This Blog is just like a teaser/trailer of the PPT (vast subject matter), I've made on this Topic, after reading and compiling 112 Articles for over 3years. I hope one day it will reach elite minds of the seniors in the Gynecological Society.
I am open for Presenting this Lecture and for discussion.
Actually its not something new but seriously missing here in regular Practice.
We need to make some modifications in our approach towards better health care.
With 30years of Dental Practice and having done my Medicolegal PG diploma, I know it is Mandatory, and strictly followed in Western and European Countries.
Do You Know Periodontitis can cause Adverse Pregnancy Outcome ? 🤰
Let me briefly explain certain terms like APO, Periodontal ligament and Periodontitis to begin with.
The term Adverse Pregnancy outcome (APO) many include several unfortunate situations during pregnancy. This may be
Low Birth weight Babies (LBW)
Preeclampsia (PE)
IUGR (Intrauterine growth restriction poor growth of a baby while in the mother's womb during pregnancy)
PROM (Premature rupture of membranes)
Miscarriage
Gestational Diabetes
Bacterial Vaginosis
Small for Gestational Age (SGA)
Periodontal ligaments are fine muscles that attach tooth to the Alveolar Bone. 👇The PDL are basically striated muscles with muscle spindles located within the fibers of the Ligaments.
So, any infection of these Periodontal ligaments is called Periodontitis which clinically looks 👇
This should not be confused with Gingivitis.
In Gingivitis there will be irritation, redness and swelling (inflammation) but NO Attachment loss/Bone loss. 👇
In Pregnancy its due to hormonal imbalance and is termed Epulis gravidarum or Pregnancy Gingivitis/Tumor. This gingivitis is due to increased levels of the hormone, progesterone, which gets reversed after pregnancy.
Often Gynecologists get confused Periodontitis vs Gingivitis. Please Note Periodontitis is not reversible and will cause aggressive damage, no doubt orally, but to the Pregnancy outcome for hosting reservoir of Bacteria.
According to a survey in India, Majority of the Practicing Gynecologists do not insist on Dental Clearance at the earlier stages nor advise women who plan pregnancy to get their Oral hygiene status evaluated as mandatory, while Dental clearance is a mandatory step in Western and European countries.
The irony is almost all other causes like
Smoking
Alcohol
Drugs
Inadequate prenatal care
Race
Low socio economic status
Maternal body mass index
Hypertension
Diabetes
Maternal age
UTI
Maternal stress
Genetic background
Multiple pregnancies
Uterine over distension
Psychological status
Vaginal ascending infections etc
has been taken into consideration in evaluating and treating issues during Pregnancy but very strangely serious infection like Periodontitis is not ever taken into consideration as possible reason for APO. The screening of Oral descending infections has not been taken seriously in regular gynec practice.
Historically, since long time intra uterine infection has only been implicated in APO among Gynecological Society. They know very well about the Bacterial causing Bacterial Vaginosis, its Potency, habits/habitants...which are totally different from Oral Bacteria.
Numerous Recent Evidences are enough to suggest Infections remote from the Fetal Site will also cause APO
Lets discuss this Descending infection.
The Bacteria commonly causing Periodontitis are
Aggregatibacter Actinomycetemcomitans
Porphyromonas gingivalis (P gingivalis)
Prevotella intermedia
Tannerella forsythia
Fusobacterium nucleatum
Peptostreptococcus
So, all these Bacterial Species cause Periodontitis and colonize on share basis in the Periodontium....we can say Periodontium is a huge reservoir of Bacteria & its Inflammatory Mediators.
Now lets discuss How & what all possible ways these cause APO
Bacteria directly entering blood & causing Bacteremia
The inflammatory mediators dissemination
The gene polymorphism of these mediators,
I) BACTERIA DIRECTLY SPREADING
Bacteria entering into the blood stream and reaching the Fetus is a novel way.
Pathogens are able to enter and survive inside the host immune cells for atleast a portion of their life cycle. Macrophages, ingest and kill microorganisms in a process called phagocytosis. These Intracellular bacterial pathogens can replicate within host cells, including macrophages and do not get Phagocytosed at times.
These bacteria produce certain toxins and mediators which inhibit the phagocytosis potency of the macrophages.
