Relationship between periodontal disease and preterm low birth weight: systematic review

Introduction Periodontal disease is a neglected bacterial infection that causes destruction of the periodontium in pregnant women. Yet its impact on the occurrence of adverse pregnancy outcomes has not systematically evaluated and there is no clear statement on the relationship between periodontal disease and preterm low birth weight. The objective of this study was to summarize the evidence on the impact of periodontal disease on preterm low birth weight. Methods We searched the following data bases from January 2005 to December 2015: CINAHL (cumulative index to nursing and allied health literature), MEDLINE, AMED, EMBASE (excerpta medica database), Cochrane library and Google scholar. Only case-control studies with full text in English were eligible. Critical appraisal of the identified articles was done by two authors independently to provide the possible relevance of the papers for inclusion in the review process. The selected Case control studies were critically appraised with 12 items structured checklist adapted from national institute of health (NIH). Odds ratio (OR) or risk ratios (RR) were extracted from the selected studies. The two reviewers who selected the appropriate studies also extracted the data and evaluated the risk of bias. Results Of 229 articles, ten studies with a total of 2423 participants with a mean age ranged from 13 to 49 years were met the inclusion criteria. The studies focused on preterm birth, low birth weight and /or preterm low birth weight and periodontitis. Of the selected studies, 9 implied an association between periodontal disease and increased risk of preterm birth, low birth weight and /or preterm low birth weight outcome (ORs ranging from 2.04 to 4.19) and only one study found no evidence of association. Conclusion Periodontal disease may be one of the possible risk factor for preterm low birth weight infant. However, more precise studies with randomized clinical trial with sufficient follow-up period must be done to confirm the association.


Introduction
Periodontal diseases are bacterial infections of the tooth supporting structures, which causes inflammation and destruction of the periodontium. This bacterial infections are adhered to the periodontal tissue by biofilm, which is a complex structure of bacteria and discernable by the excretion of a protective and adhesive matrix [1]. The progression of bacterial infection leads the periodontium to become severely destructed and causes a chronic and systemic challenge with bacterial substance and host-derived inflammatory mediators are capable of initiating and promoting systemic diseases [2]. Oral health and its relationship to systemic health is a global health concern due to 90% of the population is affected by periodontal disease-either gingivitis or periodontitis [3].
There is emerging evidence that suggested periodontal disease is associated with cardiac disease, diabetes mellitus, respiratory infection and adverse pregnancy outcomes [4]. The prevalence of Periodontitis is high in pregnant mothers (40%) [5], and all these mothers with periodontitis have seven times at risk of having preterm or low birth weight baby [6]. The hormonal changes during pregnancy, promotes inflammatory response that facilitates the occurrence of periodontal disease. Due to the change in hormonal level 50-70% of women develop gingivitis during their pregnancy.
The increased level of progesterone and estrogen in plasma during pregnancy can affect periodontal structure through interference in sub gingival micro flora composition, maternal immune system, and facilitates pro-inflammatory mediator production [7]. Preterm birth (PTB) and Low birth weight (LBW) are considered a primary public health challenge and the most relevant biological determinant of new-borns' survival, both in developed and in developing countries.
They have a marked effect or influence on both the health care system and the individual families. This necessitates the uninterrupted search for risk factors for preterm birth and LBW that are amenable to prevention [8]. The importance of preterm birth and LBW not only comes from its capacity to predict increased risk of mortality and morbidity among infants born with this condition but it also reflects the mother's exposure to other risk factors such as unfavourable socio-economic conditions, malnutrition and diseases of the mother, among others [9]. A case-control study done by Offenbacher et al in 1996 showed that, periodontal disease is a significant risk factor for preterm low birth weight with odds ratio of 7.9 [6]. Other similar study done by Hill (1998) found that periodontal bacteria's have the potential to produce infection in the upper genital tract in pregnant women, causing preterm birth. Hill also found bacterial species of Fusobacterium nucleatum and Capnocytophaga in the amniotic fluid cultures in women with preterm labor [10]. A randomized controlled trial done by lopez et al [11] showed that periodontal therapy reduced the incidence of preterm and low birth weight in women with periodontal disease.
However, Michalowicz et al revealed that periodontal therapy had no effect on the incidence of preterm birth [12]. The past 10 years have witnessed in an increase in research to explore the association between periodontal disease and adverse pregnancy outcomes.
Some of the previous studies have found a significant relationship between preterm birth and periodontal disease [13][14][15]. However, there are evidences which disapprove the adverse effects of Periodontitis on pregnant women [16,17]. Due to this inconsistency between different studies on the association between periodontal and preterm low birth weight, a confirmation of periodontal disease as a possible risk factor for this adverse effect would be of great public health problem due to its preventive and curable nature of the disease. Synthesising evidence on the impact of periodontal disease on adverse pregnancy outcomes (preterm low birth weight) can help to develop public health awareness and inform the health system to implement relevant measures and dental follow-up of pregnant mother during their ANC follow-up time, to define the role of each health professionals on pregnant mother. Our objectives were to summarize the evidence on the impact of periodontal disease on preterm low birth weight.

