Association of pregnant women periodontal status to preterm and low-birth weight babies: A systematic and evidence-based review.

The mouth serves as a mirror to general health and also as a portal for disease to the rest of the body. Since the old wives' tale of "the loss of a tooth for every pregnancy", oral health during pregnancy has long been a focus of interest. In the past decade, there has been mounting scientific evidence suggesting that periodontal disease may play an important role as a risk factor for adverse pregnancy outcomes. Considering all the above stated factors this systematic review is aimed to focus on the association of periodontal diseases to preterm and low-birth weight (LBW) babies. In view of the large body of literature the review is limited to studies identified by computer searching. Hand searching of journals and gathering of unpublished reports and conference proceedings was outside the scope of the review. The PubMed database was searched using the search terms: periodontitis, preterm, LBW. The titles, authors, and abstracts from all studies identified by the electronic search were printed and reviewed independently on the basis of keywords, title and abstract, to determine whether these met the inclusion criteria. The electronic search identified 68 papers. After review of the study title, keywords and abstracts, 62 papers were identified potentially meeting inclusion criteria. Generally, all the studies reviewed in the paper suggest that periodontal disease may be a potential risk factor for preterm LBW babies.

INTRODUCTION

The mouth serves as a mirror to general health and also as a portal for disease to the rest of the body.[1] Since the old wives’ tale of “the loss of a tooth for every pregnancy”, oral health during pregnancy has long been a focus of interest.[2] It is well known that hormonal changes during pregnancy are associated with oral mucosal changes most of which are reversible clinically.[34] The reasons for these changes are not well established. However, they can complicate pregnancy.[5] Of all the changes, the ones most well written about is pregnancy gingivitis and pregnancy epulis (alternate names – pregnancy tumour, epulis gra-vidarum, pregnancy granuloma.[6]

Periodontitis can be considered a continuous pathogenic and inflammatory challenge at a systemic level, due to the large epithelium surface that could be ulcerated in the periodontal pockets. This fact allows bacteria and their products to reach other parts of the organism, creating lesions at different levels. Some bacterial species, like Porphyromona gingivalis and Aggregatibacter actinomycetemcomitans (previously named Actinobacillus actinomycetemcomitans) can directly invade cells and tissues. This exposition to Gram-negative bacteria and their products can generate an immuno-inflamatory response with potential damage to different organs and systems. Thus, in the last decade, periodontal infections have been associated with different systemic diseases, e.g., preterm low birth weight (LBW).[7]

Pre-term (PT) birth is a major cause of infant mortality and morbidity that has considerable societal, medical, and economic repercussions. The rate of PT birth appears to be increasing worldwide and efforts to prevent or reduce its prevalence have been largely unsuccessful. If periodontal disease is associated with higher risk of adverse pregnancy outcome in these specific populations, large multicenter randomized-controlled trials will be needed to determine if prevention or treatment of periodontal disease, perhaps combined with other interventions, has an effect on adverse pregnancy outcome in these women.[8]

LBW, which is defined by WHO[9] as a birth weight of less than 2500 gms is a well documented risk factor for neonatal and infant morbidity as well as mortality. The theory that periodontal infection may contribute to LBW was first tested by Collins et al. (Collins, 1994) who demonstrated significant mechanisms that involve bacterially induced activation of cell-mediated immunity, which leads to production of cytokines (such as interleukins [IL-1 and IL-6] and tumor necrosis factor alpha [TNF-α]) and the ensuing synthesis and release of prostaglandins (especially prostaglandin E2 [PGE2]). In the past decade, there has been mounting scientific evidence suggesting that periodontal disease may play an important role as a risk factor for adverse pregnancy outcomes. Considering all the above stated factors this systematic review is aimed to focus on the association of periodontal diseases to preterm and LBW babies.

PROPOSED HYPOTHETICAL MODEL OF PERIODONTITIS CAUSING PRETERM LOW-BIRTH WEIGHT BABIES (PLBW)

Proposed hypothetical model cited in the article of Yeo et al.[10] 2005 is illustrated in a modified version in Figure 1.

Figure 1

Proposed hypothetical model cited in the article of Yeo et al. 2005 is illustrated in a modified version

Periodontitis is a multifactorial disease. Although the primary etiology of periodontal diseases is bacterial, host and environmental factors modulate the severity of the disease. Host and environmental factors include genetics, chronic disease, tobacco use, socioeconomic level, educational level, frequency of dental visits, and both local and systemic nutrition and host response and its impact on periodontal disease. Dental professionals need to routinely assess the optimal functioning of the immune system in combating infection and to promote optimal periodontal health.[11]

EVIDENCE OF PERIODONTAL PATHOLOGIES AS A POTENTIAL RISK FACTOR FOR PLBW

Chronic periodontitis has been proposed as a risk factor for preterm birth.[12] Multiple factors coupled with periodontitis have been associated with LBW along with the summarization of few supporting articles are charted out in Table 1.

Table 1

Risk factors for preterm birth

In an attempt to identify modifiable risk factors for LBW, Dasanayake et al.[18] in 2001 have reported that a pregnant woman's poor periodontal health may be an independent risk factor for LBW. The periodontal diseases share many common risk factors with PLBW. Few risk factors and the corresponding reference articles supporting this are enumerated in Table 2.