These blood borne pathogens arrive at the Placenta via transportation inside the Maternal Leukocytes that enter the Decidua in early Pregnancy.
Extravillous trophoblasts get infected in Decidua and spread infection to other layers in the Placenta.
The Decidua actively recruits Leukocytes to the Endometrium during Secretory phase of Menstrual cycle and during implantation phase of the early Pregnancy.
Once the Monocytes are localized in the Decidua they differentiate into Decidual Macrophages and the Microbes hiding inside have excellent opportunity to infect the Trophoblasts. This is based on Histological examination of human placenta.
Once the bacteria P gingivalis enter & infect the trophoblasts👆 Trophoblasts have pattern recognition receptors & can evoke elevated levels of cytokines IL 1, IL6, IL8,
IL 10, TNF-a & Prostaglandins (PG E2) which trigger preterm birth
When sudden Surge in Prostaglandins, in response to inflammatory mediators, the body interprets this as signal/time to go into Labor and thus premature babies or underweight babies
Normal Parturition is controlled by inflammatory signaling.
What happens In normal pregnancy is prostaglandins gradually increase. As pregnancy progress amniotic fluid levels of prostaglandins Pge2, inflammatory cytokines IL, TNF-a steadily rise until certain threshold & in concentrations of receptors for hormone oxytocin & neurogenic reflex to induce rupture of amniotic sac membrane, uterine contraction, cervical dilation & delivery.
Further more P gingivalis induced proinflammatory mediators can recruit & activate neutrophils resulting in release of MMPs . These MMPs damage chorioamniotic membrane.
There is evidence showing P gingivalis within the villous Mesenchyme & umbilical cord associated with APO
The Location of the P gingivalis within the placenta was different
in the Umbilical Cord- Preeclampsia, Villous Mesenchyme-Preterm Birth (PTB)
F. nucleatum was not found in the Vagina but was found in neonatal Gastric aspirates & oral samples of Mothers with Pre Term Delivery
P gingivalis within the human trophoblast cells (HTR-8) Cause arrest of G1 phase of cell cycle & Trophoblast cell unable to proliferate became Apoptotic.
II) INFLAMMATORY PRODUCT DISSEMINATION
The immune system responds to Periodontal tissue injury or irritation through an innate cascade known as inflammation, to produce Inflammatory mediators, in defense, which include
Proteins
Peptides
Glycoproteins
Cytokines
Arachidonic acid metabolites (prostaglandins and leukotrienes)
Nitric oxide
Oxygen free radicals
Gingival crevicular fluid (GCF) is a huge reservoir of all such Mediators. 👇
Especially in Pregnancy the Hormonal changes due to elevated levels of Estrogen and Progesterone cause more permeability in Gingival/Periodontal tissues as a consequence the bacteria and their inflammatory mediators can diffuse more rapidly.
To briefly explain the cascading events 👆 👇
TNF Alfa increases vascular permeability and the expression of adhesion molecules such as
intercellular adhesion molecule-1 (ICAM-1) and P-selectin on endothelial cell surfaces.
This process recruits PMNs into the tissue, where they release lysosomal enzymes, which
contribute to tissue degradation.
Bacterial components, such as lipopolysaccharides (LPS), peptidoglycans, lipoteichoic acids, proteases and toxins, which instigate the inflammatory reaction, can be found in the biofilm on tooth surfaces which are recognized by toll-like receptors (TLRs) on the surface of host cells, which initiates an inflammatory response.
Interleukins (IL) IL-1, IL-6, IL-12, IL-17, IL-18, IL-21, TNFα and IFN-γ have been demonstrated to be involved in the pathogenesis of periodontitis. Increased levels of IL1Beta, IL6, TNF-alfa, PGE2, fibronectin are associated with Preterm birth.
PAMPS activate Innate Immune response.
Bacterial endotoxins and Lipopolysaccharides (LPS) produced by the Periodontal pathogens activate Pattern Recognition Molecules TLR2 and TRL4 on Host cell surface and stimulate increased TNF Alfa and MMPs. (Matrix Metalloproteinase)
MMPs in the systemic circulation and at the site of the HTR cause damage to the Chorioamniotic Membrane and also increased expression of MMPs result in degradation of the extracellular matrix and contribute to Cervical ripening and Labor.
