Dental caries and preterm birth: a systematic review and meta-analysis.

OBJECTIVES: The primary objective of this systematic review was to evaluate the association between dental caries and preterm birth (PTB). The secondary objective was ascertaining the difference between women with dental caries who experienced PTB and those who did not with regard to decayed, missing and filled teeth (DMFT), and decayed, missing and filled surfaces (DMFS) indices.
METHODS: MEDLINE, Embase, CINAHL and Cochrane databases were searched initially in November 2015 and repeated in December 2016. We included observational cohort and case-control studies. Only studies reporting the risk of PTB in women affected compared with those not affected by dental caries in pregnancy were included. Random-effect meta-analyses were used to compute the summary OR of PTB among women with caries versus women without caries, and the mean difference in either DMFT or DMFS indices between women experiencing PTB and those without PTB.
RESULTS: Nine observational studies (4826 pregnancies) were included. Women affected by dental caries during pregnancy did not show a significantly higher risk of PTB (OR: 1.16, 95% CI 0.90 to 1.49, P=0.25, I2=35%). Also, the women with PTB did not show significantly higher DMFT or DMFS indices (summary mean differences: 1.56, P=0.10; I2=92% and -0.15, P=0.9, I2=89%, respectively).
CONCLUSION: Dental caries does not appear to be a substantial risk factor for PTB. TRIAL REGISTRATION NUMBER: NCT01675180; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Strength of the study is its robust methodology. We tried to cover all available studies, access data quality and synthesise suitable data.

Small number of cases in some of the included studies, their design, different follow-up periods and dissimilarity of the population studies are the limitations.

Similarly, the lack of description or classification of dental caries stage is another limitation due to which the stratification of analysis according to the disease severity could not be performed.

Introduction

Preterm birth (PTB) is the major cause of perinatal mortality and morbidity in the developed countries, with an estimated incidence of 5%–13%.1–4 Although advances in neonatal care have led to a reduction in the neonatal mortality rate, infants born prematurely remain at a risk of developing a wide array of short-term and long-term complications such as respiratory, gastrointestinal and neurodevelopmental disabilities.4

Several risk factors have been associated with PTB1 5; among these, intrauterine infection has emerged as one of the most important factors. Despite this, PTB cannot be considered a unique disease but rather a syndrome characterised by multiple aetiology and in which different factors may play a peculiar role.5

Periodontal disease has been shown to carry an increased risk for PTB; the rationale for this association is based on the suggestion that periodontitis may lead to maternal and fetal inflammation, thus triggering the common pathway of preterm parturition syndrome including increased uterine contractility, cervical ripening and decidua/membrane activation.6–11 Although dental caries, defined as a localised destruction of the tooth and its structure by the acidic by-product produced by the bacteria during the dietary carbohydrate fermentation,12 is one of the major oral health problems in developed countries, the effects of dental caries on pregnancy outcome have not been consistently explored. Pregnant women are more susceptible to dental caries and gingivitis compared with their non-pregnant counterparts13 because of the change in their diet, frequent snacking due to food craving and oral health negligence.14 If left untreated, dental caries may result in further inflammatory complications,15 which could influence pregnancy outcomes. Several studies reported that dental caries causing bacteria may have some influence on the pregnancy outcome as PTB and/or low birth weight, while in contrary, the other showed no association between these two factors.16–27

The primary aim of this systematic review was to explore the association between dental caries and PTB; the secondary aim was to ascertain the differences in dental caries characteristics between women who deliver preterm and those who do not deliver preterm.

Methodology

Protocol, eligibility criteria, information sources and search

This review was performed according to an a priori designed protocol and recommended for systematic reviews and meta-analysis.28 29

We developed a search strategy, and a systematic literature search was performed in the following databases: Ovid MEDLINE (In-Process and Other Non-Indexed Citations, Ovid MEDLINE, Daily, Ovid MEDLINE and Ovid OLDMEDLINE, Embase Classic + EMBASE (Ovid), The Web of Science (Thomson Reuters), The Cochrane Library (Wiley) and CINAHL Plus (EBSCOhost).

