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1. INFLUENCE OF PERIODONTAL DISEASE
ON
CVS & DIABETUS
UNDER SUPERVISON OF
PROFESSOR DR. HALA KAMAL
ASS.PROF.DR. AHMED AMR
DONE BY
SHEHAD WAEL
LUBNAAMRO
ANAS BELAL
MOHAMED GILANY
MOHAMED SAMY
AHMED ASHRAF

2. I- INTRODUCTION
- Focal infection Theory
- Possible Pathways linking oral infection to 2ry non oral disease.
-Periodontal disease affects susceptibility to systemic disease

3. FOCAL INFECTION THEORY
• The theory of focal infection first established by Koch and Pasteur in the
mid-19th century stated that “foci” of sepsis were responsible for the
initiation and progression of a variety of inflammatory diseases such as
arthritis, peptic ulcers, and appendicitis.
Scannapieco, F. A. 1998. Position paper: periodontal disease as a potential risk factor for systemic diseases. J. Periodontol. 69:841–850.

4. • Pathological oral conditions, such as periapical inflammation and periodontitis, can
cause bacteremia, and dissemination of oral pathogens to non-oral sites can
subsequently cause infections in extraoral tissues and organs. Cardiovascular infections
and brain abscesses are the most common of these.
van Winkelhoff A. J., Abbas F., Siebers T. J. H. A renewed focus on extra-oral manifestations of oral infections. Nederlands Tijdschrift Voor Tandheelkunde. 2018

5. • However, because it became clear that it was
impossible to correlate with confidence a
particular systemic disease with a preceding
oral infection or dental procedure, the focal-
infection hypothesis fell from favor by the
middle of the 20th century.

6. PATHWAYS LINKING ORAL INFECTION TO
SECONDARY NON-ORAL DISEASE

7. PERIODONTAL DISEASE AFFECTS SUSCEPTIBILITY TO
SYSTEMIC DISEASE
1) Shared risk factors
Priyamvara, A., Dey, A.K., Bandyopadhyay, D. et al. Periodontal Inflammation and the Risk of Cardiovascular Disease. Curr Atheroscler Rep 22, 28
(2020)

8. Stimulation of accelerated atherosclerosis.
The possible underlying mechanisms can
be summarized as follows:
(i) inflammation, (ii) endothelial injury, (iii)
lipid peroxidation, and (iv) molecular
mimicry. ox-LDL: oxidized low-density
lipoprotein.
Mei, Feng, Mengru Xie, Xiaofei Huang, Yanlin Long, Xiaofeng Lu, Xiaoli Wang, and Lili Chen. 2020. "Porphyromonas gingivalis and
Its Systemic Impact: Current Status" Pathogens 9, no. 11: 944.

9. 3) Periodontium as cytokine reservoir
Konkel, Joanne E., Conor O'Boyle, and Siddharth Krishnan. "Distal consequences of oral inflammation." Frontiers in immunology 10 (2019): 1403.

10. II- ROLE OF PERIODONTAL DISEASE ON
A- Cardiovascular diseases & stroke
B- Diabetus mellitus
C- Pulmonary diseases
D- Pregnancy

11. A- ROLE OF PERIODONTAL DISEASE ON CVS & STROKE

12. CVS
PREVALENCE
• (Roth et al., 2017)
• NCD
(Non‐communicabl
e diseases )
17.9 million deaths 1/3
mortality in USA
The greatest global NCD
is due to cardiovascular
In Europe, 3.9 million
deaths (45% of deaths)
45% of NCD‐induced
mortality

13. • cause over 95% of CVD‐related deaths
• (Roth et al., 2015)
CVS
diseases
Atrial
Fibrillation
Acute
myocardial
infarction
Atherosclerosis
Coronary heart
disease
Ischemia,
Stroke
Infective
endocarditis,
Rheumatic
Heart
Disease
Peripheral artery
disease
(PVD),cerebrovas
cular disease
Hypertension
(leading to
heart failure),

15. Joint workshop between the European Federation of Periodontology
(EFP) and the American Academy of Periodontology to review the
literature relating periodontitis and systemic diseases.

