Effect of Periodontal Effect of Periodontal Infections on Fetal Development Infections on Fetal Development

& Pregnancy Outcomes& Pregnancy Outcomes

National Academy for State Health PolicyNational Academy for State Health PolicyDenver, Colorado October 15, 2007Denver, Colorado October 15, 2007

Gary C. Armitage, DDS, MSGary C. Armitage, DDS, MSProfessor of Periodontology, UCSFProfessor of Periodontology, UCSF

Special SupplementSpecial SupplementScientific AmericanScientific American

(October 2006)(October 2006)

““Growing evidence suggestsGrowing evidence suggeststhat poor oral hygiene duringthat poor oral hygiene duringpregnancy can adversely affectpregnancy can adversely affectthe health of newborns.”the health of newborns.”

For reprints: Call Crest Oral-BFor reprints: Call Crest Oral-BNorth American CustomerNorth American CustomerService at 800-543-2577.Service at 800-543-2577.

Two Major Two Major QuestionsQuestions

1. Does the presence of periodontal1. Does the presence of periodontal(or oral) infections (or oral) infections increaseincrease the risk the riskof experiencing adverse pregnancyof experiencing adverse pregnancyoutcomes? outcomes? [Risk factor question][Risk factor question]

2. Does the treatment of periodontal2. Does the treatment of periodontal(or oral) infections (or oral) infections decreasedecrease the risk the riskof experiencing adverse pregnancyof experiencing adverse pregnancyoutcomes? outcomes? [Intervention question][Intervention question]

Systemic Diseases Caused by Oral Systemic Diseases Caused by Oral Infections (1916)Infections (1916)

• • Ophthalmic DisturbancesOphthalmic Disturbances (infectious conjunctivitis, (infectious conjunctivitis, suppurating keratitis, scleritis, cyclitis, iritis, retinitis, optic suppurating keratitis, scleritis, cyclitis, iritis, retinitis, optic neuritis, glaucoma)neuritis, glaucoma)• • Aural DisturbancesAural Disturbances (otitis media, otlagia)(otitis media, otlagia)• • Diseases of the Alimentary CanalDiseases of the Alimentary Canal (septic gastritis, (septic gastritis, septic enteritis, colitis, appendicitis, proctitis, gastric and septic enteritis, colitis, appendicitis, proctitis, gastric and duodenal ulcers)duodenal ulcers)• • Diseases of the BloodDiseases of the Blood (pernicious anemia, septic anemia)(pernicious anemia, septic anemia)• • Infectious Diseases of the HeartInfectious Diseases of the Heart (pericarditis, myo- (pericarditis, myo- carditis, endocarditis)carditis, endocarditis)• • Affections of the Nervous SystemAffections of the Nervous System (neuritis, trifacial(neuritis, trifacialneuralgia, chorea, mental depression and melancholia)neuralgia, chorea, mental depression and melancholia)• • Diseases of the JointsDiseases of the Joints (acute arthritis, gouty arthritis)(acute arthritis, gouty arthritis)

Potential Associations Between Potential Associations Between Periodontal Infections and Periodontal Infections and Adverse Systemic OutcomesAdverse Systemic Outcomes

• • Heart DiseasesHeart Diseases �� Infective endocarditisInfective endocarditis �� Coronary heart disease Coronary heart disease (Atherosclerosis)(Atherosclerosis)

• • ArthritisArthritis and Failure of Artificial and Failure of Artificial JointsJoints

• • Neurological DiseasesNeurological Diseases �� Cerebrovascular disease Cerebrovascular disease (Nonhemorrhagic      stroke)(Nonhemorrhagic      stroke) �� Brain abscesses Brain abscesses �� Alzheimer’s disease Alzheimer’s disease �� Meningitis Meningitis

20072007

Potential Associations Between Potential Associations Between Periodontal Infections and Periodontal Infections and Adverse Systemic OutcomesAdverse Systemic Outcomes

• • Adverse Pregnancy OutcomesAdverse Pregnancy Outcomes ��Preterm birth; PreeclampsiaPreterm birth; Preeclampsia ��Fetal growth restrictionFetal growth restriction

• • Pulmonary DiseasesPulmonary DiseasesAspiration & Ventilator-associated Aspiration & Ventilator-associated pneumoniapneumoniaChronic obstructive pulmonary diseaseChronic obstructive pulmonary disease