The full search was performed in November 2015 and repeated in December 2016. The online supplementary material 1 shows the complete search string as it was performed in MEDLINE. The controlled vocabulary of Medical Subject Headings (MeSH) from MEDLINE and the Emtree thesaurus from Embase, including subheadings, were used when applicable. In addition, the search fields, title, abstract and keywords, were searched when applicable. In The Web of Science, the search fields, title and topic were used. All references were exported to Endnote (X7.4, Thompson Reuters), where duplicates were removed. There were no restrictions regarding languages or publication year for the searches.

Reference lists of relevant articles and reviews were hand searched for additional reports. Meta-analysis of observational studies in epidemiology (MOOSE) guidelines were followed.30

The study was registered with the PROSPERO database (registration number: CRD42017062573).

Study selection, data collection and data items

We aimed to compare the incidence of PTB among the pregnant women population with dental caries with those who do not have dental caries.

The primary outcome was the occurrence of PTB, defined as birth <37 weeks of gestation. We aimed to categorise the analysis according to the type of PTB (spontaneous vs iatrogenic vs term) and according to the gestational age at birth moderate to late preterm (32 to <37 weeks), very preterm (28 to <32 weeks) and extremely preterm <28 weeks31.

The secondary objective was to ascertain the difference between women with dental caries who experienced PTB and those who did not experience PTB in either decayed, missing and filled teeth (DMFT) or decayed, missing and filled surfaces (DMFS) indices.32

DMFT and DMFS indices are numerical expressions of the caries prevalence of an individual or groups and are widely used in epidemiological surveys of oral health. DMFT/DMFS is calculated by adding up permanent teeth that are caries affected wherein D is for decay, M is missing due to caries and F is filled teeth (T) or surfaces (S). If one tooth has filling as well as a caries lesion, then it is counted as D for the DMFT index, whereas the filling+caries surface is counted as D but if there is F on one and D in other surface, then they are counted differently for the DMFS index. The anterior teeth up to canine have four and premolars and molars teeth have five surfaces, respectively, in the DMFS index. D+M+F=caries prevalence of an individual [maximum of 28 for DMFT and 128 for DMFS, if 28 permanent teeth are included (excluding 4 wisdom molar teeth)].32 33

Studies were assessed according to the following criteria: population, outcome, gestational age at birth and clinical characteristics of the caries during pregnancy. Observational cohort and case–control studies were included. Similarly, studies reporting the occurrence of PTB in women affected compared with those not affected by dental caries in pregnancies and the full-text articles were considered suitable for the inclusion in the present systematic review. Case reports, conference abstracts and case series with fewer than three cases were also excluded to avoid publication bias.

Two authors (MW and FD) reviewed all abstracts independently. Agreement regarding potential relevance was reached by consensus; full-text copies of those papers were obtained and the same two reviewers independently extracted relevant data regarding study characteristics and pregnancy outcome. Inconsistencies were discussed among the reviewers and consensus reached. Any dispute was resolved by discussion with a third author. If more than one study was published for the same cohort with identical endpoints, the report containing the most comprehensive information on the population was included to avoid overlapping populations. For those articles in which information was not reported but the methodology was such that this information would have been recorded initially, the authors were contacted.

Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale (NOS)34; according to NOS, each study is judged on three broad perspectives: the selection of the study groups, the comparability of the groups and ascertainment outcome of interest. An assessment of the selection of a study includes the evaluation of the representativeness of the exposed cohort, selection of the non-exposed cohort, ascertainment of exposure and the demonstration that outcome of interest was not present at the start of study. The NOS tool for the quality assessment of the studies is provided in the online supplementary material 2. According to the tool, a study can be awarded a maximum of one star for each numbered item within the selection and outcome categories. A maximum of two stars can be given for comparability.34

Statistical analysis

A first random-effect meta-analysis of binary outcomes was used to compute the summary OR (and relative 95% CI) of PTB among women with caries versus women without caries (controls).

Other two meta-analyses evaluated continuous outcomes: DMFT and DMFS. As the included studies did not differ in their outcome definitions, we used a random-effect approach to compute the mean difference in either DMFT or DMFS between PTB and non-PTB. In one study by Martinez-Martinez et al,35 the SD were not available, and we thus conservatively used the largest values recorded in the other included studies.

For all meta-analyses, the heterogeneity across studies was quantified using I2 statistic, and all computations were made using Review Manager (RevMan), V.5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Results

General characteristics

A total of 1786 articles were identified, 20 were assessed with respect to their eligibility for inclusion (online supplementary material 3) and 9 studies were included in the systematic review (table 1, figure 1). These nine studies included 4826 pregnancies.

