Running head: PERIODONTAL DISEASE AND PREGNANCY OUTCOMES 1

Literature Review: Assessing the Effectiveness of Periodontal Therapy to Reduce Adverse

Pregnancy Outcomes in Pregnant Women with Periodontal Disease

by

Carolyn Lee & Yezi Pang

In partial fulfillment

of the requirements for

Lake Washington Institute of Technology

DHYG 331 Research II

Spring 2019

May 29, 2019

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Introduction & Literature Review

Introduction to the Research Question

Periodontal disease is a pathological process caused by a group of bacteria in the

periodontium, a group of specialized tissues in the oral cavity which includes the gingiva,

periodontal ligaments, cementum, and the alveolar bone. Periodontal disease is among the most

common diseases worldwide, with estimates of gingivitis affecting 50-90% of all adults, and

periodontitis affecting more than 10% of the world’s population in 2010 (Daalderop et al., 2017).

Pregnant women are more vulnerable to periodontal diseases due to the weakened

maternal immune system and the increased estrogen level (Otomo-Corgel, Pucher, Rethman &

Reynolds, 2012). Periodontal diseases among pregnant individuals are linked to several adverse

pregnancy outcomes based on two pathogenic mechanisms. First, periodontal pathogens are

capable of translocating from the oral cavity to the placenta. An animal study demonstrated that

P. gingivalis was able to translocate from infected oral tissue to the placenta and induce an

increased inflammatory response (Komine-Aizawa, Aizawa, & Hayakawa, 2019). Second, the

oral inflammation has potential systemic inflammatory mediating effects. Increased maternal

levels of circulating inflammatory cytokines were found in the same animal study, indicating that

a systemic inflammatory response was triggered by the oral pathogens (Komine-Aizawa et al.,

2019). As a result, periodontal diseases are considered as risk factors for several adverse

pregnancy outcomes, including premature birth, low birthweight, restricted fetus growth, pre-

eclampsia and gestational diabetes (Da Silva et al., 2017; Daalderop et al., 2018; Ilheozor-

Ejiofor, Middleton, Esposito, & Glenny, 2017; Komine-Aizawa et al., 2019; Teshome &

Yitayeh, 2016). Estimates for periodontal disease in pregnant women have varied widely, from
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11-100%, indicating a need for further clarification on the prevalence and mechanism by which

adverse pregnancy outcomes arise (Daalderop et al., 2018; Teshome & Yitayeh, 2016).

In recent years, research attention has been given to search for the effectiveness of

periodontal treatments to reduce adverse pregnancy outcomes. The most commonly performed

procedure to treat periodontitis in pregnant individuals is scaling and root planing (Polyzos et al.,

2010). The effectiveness of scaling and root planing on reducing the adverse pregnancy

outcomes has been studied through a variety of research methods, including observational

studies, case reports, randomized clinical trials, and animal models (Da Silva et al., 2017;

Komine-Aizawa et al., 2019). Certain researchers also use inflammatory biomarkers as a

measure by which to assess risk level in pregnant women with periodontal disease. In pregnancy,

inflammatory biomarkers rise naturally until a threshold is reached, at which point an

inflammatory signaling process induces labor (Da Silva et al., 2017). Researchers hypothesize

that periodontal disease, which has systemic inflammatory mediating effects, can prematurely

trigger this inflammatory signaling process for labor, thus resulting in increased incidence of

preterm births and other adverse pregnancy outcomes (Da Silva et al., 2017; Teshome &

Yitayeh, 2016). If the periodontal disease can be treated, the inflammatory signaling process can

then theoretically be minimized and thus reduce the incidence of adverse pregnancy outcomes.

Statement of the Problem

The aim of this literature review is to assess the effectiveness of such periodontal

treatment on pregnant women to reduce the incidence of adverse pregnancy outcomes. However,

limited compelling evidence for this has been identified. Most studies have found no significant

evidence between periodontal treatment and the reduction of adverse pregnancy outcomes (Da

Silva et al., 2017; Ilheozor-Ejiofor et al., 2017; Otomo-Corgel et al., 2012). Due to difficulties in
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study design and bias control on pregnant individuals, more attention has been drawn to provide

periodontal treatments to pre-pregnant individuals in reducing future adverse pregnancy

outcomes (Xiong, Buekens, Goldenberg, Offenbacher & Qian, 2011).