• • Diabetes Mellitus (Onset & Control)Diabetes Mellitus (Onset & Control)• • Gastrointestinal DiseasesGastrointestinal Diseases

Gastric ulcersGastric ulcers Stomach cancerStomach cancer

20072007

28 y.o. WF28 y.o. WF Common Gingival ChangesCommon Gingival ChangesDuring Pregnancy:During Pregnancy: Pyogenic GranulomaPyogenic Granuloma (“Pregnancy Tumor”)(“Pregnancy Tumor”) Pregnancy GingivitisPregnancy GingivitisSecond TrimesterSecond Trimester

30 y.o. WF30 y.o. WF

Second TrimesterSecond Trimester

In addition toIn addition tothe pyogenicthe pyogenicgranuloma ingranuloma inthis patientthis patientthere is markedthere is markedgingival inflam-gingival inflam-mation aroundmation aroundmost teethmost teeth(arrows). (arrows).

Initiation & Progression of Initiation & Progression of Periodontal Disease Periodontal Disease

(The Health (The Health Gingivitis Gingivitis Periodontitis Paradigm)Periodontitis Paradigm)

• Shallow gingival sulcus• Apical termination of JE at CEJ

• Shallow periodontal pocket• Apical termination of JE at CEJ• Inflamed connective tissue

• Deepened periodontal pocket• Loss of CT attachment &     bone JE on root surface• Inflamed connective tissue

Clinical Appearance of Clinical Appearance of Healthy & Diseased Healthy & Diseased Periodontal TissuesPeriodontal Tissues

No signs of inflammationNo signs of inflammationNo gingival recessionNo gingival recessionShallow probing depthsShallow probing depthsNormal architecture (shape)Normal architecture (shape)

Signs of inflammationSigns of inflammationGingival recessionGingival recessionDeep probing depths (pockets)Deep probing depths (pockets)Abnormal architectureAbnormal architecture

Purulent Exudate (Pus) is Purulent Exudate (Pus) is Often Seen in Cases of Often Seen in Cases of Chronic PeriodontitisChronic Periodontitis

Redness &Swelling

PurulentExudate (Pus)

Purulent exudate is a sign of inflammation.Purulent exudate is a sign of inflammation.

55 y.o. WF55 y.o. WF

Bleeding on probing (BOP) is Bleeding on probing (BOP) is sign of periodontal sign of periodontal

inflammation.inflammation.DD CC

BOP occurs because the epithelial lining of theBOP occurs because the epithelial lining of thepocket wall is thin & often ulcerated (arrow).pocket wall is thin & often ulcerated (arrow).

aa

D = Dentin D = Dentin CC = Cementum = Cementumaa = artifact = artifact

x16x16

AlveolarAlveolarBoneBone

(Offenbacher S. (Offenbacher S. Scientific AmericanScientific American 2006 (October);Special Supplement, pp. 24-29.) 2006 (October);Special Supplement, pp. 24-29.)

ToothToothEnamelEnamel(Crown)(Crown)

Root ofRoot ofToothTooth

DentalDentalBiofilmBiofilm

(Dental Plaque(Dental Plaqueand Calculus)and Calculus)

Periodontal PocketPeriodontal Pocket(with ulcerated wall)(with ulcerated wall)

BREAKING THROUGH: When oralbacteria in the mother’s blood breachesthe placenta and reaches the fetus, ittriggers an immune and inflammatoryresponse, stressing the unborn child.Infections may account for up to 50%of premature births.

““What Every WomanWhat Every WomanNeeds to Know”Needs to Know”

Steven OffenbacherSteven OffenbacherScientific AmericanScientific American

(Special Supplement: October, 2006)(Special Supplement: October, 2006)

Campylobacter rectusBergeyella sp. clone AF14 (AK152)

A higher percentage of fetal cord blood A higher percentage of fetal cord blood samples from preterm infants (20.0%) are samples from preterm infants (20.0%) are

positive for IgM against positive for IgM against C. rectusC. rectus than those than those obtained from term infants (6.3%) [P < 0002].obtained from term infants (6.3%) [P < 0002].

SS

OMOM

CMCM

0.1 µm0.1 µm

(Borinski & Holt. (Borinski & Holt. Infect ImmunInfect Immun 1990;58:2770-2776.) 1990;58:2770-2776.) (Sára & Sleytr. (Sára & Sleytr. J BacteriolJ Bacteriol 2000;182:859-868.) 2000;182:859-868.)

