Keywords
Periodontal-systemic disease interactions - pregnancy - pregnancy complications
Introduction
Periodontal diseases (PDs) are common chronic infections affecting tooth-supporting
tissues, with an incidence of 46% of the adult population in the United States.[[1]] It is probably caused by the disequilibrium between infectious pathogens and host-immune
response.[[2]] PDs are considered a potential risk factor for some systemic inflammatory conditions
such as cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, and respiratory
diseases.[[3]],[[4]] Moreover, it has been found to be related with adverse pregnancy outcomes, and
the main accused mechanism is inflammation for such adverse events.[[5]]
Previous studies have demonstrated that pregnant women with PD have a higher incidence
of low-birth weight, preterm birth, and preeclampsia.[[6]],[[7]] The effect of periodontal inflammation on adverse pregnancy outcomes has been theorized
with two different pathways: direct and indirect. First, periodontal bacteria and/or
their pathogenic products may directly spread to the fetal-placental unit hematologically
or along the genitourinary tract from the oral cavity. Indirectly, local inflammatory
mediators such as prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF)-α,
which are produced in response to periodontal pathogens may enter the bloodstream,
arrive the fetal-placental unit, and amplify the accumulation of this mediators. Similarly,
they enter the liver and increase acute-phase protein reaction such as C-reactive
protein (CRP) synthesis, and by this way, inflammation in the fetal-placental unit
may become more severe.[[2]]
Furthermore, it has been considered that pregnancy could increase the severity of
PDs due to hormonal changes. Increasing of sex steroid hormone levels during pregnancy
cause vascular dilatation that leads swelling, bleeding, and redness of the gingiva.
Tilakaratne et al. reported that gingival index (GI) scores were significantly higher in pregnant women
than nonpregnant women even if there were no statistically significant differences
between the plaque index (PI) scores of the groups.[[8]] Furthermore, many studies revealed that probing pocket depth (PPD) scores and bleeding
on probing measurements are significantly elevated during pregnancy.[[9]],[[10]]
Hyperemesis gravidarum (HG), which is a condition of severe nausea and vomiting during
pregnancy, can lead to electrolyte and fluid imbalance, weight loss, nutrition deficiency,
and ketonuria.[[11]],[[12]] Moreover, it has some catastrophic consequences such as central pontine myelinolysis,
Wernicke's encephalopathy, vasospasm of cerebral arteries, rabdomyolysis, coagulopathy,
and maternal and fetal death.[[13]],[[14]],[[15]] While HG generally occurs between the 8th and 10th gestational weeks of pregnancy,
in 10% of all HG cases, it persists until the birth.[[12]] Previous HG history, multiple and molar pregnancy, gestational trophoblastic neoplasia,
hyperthyroidism, gastrointestinal disorders, female offspring, and psychiatric disorders
are the main risk factors for HG.[[16]] Increased human chorionic gonadotropin (β-hcg), thyroxine, prolactin, estrogen
and progesterone levels, gastrointestinal dysmotility, decreased lower esophageal
sphincter pressure, Helicobacter pylori infection, immunologic factors, disturbances in hypothalamic-pituitary-adrenal axis,
and psychological factors are well-known proposed mechanisms.[[17]],[[18]] Although the exact pathophysiological mechanisms have not been fully elucidated,
inflammation is claimed to play a crucial role in its etiopathogenesis.[[12]],[[19]]
Recent studies have demonstrated the increased levels of inflammatory markers such
as interleukin (IL)-6, TNF-α, paraoxonase-1, and CRP in HG patients, which may be
a sign to recognize HG as an inflammatory condition.[[10]],[[18]] Another finding from the previous studies that led to this thought is related to
the role of steroids in the treatment of HG. Steroids, which reduce the IL levels
and provide dramatic responses even with a brief course, support the role of inflammation
in HG.[[19]]
The main hypothesis of this study was that periodontal inflammation is more common
in HG cases, and periodontal parameters are higher in a patient with HG than healthy
pregnant women. In this study, we aimed for the first time to demonstrate the relationship
between PD and HG.
Materials and Methods
This study was conducted on pregnant women at the obstetrics and gynecology department
between the dates of March 2019 and August 2019. The present study was granted ethical
approval by the Ethical Committee (Protocol Number: 108400-604.01.01-E.12586) and
conducted in accordance with the guidelines of the Helsinki Declaration of 1975, as
revised in 2000. All the participants were enlightened about the purpose and design
of the study and signed written informed consent forms before the study. A total of
60 volunteer pregnant women ranging from the age group of 18 to 40 years participated
in this study. Patients were allocated to two groups: the first group was constituted
of participants with HG and named the HG group, and the second group was constituted
of healthy pregnant women and named the control group.
