healthcare
Review
Periodontitis in Pregnant Women: A Possible Link to Adverse
Pregnancy Outcomes
Andrea Butera 1, * , Carolina Maiorani 1, * , Annalaura Morandini 2 , Julia Trombini 2 , Manuela Simonini 2 ,
Chiara Ogliari 3 and Andrea Scribante 1,4
Citation: Butera, A.; Maiorani, C.;
Morandini, A.; Trombini, J.; Simonini,
M.; Ogliari, C.; Scribante, A.
Periodontitis in Pregnant Women: A
Possible Link to Adverse Pregnancy
Outcomes. Healthcare 2023, 11, 1372.
https://doi.org/10.3390/
healthcare11101372
Academic Editors: Massimo
Corsalini and Takahiro Kanno
Received: 30 January 2023
Revised: 6 May 2023
Accepted: 8 May 2023
Published: 10 May 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Healthcare 2023, 11, 1372. https://doi.org/10.3390/healthcare11101372
1 Unit of Dental Hygiene, Section of Dentistry, Department of Clinical, Surgical, Diagnostic and Pediatric
Sciences, University of Pavia, 27100 Pavia, Italy
2 Member Association: “Mamme & Igieniste”, 24125 Bergamo, Italy
3 Policlinico San Matteo, 27100 Pavia, Italy
4 Unit of Orthodontics and Pediatric Dentistry, Section of Dentistry, Department of Clinical, Surgical,
Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
* Correspondence: andrea.butera@unipv.it (A.B.); carolinamaiorani@outlook.it (C.M.)
Abstract: 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.
Keywords: periodontitis; pregnancy; oral health; adverse pregnancy outcomes
1. 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% de-
velop periodontitis, which can cause the destruction of periodontal tissue and the distribu-
tion 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].
https://www.mdpi.com/journal/healthcare
Healthcare 2023, 11, 1372 2 of 12

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 peri-
odontitis 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 pla-
centa, 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 pe-
riodontal 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 pro-
inflammatory effects on the gums mainly on vascular proliferation, on the production of
collagen, on epithelial keratinization and the fluid content of the connective tissue [17–19].
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.

2. Materials and Methods

2.1. 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].

2.2. Eligibility Criteria

Studies in accordance with the following inclusion criteria:
Type of studies: case-control, cross-sectional, cohort studies, and clinical trials pub-
lished 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.
Healthcare 2023, 11, 1372 3 of 12

2.3. 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.

2.4. Research
We performed the search using the following keywords: “pregnancy” AND “periodon-
tal disease”; “pregnancy” AND “periodontitis”; “periodontitis” AND “adverse outcomes”
IN “pregnancy”; “periodontitis” AND “low-birth weight” IN “pregnancy”; “periodontitis”
AND “pre-term birth” IN “pregnancy”; “periodontitis” AND “pre-eclampsia” IN “preg-
nancy”; “alterations” IN “oral health” AND “adverse outcomes” IN “pregnancy”. The
search has had a similar temporal range from 2003 to 2023.

2.5. 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
Healthcare 2022, 10, x FOR PEER REVIEW
between
4 of 13
periodontitis and adverse outcomes in pregnancy. Articles were analyzed and grouped to
assess the possible association between periodontitis and adverse outcomes in pregnancy.

Flowchart
Figure1.1.Flow
Figure chartof
of included
includedstudies:
studies:from
from593
593 articles,
articles, duplicates
duplicates were
were eliminated,
eliminated, and
and 281
281 articles
articles remained;
remained; from them,
from them, 16 articles
16 articles werewere analyzed.
analyzed.

2.6. 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
Healthcare 2023, 11, 1372 4 of 12

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 dupli-
cate 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, cross-
sectional, 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.

2.6. 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].

3. Results
In pregnant women with periodontal disease, some adverse events were found.
Among these, preterm birth and the low weight of the unborn child are among the most
frequent consequences (respectively 50% and 50% of articles); pre-eclampsia is also linked
to this condition (12.5% of articles); and perinatal mortality (12.5% of articles) [22–37]
Table 1.

Risk of Bias
Randomization, allocation concealment, blinding, outcome data, and outcome record-
ing 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.
Healthcare 2023, 11, 1372 5 of 12

Table 1. Articles examined.