100 nm100 nm

S-Layer of S-Layer of C. rectusC. rectus

Production of IgM Production of IgM by the fetus clearly by the fetus clearly shows that certain shows that certain oral bacteria cross oral bacteria cross the placenta and the placenta and gain access to the gain access to the immune system ofimmune system ofthe baby.the baby.

(Madianos et al.(Madianos et al.Ann PeriodontolAnn Periodontol2001;6:175-182.)2001;6:175-182.)

Lines of Evidence Suggesting Lines of Evidence Suggesting Periodontal Disease as a Risk Factor Periodontal Disease as a Risk Factor for Preterm Birth & Low Birthweightfor Preterm Birth & Low Birthweight

Natal Tooth; Navajo Baby Girl; 1-day old

• • Some epidemiologic studiesSome epidemiologic studies• • Detection of fetal cord bloodDetection of fetal cord bloodIgM against IgM against C. rectusC. rectus and and P.P.intermediaintermedia.*.*• • Many plausible mechanismsMany plausible mechanismsby which periodontal bacteriaby which periodontal bacteriaand inflammatory mediatorsand inflammatory mediators(PGE(PGE22) might trigger preterm) might trigger pretermbirth.birth.• • Preliminary interventionPreliminary interventiondata suggest that periodontaldata suggest that periodontaltreatment lowers risk.**treatment lowers risk.**

*Madianos et al. Ann Periodontol 2001;6:175-182.

**López et al. J Periodontol 2002;73:911-924.**Jeffcoat et al. J Periodontol 2003;74:1214-1218.

Mothers who gave birth to preterm low Mothers who gave birth to preterm low birthweight infants had statistically birthweight infants had statistically significant increased amounts of mean significant increased amounts of mean

clinical attachment loss (CAL) – OCAP Study clinical attachment loss (CAL) – OCAP Study Results. Results.

(Offenbacher et al. (Offenbacher et al. J PeriodontolJ Periodontol 1996;67:1103-1113.) 1996;67:1103-1113.)

Primi = primiparous (no previous birth); NBW = Normal Birth Weight

OR = 7.5 OR = 7.5 (CI, 1.95 – 28.8)(CI, 1.95 – 28.8)

N = 93 cases and 31 controls

Periodontal infection and preterm Periodontal infection and preterm birth. birth.

Results of a prospective study. Results of a prospective study. (Jeffcoat et al. (Jeffcoat et al. J Am Dent AssocJ Am Dent Assoc 2001;132:875-880) 2001;132:875-880)

Adjusted oddsAdjusted oddsratios for pretermratios for pretermbirths in patientsbirths in patientswith generalizedwith generalizedperiodontitis. Theperiodontitis. Theodds ratios haveodds ratios havebeen adjusted forbeen adjusted forsmoking, parity,smoking, parity,race, and maternalrace, and maternalage.age.

4.455.28

7.07

Number in each groupNumber in each groupnot specified.not specified.

< 37 weeks (OR = 4.45;C, I2.16-9.18)< 35 weeks (OR = 5.28; CI, 2.05-13.60)< 32 weeks (OR = 7.07; CI, 1.70-27.40)

N = 167(estimated)

Periodontitis Case = Women with ≥ 90 sites with ≥ 3 mm of attachment loss.Periodontitis Case = Women with ≥ 90 sites with ≥ 3 mm of attachment loss.

Higher risk of preterm birth and Higher risk of preterm birth and low birth weight in women with low birth weight in women with

periodontal disease.periodontal disease.(López et al. (López et al. J Dent ResJ Dent Res 2002;81:58-63.) 2002;81:58-63.)

Adjusted Risk Ratios and P Values for Risk Factors Associated with Preterm Birth/Low Birth Weight (PLBW) and with Preterm Birth (PTB) Risk Ratio Risk Ratio for PLBW for PTB (95% CI) P Value (95% CI) P Value

Previous PLBW 4.8 (1.6-14.0) 0.0004 7.5 (2.2-24.8) 0.001

< 6 Prenatal visits 4.7 (1.9-11.1) < 0.0001 7.5 (2.6-20.6) 0.0001

Periodontitis 3.5 (1.5-7.9) 0.003 2.9 (1.0-8.1) 0.045

Low maternal weight gain 2.6 (1.1-6.5) 0.030 ––– –––

Rate of delivery of a small-for-gestational-Rate of delivery of a small-for-gestational-age (SGA) infant by maternal periodontal age (SGA) infant by maternal periodontal disease category (health vs. mild vs. disease category (health vs. mild vs. moderate/severe) and serum C-reactive moderate/severe) and serum C-reactive

protein quartiles.protein quartiles.