16. EPIDEMIOLOGIC EVIDENCE ON
THE
ASSOCIATION BETWEEN
PERIODONTITIS
AND CVD

17. SUBCLINICAL CARDIOVASCULAR DISEASE
Endothelial
dysfunction
Flow‐med
iated
dilation
(FMD
Elevated
arterial
calcificati
on scores
Greater
thickness
of the
carotid
intima
media
Arterial
stiffness

18. ARTERIAL CALCIFICATIONS
• Subclinical
• Carotid Calcifications found by chance in panoramic radiograph
• Positive association with periodontitis

19. SUSCEPTIBILITY
There is one imaging study (ATHEROREMO‐IVUS study) associating high
levels of antibodies against periodontal pathogens and a lower extent of
positive atheromatous plaque remodelling (decreased compensatory response
to prevent lumen loss caused by plaque formation)
(de Boer et al.,
2014).

20. MYOCARDIAL INFARCTION /CORONARY EVENTS
(Dietrich et al., 2013)
Positive association between periodontitis and coronary
heart disease.
6 case–control and co‐hort studies epidemiological studies,
Increased risk of a first coronary event in periodontitis
patients
More severe symptoms compared to patients without
periodontitis or less severe periodontitis.
(Meurman et al.
2003, Bahekar et al. 2007,
Mustapha
et al. 2007).

21. CORONARY HEART DISEASE
• Bahekar et al.(2007)
5 cohort
(86,092 patients)
Periodontitis patient
1.14 x more risk of
developing coronary
artery disease

22. CEREBROVASCULAR DISEASE AND RISK OF
STROKE
Positive association between periodontitis
and cerebrovascular disease.
Increased risk of a first cerebrovascular
event in patients with clinically diagnosed
periodontitis ( 3 case reports )
More severe symptoms compared to patients
without periodontitis or less severe
periodontitis

23. PREVALENCE AND INCIDENCE OF PERIPHERAL
ARTERY
DISEASE (PAD)
• (Yang et al., 2018).
Limited but
consistent evidence
Periodontitis patients
have a higher
prevalence &
incidence
Compared to individuals
without periodontitis

24. HEART FAILURE/ ATRIAL FIBRILLATION?
• Positive association between periodontitis and heart failure.
• Significantly higher incidence of atrial fibrillation in periodontitis patients
compared to individuals without periodontal .
• (Chen, Lin, Chen, & Chen, 2016).

25. SUBSEQUENT CVS EVENT
• 1 small study showed a positive association between periodontitis and
secondary cardiovascular events, ( only 100 subjects ; Sen et al., 2013).
• 2 large studies did not find a significant association (Dorn et al., 2010;
Reichert et al., 2016)

26. PERIODONTITIS & DIABETES & CVS
• Pro-inflammatory mediators implicated in hyperglycemia have
been associated with periodontitis & increased cardiovascular
disease risks (Janket et al. 2007).

27. • Link / Positive Association between
periodontitis & Cardiovascular disease has
been reported by many studies however more
research is needed to establish CAUSALITY.
• (Reyes et al ,2013)

29. • Study done on
15828 candidate
with stable CHD
• Questionaire,
Physical Status , &
Blood samples

30. COMMON ETIOLOGY
Older Age,
Socioeconomic
Education level
Smoking
Alcohol
Poor Diet
Lack of Exercise
Obesity/High
Cholestrol
Male
Gender
Common
Genetic
Polymorphisms
Diabetes
• Extent of Tooth loss is proportional to extent of CVD

31. SMOKING
• Data suggest that since a public smoking ban was
introduced in New York city the rate of hospital
admissions with a diagnosis of acute coronary syndrome
decreased by 8%.
• This was solely accounted for by the impact of reduced
smoking. (Juster et al. 2007).

32. MECHANISMS THAT MAY
EXPLAIN
THE EPIDEMIOLOGICAL
ASSOCIATIONS
BETWEEN PERIODONTITIS AND
CVD

33. Bacteremia
Thrombotic
Factors
Overexpress
ion
Inflammatory
Mediators
Genetic
Factors
Oxidative
stress
Elevated
serum
antibody
Dyslipidemia

34. BACTEREMIA
• Oral Bacteria Enters blood stream from daily life activities &
following professional interventions (Tomas, Diz, Tobias, Scully, &
Donos, 2012).
• Periodontal therapy induced bacteraemia in both gingivitis and
periodontitis patients, but the magnitude and frequency were
greater among periodontitis patients (Balejo et al., 2017).