Intervent/
Authors Type of Study (Problem-Population) Outcomes Association
Control
Clinical parameters: PI, BoP, PPD, Gingival recession,
Problem: the association between periodontal Microbiological samples.
The periodontal condition was not associated with
disease, and adverse pregnancy outcomes. Demographic and medical data: gestational age, race,
Santa Cruz et al., adverse pregnancy: preterm birth, low-weight-
Cohort study Population: 170 women were included (mean maternal weight before pregnancy, maternal height, No
2013 [26] birth, preterm and low-birth weight and preterm or
age 31.9, rangin 20–40) between the previous deliveries, previous PTB or LBW, maternal
low-birth weight.
8th to 26th wk of pregnancy diseases, metabolic or genetic alterations,
socio-economic, and educational status
The periodontal condition was associated with
delivery of a small-for-gestational-age infant.
Problem: the association between periodontal Clinical parameters: PPD, CAL, BoP. The small-for-gestational-age rate was higher
disease and delivery of a Demographic and medical data: gestational age, among women with moderate or severe periodontal
Boggess et al.,
Cohort study small-for-gestational-age infant (less than the maternal weight, previous deliveries less than 37th, disease, compared with those with health or mild Yes
2006 [27]
10th percentile for gestational age) deliveries less than 37th, pre-eclampsia, tobacco, alcohol, disease (13.8% versus 3.2% versus 6.5%, p < 0.001).
Population: 1017 women were included and drug consumption. Moderate or severe periodontal disease was
associated with a small-for-gestational-age infant, a
risk ratio of 2.3 (1.1 to 4.7).
Problem: the association between periodontal Clinical parameters: PPD, CAL, BoP. After adjustment for potential confounders using
disease, and low birth weight Demographic and medical data: haemoglobin level, rate multiple logistic regression analysis, significant
Saddki et al.,
Cohort study Population: 472 women were included (ranges of weight gain, history of pre-term birth, history of association was found between maternal Yes
2008 [28]
from 14 to 46 years old) in the second trimester abortion, history of low-birth weight, socio-economic, periodontitis and LBW (OR = 3.84;
of pregnancy and educational status 95% CI: 1.34–11.05).
The study shows a significant association between
periodontitis (but not with gingivitis) and adverse
Problem: the association between periodontal Clinical parameters: BoP, PPD, CAL, Gingival recession. pregnancy outcomes. Maternal periodontitis is
disease, and adverse pregnancy outcomes. Demographic and medical data: gestational age, associated with an increased risk of pre-eclampsia,
Kumar et al.,
Cohort study Population: 340 women were included (ranges socio-economic and educational status, pre-eclampsia, intrauterine growth restriction, preterm delivery Yes
2013 [29]
from 18 to 35 years old) at 14–20 weeks IUGR abruption placenta, type of labor, ode of delivery, and low birthweight infants with odds ratios
of pregnancy neonatal outcome, and birthweight (95% confidence interval) of 7.48 (2.72–22.42),
3.35 (1.20–9.55), 2.72 (1.30–5.68) and
3.03 (1.53–5.97), respectively.
Clinical parameters: PI, BoP, PPD, CAL.
Problem: the association between periodontal Demographic and medical data: gestational age,
Cross- Periodontal disease in pregnant women is
Marin et al., disease and low birth weight educational status, maternal height, previous live births,
sectional statistically associated with a reduction in the infant Yes
2005 [30] Population: 152 women were included (ranges previous aborts, previous preterm low birth weight,
study birth weight.
from 14 to 39 years old) gestational age, maternal gain in weight, infant birth
weight, tobacco, alcohol, and drug consumption.
Healthcare 2023, 11, 1372
Table 1. Cont.
Authors Type of Study (Problem-Population)
Problem: the association between periodontal