Table 1

General characteristics of the included studies

Author	Year	Country	Period analysed (year)	Study design	Gestational age at dental examination	Number of subject (n)	Definition of PTB
Martinez-Martinez et al35	2016	Mexico	2013–2014	Retrospective	From the first trimester of pregnancy until 8 weeks postpartum	70	<37 weeks
Harjunmaa et al24	2015	Malawi	2011–2013	Prospective	Within 6 weeks after delivery	1024	<37 weeks
Acharya et al23	2013	India	2009	Retrospective	Within 1 day after delivery	316	<37 weeks
Vergnes et al22	2011	France	2003–2006	Retrospective	Within 2–4 days post partum	2201	<37 weeks
Ryalat et al21	2011	Jordan	2009	Prospective	Within 1 week post partum	200	<37 weeks
Durand et al17	2009	France	2005–2006	Prospective	Within 8 weeks after delivery	107	<37 weeks
Heimonen et al20	2008	Finland	2002–2004	Retrospective	Within 2 days post partum	328	<37 weeks
Mumghamba and Manji19	2007	Tanzania	NS	Retrospective	Within 40 days from delivery	373	<37 weeks
Meurman et al18	2006	Finland	1998–2000	Retrospective	From the first trimester of pregnancy	207	<37 weeks

PTB, preterm birth.

Figure 1

Systematic review flow chart.

Results of quality assessment of the included studies using NOS for cohort studies are presented in table 2. Most of the included studies scored at least one star in each of the three categories: the selection and comparability of the study groups, and ascertainment of the outcome of interest. The main weaknesses of these studies were their retrospective design, small sample size with even smaller number of events (PTB) and different gestational ages at assessment.

Table 2

Quality assessment of the included studies according to Newcastle-Ottawa Scale, a study can be awarded a maximum of one star for each numbered item within the selection and outcome categories

Author	Year	Selection	Comparability	Outcome
Martinez-Martinez et al35	2016	★★	★	★
Harjunmaa et al24	2015	★★	★	★
Acharya et al23	2013	★★	★	★★
Vergnes et al22	2011	★★★	★★	★
Ryalat et al21	2011	★★★	★	★★
Durand et al17	2009	★★★	★★	★★
Heimonen et al20	2008	★★	★	★
Mumghamba and Manji19	2007	★★	★	★
Meurman et al18	2006	★★	★	★

A maximum of two stars can be given for comparability.

Synthesis of the results

Five studies explored the risk of PTB in women who had caries compared with those who did not have caries during pregnancy and reported that women affected by caries in pregnancy did not have an increased risk of delivering <37 weeks of gestation (OR: 1.16, 95% CI 0.90 to 1.49, P=0.25; I2: 35%) (figure 2).

Figure 2

Pooled OR for the risk of preterm birth in women compared with those without dental caries.

Stratification according to DMFT and DMFS indices to evaluate the association between caries and PTB was performed only by five and three studies, respectively. There was no difference in either DMFT (1.56, 95% CI −0.28 to 3.41, P=0.10) and DMFS (−0.15, 95% CI −3.40 to 3.09, P=0.9) (table 3 and figure 3).

Table 3

Selected outcomes evaluating the association between dental caries and PTB

Outcomes	N studies (n/N)	OR (95% CI)	P	I2 %*
PTB, women with dental caries versus controls	5 (1472/4246)	1.16 (0.90 to 1.49)	0.25	35
DMFT (PTB vs non-PTB)	5 (2963)	1.56 (−0.28 to 3.41)	0.10	92
DMFS (PTB vs non-PTB)	3 (2594)	−0.15 (−3.40 to 3.09)	0.9	89

*I2 is a measure of the heterogeneity among the included studies. a value ≥50% indicates high while <50% low heterogeneity.

DMFT, decayed, missed and filled teeth; DMFS, decayed, missed and filled surface; n, number of events; N, total number of participants; PTB, preterm birth.

Figure 3

Mean differences in DMFT and DMFS indices in women with dental caries compared with those who did not experience PTB. DMFS, decayed, missing and filled surface; DMFT, decayed, missing and filled teeth; PTB, preterm birth.

Due to very small number of included cases and lack of information from the original study, it was not possible to perform any subanalysis according to different gestational age at birth and type of PTB (spontaneous vs iatrogenic vs term).

