**1.8 Two-way relationship between periodontitis and pregnancy**

Periodontal disease (PD) per se causes little clinical features and goes unnoticed until late in disease status. The tissue destruction is characterized by the formation of periodontal pocket that acts as reservoirs for bacterial colonization in the dentogingival environment.

Multiple factors have been associated with preterm baby (PB) and/or LBW such as smoking, drug use, high or low maternal age, low socioeconomic strata, inadequate prenatal care, low maternal body mass index (BMI), hypertension, genitourinary tract infections, cervical incompetence, diabetes, low nutritional status, stress, and multiple pregnancies [31]. However, more than 50% of the cases do not show the presence of these risk factors and are still affected by PB and/or LBW [15]. The search continues for other causes including the presence of the chronic infectious diseases like periodontal infection.

The hypothesis that infection remote from the fetal-placental unit may influence PLBW has led to an increased awareness of the potential role of chronic bacterial infections elsewhere in the body. Periodontal disease is associated with a "chronic gram-negative infection" of the periodontal tissues which results in long-term local elevation of pro-inflammatory prostaglandins and cytokines [8] and an increase in the systemic levels of some of these inflammatory mediators [20]. Hence, periodontal disease has a potential to influence PLBW through an indirect mechanism, involving inflammatory mediators or a direct bacterial assault on the amnion [28].

Multiple factors have been associated with the delivery of preterm and low birth weight infants. The evidence suggests that an infectious etiology is the main cause for a large percentage of cases for preterm birth. Genitourinary tract infections, such as bacterial vaginosis, and inflammatory mediators resulting from such infections have been considered a biologically plausible pathway for preterm labor and premature rupture of the membranes. Alternatively, it was hypothesized that preterm low birth weight may be indirectly mediated through distant infections resulting in translocation of bacterial vesicles and lipopolysaccharide (LPS) in the systemic circulation. However, the exact mechanisms for the proposed relationship remain unclear. The periodontal infection is initiated by predominantly gram-negative, anaerobic, and microaerophilic bacteria that colonize the subgingival area. Host defense mechanisms play integral role in the pathogenesis of periodontal disease. It has been postulated that the association between periodontal disease and preterm low birth weight (PLBW) may have similar pathogenic mechanisms as other maternal infections [32]. Inflamed periodontal tissues produce significant amounts of pro-inflammatory cytokines, mainly interleukin 1 (IL-1b), IL-6, prostaglandin E2, and tumor necrosis factor-alpha (TNF-α), which may have systemic effects on the host, leading to premature rupture of membrane. Hence, periodontal disease has the potential to influence preterm low birth weight through an indirect mechanism involving inflammatory mediators or a direct bacterial assault on the amnion [8, 33] (**Figure 2**).

The inflammation and infection caused during the periodontal disease is not just limited to the oral cavity but also enters the systemic circulation. The systemic immune response gets activated due to the episodes of bacteraemia and dissemination of endotoxins from periodontal pockets. Systemic circulation may induce pro-inflammatory cytokine production due to the presence of bacteria or bacterial endotoxins in the systemic circulation. IL-6 and C-reactive protein that are released during chronic lowgrade inflammation are further activated due to presence of cytokines in the systemic circulation. The endothelial dysfunction may result due to inflammatory response of endothelial cells. The immune response plays a pivotal role in maintaining a healthy equilibrium between the mother and fetus, during pregnancy. The specific immune response is shifted toward a Th2-type immune response, and the inflammatory

**Figure 2.** *Schematic representation of role of bacterial infection in preterm labor.*

response is also activated, during a normal pregnancy. During pregnancy there is an increase in expression of activation markers on monocytes and granulocytes, differences in monocyte cytokine production, and increased circulating levels of proinflammatory cytokines and inflammatory markers, such as C-reactive protein.