35. BACTEREMIA
• Bacteria associated with periodontitis was identified from aorta and heart
valves (Meurmanet al. 2003, Mustapha et al. 2007)
• Traces of DNA, RNA or antigens periodontal pathogens, have been identified
in atherothrombotic tissues.
• Viable P. gingivalis and A. actinomycetemcomitans in atherothrombotic
tissue (Armingohar, Jørgensen, Kristoffersen, Abesha‐Belay, & Olsen, 2014;
Mahendra, Mahendra, Felix, & Romanos, 2013).

36. BACTEREMIA
• Elevated antibody titres to bacteria associated with
periodontitis can be linked to cardiovascular disease
risk (Meurman et al. 2003, Mustapha et al. 2007)

37. BACTEREMIA
• High antibody titers to A. actinomycetemcomitans specifically
have been associated with coronary heart disease (Pussinen et al.2004a,
b, 2005, 2007a, b, Beck et al.2005, Vilkuna-Rautiainen et al. 2006).
• Serum immunoglobulin A (IgA) and IgG antibody titres to A.
actinomycetemcomitans have also been linked to future stroke
event (Pussinen et al. 2004a)

38. BACTERIAL PRODUCTS AND VIRULENCE
• P. gingivalis has been shown to accelerate atherosclerosis in
murine models, to induce fatty streaks in the aorta of rabbits and
to induce aortic and coronary lesions after bacteremia in
normocholesterolaemic pigs
• (Schenkein & Loos, 2013).

39. • There is also in vitro evidence of intracellular entry by
periodontal pathogens (P. gingivalis, A.
actinomycetemcomitans, etc.) (Reyes et al., 2013).
• Fimbriae of P. gingivalis to host cell entry and to
promote atherothrombotic lesions in experimental
models (Yang et al., 2014).
BACTERIAL PRODUCTS AND VIRULENCE

40. OXIDATIVE STRESS
• A polymicrobial infection was shown to induce aortic toll‐like
receptor (TLR) and inflammasome signalling, with an enhanced
oxidative stress reaction generated within the aortic endothelial
cells ( More free radicals) (Chukkapalli et al., 2015; Velsko et al., 2014, 2015).

41. INFLAMMATORY MEDIATORS
• Higher levels of C‐reactive protein (CRP) in periodontitis patients
and in CVD and periodontitis patients compared with either
condition alone.
• The effect of periodontal therapy has been shown to associate
with a significant decrease in CRP levels,
(Demmer et al., 2013; Koppolu et al., 2013; Patil & Desai, 2013).

42. INFLAMMATORY MEDIATORS
• There is evidence of elevated levels of serum interleukin
(IL)‐6 in periodontitis patients and lower levels of IL‐4 and
IL‐18.
• Periodontal therapy only partially reduces the cytokine
hyper‐reactivity with some evidence of a constitutively
elevated response (Ling, Chapple, & Matthews, 2016)

43. THROMBOTIC FACTORS
• Higher levels of fibrinogen in periodontitis patients versus healthy controls,
and in CVD and periodontitis patients compared with either condition alone
(Chandy et al., 2017).
• Decrease in fibrinogen levels after therapy (Lopez et al., 2012; Vidal, Cordovil,
Figueredo, & Fischer, 2013).
• Higher levels of platelet activation markers in periodontitis patients and that
these higher levels may be reversed by periodontal therapy (Arvanitidis, Bizzarro, Alvarez
Rodriguez, Loos, & Nicu, 2017).

44. ELEVATED SERUM ANTIBODY LEVELS
CROSS REACTION
Periodontal pathogens generate antibodies that can cross‐react with
human HSPs ( heat shock proteins / ischemia) & activate cytokine
production, as well as monocyte and endothelial cell activation.
• The presence of anti‐cardiolipin antibodies has been significantly
associated with periodontitis patients, which reversed following
periodontal therapy.
• periodontal pathogens can elicit antibodies ( associated with
higher clotting risks.) that cross‐react with cardiolipin (Schenkein &
Loos., 2003).

