1. Periodontal Disease and Preterm Birth Gazabpreet Bhandal 1 st year Resident, Dept. of Periodontics

2. Outline Pathogenesis of Periodontitis Pathogenesis of Preterm Birth Inter-relationship between Periodontitis and Preterm Birth Conclusion

3. Periodontal Disease An infectious disease resulting in inflammation within the supporting tissues of the teeth, progressive attachment and bone loss and is characterized by pocket formation and/or recession of the gingiva. RISK FACTORS: 1.Bacterial factors 2.Smoking 3.Age 4.Host Response Related -Systemic ( eg: Diabetes, Pregnancy ) -Stress -Genetics * Periodontal diseases are “a specific mixed infections which cause periodontal destruction in the appropriately susceptible host” (Offenbacher 1996)

4. Bacterium involved: Microbial complexes in subgingival plaque: Socransky et al, 1998

5. Pathophysiology of the Periodontal Disease Periodontal Disease Direct effects of bacteria: Inc. edema Inc. GCF Proteases, Collagenases, Fibrinolysin, phospholipase A H2S, NH3 Genetic Risk Factors: Host Immuno- inflammatory response Connective tissue and bone metabolism Environmental and Acquired Risk factors Indirect Effects of bacteria: PMNs Lymphocytes Monocytes Fibroblasts LPS Pro-inflammatory cytokines: (IL-1,IL-6,IL-8,TNF- α, PGE- 2, MMPs)

6. Organic MoleculeFunction CollagenaseBreaks peptide bonds in collagen. Virulence factor FibrinolysinInactivates fibrin molecules occurring in undesirable exudates Phospholipase AInvolved in breakdown of phospholipids to Fatty Acids MMPsZn dependent endopeptidases responsible for degradation of extracellular matrix TNF-alphaAdipokine ; Produced chiefly by activated macrophages. LPSEndotoxin; binds to CD14/TLR4/MD2 receptor complex  stimulates pro- inflammatory cytokines and NO.

7. CD14/TLR4/MD2 receptor complex

8. Pathogenesis

9. Low Birth Weight Preterm Birth According to WHO, preterm birth is defined as delivery before 37 completed weeks of gestation. Low Birth Weight is defined as weight less than 2,300gms

10. Pathophysiology of Preterm Birth

11. Chorioamnionitis Chorioamnionitis or intraamniotic infection is an acute inflammation of the membranes and chorion of the placenta, typically due to ascending microbial infection in the setting of membrane rupture. Overall, 1-4% of all births in the US are complicated by chorioamnionitis.

12. Routes of chorioemnionitis

13. Ascending Infection Microorganisms residing in the external genitalia gain access to the amniotic sac Debilitation and rupture of the sac Spread of the infectious agent into the amniotic fluid

14. Role of pro-inflammatory cytokines in preterm birth Infected sites (eg: Periodontium) or Placenta Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) Stimulation of PGE2 synthesis by human placenta and chorioamnion Induction of Abortion or labor Examination of effect of P.gingivalis on pregnant hamsters revealed elevation of PGE2 and TNF-alpha levels (Collins 1994)

15. PGE2 synthesis

16. Inter-relationship between Periodontal disease and Preterm Birth

17. Offenbacher (1996), Jeffcoat (2001), Jarjoura (2005) : Proposed that periodontal disease is a risk factor for PLBW. Scaling and Root Planing in pregnant females reduced the incidence of preterm birth (Jeffcoat 2001)

18. Negative evidences: Davenport et al(2002), Noack et al(2004), Veltore et al (2008), Rajapakse et al(2005): No evidence for association between periodontal disease and preterm low birth weight. Hoolbrook et al(2004), Moore et al(2005) : Reported no association between the severity of the periodontal disease and pregnancy outcome. Buduneti et al(2005): No difference in dental and periodontal parameters between cases and controls.

19. Sources of Bias: 1.Variation in the definition of the periodontal disease. 2.Variation in the definition of the Adverse Pregnancy Outcomes (APOs) 3.Confounding factors (eg: socio-economic status and smoking)

20. Conclusion There are numerous studies that support a positive association between periodontal disease and preterm birth but unfortunately trials of antibiotic treatment have not shown any significant decrease in the rate of preterm birth. The effectiveness of antimicrobial therapy in eradicating these infections suggests that its failure to prevent preterm births is evidence that the infections alone are not causal. Longitudinal studies are warranted to establish a stronger and causal relationship between the two.