 and 6 years.
Luz et al. and Thomaz et al. 30,31 examined the association between breastfeeding and dental/skeletal class II in mixed dentition and Nahas-Scocate et al., Caramez da Silva et al., Feldens et al. and Agarwal et al. 13,14,32,33 investigated the same association in primary dentition. The relationship between breastfeeding and the development of occlusion/malocclusion was analyzed in nine studies, all in primary dentition 5-7, 10-12, 18, 34, 35 .
The relationship between breastfeeding and the presence/absence of interdental spaces in primary dentition was examined by three studies 9,11,33 . Only one study 36 investigated the association between breastfeeding and palate depth in primary dentition, and one other 37 looked at the association between breastfeeding and facial pattern in mixed dentition.
Tables 1 and 2 summarize the data collected from all the studies in mixed and primary dentition, respectively.
Qualitative synthesis. The quality of the thirty-one observational studies was moderate to high in all cases according to the Newcastle-Ottawa Scale (Tables 3 and 4). As regards the relationship between breastfeeding and posterior crossbite in mixed dentition, Limeira et al. 8 found that no breastfeeding or a short period of breastfeeding were more often associated with this malocclusion. In primary dentition, most authors observed a greater prevalence of posterior crossbite in the no breastfeeding or breastfeeding for up to 6 months groups 4,[9][10][11][19][20][21][22][23][24] . Only one study found no association between the duration of breastfeeding and posterior crossbite in primary dentition 24 .
Concerning anterior openbite, relationships have been reported between few months of breastfeeding 6, 21, 24, 25 or absence of breastfeeding 12 and greater prevalence of this malocclusion. Peres et al. 10   observed a greater prevalence of anterior openbite in patients with few months of breastfeeding, and Massuia et al. 18 found that breastfeeding was a protective factor against anterior openbite.
In relation to overbite, the results are contradictory. Lescano de Ferrer et al. 20 and Moimaz et al. 28 observed greater overbite in children with over twelve months' breastfeeding but Bueno et al. 27 observed the opposite. Sum et al. 29 found no association between breastfeeding and openbite or overbite.
With regard to overjet, some authors reported a relationship between longer breastfeeding and less overjet 10, 18, 29 , but Moimaz et al. 28 found greater overjet in children with more than twelve months' breastfeeding.
Lastly, Lescano de Ferrer et al. 20 observed a lower prevalence of anterior crossbite in children who had been breastfed.
Some of the authors who examined the relationship between breastfeeding and dental class II found that a longer period of breastfeeding was associated with less prevalence of this class of malocclusion in mixed dentition 31 and in primary dentition 13,14,32 However, no relationship between class II and breastfeeding was found by Luz et al. 30 in mixed dentition or by Karjalainen et al. or Agarwal et al. 19,33 in primary dentition.
Of the authors who examined the association between breastfeeding and occlusion development, three studies concluded that breastfeeding favors better occlusion 10,11,34 and two found greater malocclusion prevalence in the absence of breastfeeding 12,35 or with up to six months' breastfeeding 18 . In contrast, three groups of researchers found no association between these two variables [5][6][7] .
Three studies examined the relationship between breastfeeding and the presence or absence of interdental spaces in primary dentition. Two concluded that breastfeeding for up to six months is related to an absence of maxillary spaces 9, 33 , while the third related the existence of breastfeeding to diastema and primate spaces 11 .
Lastly, Diouf et al. 36 analyzed breastfeeding and palate depth in primary dentition and found that a combination of breastfeeding and bottle feeding produced a longer and deeper maxilla than breastfeeding alone. Sanchez Molins et al. 37 examined the association between breastfeeding and facial pattern in mixed dentition and found a greater prevalence of brachyfacial pattern in children who had been breastfed.
Quantitative synthesis. Nine studies were included in the quantitative synthesis.
Association between no breastfeeding and posterior crossbite. Children who were not breastfed presented 1.7 times more posterior crossbite than those who had been breastfed for between one and six months (OR = 1.70, 95% CI 1.22-2.39). Heterogeneity was very low (I 2 = 0%, Q test p = 0.527). On comparing children who had not been breastfed with those who had been breastfed for over six months, the odds ratio for posterior crossbite rose to 3.76 (95% CI 2.01-7.03), with low heterogeneity (I 2 = 47%, Q test p = 0.169). On comparing no breastfeeding with breastfeeding for over twelve months, the odds ratio rose to 8.78 (95% CI 1.67-46.1) (I 2 = 80%, Q test, p = 0.026) (Fig. 2).
Association between exclusive breastfeeding and posterior crossbite. The data for the exclusively breastfed groups proved very similar (Fig. 3). Children who were not breastfed presented 1.52 times more posterior crossbite than those exclusively breastfed for between one and six months (OR = 1.52, 95% CI 1.10-2.10). Moreover, on Raftowicz-Wojcik et al. 6 (2011) Crosssectional
Association between duration of breastfeeding and posterior crossbite. Figure 4 shows that children who were breastfed for up to 6 months presented 2.77 times more posterior crossbite than those who had been breastfed for over 6 months (OR = 2.77, 95% CI 1.79-4.31). The heterogeneity was low (I 2 = 43%, Q test p = 0.133). The data for exclusively breastfed children (Fig. 3) were very similar (OR = 2.52, 95% CI 1.52-4.14). Additionally, the odds ratio in children breastfed for between one and six months was five times greater than for those breastfed for over twelve months (OR = 4.99, 95% CI 0.72-34.6), though the differences were not statistically significant. The heterogeneity was I 2 = 87% (Q test p = 0.005) (Fig. 4). Figure 5 shows the relationship between openbite and patients who were breastfed for up to six months and for over six months. There were no significant differences between the two groups (OR = 1.76, 95% CI 0.55-5.61) and the heterogeneity was high (I 2 = 75%, Q test p = 0.019).