disease and adverse pregnancy outcomes
Srinivas et al.,
Cohort study (preterm birth, preeclampsia, fetal growth
2009 [31]
restriction, or perinatal death)
Population: 152 women were included
Problem: the association between periodontal
Agueda et al., disease and preterm birth, low birth weight,
Cohort study
2008 [32] and preterm low birth weight
Population: 1296 women were included
Problem: the association between periodontal
disease and preterm birth, low birth weight,
Offenbacher
Cohort study and preterm low birth weight
et al., 2006 [33]
Population: 1020 women were included before
26 weeks of pregnancy
Problem: the association between periodontal
Rakoto-Alson disease and preterm birth, and low birth weight
Cohort study
et al., 2010 [34] Population: 204 women were included
(25.6 years old) at 20–34 weeks of pregnancy
Problem: the association between periodontal
disease and preterm birth, low birth weight,
Moore et al.,
Cohort study and late miscarriage
2004 [35]
Population: 3738 women were included
(29.5 years old) at 12 weeks of pregnancy
Intervent/
Control
Clinical parameters: PPD, CAL.
Demographic and medical data: gestational age,
maternal height, previous live births, previous abortions,
previous preterm deliveries, pre-eclampsia
Clinical parameters: PI, BoP, PPD, CAL.
Demographic and medical data: socio-economic and
educational status, residence, ethnicity, body mass index,
previous preterm delivery, previous low birth weight,
previous miscarriage, pregnancy complications,
gestational diabetes, caesarian delivery, antibiotic intake,
systemic diseases, and tobacco consumption
Clinical parameters: PI, BoP, PPD, CAL.
Demographic and medical data: maternal age, maternal
weight, previous preterm delivery, medical insurance,
tobacco, alcohol, and drug consumption.
Clinical parameters: PI, PBI, PPD.
Demographic and medical data: socio-economic and
educational status, gestational age, birth weight, type of
delivery, and previous pregnancy.
Clinical parameters: PI, BS, PPD, CAL.
Demographic and medical data: socio-economic status,
ethnicity, previous preterm delivery, previous
miscarriage, medications in 1st trimester, antibiotics in
1st trimester, urinary tract infection in 1st trimester,
alcohol, and tobacco consumption.
6 of 12
Outcomes Association
There was no association between PD and the
composite outcome (adjusted odds ratio [AOR],
0.81; 95% confidence interval [CI], 0.58–1.15;
p = 0.24), preeclampsia (AOR, 0.71; 95% CI, No
0.37–1.36; p = 0.30), or preterm birth (AOR, 0.77;
95% CI, 0.49–1.21; p = 0.25) after adjusting for
relevant confounders.
The factors involved in many cases of adverse
pregnancy outcomes have still not been identified,
although systemic infections may play a role. This
study found a modest association between Yes
periodontitis and PB.
Further research is required to establish whether
periodontitis is a risk factor for PB and/or LBW.
Antepartum moderate-severe periodontal disease
was associated with an increased incidence of
spontaneous preterm births (15.2% versus 24.9%,
adjusted RR 2.0, 95% CI 1.2–3.2). Similarly, the
unadjusted rate of very preterm delivery was Yes
6.4% among women with periodontal disease
progression, significantly higher than the 1.8% rate
among women without disease progression
(adjusted RR 2.4, 95% CI 1.1–5.2).
Periodontitis (at least three sites from different teeth
with clinical AL > or = 4 mm) was significantly
associated with PB (p < 0.001), LBW (p < 0.001), and
PLBW (p < 0.01). The rates of periodontitis were
Yes
considerably higher in the PB (78.6%), LBW (77.3%),
and PLBW (77.8%) groups than in the full-term
(8.6%), normal weight (16.5%), and normal birth
(2.7%) groups.
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 No
appear to be a correlation between poorer
periodontal health and those that experienced a
late miscarriage.
Healthcare 2023, 11, 1372 7 of 12