Overview of Research

Several randomized clinical trials (RCTs) and observational studies demonstrated no

significant effect of periodontal treatment in reducing adverse pregnancy outcomes in the

pregnant population. According to a meta-analysis performed by Schwendicke, Karimbux,

Allareddy, and Gluud (2015) on thirteen RCTs involving 6283 pregnant individuals, results

showed, “Periodontal treatment had no significant effect on preterm birth (odds ratio [95%

confidence interval] 0.79) or low birth weight (odds ratio [95% confidence interval] 0.69).”

Another meta-analysis published in The British Journal of Medicine reviewed eleven

RCTs involving 6558 participants regarding the effectiveness of periodontal treatment on

reducing preterm birth, low birthweight (<2500 g), and spontaneous abortion/stillbirth (Polyzos

et al., 2010). Among the 6558 participants, 3438 of them were allocated to the periodontal

treatment group and 3120 were allocated to the placebo group. In regard to the effect on preterm

birth, 364 preterm births were reported in the treatment group and 366 in the placebo group,

indicating that periodontal treatment had no effect on reducing preterm birth. In regard to the

effect of low birthweight, there were 214 cases reported in the treatment group and 329 in the

placebo group, which indicated no significant difference between the two groups. With the effect

on spontaneous/stillbirth, 56 incidences were reported in the treatment group and 63 incidences

reported in the placebo group, which again showed no significant difference between two

groups. Overall, periodontal treatments demonstrated little benefit to pregnant individuals in

reducing adverse pregnancy outcomes (Polyzos et al., 2010).

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These conclusions showing periodontal therapy on pregnant women with periodontal

disease having an insignificant effect are further supported in the systematic review with meta-

analysis by Da Silva et al. (2017). Following a comprehensive electronic search of five databases

yielding 565 references, four studies were found to be eligible for examination (Da Silva et al.,

2017). These four studies involving a total of 349 participants, all RCTs, investigated the various

inflammatory biomarkers associated with periodontal disease (Da Silva et al., 2017). Intra-

pregnancy nonsurgical periodontal therapy was found to be effective in reducing periodontal

pathogens and inflammatory response, however it did not significantly reduce inflammatory

biomarker levels in blood serum nor in umbilical cord blood (Da Silva et al., 2017). Authors thus

concluded that periodontal therapy in pregnant women was ineffective in reducing adverse

pregnancy outcomes (Da Silva et al., 2017). Da Silva et al. (2017) hypothesize that periodontal

disease during pregnancy triggers a cascade inflammatory response, which is intensified by

pregnancy and unresponsive to periodontal therapy.

Gaps in the Current Knowledge

Several large RCTs and systematic reviews failed to find that periodontal treatment

during pregnancy reduced the incidence of adverse pregnancy outcomes (Da Silva et al., 2017;

Ilheozor-Ejiofor et al., 2017; Polyzos et al., 2010; Schwendicke et al., 2015). Researchers

hypothesize that treating periodontal diseases during pregnancy may be too late to reduce the

inflammatory effects associated with the adverse pregnancy outcomes (Xiong et al., 2011). This

lack of understanding regarding the best timing of periodontal interventions represents a gap in

current knowledge that needs further examination.

The actual mechanism by which periodontal disease affects pregnancy and increases

adverse pregnancy outcomes is also still not well-understood (Daalderop et al., 2017; Teshome
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& Yitayeh, 2016). Current theories hypothesize that periodontal disease triggers systemic

inflammatory mediating effects, which then prematurely triggers the natural inflammatory

signaling labor process, resulting in adverse pregnancy outcomes (Da Silva et al., 2017). The

very fact that periodontal therapy on pregnant women has been found to be ineffective in

reducing adverse pregnancy outcomes, however, suggests that there is still more to be learned in

the relationship between pregnancy and periodontal disease. Further research is required to

deepen current understanding in order to better guide the development of therapies and

preventive strategies.