45. DYSLIPIDIMIA & PERIODONTITIS
• serum total cholesterol levels, low‐density lipoproteins (LDL),
triglycerides, very‐low‐density lipoproteins (VLDL), oxidized LDL
and phospholipase A2 are elevated in periodontitis. (Increase
harmful Cholestrol)
• High‐density lipoprotein (HDL) levels are reduced in periodontitis
patients compared with controls (Schenkein & Loos., 2003). These
levels are reversed after periodontal therapy (Teeuw et al.,
2014).(Decrease helpful cholesterol)

46. GENETIC RISK FACTORS
• The highly pleiotropic genetic locus CDKN2B‐AS1 (chromosome 9, p21.3)
associated with coronary artery disease, type 2 diabetes, ischaemic stroke
and Alzheimer’s disease is associated with periodontitis (Aarabi et al., 2017; Ernst et
al., 2010; Loos, Papantonopoulos, Jepsen, & Laine, 2015; Munz et al., 2018).
• Genetic susceptibility locus for coronary artery disease, is associated with
periodontitis (Schaefer et al., 2015).
• There is evidence for plasminogen (PLG) as a shared genetic risk factor for
coronary artery disease and periodontitis (Schaefer et al., 2015).

47. RECOMMENDATIONS

48. • (Tonetti et al., 2013)
Poor oral hygiene
/ periodontal
disease
CVD

49. ROLE OF DENTIST
Patients with periodontitis should be advised that there is a higher
risk for cardiovascular diseases, such as myocardial infarction or
Stroke.

50. B- ROLE OF PERIODONTAL DISEASE
ON DIABETES

52. • Diabetes mellitus is a hormonal disease characterized by changes in
carbohydrate, protein, and lipid metabolism. The main feature of diabetes is
an increase in blood glucose levels (hyperglycemia).
• According to the new classification of periodontitis, the level of glycemic
control in diabetes influences the grading of periodontitis.

53. LINKING MECHANISMS BETWEEN PERIODONTITIS AND
DIABETES:
• 1-Specific oral bacteria in the periodontal pocket may gain bloodstream
access through ulcerated pocket epithelium.
• 2-Inflammatory mediators from the periodontium may enter the bloodstream
and activate liver acute phase proteins, such as C‐reactive protein (CRP),
inflammatory cytokines. which further amplify systemic inflammation levels.
• 3-periodontitis contributes to the overall inflammatory burden of the
individual which is strongly implicated in Type II diabetes and many other
systemic diseases.

54. • Inflammation is a common link between periodontal diseases and diabetes.
• In patients with diabetes, hyper inflammatory immune cells can exacerbate
the elevated production of proinflammatory cytokines. This has the potential
to increase insulin resistance.
• periodontal treatment that decreases inflammation and help decrease insulin
resistance.

55. Many studies have examined the effect of periodontal infection on the
control of diabetes, however, such studies are difficult
to perform because of the influence of ongoing
medical management on diabetes control during the study.
The effect of periodontal condition
on glycemic control:

57. How does periodontits worsen glycemic
control and DM complications?

58. • 1) circulating proinflammatory mediators as TNF-α, CRP, and
mediators of oxidative stress are elevated in patients with both
diseases and these subjectstendto demonstratehigherdyslipidemia.
• 2) In response to endotoxins such as lipopolysaccharide (LPS)
produced by periodontal microorganisms, the production of
proinflammatory cytokines, chemokines, reactive oxygen species
(ROS), and C-reactive protein (CRP) that can alter lipid metabolism
and insulin resistance, leading to hyperlipidemia and hyperglycemia.
• 3) TNF-α has been identifiedas a potent insulinreceptor blocker.

59. • 4) In severe periodontitis, the ulcerated epithelium of the
periodontal pockets constitutes a portal of entry for
pathogenic bacteria, products, endotoxins such as LPS,and
stimulated inflammatory mediators to reach the systemic
circulation.
• 5) Periodontal microorganisms as well as their antigens, when
systemically dispersed, can cause significant systemic
inflammation and contribute to DM complications.

60. Poorly controlled type II diabetes
Treatment with scaling and root planning, and systemic antibiotics
(doxycycline therapy for two weeks) resulted in decreased insulin demand.
Treated with doxycycline had a greater reduction in the prevalence of
P. gingivalis.