Table 1. Cont.

Intervent/
Authors Type of Study (Problem-Population) Outcomes Association
Control
The transmission of some periodontal pathogens
Problem: the association between periodontal Clinical parameters: PI, BoP, PPD, CAL, GI, from the oral cavity of the mother may cause
disease and preterm birth, low birth weight, microbiological samples. adverse pregnancy outcomes. The results contribute
Ercan et al.,
Cohort study and late miscarriage Demographic and medical data: marital and to an understanding of the association between Yes
2013 [36]
Population: 50 women undergoing educational status, gestational age, and periodontal disease and PTLBW, but further studies
amniocentesis were included birth weight are required to better clarify the
possible relationship.
A relationship was observed between low-weight
Problem: the association between periodontal
birth and probing depth measurements, especially
Moreu et al., disease and preterm birth, and low birth weight Clinical parameters: PI, GI, PPD.
Cohort study the percentage of sites of >3 mm depth, which was Yes
2005 [37] Population: 96 women were included (ranges Demographic and medical data: unknown
statistically significant (p = 0.0038) even when
from 18 to 40 years old)
gestational age was controlled for.
As various measures of the severity of the
periodontal disease increased, both stillbirth and
Clinical parameters: PI, GI, PPD, CAL.
Problem: the association between periodontal neonatal death increased, accompanied by a
Mobeen et al., Demographic and medical data: ethnicity,
Cohort study disease, and birth outcomes. non-significant increase in early preterm birth. It is No
2008 [38] educational status, number of pregnancies,
Population: 1037 women were included unknown if treatment of periodontal disease either
previous miscarriage/abortion, previous stillbirth
before or during pregnancy would improve these
adverse pregnancy outcomes.
Clinical parameters: PPD, CAL, BoP.
Problem: the association between periodontal
Lopez et al., Demographic and medical data: systemic disease, This study found a modest association between
Cohort study disease, and adverse pregnancy outcomes. Yes
2008 [39] onset of prenatal care, previous PB, complications periodontitis and PB.
Population: 1404 women were included
of pregnancy, and type of delivery.
Clinical parameters: PI, GR, PPD, CAL, BoP.
Demographic and medical data:
socio-demographic variables (age, parity,
Problem: the association between periodontal race/color, years of schooling, marital status, PD was associated with a higher risk of PTB (RRadj.
disease, and adverse pregnancy outcomes. body mass index-BMI-estimated with the 3.47 95%CI 1.62–7.43), LBW (RRadj. 2.93 95%CI
Vogt et al.,
Cohort study Population: 327 women were included (ranges pregnancy weight, and any systemic diseases); 1.36–6.34) and PROM (RRadj. 2.48 95%CI 1.35–4.56), Yes
2010 [40]
from 18 to 42 years old) before 32 weeks habit variables (smoking and alcohol but not with SGA neonates (RR 2.38
of pregnant consumption); and gestacional variables (number 95%CI 0.93–6.10).
of prenatal visits, bacterial vaginosis, vaginal
delivery, and the newborn Apgar scores at the
first and fifth minute of life).
Problem: the association between periodontal Clinical parameters: PI, GI, CAL. Significant associations were found between
Turton et al., disease, and adverse pregnancy outcomes. Demographic and medical data: age, race, pregnancy outcomes and maternal periodontal
Cohort study Yes
2017 [41] Population: 443 women were included (ranges educational level, stage of pregnancy, and index scores (low birth weight and
from 18 to 42 years old) medical history. preterm delivery).
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Healthcare 2023, 11, 1372 9 of 12

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 [13–16].
The results of the articles analyzed in this review are in line with what is already
present in the literature [40–45].
Periodontal disease in pregnant women would appear to develop unexpected and adverse
results, such as preterm birth [25,28–30,32,35–37], low birth weight [24–26,30,32,33,36,37], 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 un-
derweight 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 [40,53–57].
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
Healthcare 2023, 11, 1372 10 of 12

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.

5. 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 posi-
tive association.
In light of this link, it is important to assess the oral health of pregnant women in order
to intercept any risky situations.

Author Contributions: Conceptualization, A.B. and A.S.; methodology, C.M.; software, A.S.; valida-
tion, A.B., C.M. and A.S.; formal analysis, A.S.; investigation, A.M., M.S. and C.O.; resources, A.B.,
C.O., M.S. and J.T. data curation, A.B.; writing—original draft preparation, C.M.; writing—review
and editing, A.B.; visualization, A.S.; supervision, A.S. and A.B.; project administration A.B.; fund-
ing acquisition, J.T., M.S. and A.M. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
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.