Seventeen patients were excluded from this study according to the following criteria:
antibiotic treatment within the past 6 months, any periodontal therapy and mouth rinse
use within the previous 3 months, systemic diseases and chronic infections other than
periodontitis, smokers, and presence of <20 teeth on oral examination. HG was diagnosed
if the followings were present, at least one-positive ketonuria, >5% weight loss,
and severe vomiting which is more than two times a day.
All clinical examination was performed within the 8th–10th week of pregnancy, periodontology
department. Periodontal status was evaluated by PI,[[20]] GI,[[21]] PPD, and bleeding on probing index (BOPI).[[22]] All the measurements were recorded by the same, blinded and experienced researcher
at 6 points of each tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual,
and distolingual) by using Williams marked probe. The patients were classified as
gingivitis (patients who had no periodontal pocket but had bleeding on more than 10%
of the surfaces after light mechanical stimulation) and periodontitis (patients who
had ≥4 mm pocket depth on two or more surfaces) based on the collected data.[[23]]
The prevalence of PD in pregnancy was reported between 30% and 100%. We expected the
rate of PD in HG group (90%). Thus, the post hoc sample size and power calculation test revealed that >27 patients in each group would
meet the statistical power with the following assumptions: 5% of α level, 0.8 of anticipated
effect size, and 80% of statistical power level. Descriptive statistics are presented
with frequency, percentage, mean, standard deviation, median, minimum, and maximum
values. Pearson Chi-square test was used to analyze the categorical data. The normality
assumption was evaluated by the Shapiro–Wilk test. In the analysis of the difference
between the numerical data of the two groups, independent samples t-test was used in cases where the data corresponded to the normal distribution. Mann–Whitney
U-test was used for nonnormally distributed variables. The analyses were performed
using the IBM SPSS software version 23.0 program (Chicago, IL, USA). P < 0.05 was considered statistically significant.
Results
During the research period, sixty pregnant women who met the inclusion criteria were
evaluated. [[Table 1]] shows the patient's characteristics. There were no statistically significant differences
between the two groups in terms of age, gravida, and parity. In the HG group, the
number of patients with periodontitis was statistically significantly higher than
that of the control group (P < 0.001) [[Table 2]].
Table 1:
Characteristics of study participants
|
Control
|
HG
|
P
|
|
Age (year)
|
28±4
|
29±3
|
0.421
|
|
Gravida
|
1.7±1.23
|
1.9±1.15
|
0.524
|
|
Parity (range)
|
0±1
|
1±0.8
|
0.54
|
HG: Hyperemesis gravidarum
Table 2:
Multiple comparisons among the different periodontal measurements
|
Group Diagnosis[$]
|
Control, n (%)
|
HG, n (%)
|
P
|
|
Gingivitis
|
24 (80)
|
11 (36.67)
|
<0.001[*]
|
|
Periodontitis
|
6 (20)
|
19 (63.33)
|
|
$ Pearson Chi-square test, *P<0.05. HG: Hyperemesis gravidarum
The mean values of the clinical parameters indicating that oral hygiene and periodontal
status of the HG and control groups are given in [[Table 3]]. The results showed that HG group had statistically significantly higher PI, GI,
PPD, and BOPI levels (P < 0.05) compared with the control group [[Table 2]]. The distributions of PI, GI, PPD, and BOPI of HG and control groups are shown
in the box-plot graph format [[Figure 1]] and [[Figure 2]].