Periodontitis sites and subjects harbor specific microorganisms or groups of microorganisms. *Aggregatibacter actinomycetemcomitans*, *Porphyromonas gingivalis*, *Tannerella forsythia*, and *Treponema denticola* are observed more frequently and/or in higher levels and proportions in periodontitis subjects, and *Actinomyces* genus are observed with periodontal health [34, 35]. *Fusobacterium nucleatum*, a bacterium, has been linked with adverse pregnancy outcomes. *F. nucleatum* is associated with periodontal infections and not observed during genital or uterine infections. The infection does not enter the womb through the genital tract; rather it enters the mother's bloodstream making its way down from the oral cavity. The liver produces C-reactive protein (CRP), an acute-phase reactant in response to the inflammatory cytokine's interleukin IL-6, IL-1, and tumor necrosis factor-alpha. Periodontal diseases are associated with raised level of circulating CRP levels and elevation of pro-inflammatory cytokines and prostaglandin [26, 29]. Adverse pregnancy outcomes have been associated with increase in CRP levels. The CRP levels are raised in elevated immunoglobulin G induced by bacterial species found in destructive periodontal diseases [8].

The absence of the mother's IgG antibody against organisms of the red complex is associated with an increased risk of premature birth of the baby. Mothers without a protective red complex IgG response coupled with a fetal IgM response to orange complex microbes had the highest rate of prematurity. This evidence suggests the concept that prematurity in pregnant women may be due to systemic dissemination of oral organisms that translocate to the fetus in the absence of a protective maternal antibody response and trigger preterm babies. The high prevalence of elevated fetal IgM to *C. rectus* among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

#### **1.9 Effect of periodontal therapy on pregnancy outcomes**

No definitive conclusions can be arrived about periodontal disease (PD) treatment during pregnancy. Attempts to improve oral health in women during

**25**

*Periodontal Disease and Pregnancy Outcome DOI: http://dx.doi.org/10.5772/intechopen.84949*

clinical randomized controlled trials [36].

women) may reduce APOs [37].

**2. Conclusion**

significant improvements in their periodontal assessments.

pregnancy have not reduced adverse pregnancy outcome (APO). No reduction in APOs was observed with standard PD therapy during pregnancy in several large

The dilemma of performing periodontal treatment during pregnancy to reduce the APOs has not been answered. Periodontal treatment even if undertaken during pregnancy will not be thorough and completely eradicate the disease process, due to fear of bacteraemia which may cause APO. Pre-conception period is most appropriate time for periodontal treatment. Periodontal treatment to create a healthy mouth before conception may reduce the occurrence of APOs. The local and systemic inflammation caused by periodontal pathogens may not be controlled by periodontal treatment during pregnancy. Periodontal treatment before pregnancy (for nulliparous women) or in the period between pregnancies (for multiparous

There was a deep-seated bias in the medical/dental community against nonsurgical periodontal interventions during pregnancy [38]. After long-term studies and analysis, the medical and dental fraternity is in a general agreement that pregnant patients can safely undergo dental cleaning [39]. Interventions to reduce the morbidity and mortality associated with preterm birth can be classified as primary, secondary, and tertiary. All interventions examined by existing studies on the effects of periodontal therapy on pregnancy outcomes can be classified as secondary interventions [38]. It has been known for many years that nonsurgical periodontal therapy is effective in reducing the increased amount of periodontal inflammation associated with pregnancy [33, 40, 41]. Data clearly show that this therapy is safe and does not trigger an increase in adverse pregnancy outcomes. It has not been shown that routine nonsurgical periodontal therapy decreases the incidence of these outcomes. In general, women assigned to the periodontal treatment groups showed statistically

Pregnancy in woman brings about profound changes in innate and adaptive immunity of the mother and fetus; these changes play a major role altering the clinical course of a number of infectious diseases, including periodontal diseases. The severity of gingival and periodontal diseases increases during the course of normal pregnancy. Gingival inflammation and tissue response toward the microbial plaque is exaggerated during pregnancy due to the hormonal factors and is accepted by the scientific community. Pregnant women with previously existing periodontal disease will have increased destruction of the periodontal structures. The gingival changes observed during pregnancy return to normal limits immediately after delivery of the baby, if the local irritants are removed; this phenomenon is called as "immune reconstitution syndrome." Gestational diabetes which occurs in certain pregnant women can increase the risk for periodontal diseases, and it should be well controlled by treating gynecologist. Preeclampsia if not detected and treated can cause serious condition eclampsia leading to convulsions, coma, and death of the mother. Large numbers of epidemiological studies suggest that periodontal infection is a modest risk factor for several adverse pregnancy outcomes. The studies conducted to link between periodontal diseases and adverse pregnancy outcomes have had contradictory results, as they were carried out in different sets of populations or with different study designs. It is better to consider periodontal disease as a risk factor for adverse pregnancy outcome, as thorough oral health maintenance helps the pregnant women attain a better oral health which is part of general health.