References
1. Nazir, M.; Al-Ansari, A.; Al-Khalifa, K.; Alhareky, M.; Gaffar, B.; Almas, K. Global Prevalence of Periodontal Disease and Lack of
Its Surveillance. Sci. World J. 2020, 2020, 2146160. [CrossRef] [PubMed]
2. World Health Organization. Oral Health; World Health Organization: Geneva, Switzerland, 2018.
3. Ameet, M.M.; Avneesh, H.T.; Babita, R.P.; Pramod, P.M. The relationship between periodontitis and systemic diseases—Hype or
hope? J. Clin. Diagn. Res. 2013, 7, 758–762. [CrossRef] [PubMed]
4. Chaudhry, A.; Kassim, N.K.; Zainuddin, S.L.A.; Taib, H.; Ibrahim, H.A.; Ahmad, B.; Hanafi, M.H.; Adnan, A.S. Potential Effects
of Non-Surgical Periodontal Therapy on Periodontal Parameters, Inflammatory Markers, and Kidney Function Indicators in
Chronic Kidney Disease Patients with Chronic Periodontitis. Biomedicines 2022, 10, 2752. [CrossRef] [PubMed]
5. Jepsen, S.; Caton, J.G.; Albandar, J.M.; Bissada, N.F.; Bouchard, P.; Cortellini, P.; Demirel, K.; de Sanctis, M.; Ercoli, C.; Fan, J.; et al.
Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup
3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Clin. Periodontol.
2018, 45, S219–S229. [CrossRef]
6. Benedetto, C.; Marozio, L.; Tavella, A.M.; Maulà, V.; Carmignani, D.; Curti, A. Response to activated protein C decreases
throughout pregnancy. Acta Obstet. Gynecol. Scand. 2002, 81, 1028–1032. [CrossRef]
Healthcare 2023, 11, 1372 11 of 12

