Periodontitis in Pregnant Women: A Possible Link to Adverse Pregnancy Outcomes

Background: Periodontitis develops in 11% of pregnant women, and it is independently linked to severe complications during pregnancy such as preterm birth, low birth weight, and gestational diabetes. Methods: A literature search (Pubmed/MEDLINE, and Scopus) from 2003 to 2023 was conducted to analyze studies focused on periodontitis and adverse pregnancy outcomes. Results: 16 articles have been included. Most of the studies showed adverse outcomes, like preterm birth and the low weight of the unborn child, are among the most frequent consequences (respectively 62.5% and 68.7% of articles); pre-eclampsia is also linked to this condition (12.5% of articles); and perinatal mortality (12.5% of articles). Conclusions: Periodontal disease appears to be associated with adverse events in pregnancy due to the transport of biofilm bacteria into the bloodstream and into placental tissue; what would cause adverse events is the body’s immune response to infection.


Introduction
Periodontal disease is a chronic and irreversible pathology of the supporting tissues of the tooth that affects between 20% and 50% of the world population; the distribution in adults differs significantly in low (28.7%), lower-middle (10%), upper-middle (42.5%), and high-income countries (43.7%) [1,2].
Periodontal disease is one of the risk factors for other systemic diseases, such as pneumonia, diabetes mellitus, arteriosclerosis, and coronary heart disease [3]. Numerous studies show that periodontitis sufferers have higher circulating neutrophil granulocyte values and higher systemic inflammatory parameters (such as reactive protein C) compared to healthy people. In particular, the latter parameter is an excellent predictor for the development of ischemic diseases, atherosclerosis, and the imperfect metabolic control of diabetes [4,5]. In addition, it seems to be one of the risk factors for complications during pregnancy [6]. About 14.2 to 54.8% of pregnant women suffer from periodontal disease, and 11% develop periodontitis, which can cause the destruction of periodontal tissue and the distribution of bacteria and other inflammatory mediators [7].
Periodontitis is independently linked to severe complications during pregnancy, such as preterm birth, low birth weight, and gestational diabetes. [7,8]: the reason could be linked to the translocation of pathogenic bacteria to the fetus-placenta unit or the effect of inflammatory mediators such as interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), or prostaglandin E2 (PGE2) on the fetus-placenta unit [9,10].

Bacteremia is the transient or continuous presence of viable bacteria in the bloodstream.
In people with periodontal disease, subgingival microflora is contracted with the damaged inner epithelium of periodontal pockets, which allows bacteria to enter the bloodstream [11]. This would seem to be the mechanism for the association between periodontal disease and adverse events during pregnancy [12].
Two experimental hypotheses support the correlation between periodontitis and pregnancy-related negative events. The first is based on the possibility that women with periodontitis are subject to frequent bacteremia. Bacteria activate a cascade of inflammatory processes at the level of the placenta and the fetus, with the risk of pre-term delivery and/or birth of underweight children [13]. The second hypothesis is based on the fact that periodontitis can cause a generalized increase in cytokines, substances with pro-inflammatory activity that cause alterations to the placenta and the fetus [14]. The periodontal bacteria (in particular Porphyromonas Gingivalis) can in fact enter the bloodstream, reach the placenta, and generate toxins inside the amniotic fluid that result in inflammation, potentially causing premature birth [15]. In addition to premature birth, other related adverse events include reduced body weight gain of the unborn child and the development of premature uterine contractions, with the risk of pre-term delivery and/or the birth of underweight children [16].
The onset of periodontal disease appears to be linked to a change in the composition of sub-bacterial gingival flora with an increase in the relative amount of pathogenic periodontal anaerobic bacteria associated with increased circulating levels of estrogen and progesterone and these would be a factor promoting the growth of pathogenic periodontal anaerobes; alteration of the local immune response with increased susceptibility to gum inflammation and depression of the chemotactic and phagocytic response of neutrophil granulocytes and other cellular-immune functions mediated, which contributes to the stimulation of the production of prostaglandins induced by varicose veins; to the proinflammatory effects on the gums mainly on vascular proliferation, on the production of collagen, on epithelial keratinization and the fluid content of the connective tissue [17][18][19].
On the basis of these considerations, a review has been carried out to investigate the correlation between periodontal disease and adverse events in pregnancy, according to the most recent literature.

Focused Question
The present literature review aims to investigate the correlation between periodontal disease and adverse events in pregnancy, according to the most recent literature [20].

Eligibility Criteria
Studies in accordance with the following inclusion criteria: Type of studies: case-control, cross-sectional, cohort studies, and clinical trials published in English.
Type of participants: pregnant women with periodontal disease. Type of interventions: case-control, cross-sectional, cohort studies, clinical trials, and reviews that have evaluated the association between periodontal disease and adverse events in pregnancy.
Outcome type: adverse events in pregnancy.
In the second phase, were included studies that met all the inclusion criteria, that is to say, the analysis of the selected studies according to the exclusion criteria: (I) studies where the authors had not reported outcome; (II) in vitro or animal clinical studies; (III) studies carried out without the approval of the Ethics Committee; (IV) reviews and metanalysis.