Table 2

Risk factors for low birth weight babies

ROLE OF INFECTION IN PLBW

Infection is now considered one of the major causes of PLBW deliveries, responsible for somewhere between 30% and 50% of all cases. Bacterial infection of the chorioamnion, or extraplacental membrane, may lead to chorioamnionitis, a condition strongly associated with premature membrane rupture and preterm delivery.[21]

REVIEW OF EPIDEMIOLOGICAL STUDIES ON PERIODONTITIS AND PLBW

Offenbacher et al.[26] conducted a case-control study of 124 pregnant or postpartum women in 1996. Multivariate logistic regression models, controlling for other risk factors and covariates, indicated that periodontal disease is a significant risk factor, with impressively high odds ratios of 7.9 for mothers of preterm LBW babies and 7.5 for mothers giving birth for the first time.

Offenbacher et al. in 1998[27] a study of 48 women between cases and controls, found that the case group, i.e., mothers of preterm had worse periodontal disease than control group, finding them in higher levels of PGE2 and IL - lb, as well as periodontal pathogens. In that sense, these biochemical and microbiological tests, more accurately diagnosed with periodontal status.

Hill. (1998)[28] suggested the potential of periodontal bacteria to produce infection in the upper genital tract in pregnant women, leading to preterm delivery. Found species of Fusobacterium nucleatum and Capnocytophaga in the amniotic fluid cultures in women with preterm labor. He indicated that at least a portion of the bacteria responsible for genital infection cannot occur in the vagina, but in the patient's mouth.

More recently, Offenbacher's group in 1999[29] analyzed blood samples from fetal cords for the presence of immunoglobulin M (IgM) antibody against various periodontal pathogens. Of the PLBW samples, 33.3% tested positive for IgM against the test bacteria, whereas only 17.9% of the normal birth weight samples tested positive. Of the 13 periodontal pathogens included in the analysis, IgM antibodies against Campylobacter rectus, P. gingivalis and F. nucleatum were most often encountered. Although both preterm and normal birth weight infants had foetal cord IgM directed against specific bacteria, these fetal immune responses indicate that maternal periodontal infections can provide a systemic challenge to the foetus in uteri. Collectively, these animal and clinical studies clearly indicate an association between periodontal infection and adverse pregnancy outcomes.

Engebretson et al. in 2000[30] determined from a study of 164 women, mothers of preterm had significantly higher levels of periodontal pathogens. Furthermore, they suggested that periodontal treatment in pregnant women may substantially reduce the risk of having premature babies with LBW.

Recent review by Xiong et al. in 2006[31] suggest periodontal disease, as a source of sub clinical and persistent infection, may induce systemic inflammatory responses that increase the risk of adverse pregnancy outcomes. Periodontal disease may be associated with an increased risk of adverse pregnancy outcomes. However, more methodically rigorous studies are needed for confirmation.

To examine the existing evidence on the relationship between periodontal disease and adverse pregnancy outcomes, Xiong et al.[32] conducted a systematic review of studies published up to December 2006. Studies published in full text were identified by searching computerized databases (e.g., Medline, Embase). A meta-analysis was performed to pool the effect size of the clinical trials. Forty-four studies were identified (26 case-control studies, 13 cohort studies, and 5 controlled trials). The studies focused on preterm LBW, preterm birth, and birth weight by gestational age, miscarriage or pregnancy loss, preeclampsia, and gestational diabetes mellitus. Of the chosen studies, 29 suggested an association between periodontal disease and increased risk of adverse pregnancy outcome (odds ratios [ORs] ranging from 1.10 to 20.0) and 15 found no evidence of an association (ORs ranging from 0.78 to 2.54). A meta-analysis of the clinical trials suggested that oral prophylaxis and periodontal treatment may reduce the rate of preterm LBW (pooled risk ratio (RR): 0.53, 95% confidence interval [CI]: 0.30-0.95, P < 0.05), but did not significantly reduce the rates of preterm birth (pooled RR: 0.79, 95% CI: 0.55-1.11, P > 0.05) or LBW (pooled RR: 0.86, 95% CI: 0.58% 1.29, P > 0.05). The authors conclude that periodontal disease may be associated with increased risk of adverse pregnancy outcomes.

TRANSLOCATION OF PERIODONTAL PATHOGENS TO THE FETOPLACENTAL UNIT

No bacterial organisms are identified in 18% to 49% of histologically inflamed chorioamnionic membranes.[3334] As a result, it is generally maintained that the role of periodontal infection as a possible risk factor for PLBW more likely involves translocation of bacterial products (specifically LPS) or inflammatory mediators (specifically IL-1, IL-6, TNF-α, and PGE2) rather than bacteremic spread and translocation of the bacteria themselves.[35] Most bacteria associated with progressive periodontitis are anaerobes, which find aerobic settings so inimical that they would rarely survive to enter the bloodstream,[36] let alone establishing an infection in the foeto-placental unit. According to Qureshi et al. in 2005[37] histologically confirmed that chorioamnionitis is not associated with active infection in genito-urinary tract and results of the culture are negative.