Limitations of Theories and Points of View

There are several challenges and limitations that have been identified in studying the

effectiveness of periodontal treatment in reducing adverse pregnancy outcomes. Although

providing root planing and scaling is considered safe in all trimesters, aggressive treatment may

cause bacteremia which can be harmful to both the mother and the fetus. As a result, the

conduction of RCTs on pregnant individuals may be ethically challenging. Risks of bias, risks of

random errors, and unclear effects of confounding factors are also considered major limitations

in terms of research design (Schwendicke et al., 2015).

Areas for Further Research

Several large RCTs failed to find that periodontal treatments during pregnancy can

reduce adverse pregnancy outcomes. Researchers hypothesize that during pregnancy with

periodontal disease, inflammatory processes are already well underway and is at too late of a

stage for treatment to be effective. Current findings suggest that pre-pregnancy may be a better

timing than during pregnancy based on the following several reasons (Xiong et al., 2011). First,

more intensive periodontal treatment can be performed on pre-pregnant individuals compared to

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pregnant individuals which may provide a better resolution to periodontal diseases. Second, pre-

pregnancy treatments may provide more definitive conclusions from a statistical point of view

due to less bias and confounding factors. And finally, periodontal treatment may trigger an

inflammatory cascade in the body through bacteremia, which may pose risk to the mother and

the fetus (Xiong et al., 2011). Treating periodontal diseases before pregnancy may be more

effective than during pregnancy, however, further study is required to confirm this hypothesis

(Xiong et al., 2011).

Areas of Controversy

There is some debate as to whether the relationship between periodontal disease and

adverse pregnancy outcomes is correlational or causal (Ilheozor-Ejiofor et al., 2017). Some

evidence from human and animal experimental studies exists which confer at least a partly causal

relationship (Ilheozor-Ejiofor et al., 2017). Recent findings also indicate that the oral

microbiome very closely resembles the placental microbiome, and that the presence of certain

bacteria in the oral microbiome can then appear in the placenta, amniotic cavity, fetal

membranes, and cord blood (Ilheozor-Ejiofor et al., 2017; Komine-Aizawa et al., 2019).

Nevertheless, researchers assert that this evidence is not yet strong enough to definitively assert a

causal relationship, and that further investigation is required to better understand the underlying

mechanism of action (Ilheozor-Ejiofor et al., 2017).

Conclusion

Current research shows periodontal treatment on pregnant women to be ineffective in

reducing adverse pregnancy outcomes (Da Silva et al., 2017; Ilheozor-Ejiofor et al., 2017;

Schwendicke et al., 2015; Xiong et al., 2011). Although periodontal treatment did improve

probing depth, clinical attachment level, bleeding on probing, and gingival index, indicating that
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treatment of the periodontal disease was effective, there was an insignificant effect on reducing

adverse pregnancy outcomes (Ilheozor-Ejiofor et al., 2017). Researchers hypothesize that once

the systemic inflammatory mediating effects are triggered by periodontal disease, treatment

during pregnancy is already too late to halt the inflammatory cascade effect (Da Silva et al.,

2017). Conjecture related to the current literature recommends beginning periodontal treatment

before pregnancy to reduce adverse pregnancy outcomes. (Da Silva et al., 2017).
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References

Da Silva, H. E. C., Stefani, C. M., de Santos Melo, N., de Lima, A. D. A., Rosing, C. K.

Porporatti, A. L., & de Luca Canto, G. (2017). Effect of intra-pregnancy nonsurgical

periodontal therapy on inflammatory biomarkers and adverse pregnancy outcomes: a

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doi:10.1186/s13643-017-0587-3.

Daalderop, L. A., Wieland, B. V., Tomsin, K., Reyes, L., Kramer, B.W., Vanterpool, S. F., &

Been J. V. (2018). Periodontal disease and pregnancy outcomes: overview of systematic

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PERIODONTAL DISEASE AND PREGNANCY OUTCOMES 10

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