The bacterial antigens eventually encounter antigen presenting cells such as dendritic cells, macrophages and B cells. When naïve CD4 T helper cells (Th0) interact with antigen presenting cells, naïve T cells differentiate into various subsets of cells including Th1, Th2, Th17 and regulatory T cells (Tregs), depending on the cytokines which they produce.
Th17 and TREGS play a key role in
Immunosuppressive Feature
Promote Invasiveness
Preferential Production of TH2 Cytokines
Reduced Cytotoxicity of Decidual Natural Killer (DNK) cells
Imbalance in TH17/TREGS cause Recurrent Pregnancy loss
Th1 plays a key role in Fetal loss induction cause. Th1 response leads to activation of Decidual macrophages which secrete toxic levels of Nitric Oxide and TNF alfa leading to Maternal rejection of implanted Embryo.
Elevated levels of CRP in response to severe oral infection --risk for IUGR & Preeclampsia (PE)
Preeclamptic patients with periodontal disease had elevated levels of both IL-12 and IFN-ϒ when compared to preeclamptic patients without periodontal disease
IL6 & TNF-alfa interfere with carbohydrate metabolism & consequently cause glucose intolerance resulting in Gestational Diabetes Mellites (GDM).
III) GENE POLYMORPHISM
Gene polymorphisms has been noted in response to Periodontal Pathogens.
Gene Polymorphism in the genes for IL-1, TNFα, IL-6 and IL-10 as well as
combined genotypes of TNFα and lymphotoxin alpha have been reported in patients with Periodontitis 👇
Further more Polymorphism in Cyclooxygenase-2 (COX2) Gene (and also the Methylation levels within the COX2 affect COX2 MRNA expression) has been repeatedly implicated in Periodontitis.
Increased circulating systemic levels of IL-6 decreased, after nonsurgical periodontal
therapy, resulting in clinical improvement of the Periodontal status.
In the clinical context, TNFα and IL-1β have been found in increased concentrations in GCF and levels are reported to decrease after treatment of periodontal disease.
In addition, enhanced levels of IL-8 were demonstrated in the GCF collected from periodontitis sites compared with healthy control sites and IL-8 levels decreased after periodontal therapy.
High levels of the chemokines IL-8, Monocyte chemoattractant
protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP1α) and RANTES (regulated on activation, normal T cell expressed and secreted), in periodontitis is
supported by studies demonstrating increased levels of these chemokines in gingival biopsies and/or GCF of patients with periodontitis as well as decreased levels of chemokines in the GCF after periodontal treatment.
Monocyte chemoattractant protein-1 (MCP-1) is the most important chemokine that regulates migration and infiltration of monocytes/macrophages.
Significantly elevated MCP-1 concentrations is found in preeclamptic patients.
A range of Arachidonic acid metabolites are produced in the Periodontal Tissues. These Eicosanoids include Prostanoids and Leukotrienes.
Leukotriene B4 (LTB4) is markedly increased in Chorioamnionitis associated Preterm Labor.
Biomarkers
Supine hypotensive syndrome (also referred to as inferior vena cava compression syndrome) is caused when the gravid uterus compresses the inferior vena cava when a pregnant woman is in a supine position, leading to decreased venous return centrally.
The ideal position of the Pregnant patient in the dental chair is the left lateral decubitus position with the right buttock and hip elevated by 15°.
Abbreviations
MEK3--MITOGEN ACTIVATED PROTEIN kinases, IFN-γ, interferon-γ; IL, interleukin;
LPS, Lipopolysaccharide; MMP, Matrix metalloproteinase; PTB pre term birth,
OPG, osteoprotegerin; PAMPs, pathogen-associated molecular patterns;
PGE2, prostaglandin E2; PMN, polymorphonuclear leukocytes;
RANK, receptor activator of nuclear factor-κB;
RANKL, receptor activator of nuclear factor-κB ligand;
TGF-β, transforming growth factor β; TLRs, toll-like receptors;
TNFα, tumor necrosis factor α; and Treg, regulatory T cell
Issued in Public Interest
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