Results
Search yield: The search from the databases and manual search from Google retrieved 229 articles, after removal of duplicates. After screening title, abstracts and references 154 papers were removed.
Full text was obtained for 75 papers. Of which, 65 papers were eliminated as they did not meet inclusion criteria and finally, a total of 10 articles were considered for the systematic review ( Figure 1).
The studies were conducted in seven countries: 3 articles in India, 2 articles in Brazil, and one each from Iran, Argentina, Jordan, Senegal, and Tanzania each ( Table 2, Table 3).
Quality: The quality assessment scores and the decisions of each item for the included case control studies are shown in Table 1.
Characteristics of included studies: The characteristics of the 10 case-controlled studies are listed in Table 2, Table 3. All included studies were case-control studies. The mean age of the participants ranged from 13 to 49 years. Women with known last menstrual period and first trimester dating scan were included ( Table 2,Table 3).

Discussion
Periodontal and other oral health problems have been supposed to be a risk factor for preterm birth and /or low birth weight in many literatures. Nevertheless, the association between periodontal health status of a pregnant women and adverse pregnancy outcomes is still controversial. In this review, it has been tried to focus on the results of all case control studies extracted from the literature, which had been conducted to find out the association between Page number not for citation purposes 4 periodontal disease and two adverse pregnancy outcomes namely low birth weight and preterm birth. However, the operational definition of Periodontitis differed widely among the selected and reviewed studies since each articles considered special criteria. In this systematic review, nine of the included articles found that periodontal disease is associated with low birth weight and preterm birth [18][19][20][21][22][23][24][25][26]. Other epidemiological studies which have been done in the past found associations between periodontal status and preterm birth alone (PB) [28] low birth weight (LBW), or preterm birth associated to low birth weight (PLBW) [29]. Even though, the magnitude of the association status varies from adjusted odds ratio of (2.09 to 4.19), this systematic review found that a pregnant woman who is diagnosed as having Periodontitis has a high chance of delivering either a low birth infant or prematurely or both preterm low birth weight infant than a pregnant woman with healthy periodontium. A cohort study done among middle class women of USA found that there was a significant association between having periodontitis and preterm birth and/or low birth weight (A OR 2.26: 95%CI 1.05-4.85) [30]. On the contrary, in this systematic review a single study done in Tanzania found no significant association between periodontal disease and low birth weight or preterm birth and/or PLBW [27]. The reason could be, in this study all subjects were urban dwellers which excludes the rural population that has been reported to have a slightly worse periodontal health compared to urban residents [27]. The reason for controversial evidence could be due to noted potential biases among selected studies. The first and great variation, despite the same methodology, among included studies is that the difference in operational definition of periodontitis. Because there is no universally accepted standard for periodontal disease diagnosis, most of the researchers used their own case definitions (mostly based on disease distribution within the study population) that combined PD and CAL [14]. The additional reason for difference in evidence regarding the adverse outcomes of periodontal disease among pregnant women may be different in maternal socioeconomic status and access to dental care. The majority of the studies done in developing countries, especially those carried out in economically disadvantaged populations who reside in rural settings, suggest that periodontitis is associated with increased risk of preterm birth and low birth weight [10]. We noted potential bias during this systematic review.

Competing interests
The authors declare that there is no competing interests. There was no financial support for the study.

Authors' contributions
Amare Teshome: participated in article search, article selection, quality assessment of the articles, data extraction and analysis.
Asmare Yitayeh: participated in article search, article selection, quality assessment of the articles, data extraction and analysis Tables and figure   Table 1: quality assessment result of the selected case-control studies