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Periodontal Disease and Risk for Preterm Birth

Periodontal Disease and Risk for Preterm Birth. Bryan Michalowicz, DDS University of Minnesota School of Dentistry. Health Consequences of Preterm Birth. Short-term :

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Periodontal Disease and Risk for Preterm Birth

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  1. Periodontal Disease and Risk for Preterm Birth Bryan Michalowicz, DDS University of Minnesota School of Dentistry

  2. Health Consequences of Preterm Birth Short-term: Respiratory distress syndrome , Intraventricular hemorrhage, Periventricular hemorrhagic infarction, Periventricular leukomalacia, Necrotizing enterocolitis, Bronchopulmonary dysplasia, Sepsis, Patent ductus arteriosus Long-term: Cerebral palsy, Attention deficit disorder, Retinopathy of prematurity, Mental retardation, Cardiovascular malformations

  3. USA Today, November 14, 2006

  4. Primary Predictors Black race, Young mother, Domestic violence, Low socioeconomic status, Stress or depression, Cigarette smoking, Cocaine or heroin use, Low Body Mass Index, Low maternal weight gain before pregnancy, Previous preterm birth or second trimester pregnancy loss, Previous induced abortion, Family history/ inflammatory gene polymorphisms, Chronic lung disease, Chronic hypertension, Diabetes, Renal disease Secondary Predictors No or inadequate prenatal care, In vitro fertilization, Low maternal weight gain late in pregnancy, Iron-deficiency anemia, Pre-eclampsia, Elevated fetal fibronectin, α-fetoprotein, alkaline phosphatase, or G-CSF, Early Contractions, Vaginal bleeding in first or second trimester, Short cervical length, Bacterial vaginosis, especially early in pregnancy, Chorioamnionitis, Placental abruption, Placenta previa, Hydramniosis, Pre-eclampsia, Multiple fetuses

  5. Gingivitis

  6. Chronic Periodontitis

  7. Periodontal Diagnosis

  8. Why periodontal disease and preterm birth? • Some infections are risk factors for PTB. • Periodontal pathogens can enter the blood stream through infected gums. • Chronic periodontal inflammation involves mediators that are associated with PTB (e.g., PGE2, IL-1, IL-6). • Supporting evidence in animal models

  9. Periodontitis has been associated with: • Bacterial pneumonia • Osteoporosis • Poor physical fitness • Foot balance • Rheumatoid arthritis • Obesity (young adults) • Vitamin C intake • Oral Cancer • Gastric cancer • Smoking • CVD • PAD • Stroke/TIA • Diabetes • Pre-eclampsia • Low birth weight • Preterm birth • COPD • Gastric cancer

  10. Offenbacher et al, 1996 • 124 women examined either at pre-natal visit or within 72 hours post-partum • Cases (n=93): current or previous LBW baby (< 2,500 g) and spontaneous abortion < 12 wks, pre-term labor, PROM with resultant delivery < 36 wks, or delivery < 36 wks • Controls (n=31): all birth weights > 2,500 g and no PTL or PROM

  11. Mean CAL (mm) in cases and controls * * * P = 0.04 compared to NBW controls

  12. Offenbacher et al, 1996 • Adjusted* odd ratios for association between severe periodontitis (60% of sites with 3+ mm CAL) and PLBW were: 7.9 (1.95 – 28.8) for all PLBW cases 7.5 (1.52 – 41.4) for primiparous cases * Adjusted for race, age, previous births, tobacco use, BV, Hx of bacteriuria

  13. Offenbacher et al., Obstetrics & Gynecology 2006;107:29-36

  14. December 2006 Review by Xiong et al. • 44 studies exploring association between periodontitis and adverse pregnancy outcomes (26 case-control, 13 cohort, 5 controlled clinical trials) • 29 suggest a positive association • Many reports based on small samples or may not have controlled fro confounders

  15. Vergnes JN, Sixou M. Preterm low birth weight and maternal periodontal status: a meta-analysis. Am J Obstet Gynecol. 2007 Feb;196(2):135.e1-7. “RESULTS: The literature search revealed 17 articles that met the inclusion criteria. Seven thousand one hundred fifty-one women participated in the studies, 1056 of whom delivered a preterm and/or low birthweight infant. The overall odds ratio was 2.83 (95% CI: 1.95-4.10, P < .0001). This pooled value needed to be interpreted cautiously because there appeared to be a clear trend for the better quality studies to be of lower association strength. CONCLUSION: These findings indicate a likely association, but it needs to be confirmed by large, well-designed, multicenter trials.”