61. Well controlled type II diabetes:
Some studies show improvements in glycemic control
after scaling and root planing without antibiotics.
Type I diabetes:
Research suggests that periodontal therapy may have a smaller
impact on glycemic control in patients with type I diabetes than
with type II disease.

62. C- ROLE OF PERIODONTAL DISEASE ON PULMONARY

64. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(COPD)
Characterized by air flow obstruction resulting from bronchitis or emphysema
• Chronic Bronchitis : is narrowing of airways proximal to distal bronchi due
reactive hyperplasia of bronchial mucous gland and hypertrophy of smooth
muscles
• Emphysema : is a chronic enlargement of airways distal to bronchiols due to
bronchiolar smooth muscle and elastic fiber destruction
• Risk factor of COPD
• 1-Cigarrete smoking
• 2- Industrial smoke
• 3- Genetic condition (defective alpha1antitrypsin –alpha1antichymotrypsin-
alpha2macroglobulin-vitamin D binding protien)

65. PERIODONTITIS AND CHRONIC OBSTRUCTIVE PULMONARY
DISEASES—THE SHARED LINK
• COPD and periodontal diseases are both chronic inflammatory
diseases and they share certain pathophysiologic features, the
relation between the two diseases has been investigated.
• Large epidemiologic studies have revealed a significant association
between COPD and poor oral hygiene, alveolar bone loss, and
smoking.
• In an analysis of data from the NHANES III study, patients with COPD
had significantly more clinical attachment loss than did subjects
without COPD. These studies demonstrate an association between
periodontal diseases and COPD, but they do not show causation.
• Additional longitudinal studies would be required to validate the
associations, and intervention trials are needed to determine if
periodontal therapy can reduce the risk for COPD

66. -The common attributed factor is the alteration
in neutrophil function
- neutrophils and macrophages secrete large
amounts of reactive oxygen species (ROS).
Excess ROS mediates tissue damage by making
them more susceptible to proteolytic
degradation , In periodontitis, hyperactive
neutrophils are identified to produce large
amounts of ROS that can damage alveolar tissue
in the lung
- Release of neutrophil extracellular traps (NETs)
has been implicated in lung inflammation and
plays a vital role in degradation of lung tissue
and pathogenesis of COPD
- Extracellular DNase production by periodontal
bacteria like Porphyromonas
gingivalis and Fusobacterium nucleatum can
degrade NETs and release them

67. BACTERIAL PNEUMONIA
Pneumonia is a life-threatening infection
Pneumonia : is the inflammation of lung tissues followed by the accumulation of blood cells,
fibrin & exudates in the alveoli .
• It is caused by a wide variety of infectious agents, including bacteria, mycoplasma, fungi,
parasites, & viruses resulting in the infection of the pulmonary parenchyma
.The lower respiratory tract can get infected by one of the four causes: aspiration of
oropharyngeal contents, inhalation of infectious substances, spread of infections from
extrapulmonary sites, and hematogenous spread
Bacterial Pneumonia can be classified as :
• Community acquired
• Hospital acquired (nosocomial)

68. • Community acquired bacterial pneumonia :
- is caused by aspiration of oropharyngeal organisms such as ( Streptococcus
pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae)
- Community-acquired bacterial pneumonia has a low mortality rate and generally
responds well to treatment.
- There is no evidence that periodontal disease or oral hygiene alters the risk for
community-acquired pneumonia
• Nosocomial pneumonia :
- it usually results from infection with organisms that do not normally colonize the
oropharynx, such as ( Klebsiella pneumoniae, Pseudomonas aeruginosa,
Staphylococcus aureus, and Escherichia coli) .
- These organisms, called potential respiratory pathogens (PRPs), are generally found
in the gastrointestinal tract, but may be passed into the oropharynx through
esophageal reflux.
- If subsequently aspirated, the PRPs may initiate pneumonia

69. PERIODONTITIS AND PNEUMONIA—THE SHARED LINK
- A patient with PRPs colonizing the mouth and oropharynx is at increased risk for pneumonia
- Oral colonization with PRPs increases during hospitalization, and the longer a patient is
hospitalized the greater their prevalence.
- Bacterial plaque associated with the teeth can serve as reservoirs for PRPs, particularly during
prolonged hospitalization.
- Poor oral hygiene is common in hospitals or nursing home settings, especially in patients who are
quite ill
- Colonization of dental plaque and the oral mucosa by PRPs is much more common in patients in
the intensive care unit compared with patients in an outpatient dental clinic setting. The risk for
pneumonia was found to be nine times greater in patients in the intensive care unit whose dental
plaque was colonized by PRPs compared with those not colonized by these organisms.