Search Strategy
The review is based on the research of studies identified through bibliographic research in electronic databases and by examining the bibliographies of articles on Pubmed/MEDLINE, and Scopus. Initially, all study abstracts were taken into consideration.

Screening and Selection of Articles
The search produced 593 titles matching the search keywords. The following flowchart shows the selection criteria used to select the final 16 articles that were used for the review analysis. Figure 1. The results were filtered for relevance to the association between periodontitis and adverse outcomes in pregnancy. Articles were analyzed and grouped to assess the possible association between periodontitis and adverse outcomes in pregnancy.

Risk of Bias and Results
From the analysis of the articles, a reviewer was concerned to highlight the results obtained from reading the selected articles. Articles have been included in a table on the basis of the adverse event found and its association with periodontal disease or not. Then All articles that did not meet the eligibility criteria were rejected. In the first phase, all the abstracts have been included, and successively, all the duplicate articles from the searches carried out by three auditors independently are excluded.
At a later stage, abstracts were analyzed by the same authors for consistency with the eligibility criteria; therefore, at this stage, all articles that were not case-control, crosssectional, cohort studies, clinical trials, or any articles that did aim to evaluate periodontal disease and its effects on adverse events in pregnancy are excluded. Ultimately, the remaining articles were read in full. A further skimming was therefore carried out: some selected articles were not available in English, and some (not having mentioned the objective in the abstract) were excluded because they were not focused on the association between periodontal disease and adverse events in pregnancy. The last phase, that of reading and ulterior exclusion, has been carried out by two other reviewers not involved in the first two phases.

Risk of Bias and Results
From the analysis of the articles, a reviewer was concerned to highlight the results obtained from reading the selected articles. Articles have been included in a table on the basis of the adverse event found and its association with periodontal disease or not. Then a final reviewer evaluated the risk of bias of each study involved; the quality of the studies has been assessed on the basis of the information provided [21].

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias. Regression analysis indicated that there were no significant relationships between the severity of periodontal disease and either preterm birth (PTB) or low birth weight (LBW). In contrast, there did appear to be a correlation between poorer periodontal health and those that experienced a late miscarriage.   [26] symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Boggess et al., 2006 [27] Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Saddki et al., 2008 [28] Risk of Bias Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Kumar et al., 2013 [29] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Marin et al., 2005 [30] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Srinivas et al., 2009 [31] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Agueda et al., 2008 [32] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a Offenbacher et al., 2006 [33] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f bacterial plaque. This can lead to an increase in gingival volume, often bleeding, or even the onset of periodontal disease, which usually regres

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen bacterial plaque. This can lead to an increase in gingiv bleeding, or even the onset of periodontal disease, whic

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including bacterial plaque. This can lead to an increase in gingival volume, often associated with bleeding, or even the onset of periodontal disease, which usually regresses at the end of

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor bacterial plaque. This can lead to an increase in gingival volume, often asso bleeding, or even the onset of periodontal disease, which usually regresses a

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm flow.
High levels of estrogen can cause gingival hypersensitivity to local f Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc flow.
High levels of estrogen can cause gingival hypersen

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood flow.
High levels of estrogen can cause gingival hypersensitivity to local factors, including Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone flow.
High levels of estrogen can cause gingival hypersensitivity to local factor Moore et al., 2004 [35] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems durin third trimesters of pregnancy due to the change and increase in sex horm

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Discussion
Several studies have shown the onset of periodonta third trimesters of pregnancy due to the change and inc

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the second and third trimesters of pregnancy due to the change and increase in sex hormones and blood

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Discussion
Several studies have shown the onset of periodontal problems during the third trimesters of pregnancy due to the change and increase in sex hormone Ercan et al., 2013 [36] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Discussion
Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Discussion
Healthcare 2023, 11, x FOR PEER REVIEW

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.  Moreu et al., 2005 [37] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias. Table 2. Risk of bias in the articles examined; green symbol indicates a low risk of err yellow symbol indicates moderate risk of bias. Mobeen et al., 2008 [38] Healthcare 2023, 11, x FOR PEER REVIEW 8 of 13

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias. Table 2. Risk of bias in the articles examined; green symbol indicates a low risk of err yellow symbol indicates moderate risk of bias.