  16. Intervention Studies

  17. Lopez et al. J Periodontol, 2002 • 18-35 year old women in Santiago, Chile • 9-21 wks of gestation with fewer than 18 teeth and 4+ teeth with 4 mm PD and 3+ mm CAL • Randomized to receive either SCRP + and pxs q2-3 weeks before 28 wks or no treatment • 29 in treatment group received amoxicillin + metronidazole for severe AgP

  18. Intent-to-treat analysis Lopez et al. J Periodontol, 2002

  19. Jeffcoat, Hauth, et al. J Periodontol 2003 • 368 women between 21-25 weeks of gestation and >3 tooth sites with 3+mm CAL (UAB) • Randomized to receive: • Dental cleaning + placebo (tid) • SCRP + placebo • SCRP + metronidazole (250 mg tid for 1 wk) • Randomization stratified on BMI, BV, and history of SPTB prior to 35 wks • 723 additional women with periodontitis as controls

  20. Jeffcoat, Hauth, et al, 2003 p = 0.12

  21. Obstetrics and Periodontal Therapy Trial

  22. The OPT Clinical Investigative Team • Hennepin County Medical Center: A. DiAngelis, V. Lupo, L. Simpson, J. Anderson, K. Meyer, J. Danielson, T. Thompson • University of Kentucky: M. J. Novak, J. Ferguson, D. Dawson, A. Buell, D. Mischel, P. Stein, L. Cunningham, D. Dawson • University of Mississippi Medical Center: W. Buchanan, J. Bofill, S. Vance, G. Young, A. Garner, N. Wood, K. Holmes • Harlem Hospital/Columbia University: P. Papapanou, D. Mitchell, S. Matseoane, S. Lassiter, J. Mays, J. Jackson, E. Rijo, M. Bolden, C. Spicer • University of Minnesota: B. Michalowicz, J. Hodges, A. Deinard, P. Tschida, H. Voelker, J. Osborn, I. Olson, Y. He, Q. Cao, L. Wolff, E. Delmore

  23. Hypothesis • Treatment of pregnant women with periodontitis reduces the incidence of preterm delivery.

  24. OPT Trial • Women randomly assigned to receive scaling and root planing either prior to 21 weeks (test) or after delivery (control) • Test subjects receive monthly polishings and oral hygiene reinforcement • All women receive essential dental care

  25. Inclusion Criteria • At least 16 years of age • have at least 20 natural teeth • have periodontal disease, defined as: 4 or more teeth with probing depth > 4 mm and clinical attachment loss > 2 mm, and bleeding on probing at 35 percent or more tooth sites. • Exclusion Criteria • had multiple fetuses • required antibiotic pre-medication • had a medical condition that precluded elective dental treatment • had extensive tooth decay or were likely to have fewer than 20 teeth after initial treatment.

  26. Obstetrical Outcomes • Primary: Gestational age at the end of pregnancy • Secondary: Birthweight

  27. Consented (n=939) Randomized (n=823) • TREATMENT GROUP (N=413) • Scaling & root planing before • 21 weeks + oral hygiene instruction • Received treatment (n=395) • Failed treatment visits or withdrew (n=18) CONTROL GROUP (N=410) Scaling & root planing after delivery Treatment Allocation • Monthly oral hygiene instruction • and scaling as needed • Lost to follow-up* (n=4) • Withdrew consent* (n=1) • Elective abortion* (n=1) • Brief monthly oral exams • Lost to follow-up* (n=3) • Withdrew consent* (n=1) • Elective abortion* (n=1) Follow-Up For gestational age (n=413) For gestational age (n=410) Analysis

  28. Baseline Characteristics † As a fraction of women with a previous pregnancy * As a fraction of all women with a previous live birth

  29. Baseline Dental Characteristics

  30. Cumulative Incidence of Pregnancies Ending < 37 Weeks

  31. Relative Hazard of the Pregnancy Ending < 37 weeks, According to Subgroup

  32. Birth Outcomes

  33. Birth Outcomes

  34. Neonatal Outcomes

  35. Periodontal Outcomes* *Change from baseline. Positive number indicates an improvement.

  36. Conclusions In pregnant women with periodontitis: • Non-surgical periodontal therapy delivered between 13 and 21 weeks of gestation does not significantly alter rates of preterm birth, low birthweight or fetal growth restriction • Non-surgical periodontal therapy delivered between 13 and 21 weeks of gestation is safe and effective

  37. Guy’s and St. Thomas Hospital Moore, et al.Br Dent J. 2004;197(5):251-8. • Enrolled women at 12 weeks of gestation • Conducted dental exams in hospital beds, evaluated two sites per tooth • Data available for 3,452 term, 286 preterm (< 37 wks), and 112 very preterm (< 32 wks) mothers

  38. Moore et al., Br Dent J (2004); 197, 251–258.

  39. Moore et al., Br Dent J (2004); 197, 251–258. p = 0.023

  40. Where to go from here? 1. Ongoing studies 2. Community concerns • Improve dental health awareness and access to care in pregnant women with periodontitis – care to improve oral health per se 3. Possible research questions • Does periodontal therapy delivered prior to conception affect birth outcomes? • Do comprehensive approaches that address all infections/chronic inflammatory states as well as deleterious habits and lifestyles improve birth outcomes? • What is the effect of periodontitis on early pregnancy losses? • Are periodontitis and preterm birth risk features of common phenotype?

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