70. • A number of intervention studies have shown that improved oral hygiene
measures can reduce the incidence of hospital-acquired pneumonia.
• Application of the antimicrobial chlorhexidine to the teeth, gingiva, and other
oral mucosal surfaces has been shown to significantly decrease the risk for
pneumonia, especially in patients who are on ventilators.
• In a systematic review of the evidence, Scannapieco and coworkers88
determined that oral hygiene interventions can reduce the rate of hospital-
acquired bacterial pneumonia by approximately 40%.

71. ORAL BACTERIA IN THE PATHOGENESIS OF RESPIRATORY INFECTION
1)Aspiration of oral pathogens.
2) Periodontal disease-associated enzymes in saliva may modify mucosal
surfaces to promote adhesion& colonization by respiratory pathogens
3) Periodontal disease-associated enzymes may destroy salivary pellicles on
pathogenic bacteria.
4) Cytokines originating from periodontal tissues may alterrespiratory
epithelium to promote infection by respiratory pathogens

72. ASPIRATION OF ORAL PATHOGENS
• The bacterial content of saliva is varied, & high counts of many species of
bacteria in saliva qive rise to the suspicion that direct transfer of bacteria from
the mouth to the airways is occurring.
• Normal oral flora , including , A. actinomycetemcomitans & anaerobes such as
P.gingivalis and Fusobacterium spp., can be aspirated into the lower airways
to cause pneumonia

73. PERIODONTAL DISEASE-ASSOCIATED ENZYMES IN
SALIVA MAY MODIFY MUCOSAL SURFACES

74. DESTRUCTION OF PROTECTIVE SALIVARY
PELLICLES BY ORAL BACTERIA

75. SALIVARY CYTOKINES MAY ALTER RESPIRATORY
EPITHELIUM
• In periodontal disease ,oral pathogen stimulate oral tissue
periodontium to release a wide variety of cytokines .
• Cytokines produce bu epithelial c.t in response to pathogens
such as IL-1 alpha, IL-Beta,IL-6,IL-8 ,TNF
• Epithelial cells alter expression of various cell adhesion
molecules on their surface in response to cytokine stimulation,
Variation in expression of such adhesion molecules may alter the
interaction of bacterial pathogens with the mucosal surface.
• • Cytokines entering the saliva From inflamed periodontal
tissues upregulate the expression of adhesion receptors on the
mucosal surfaces to promote respiratory pathogen colonization.

76. • Mechanism proposed for the gross airway epithelial damage observed in COPD involves release
inflammatory cytokines (i.e., pro- IL-8) from the respiratory epithelium, resulting in the recruitment and
infiltration by neutrophils which subsequently release proteolytic enzymes & toxic oxygen radicals
• the release of cytokines from respiratory epithelium may be the result of the binding of the respiratory
pathogen or their product to respiratory epithelial cell
• This mechanism has been demonstrated for pathogens such as Strepto-coccus pneumoiae & H.
influenzae, which are also known to attach to mucosal receptors & to stimulate cytokine production by
the underlying cells.
• • Oral bacteria in secretions in contact with respiratory epithelial surfaces may adhere to the mucosal
surface. These bound oral bacteria may stimulate cytokine production by mucosal Cytokines originating
from the oral tissues may contaminate the distal respiratory epithelium to stimulate respiratory
epithelial cells.
• • The stimulated respiratory cells may then release other cytokines that recruit inflammatory cells (e.q.,
neutrophils) to the site which may release hydrolytic enzymes & other modifying molecules resulting in
damaged colonization respiratory pathogens