Absence of association between breastfeeding duration and openbite.
Association between breastfeeding duration and Class II molar relationship. Children who were breastfed for up to six months presented 1.25 times more Class II relationship than those who had been breastfed for over six months. There were significant differences between the two groups (OR = 1.25, 95% CI 1.01-1.55) and the heterogeneity was moderate (I 2 = 43%, p = 0.136) (Fig. 6).
Association between breastfeeding duration and non-spaced dentition. Children who were breastfed for up to six months presented 1.73 times more non-spaced dentition than those who had been breastfed for over six months. There were significant differences between the two groups (OR = 1.73, 95% CI 1. 35-2.22) and the heterogeneity was low (I 2 = 0%, Q test p = 0.524) (Fig. 7).

Discussion
This systematic review examines the current evidence on the possible effects of breastfeeding on occlusal development. The consensus is clear on the greater prevalence of posterior crossbite in both mixed and permanent

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No association between breastfeeding and openbite or overjet. Children with posterior crossbite had shorter breastfeeding period.
-6 Table 2. Characteristics of articles studying the relationship between breastfeeding and malocclusion in primary dentition. M: male, F: female, OR: odds ratio, CI: confidence interval, PR: prevalence ratio, NNSH: non-nutritive sucking habits, (−): no information dentition in the absence of any form of breastfeeding, and also on the association between a longer breastfeeding period and a lower prevalence of posterior crossbite 4,[8][9][10][11][19][20][21][22][23] , although one study found no association 24 . A possible explanation for this association is that breastfeeding is based on advancing the mandible and raising and lowering the tongue, which promotes balanced muscular development, whereas the main action in bottle feeding is sucking, which contracts the buccinators and favors a narrower maxilla 22 . The same consensus was not found for the other malocclusions considered. For overbite, anterior openbite and overjet, the results were disparate and no homogeneous conclusion could be reached. Regarding dental and skeletal class II malocclusion, despite some discrepancies the majority of studies considered that breastfeeding Table 3. Quality of the studies on the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Criteria: (1) Representativeness of the exposed cohort. (2) Selection of the non-exposed cohort. is associated with less distocclusion in both primary 13,14,32 and mixed dentition 31 . However, other authors 19, 30,33 found no relationship between breastfeeding and class II in mixed and primary dentition, respectively. The present meta-analysis found that the risk of posterior crossbite falls as the duration of breastfeeding rises. It also found that the risk of posterior crossbite was 1.52 times higher in children who had not been breastfed than in those exclusively breastfed for between one and six months, and 3.74 times higher than in children exclusively breastfed for over six months.
As regards openbite/overbite, the results were contradictory. While Lescano de Ferrer et al. 20 and Moimaz et al. 28 observed greater overbite in children with over twelve months' breastfeeding, Bueno et al. 27 encountered the opposite, and Sum et al. 29 found no association. Massuia et al. 18 reported that breastfeeding was a protective factor  against anterior openbite. They also found that pacifiers could have a negative effect on the duration of breastfeeding, limiting its beneficial effects on occlusion development 38 .
The present meta-analysis found that children who were breastfed for up to six months presented 1.25 times more risk of Class II relationship and 1.73 times more risk of non-spaced dentition than those who had been breastfed for over six months.
A very small number of studies examined the effect of breastfeeding on palate depth and facial pattern. It would be useful for future studies to include these variables.
The sample sizes were large and representative: the smallest had 80 participants 28     Almost all the studies collected the breastfeeding data through retrospective questionnaires or interviews with the parents, which could give rise to memory bias in the parents' recollection of the number of months for which the children were breastfed. Only the 3 longitudinal studies 5, 10, 28 avoided this possible bias, collecting the data prospectively.
Some limitations of the present systematic review and meta-analysis are that most of the studies did not specify whether or not breastfeeding was exclusive, or take into account possible confounders such as digit sucking or the use of a pacifier.
In an attempt to control for publication bias, the search was conducted in three databases and was complemented by a grey literature search and hand-searching.
A further limitation in this meta-analysis is a certain heterogeneity among the studies analyzed, which limited their comparability. Additionally, they were observational studies of child populations, in which it is difficult to control for confounders.
Although two systematic reviews 39,40 and three meta-analyses 38,41,42 have been published recently, the present study provides separate assessments of the effects of breastfeeding on primary dentition and on mixed dentition, as well as a meta-analysis that examines the relations between breastfeeding and different malocclusion traits separately, including openbite, class II malocclusion and non-spaced dentition, which have not been studied in previous meta-analyses.
In conclusion, breastfeeding is a protective factor against posterior crossbite and class II malocclusion in primary and mixed dentition. The protective effect increases in line with the months of breastfeeding. There is no clear evidence for breastfeeding providing protection against other malocclusion risks such as openbite.
To avoid bias in the results would require longitudinal studies with data on the months of exclusive breastfeeding, collected prospectively through questionnaires administered to the mothers, and subsequent examination of occlusal status at the primary dentition, mixed dentition and permanent dentition stages. They should also consider confounders such as non-nutritional sucking habits and the use of baby feeding bottles. Odds Ratio for non-spaced dentition, comparing breastfeeding for <6 months with breastfeeding for >6 months.