Discussions

Summary of evidence

The findings from this systematic review showed that pregnant women with dental caries are not at increased risk for PTB. Furthermore, there was no difference in the mean DMFT and DMFS indices between women with dental caries who experienced PTB and those who did not.

Strength and limitations

This is, to our knowledge, the first systematic review exploring the strength of association between dental caries and PTB. The strength of this meta-analysis is its robust methodology. We tried to cover all available studies, access the quality of the data and synthesise all suitable data.

The small number of cases in some of the included studies, their retrospective non-randomised design, different periods of follow-up, dissimilarity of the populations studies (due to various inclusion criteria) and lack of standardised criteria for the antenatal management of pregnancies with dental caries represent the major limitations of this systematic review. Lack of data on early PTB, which is typically associated with infection and inflammation, was another major limitation of the present systematic review. Furthermore, we could not stratify the analysis according to maternal characteristics and caries stage at diagnosis in view of the lack of such information in the large majority of included studies. Assessment of the potential publication bias was also problematic because of the nature of the outcome evaluated (outcome rates with the left side limited to a value of zero), which limits the reliability of funnel plots, and because of the small number of individual studies, which strongly limits the reliability of formal tests. Finally, statistical heterogeneity among the included studies was another major limitation of the present review which may potentially bias the study findings. In view of these limitations, the findings from this systematic review should be interpreted with cautions.

Implication for clinical practice

The consequences of overall oral health including the oral health in pregnant women is of a great concern.36 Dental caries and periodontal disease are the most common oral diseases worldwide. The higher prevalence of gingival alterations during pregnancy, especially bleeding during brushing, is a problem that is commonly encountered by pregnant women. Properly maintained oral hygiene care is known to have an impact on the oral health of pregnant women37 38 and availability of free dental care also appears to influence this.39 Whereas in contrast, if proper oral hygiene is not maintained during pregnancy, the chances to develop oral health problems such as enamel erosions, dental caries40 and gingivitis increase.

There are no reports indicating that the incidence of dental caries increases during pregnancy, but the chances of getting dental caries could increase14 and the prevalence of dental caries seemed to be higher in older pregnant women.41 Despite the high dental caries prevalence in most developed countries, very few studies have explored the potential association between oral health and adverse pregnancy outcome.

Identification of women at higher risk of PTB is fundamental to prevent the likelihood of delivering preterm. Several risk factors have been associated with PTB, such as prior history of PTB, cervical disease and infection. Despite this, finding an association between a given risk factor and the occurrence of PTB is challenging.

Dental caries is a frequently encountered oral health problem in pregnancy as pregnant women are more susceptible to caries compared with non-pregnant women.13 Being caused by an infectious process, dental caries can theoretically lead to inflammation and thus increase the risk of PTB.12 Despite this, we could not find any significant association between dental caries and PTB; furthermore, we did not find any significant difference in the severity of caries assessed by DMFT and DMFS indices between women who experienced PTB compared with those who did not. In addition to this, since most of these studies have evaluated women after delivery, this may also have influenced the results.

The lack of association between dental caries and PTB is difficult to explain. The initiation and progression of the caries lesion is very slow and the destruction caused by caries in initial stage can be reversible.12 In addition to this, pregnancy itself does not cause dental caries but it may exacerbate the existing condition. Dental caries is symptomless until there is severe and irreversible destruction of teeth.42 It might be possible that bacterial spreading during caries formation and the subsequent production of proinflammatory mediators induced by oral pathogens may not be of the magnitude to cause production of proinflammatory mediators enough to initiate PTB.

Even though we found no significant relationship between the dental caries and PTB, it is still important for the health professionals to promote oral health among the pregnant women. This is because pregnant women are susceptible to dental problems and have very limited knowledge and awareness about the importance of oral health and its potential impact on pregnancy outcomes.39 43 Furthermore, the risk of transmitting the oral cariogenic flora from the mother to her infant through feeding practices and predisposing the infant to early childhood caries in the future should not be neglected.44–47 Therefore, large prospective studies aiming at ascertaining the association between dental caries and spontaneous PTB, according to the gestational age at occurrence, severity of the disease and presence of other co-morbidities are needed in order to elucidate the role, if any, of dental caries in increasing the risk of PTB.