77. REFRENCES
• Scannapieco FA, Papandonatos GD, Dunford RG: Associations between oral conditions and respiratory disease
in a national sample population, Ann Periodontol 3:251–256, 1998.
• Hayes C, Sparrow D, Cohen M et al: Periodontal disease and pulmonary function: the VA longitudinal study,
Ann Periodontol 3:257–261, 1998.
• Scannapieco FA, Ho AW: Potential associations between chronic respiratory disease and periodontal disease:
analysis of National Health and Nutrition Examination Survey III, J Periodontol 72:50–56, 2001
• Scannapieco FA, Mylotte JM: Relationships between periodontal disease and bacterial pneumonia, J
Periodontol 67:1114–1122, 1996
• Limeback H: Implications of oral infections on systemic diseases in the institutionalized elderly with a special
focus on pneumonia, Ann Periodontol 3:262–275, 1998
• . Russell SL, Boylan RJ, Kaslick RS et al: Respiratory pathogen colonization of the dental plaque of
institutionalized elders, Spec Care Dentist 19:1–7, 1999. 83. Beck JD: Periodontal implications: older adults,
Ann Periodontol 1:322– 357, 1996
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intensive care patients, Crit Care Med 20:740–745, 1992. 85.
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intensive care unit patients, Crit Care Med 26:301–308, 1998. 86.
• DeRiso AJ, Ladowski JS, Dillon TA et al: Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total
nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart
surgery, Chest 109:1556–1561, 1996.
• . Fourrier F, Cau-Pottier E, Boutigny H et al: Effects of dental plaque antiseptic decontamination on bacterial
colonization and nosocomial infections in critically ill patients, Intensive Care Med 26:1239–1247, 2000.
• . Scannapieco FA, Bush R, Paju S: Associations between periodontal diseases and risk for nosocomial bacterial
pneumonia and chronic obstructive pulmonary disease: A systematic review Ann Periodontol 8:54–69, 2003

78. D- ROLE OF PERIODONTAL DISEASE ON PREGNANCY

80. ROSE ET AL, 2004
Throughout history it was well known and documented that pregnancy affects
the status of the periodontium. It is confirmed that an increased incidence of
gingivitis may happen during pregnancy.
Periodontal disease can consist of gingivitis (reversible gingival inflammation)
and periodontitis (gingivitis with gingival recession accompanied by loss of
connective tissue and alveolar bone; Armitage 2004)

82. The variation of the level of female estrogen and
progesterone during pregnancy are responsible for
various physiological changes at this period. These
changes not only affect other parts of the body, but
also have significant influence on oral tissues as the
receptors for estrogen and progesterone have been
demonstrated in the different periodontal cells proving
the direct action of sex hormones on periodontal
tissues

83. CARTA ET AL. 2004
with these hormonal changes there is a significant rise in the anaerobic bacteria
such as F. nucleatum, T. denticola, T. forsythia, C. rectus .
However, the correlation of the effect of periodontitis on pregnancy, namely
preterm low birth weight is the controversial part.

84. What occurs in the normal physiology of pregnancy is that as the foetus grows,
the amniotic space decreases and the inflammatory mediators increases till a
certain threshold where the sac ruptures and uterine contractions begin and
delivery takes place. Hence the increased level of inflammatory mediators,
namely (IL1β, IL6, TNFα and PGE2) may induce APO’s such as preterm birth “PB”
and Preterm low birth weight “PLBW”. PLBW is a significant cause of infant
morbidity and mortality. There are a number of risk factors associated with
adverse pregnancy outcomes including low socioeconomic status, age, race,
multiple births, smoking, drug and alcohol abuse and systemic maternal
infection .

85. CORRELATION BETWEEN THE AOPS AND
PERIODONTITIS
a positive association between periodontal disease (PD) and adverse pregnancy
outcomes “APOs” the results are not always consistent and this is attributed to
the discrepancies of those studies in terms of population, methodologies, risk
factors and other factors. In a review article by Madianos et al, 2013

86. BIOLOGICAL ASSOCIATION BETWEEN PD AND APOS
1) Direct mechanism: Involves direct infection by pathogenic bacteria and their
products into foeto-placental unit, initiating inflammatory response causing APOs.
2) Indirect mechanism: Involves the diffusion of cytokines from GCF into i) foeto-
placental unit inducing more cytokines and mediators or ii) liver inducing systemic
inflammatory response.