7. Le, Q.A.; Akhter, R.; Coulton, K.M.; Vo, N.T.N.; Duong, L.T.Y.; Nong, H.V.; Yaacoub, A.; Condous, G.; Eberhard, J.; Nanan, R.
Periodontitis and Preeclampsia in Pregnancy: A Systematic Review and Meta-Analysis. Matern. Child Health J. 2022, 26, 2419–2443.
[CrossRef]
8. Nannan, M.; Xiaoping, L.; Ying, J. Periodontal disease in pregnancy and adverse pregnancy outcomes: Progress in related
mechanisms and management strategies. Front. Med. 2022, 9, 963956. [CrossRef]
9. Komine-Aizawa, S.; Aizawa, S.; Hayakawa, S. Periodontal diseases and adverse pregnancy outcomes. J. Obstet. Gynaecol. Res.
2019, 45, 5–12. [CrossRef]
10. Vesce, F.; Battisti, C.; Crudo, M. The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia.
Front. Immunol. 2022, 13, 861245. [CrossRef]
11. Waghmare, A.S.; Vhanmane, P.B.; Savitha, B.; Chawla, R.L.; Bagde, H.S. Bacteremia following scaling and root planing: A
clinico-microbiological study. J. Indian Soc. Periodontol. 2013, 17, 725–730. [CrossRef]
12. Starzyńska, A.; Wychowański, P.; Nowak, M.; Sobocki, B.K.; Jereczek-Fossa, B.A.; Słupecka-Ziemilska, M. Association between
Maternal Periodontitis and Development of Systematic Diseases in Offspring. Int. J. Mol. Sci. 2022, 23, 2473. [CrossRef]
13. Minervini, G.; Basili, M.; Franco, R.; Bollero, P.; Mancini, M.; Gozzo, L.; Romano, G.L.; Marrapodi, M.M.; Gorassini, F.; D’Amico, C.;
et al. Periodontal Disease and Pregnancy: Correlation with Underweight Birth. Eur. J. Dent. 2022. [CrossRef] [PubMed]
14. Loh, K.; Sivalingam, N. Urinary tract infections in pregnancy. Malays. Fam. Physician 2007, 2, 54–57. [PubMed]
15. Rapone, B.; Ferrara, E.; Montemurro, N.; Converti, I.; Loverro, M.; Loverro, M.T.; Gnoni, A.; Scacco, S.; Siculella, L.; Corsalini, M.;
et al. Oral Microbiome and Preterm Birth: Correlation or Coincidence? A Narrative Review. Open Access Maced. J. Med. Sci. 2020,
8, 123–132. [CrossRef]
16. Ren, H.; Du, M. Role of Maternal Periodontitis in Preterm Birth. Front. Immunol. 2017, 8, 139. [CrossRef]
17. Katz, J.; Chegini, N.; Shiverick, K.T.; Lamont, R.J. Localization of P. gingivalis in preterm delivery placenta. J. Dent. Res. 2009, 88,
575–578. [CrossRef]
18. Gallagher-Cobos, G.; Almerich-Torres, T.; Montiel-Company, J.M.; Iranzo-Cortés, J.E.; Bellot-Arcís, C.; Ortolá-Siscar, J.C.;
Almerich-Silla, J.M. Relationship between Periodontal Condition of the Pregnant Woman with Preterm Birth and Low Birth
Weight. J. Clin. Med. 2022, 11, 6857. [CrossRef]
19. Lin, W.; Jiang, W.; Hu, X.; Gao, L.; Ai, D.; Pan, H.; Niu, C.; Yuan, K.; Zhou, X.; Xu, C.; et al. Ecological Shifts of Supragingival
Microbiota in Association with Pregnancy. Front. Cell. Infect. Microbiol. 2018, 8, 24. [CrossRef]
20. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gøtzsche, P.C.; Ioannidis, J.P.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher, D.
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions:
Explanation and elaboration. BMJ 2009, 339, b2700. [CrossRef]
21. Ricciardi, W.; La Torre, G. Health Technology Assessment. Principi, Dimensioni e Strumenti; Seed: Torino, Italy, 2010.