INTERVENTION STUDIES ON THE EFFECT OF PERIODONTAL TREATMENT IN THE INCIDENCE OF PRETERM BIRTHS OR LOW BIRTH WEIGHT

Lopez et al. in 2002[38] had conducted a randomized controlled trial (RCT) in which it was concluded that periodontal treatment reduces significantly the incidence of PB or LBW in women with periodontitis.

Michalowicz et al.,[39] has done a RCT where no statistically significant differences were found and periodontal treatment did not significantly alter rates of PB.

Offenbacher et al. in 2006[40] did a RCT wherein significant differences were found and they concluded that periodontal treatment reduces the incidence of PB.

RESULTS OF THE SYSTEMATIC REVIEW

Sources of data

In view of the large body of literature on periodontitis, preterm and LBW babies the review is limited to studies identified by computer searching. The inclusion criteria of the review was randomized controlled trials, cohort studies, case-control studies, and all types of reviews with an implicit or an explicit mention of the hypothesis that periodontitis and preterm low birth babies have some association. The PubMed being a relevant computerized data base was used. We searched the Pubmed database for eligible studies from their earliest date to January 30, 2010. PubMed was searched using the keywords: periodontitis, preterm, LBW.

The titles, authors, and abstracts from all studies identified by the electronic search were printed and reviewed independently on the basis of keywords, title and abstract, to determine whether these met the inclusion criteria. Systematically all the studies that were an output of the search which included both that showed an association and that did not show an association of the study variables were included in the review.

Results of the review

The electronic search identified 68 papers. After review of the study title, keywords, and abstracts, 62 papers were identified potentially meeting inclusion criteria. Also, the references of the above mentioned studies were also checked for [Tables 3 and 4].

Table 3

Articles showing periodontitis is associated with Preterm, Low birth weight, Preterm lowbirth weight TLBW

Table 4

Articles showing periodontitis is not associated with PTLBW

LIMITATIONS OF THE REVIEW

The review's discussions, conclusions are limited to the articles searched by the authors through the computerized database. The inclusion criteria of the review are randomized controlled trials, cohort studies, case-control studies, and all types of reviews with an implicit or an explicit mention of the hypothesis that periodontitis and PLBW babies have some association. The limitations mentioned in the individual articles are also the limitations of the systematic review.

COMMUNITY PERSPECTIVE

In both developed and developing countries, PLBW has a tremendous impact on both the health care system and the individual families’ affected.[91] Periodontitis and its causal factors are the important risk factors for PTLW. At the community level there is a need for prevention of Periodontitis or at least early detection through dental visits. The community health centres’ need to provide dental camps at village/district levels so that women in general and pregnant women in particular have opportunities to rule out Periodontitis. Dental plaque is considered to be the main cause of Periodontitis. So organizing health promotion programs through dental camps and educating the rural public on various steps to be taken to prevent formation and accumulation of plaque is essential.

Oral health condition has to be investigated at rural level especially for all pregnant women and plaque formation/periodontitis has to be ruled out, so that even in case periodontitis is present, it can be cured in the initial stages. There should be an increase in the programs for pregnant women on the importance of oral health maintenance. By addressing the cause, health promotion regarding periodontitis can be done for pregnant women at a community level.

Promotion of oral health can be done through:

Health education programs at all the Maternal and Child Health Centres for the pregnant women should include dental care also.

Professional education through dental professionals and also the auxiliary personnel on the oral hygiene practices.

Marketing high quality products at affordable prices.

Reaching the unreached through NGOs or Government programs.

Organizing treatment camps on scaling throughout the reached dental centres.

Through health education programs emphasis on the various health problems that can occur in a PTLB baby.

Incorporation of skills of oral hygiene into training of health education and social care professionals.

Preventive care services should be provided during early stages of pregnancy. Preliminary evidence to date suggests that periodontal intervention may reduce adverse pregnancy outcomes.[92] However, women should be encouraged to achieve a high level of oral hygiene prior to becoming pregnant and throughout their pregnancies. Many factors associated with dental care use during pregnancy are not amenable to intervention; however, provision of counselling on oral health care by maternity care providers is a simple, low-cost intervention.[93] Clinicians and public health care providers need latest practical information concerning dental care. This will facilitate development and implementation of oral health counselling, screening, and referral strategies.[94] A diagrammatic presentation of a need for health promotion is enumerated in Figure 2.

Figure 2

A diagrammatic presentation of a need for health promotion

CONCLUSION

Generally, all the studies reviewed in the paper suggest that periodontal disease may be a potential risk factor for preterm LBW babies. The increase in the infant mortality rates due to PLBW has been on the rise. Since periodontitis and its causes may be associated risk factors for preterm LBW babies, it is suggested to include the oral health condition of a pregnant woman along with other risk factors such as BP, blood sugar etc., especially in the rural areas. In cases of necessity, case has to be referred to a dentist for the needful. Health promotion at a community level is essential to prevent periodontitis to prove the old wives’ tale of “the loss of a tooth for every pregnancy,” wrong.