#### *Periodontal Disease and Pregnancy Outcome DOI: http://dx.doi.org/10.5772/intechopen.84949*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

*Schematic representation of role of bacterial infection in preterm labor.*

response is also activated, during a normal pregnancy. During pregnancy there is an increase in expression of activation markers on monocytes and granulocytes, differences in monocyte cytokine production, and increased circulating levels of proinflammatory cytokines and inflammatory markers, such as C-reactive protein. Periodontitis sites and subjects harbor specific microorganisms or groups of microorganisms. *Aggregatibacter actinomycetemcomitans*, *Porphyromonas gingivalis*, *Tannerella forsythia*, and *Treponema denticola* are observed more frequently and/or in higher levels and proportions in periodontitis subjects, and *Actinomyces* genus are observed with periodontal health [34, 35]. *Fusobacterium nucleatum*, a bacterium, has been linked with adverse pregnancy outcomes. *F. nucleatum* is associated with periodontal infections and not observed during genital or uterine infections. The infection does not enter the womb through the genital tract; rather it enters the mother's bloodstream making its way down from the oral cavity. The liver produces C-reactive protein (CRP), an acute-phase reactant in response to the inflammatory cytokine's interleukin IL-6, IL-1, and tumor necrosis factor-alpha. Periodontal diseases are associated with raised level of circulating CRP levels and elevation of pro-inflammatory cytokines and prostaglandin [26, 29]. Adverse pregnancy outcomes have been associated with increase in CRP levels. The CRP levels are raised in elevated immunoglobulin G induced by bacterial species found in destructive

The absence of the mother's IgG antibody against organisms of the red complex is associated with an increased risk of premature birth of the baby. Mothers without a protective red complex IgG response coupled with a fetal IgM response to orange complex microbes had the highest rate of prematurity. This evidence suggests the concept that prematurity in pregnant women may be due to systemic dissemination of oral organisms that translocate to the fetus in the absence of a protective maternal antibody response and trigger preterm babies. The high prevalence of elevated fetal IgM to *C. rectus* among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

No definitive conclusions can be arrived about periodontal disease (PD) treatment during pregnancy. Attempts to improve oral health in women during

**1.9 Effect of periodontal therapy on pregnancy outcomes**

**24**

periodontal diseases [8].

**Figure 2.**

pregnancy have not reduced adverse pregnancy outcome (APO). No reduction in APOs was observed with standard PD therapy during pregnancy in several large clinical randomized controlled trials [36].

The dilemma of performing periodontal treatment during pregnancy to reduce the APOs has not been answered. Periodontal treatment even if undertaken during pregnancy will not be thorough and completely eradicate the disease process, due to fear of bacteraemia which may cause APO. Pre-conception period is most appropriate time for periodontal treatment. Periodontal treatment to create a healthy mouth before conception may reduce the occurrence of APOs. The local and systemic inflammation caused by periodontal pathogens may not be controlled by periodontal treatment during pregnancy. Periodontal treatment before pregnancy (for nulliparous women) or in the period between pregnancies (for multiparous women) may reduce APOs [37].

There was a deep-seated bias in the medical/dental community against nonsurgical periodontal interventions during pregnancy [38]. After long-term studies and analysis, the medical and dental fraternity is in a general agreement that pregnant patients can safely undergo dental cleaning [39]. Interventions to reduce the morbidity and mortality associated with preterm birth can be classified as primary, secondary, and tertiary. All interventions examined by existing studies on the effects of periodontal therapy on pregnancy outcomes can be classified as secondary interventions [38]. It has been known for many years that nonsurgical periodontal therapy is effective in reducing the increased amount of periodontal inflammation associated with pregnancy [33, 40, 41]. Data clearly show that this therapy is safe and does not trigger an increase in adverse pregnancy outcomes. It has not been shown that routine nonsurgical periodontal therapy decreases the incidence of these outcomes. In general, women assigned to the periodontal treatment groups showed statistically significant improvements in their periodontal assessments.