22. Bianchi, S.; Macchiarelli, G.; Micara, G.; Aragona, C.; Maione, M.; Nottola, S.A. Ultrastructural and morphometric evaluation of
aged cumulus-oocyte-complexes. Ital. J. Anat. Embriol. 2013, 118, 28.
23. Franzago, M.; Fraticelli, F.; Stuppia, L.; Vitacolonna, E. Nutrigenetics, epigenetics and gestational diabetes: Consequences in
mother and child. Epigenetics 2019, 14, 215–235. [CrossRef] [PubMed]
24. Sant’Ana, A.C.; Campos, M.R.; Passanezi, S.C.; Rezende, M.L.; Greghi, S.L.; Passanezi, E. Periodontal treatment during pregnancy
decreases the rate of adverse pregnancy outcome: A controlled clinical trial. J. Appl. Oral Sci. 2011, 19, 130–136. [CrossRef]
[PubMed]
25. Yenen, Z.; Ataçağ, T. Oral care in pregnancy. J. Turk. Ger. Gynecol. Assoc. 2019, 20, 264–268. [CrossRef] [PubMed]
26. Santa Cruz, I.; Herrera, D.; Martin, C.; Herrero, A.; Sanz, M. Association between periodontal status and pre-term and/or
low-birth weight in Spain: Clinical and microbiological parameters. J. Periodontal. Res. 2013, 48, 443–451. [CrossRef]
27. Boggess, K.A.; Beck, J.D.; Murtha, A.P.; Moss, K.; Offenbacher, S. Maternal periodontal disease in early pregnancy and risk for a
small-for-gestational-age infant. Am. J. Obstet. Gynecol. 2006, 194, 1316–1322. [CrossRef]
28. Saddki, N.; Bachok, N.; Hussain, N.H.; Zainudin, S.L.; Sosroseno, W. The association between maternal periodontitis and low
birth weight infants among Malay women. Community Dent. Oral Epidemiol. 2008, 36, 296–304. [CrossRef]
29. Kumar, A.; Basra, M.; Begum, N.; Rani, V.; Prasad, S.; Lamba, A.K.; Verma, M.; Agarwal, S.; Sharma, S. Association of maternal
periodontal health with adverse pregnancy outcome. J. Obstet. Gynaecol. Res. 2013, 39, 40–45. [CrossRef]
30. Marin, C.; Segura-Egea, J.J.; Martínez-Sahuquillo, A.; Bullón, P. Correlation between infant birth weight and mother’s periodontal
status. J. Clin. Periodontol. 2005, 32, 299–304. [CrossRef]
31. Srinivas, S.K.; Sammel, M.D.; Stamilio, D.M.; Clothier, B.; Jeffcoat, M.K.; Parry, S.; Macones, G.A.; Elovitz, M.A.; Metlay, J.
Periodontal disease and adverse pregnancy outcomes: Is there an association? Am. J. Obstet. Gynecol. 2009, 200, e1–e8. [CrossRef]
32. Agueda, A.; Ramón, J.M.; Manau, C.; Guerrero, A.; Echeverría, J.J. Periodontal disease as a risk factor for adverse pregnancy
outcomes: A prospective cohort study. J. Clin. Periodontol. 2008, 35, 16–22. [CrossRef]
33. Offenbacher, S.; Boggess, K.A.; Murtha, A.P.; Jared, H.L.; Lieff, S.; McKaig, R.G.; Mauriello, S.M.; Moss, K.L.; Beck, J.D. Progressive
periodontal disease and risk of very preterm delivery. Obstet. Gynecol. 2006, 107, 29–36. [CrossRef]
34. Rakoto-Alson, S.; Tenenbaum, H.; Davideau, J.L. Periodontal diseases, preterm births, and low birth weight: Findings from a
homogeneous cohort of women in Madagascar. J. Periodontol. 2010, 81, 205–213. [CrossRef] [PubMed]
35. Moore, S.; Ide, M.; Coward, P.Y.; Randhawa, M.; Borkowska, E.; Baylis, R.; Wilson, R.F. A prospective study to investigate the
relationship between periodontal disease and adverse pregnancy outcome. Br. Dent. J. 2004, 197, 251–258. [CrossRef] [PubMed]
Healthcare 2023, 11, 1372 12 of 12