87. 1) Direct mechanism:
As explained earlier, during pregnancy the combination of the effects of
hormonal changes increasing vascular permeability and the increase of the
anaerobic bacteria allows more bacterial diffusion into the blood stream. This
diffusion of inflammatory mediators or periodontal pathogens into the blood
stream crosses the placenta barrier and could induce premature labour

88. Some studies suggested that the presence of periodontal bacteria resulted in
increase in some inflammatory mediators and a significant reduction of fetal
weight by up to 25%. However, the virulence of each bacteria on the placenta is
not identified due to the large number and diversity of the microbiome.
Therefore the question remained “Do these bacterial loads entering the
circulation really affects the foeto-placental unit?

89. MADIANOS ET AL
The evidence was based on immunological data suggesting that the presence of
bacteria in the blood stream initiates the innate immune response first then if
not successful, the more sophisticate adaptive immune response is activate
resulting in the presence of IgG.
recorded that elevated IgG was associated with decreased PB and increased
birthweight which is as evidence on the effect of bacterial invasion on APOs.

90. LIN ET AL. 2007
data revealed that mothers who deliver preterm have significantly lower serum
IgG levels against P. gingivalis compared to term mothers.
However, studying the Ig levels as an indicator for APOs is controversial because
elevated levels of serum IgG antibodies could indicate either an increase
bacterial exposure or a hyper-inflammatory reaction predisposing these women
to an increased foetal. inflammatory response.

91. “HOW MANY BACTERIA ARE NECESSARY TO CAUSE
APOS?”
Leon et al, 2007 tested the ability of pathogens to reach the foeto-placental unit and only
P.gingivalis was found to have that ability. Further studies also associated P. gingivalis and
Aggregatibacter actinomycetemcomitans in PB and pre-eclampsia
Interestingly bacteria could be isolated also in normal pregnancies so bacteria could not be
responsible alone and it was not clear what clinical parameter to rely on.

92. 2) Indirect mechanism:
Other reports related the increase of inflammatory mediators with adverse
pregnancy outcomes (APOs). Elevated levels of IL-1, IL-6, TNF-α, PGE2, in the
amniotic fluid associated with PD could be connected to the APOs. (Inglis 1997
and Gursoy et al. 2010). The release of those mediators into the circulation
results in uterine contractions and may exacerbate cervical ripening leading to
an increased risk for PB. However there is little or no evidence that the presence
of those mediators in the GCF could affect AOPs. (Carta et al. 2004, Tarannum
et al. 2011 and Fiorini et al. 2012).

93. MADIANOS ET AL.
The conclusions of the review is When the bacteria enter the blood stream and
due to the slow blood flow in the placental area, it invades endothelial cells,
proliferate and enter the foetal circulation and amniotic fluid triggering the
immune response, then formation of IgM then IgG.

94. If this reaction is contained, no complications occur but if exposure was not
contained, rupture of membranes occur and uterine contractions that can lead
to miscarriage. They also concluded that accumulation of
infection/inflammation in the placenta retards the growth of the placenta and
the foetus as well. This could result in morbidity or permanent changes with the
fetus that appears throughout life.

95. However, they did not give a clear direct correlation between PD and APO’s and
the recommendation of this review was to depart from the “one-size-fits-all”
therapy and design a more specific treatment plan according to each individual’s
.

96. In a recent consensus report of the Sixth European Workshop on Periodontology
it has been concluded that although there is a possible association between PD
and an increase risk of AOPs, there is no conclusive evidence that treating PD
improves the rate of positive birth outcomes (Kinane et al., 2008). However, in a
systematic review by Scannapieco et al., 2003 it was concluded that it’s not
clear whether PD plays a casual role in APOs but the collected evidence
suggested that periodontal treatment may reduce APOs.

97. reviewing all data one can conclude that PD is not a direct clear cause of APO’s,
however it could be referred to as a risk factor. We cannot answer the critical
question of pregnant mothers that improving their periodontal status will
definitely improve their pregnancy outcomes but at the same time we can
inform them that untreated periodontal disease may increase the risk not only
of unfavorable pregnancy outcomes, but also of developing conditions that may
affect the wellbeing of the offspring and to reassure them that periodontal
treatment is safe for both the mother and the foetus

98. CONCLUSION
So it is the role of dental professional to do their best to increase awareness
among pregnant females to improve their oral hygiene and follow up their
periodontal condition, not only for improving their oral health but also to
prevent PD as being a risk factor for any possible APO’s .