Articles
Adequate Sequence recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome dat recording were evaluated; a color was assigned according to the type o symbol was assigned where the information was complete according considered (low risk of bias); the yellow symbol was assigned where the missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this r moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding recording were evaluated; a color was assigned accord symbol was assigned where the information was com considered (low risk of bias); the yellow symbol was ass missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome recording were evaluated; a color was assigned according to the type of risk. The green symbol was assigned where the information was complete according to the variable considered (low risk of bias); the yellow symbol was assigned where the information was missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review presents a moderate risk of bias.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, an recording were evaluated; a color was assigned according to the type of risk symbol was assigned where the information was complete according to considered (low risk of bias); the yellow symbol was assigned where the infor missing or not clear (moderate risk of bias) [21]. Table 2 shows the risk of bias in the main articles examined; this review moderate risk of bias. Table 2. Risk of bias in the articles examined; green symbol indicates a low risk of err yellow symbol indicates moderate risk of bias.
In this tissue, the slow venous circulation and the invasive ability of microorganisms promote possible penetration into the fetus and into the amniotic fluid. Here, an immune response is triggered that could lead to the release of pro-inflammatory cytokines. If the body is able to fight the infection, there will be no consequence; otherwise, membrane rupture and premature birth may occur. These inflammatory compounds can negatively regulate the expression of genes essential for the growth of the fetus, causing a low birth weight, and generating structural damage to the placental circulation that increases the blood pressure of the mother [13][14][15][16].
The results of the articles analyzed in this review are in line with what is already present in the literature [40][41][42][43][44][45].
Periodontal disease in pregnant women would appear to develop unexpected and adverse results, such as preterm birth [25,[28][29][30]32,[35][36][37], low birth weight [24][25][26]30,32,33,36,37], and pre-eclampsia [23]. The objective of the review was to research and highlight possible adverse events in pregnancy in women with periodontal disease. Preterm birth and low birth weight appear to be the most common events, at least according to this analysis. Preterm birth was found in 50% of the studies analysed, a result similar to that obtained by Manrique-Corredor et al. in a systematic and meta-analytical review, the authors evaluated 31 studies, and 60% of them saw an association between periodontal disease and preterm birth; Chambrone et al. also showed a positive association with preterm birth and low birth weight in 81.8% of the studies involved in the review [46,47].
The analyzed studies support these results: 50% of the studies showed an association between periodontal disease and preterm birth, and 50% had an association with low birth weight.
Periodontal diseases are associated with an increased risk of premature and/or underweight births [48]. Today, it is known that some acute inflammatory processes in the mother, even if localized far from the genitourinary tract, can play a secondary role in the appearance of pathological alterations in pregnancy [49]. Other studies, however, have not shown a clear association between periodontal disease and any adverse events [22,27,31,34].
However, although these events have often been associated, there is no clear evidence or correlation between periodontal disease and pregnancy. A predisposition can be affirmed due to the migration of bacteria present at the periodontal pockets through the bloodstream to the placenta and the fetus, which could cause muscular contractions of the uterus, cervical dilation, and premature rupture of the amniotic sac [50]. Numerous clinical studies would be needed to establish a positive association between periodontal disease and adverse events during pregnancy.
So, based on these considerations, pregnant women and women planning a pregnancy should be aware that there may be a link between their periodontal condition, general health, and possible complications of pregnancy. For this reason, periodontal treatment may be necessary, which in this case should be performed before conception; however, it could also be performed during pregnancy [51]. In addition, as negative pregnancy outcomes and periodontitis have in common some important risk factors (e.g., smoking), pregnant women should be aware of the importance of healthy habits and lifestyles [52]. It has been shown that periodontal treatment carried out in pregnancy is safe and helps to reduce the level of gingival inflammation, allowing oral health to be maintained in this delicate period. In addition, current scientific knowledge suggests that periodontal therapy before conception may reduce the risk of the related adverse effects mentioned above [8,51].
Unfortunately, very often treatments are carried out late; the ideal would be to start before pregnancy to obtain a positive outcome on the clinical result of gestation. In fact, non-surgical periodontal treatment in pregnant women would seem not to achieve an improvement of the unfavorable, probably also because the available studies are very heterogeneous. The result is mixed opinions [40,[53][54][55][56][57].
However, action should be taken against dysbiosis caused by periodontal disease, perhaps by supplementing the use of probiotics in pregnant women, which seem to have positive effects on gum bleeding indices, together with the correct oral hygiene methods for the removal of bacterial biofilm [38,58,59].
The studies involved in this review present some limitations. Although most of them have validated the association between periodontal disease and some adverse events in pregnancy, this statement cannot be generalized. The results of the individual studies are influenced by some variables such as ethnicity, socio-economic status, age, the period of pregnancy, and systemic pathologies related to the mother. It would be useful to standardize the sample taken from the studies, trying to eliminate any variable that could influence the results.
Therefore, as the studies evaluated different variables, a direct comparison is not possible. Additionally, it has been noticed that there is a lack of homogeneity among the measurements of the variables in the studies included in this review. Therefore, future clinical studies with the evaluation of the same variables are needed in order to allow a more complete review, which also requires a meta-analysis.

Conclusions
Periodontal disease appears to be associated with adverse events in pregnancy due to the transport of biofilm bacteria into the bloodstream and into placental tissue; what would cause adverse events is the body's immune response to infection.
Preterm birth and low birth weight seem to be associated with periodontal disease in pregnant women. Although numerous studies are needed to define a significant positive association.
In light of this link, it is important to assess the oral health of pregnant women in order to intercept any risky situations.

Institutional Review Board Statement:
The study was conducted in accordance with the Declaration of Helsinki.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.

Conflicts of Interest:
The authors declare no conflict of interest.