36. Ercan, E.; Eratalay, K.; Deren, O.; Gur, D.; Ozyuncu, O.; Altun, B.; Kanli, C.; Ozdemir, P.; Akincibay, H. Evaluation of periodontal
pathogens in amniotic fluid and the role of periodontal disease in pre-term birth and low birth weight. Acta Odontol. Scand. 2013,
71, 553–559. [CrossRef] [PubMed]
37. Moreu, G.; Téllez, L.; González-Jaranay, M. Relationship between maternal periodontal disease and low-birth-weight pre-term
infants. J. Clin. Periodontol. 2005, 32, 622–627. [CrossRef] [PubMed]
38. Mobeen, N.; Jehan, I.; Banday, N.; Moore, J.; McClure, E.M.; Pasha, O.; Wright, L.L.; Goldenberg, R.L. Periodontal disease and
adverse birth outcomes: A study from Pakistan. Am. J. Obstet. Gynecol. 2008, 198, 514.e1–514.e8. [CrossRef]
39. López, R. Periodontal disease and adverse pregnancy outcomes. Evid. Based Dent. 2008, 9, 48. [CrossRef]
40. Vogt, M.; Sallum, A.W.; Cecatti, J.G.; Morais, S.S. Periodontal disease and some adverse perinatal outcomes in a cohort of low risk
pregnant women. Reprod. Health 2010, 7, 29. [CrossRef]
41. Turton, M.; Africa, C.W.J. Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes. Int. Dent.
J. 2017, 67, 148–156. [CrossRef]
42. Butera, A.; Maiorani, C.; Morandini, A.; Simonini, M.; Colnaghi, A.; Morittu, S.; Barbieri, S.; Ricci, M.; Guerrisi, G.; Piloni, D.;
et al. Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review.
Microorganisms 2021, 9, 2385. [CrossRef]
43. Wu, M.; Chen, S.W.; Jiang, S.Y. Relationship between gingival inflammation and pregnancy. Mediat. Inflamm. 2015, 2015, 623427.
[CrossRef] [PubMed]
44. Bobetsis, Y.A.; Graziani, F.; Gürsoy, M.; Madianos, P.N. Periodontal disease and adverse pregnancy outcomes. Periodontol. 2000
2020, 83, 154–174. [CrossRef] [PubMed]
45. Xiong, X.; Buekens, P.; Fraser, W.D.; Beck, J.; Offenbacher, S. Periodontal disease and adverse pregnancy outcomes: A systematic
review. BJOG 2006, 113, 135–143. [CrossRef] [PubMed]
46. Shub, A.; Swain, J.R.; Newnham, J.P. Periodontal disease and adverse pregnancy outcomes. J. Matern. Fetal Neonatal Med. 2006,
19, 521–528. [CrossRef] [PubMed]
47. Sacco, G.; Carmagnola, D.; Abati, S.; Luglio, P.F.; Ottolenghi, L.; Villa, A.; Maida, C.; Campus, G. Periodontal disease and preterm
birth relationship: A review of the literature. Minerva Stomatol. 2008, 57, 233–250.
48. Manrique-Corredor, E.J.; Orozco-Beltran, D.; Lopez-Pineda, A.; Quesada, J.A.; Gil-Guillen, V.F.; Carratala-Munuera, C. Maternal
periodontitis and preterm birth: Systematic review and meta-analysis. Community Dent. Oral Epidemiol. 2019, 47, 243–251.
[CrossRef]
49. Chambrone, L.; Guglielmetti, M.R.; Pannuti, C.M.; Chambrone, L.A. Evidence grade associating periodontitis to preterm birth
and/or low birth weight: I. A systematic review of prospective cohort studies. J. Clin. Periodontol. 2011, 38, 795–808. [CrossRef]
50. Iheozor-Ejiofor, Z.; Middleton, P.; Esposito, M.; Glenny, A.M. Treating periodontal disease for preventing adverse birth outcomes
in pregnant women. Cochrane Database Syst. Rev. 2017, 6, CD005297. [CrossRef]
51. Wimmer, G.; Pihlstrom, B.L. A critical assessment of adverse pregnancy outcome and periodontal disease. J. Clin. Periodontol.
2008, 35, 380–397. [CrossRef]
52. Parihar, A.S.; Katoch, V.; Rajguru, S.A.; Rajpoot, N.; Singh, P.; Wakhle, S. Periodontal Disease: A Possible Risk-Factor for Adverse
Pregnancy Outcome. J. Int. Oral Health 2015, 7, 137–142.
53. Da Silva, H.E.C.; Stefani, C.M.; de Santos Melo, N.; de Almeida de Lima, A.; Rösing, C.K.; Porporatti, A.L.; Canto, G.L. Effect of
intra-pregnancy nonsurgical periodontal therapy on inflammatory biomarkers and adverse pregnancy outcomes: A systematic
review with meta-analysis. Syst. Rev. 2017, 6, 197. [CrossRef] [PubMed]
54. Caneiro-Queija, L.; López-Carral, J.; Martin-Lancharro, P.; Limeres-Posse, J.; Diz-Dios, P.; Blanco-Carrion, J. Non-Surgical
Treatment of Periodontal Disease in a Pregnant Caucasian Women Population: Adverse Pregnancy Outcomes of a Randomized
Clinical Trial. Int. J. Environ. Res. Public Health 2019, 16, 3638. [CrossRef]
55. Tarannum, F.; Faizuddin, M. Effect of periodontal therapy on pregnancy outcome in women affected by periodontitis. J. Periodontol.
2007, 78, 2095–2103. [CrossRef] [PubMed]
56. Macek, M.D. Non-surgical periodontal therapy may reduce adverse pregnancy outcomes. J. Evid. Based Dent. Pract. 2008, 8,
236–237. [CrossRef]
57. Michalowicz, B.S.; Hodges, J.S.; DiAngelis, A.J.; Lupo, V.R.; Novak, M.J.; Ferguson, J.E.; Buchanan, W.; Bofill, J.; Papapanou, P.N.;
Mitchell, D.A.; et al. Treatment of periodontal disease and the risk of preterm birth. N. Engl. J. Med. 2006, 355, 1885–1894.
[CrossRef] [PubMed]
58. Butera, A.; Gallo, S.; Pascadopoli, M.; Maiorani, C.; Milone, A.; Alovisi, M.; Scribante, A. Paraprobiotics in Non-Surgical
Periodontal Therapy: Clinical and Microbiological Aspects in a 6-Month Follow-Up Domiciliary Protocol for Oral Hygiene.
Microorganisms 2022, 10, 337. [CrossRef]
59. Butera, A.; Gallo, S.; Maiorani, C.; Molino, D.; Chiesa, A.; Preda, C.; Esposito, F.; Scribante, A. Probiotic Alternative to
Chlorhexidine in Periodontal Therapy: Evaluation of Clinical and Microbiological Parameters. Microorganisms 2020, 9, 69.
[CrossRef]

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