Table 3:
Comparison between clinical periodontal indices and hyperemesis gravidarum
|
Group
|
Mean±SD
|
P
|
|
P[#]
|
|
Controls
|
1.00±0.30
|
0.04[*]
|
|
HG
|
1.20±0.40
|
|
|
GI[+]
|
|
Controls
|
1.35±0.16
|
0.009[*]
|
|
HG
|
1.55±0.25
|
|
|
PPD[+]
|
|
Controls
|
1.94±0.18
|
<0.001[*]
|
|
HG
|
2.15±0.20
|
|
|
BOPI[#]
|
|
Controls
|
48.70±16.25
|
0.03[*]
|
|
HG
|
62.33±27.21
|
|
# Independent samples t-test, +Mann-Whitney U-test, *P<0.05. HG: Hyperemesis gravidarum, SD: Standard deviation,
PI: Plaque index, GI: Gingival index, PPD: Probing pocket depth, BOPI: Bleeding on
probing index
Figure 1: Distribution of plaque index, gingival index and probing pocket depth between the
groups
Figure 2: Distribution of bleeding on probing index between the groups
Discussion
PDs are known to be a risk factor for systemic conditions and diseases such as cardiovascular
diseases, rheumatoid arthritis, diabetes mellitus, respiratory diseases, and adverse
pregnancy outcomes, including premature birth, low-birth weight, miscarriage, or dead
birth.[[6]],[[9]]
The relationship between periodontal inflammation and systemic conditions could be
related to two different mechanisms. First, translocation of bacteria from the inflamed
periodontal tissues into the systemic circulation can cause bacteremia.[[4]] Furthermore, it is shown that levels of proinflammatory cytokines such as IL-1,
IL-6, PGE2, and TNFα are high in inflammatory gingival tissues, gingival crevicular
fluids, and plasma in periodontitis patients.[[24]] This locally derived mediators can enter the bloodstream and stimulate acute-phase
protein production such as CRP in the liver.[[2]],[[4]]
Nausea and vomiting affect more than 80% of pregnant women, especially during the
first trimester.[[25]] HG is a rare (0.3%–1.5%) and stringent condition of nausea and vomiting that may
cause nutritional deficiencies, dehydration, electrolyte imbalance, and ketonuria
and has a significant detrimental impact on the quality of life.[[26]],[[27]] Even if the etiology of HG is not well understood, inflammation could be a risk
factor for its development. Kaplan et al. were found significantly elevated serum levels of TNF-α, IL-1, and IL-6 in patients
with HG compared with nonpregnant women and healthy pregnant women.[[18]] Kuscu et al. also observed higher levels of IL-6 in HG patients.[[19]] In addition, in another study showed that significantly higher immunoglobulin (Ig)
G, IgM, C3, C4 levels, and lymphocyte count in HG patients.[[28]] Thus, the immune reactions may play a role in the etiology of HG. However, it is
not clear yet whether the high levels of inflammatory markers in patients with HG
cause or are produced by hyperemesis.
The previous studies showed that pregnant women exhibited significantly higher levels
of gingivitis than nonpregnant women. Although the plaque levels remained unchanged,
the results indicate that gingival scores and PPDs were significantly greater in pregnant
women compared with nonpregnant controls.[[8]],[[9]] The increase in severity of gingivitis during pregnancy has been attributed to
increased hormonal levels of estrogen and progesterone. Although this may cause hyperemia,
edema, increased gingival exudate, and bleeding in periodontal tissues could not affect
periodontal attachment.[[29]],[[30]] The possible reason for the lack of attachment loss is probably that a 9-month
period is insufficient to cause periodontal destruction.
Taani et al. observed a positive correlation between GI and PPDs in patients who vomited during
pregnancy compared with those who did not.[[9]] Gürsoy et al. reported the greatest peak in the plaque scores appeared during the first trimester.[[10]] They speculated that brushing may stimulate a gagging reflex and vomiting, and
women may avoid brushing their teeth. Toygar et al. in their study of 3576 women found that GI and PD were increased with vomiting and
nausea, but did not find a relationship between periodontal status and nausea and
vomiting.[[6]] However, none of these studies evaluated the severity of nausea and vomiting. This
is the first study comparing the gingival inflammation and oral hygiene between pregnant
women with and without HG. In our study, we found a significant association between
PI, GI, PPD, BOPI, and HG. At the same time, the number of patients with periodontitis
in the HG group was significantly higher than the control group. Although patients
with HG may have difficulties in brushing their teeth, this is not expected to increase
periodontal attachment loss in such a short time. In this case, periodontitis may
contribute to the formation of HG by increased inflammatory mediators in the systemic
circulation.
Conclusions
There could be a two-way relationship between HG and periodontitis. We assume that
periodontitis can contribute the etiopathogenesis of HG, and thus, patients with an
increased incidence of vomiting cannot brush their teeth properly, and PI, GI, and
BOPI may increase. These findings indicate a likely association, but large and well-designed
further studies are needed to determine the possible relationship with HG and periodontal
inflammation.
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