Q1

Q2

Q3

Q4

CRPQuartiles

PeriodontalHealth

MildPeriodontitis

Moderate-SeverePeriodontitis

SGA(%)

20

15

10

5

0

(Boggess et al. (Boggess et al. Am J Obstet GynecolAm J Obstet Gynecol 2006;194:1316-1322.) 2006;194:1316-1322.)

North Carolina Population (University of North Carolina & Duke Medical Center)

[N = 1,017 women of whom[N = 1,017 women of whom67 (6.6%) delivered an67 (6.6%) delivered anSGA infant]SGA infant]

(n = 145)(n = 588)(n = 284)

13.8%13.8%

6.5%6.5%3.2%3.2%

(P < 0.001)(P < 0.001)

(Offenbacher at al. (Offenbacher at al. Obstet GynecolObstet Gynecol 2006;107:29-36.) 2006;107:29-36.)

Maternal age (P < 0.001)Maternal age (P < 0.001)African American (P < 0.001)African American (P < 0.001)

Not married (P < 0.005)Not married (P < 0.005)Food stamp eligible (P < 0.05)Food stamp eligible (P < 0.05)

No medical insurance (P < 0.05)No medical insurance (P < 0.05)

Previous preterm deliveryPrevious preterm delivery(P < 0.001)(P < 0.001)

Chorioamnionitis (P < 0.001)Chorioamnionitis (P < 0.001)[However, n = only 10/13][However, n = only 10/13]

Moderate-Severe Periodontal Moderate-Severe Periodontal Disease (P < 0.001)Disease (P < 0.001)

Progression of PeriodontalProgression of PeriodontalDisease (P < 0.001)Disease (P < 0.001)

Kaplan-Meier curves forKaplan-Meier curves forpregnancy-gestational ageoutcomes among 891 motherswhen both antepartum andpostpartum periodontal examdata were available.

Delivery outcomes for mothersDelivery outcomes for motherswith no progression of periodontalwith no progression of periodontaldisease (n = 658) or with progress-disease (n = 658) or with progress-ion (n = 233). Progression wasion (n = 233). Progression wasdefined as ≥ 4 sites with ≥ 2 mmdefined as ≥ 4 sites with ≥ 2 mmincrease in probing depths (PD),increase in probing depths (PD),with the postpartum PD ≥ 4 mm.with the postpartum PD ≥ 4 mm.

(Offenbacher at al. Progressive periodontal(Offenbacher at al. Progressive periodontaldisease and risk of very preterm delivery.disease and risk of very preterm delivery.Obstet GynecolObstet Gynecol 2006;107:29-36.) 2006;107:29-36.)

Definition of PreeclampsiaDefinition of Preeclampsia

A complication of pregnancy characterized byA complication of pregnancy characterized byhypertension, edema, and/or proteinuria; whenhypertension, edema, and/or proteinuria; whenconvulsions and coma are associated it isconvulsions and coma are associated it iscalled called eclampsiaeclampsia..

Riché et al. Periodontal disease Riché et al. Periodontal disease increases the risk of preterm delivery increases the risk of preterm delivery among preecalamptic women. among preecalamptic women. Ann Ann PeriodontolPeriodontol 2002;7:95-101. 2002;7:95-101.

Boggess et al. Maternal periodontal Boggess et al. Maternal periodontal disease is associated with an increased disease is associated with an increased risk of preeclampsia. risk of preeclampsia. Obstet GynecolObstet Gynecol 2003;101:227-231.2003;101:227-231.

General linear model of the effect of General linear model of the effect of changes in periodontal status during changes in periodontal status during

pregnancy on the adjusted rates of preterm pregnancy on the adjusted rates of preterm delivery in preeclamptic and non-delivery in preeclamptic and non-

preeclamptic mothers.preeclamptic mothers.

From: Riché et al. Ann Periodontol 2002;7:95-101.

Estimates of prevalenceEstimates of prevalencerates were adjusted forrates were adjusted formaternal race, age,maternal race, age,marital status, foodmarital status, foodstamp usage, insurance,stamp usage, insurance,previous preterm deliv-previous preterm deliv-ery, and chorioamnion-ery, and chorioamnion-itis.itis.

*P = 0.26 (NS)*P = 0.26 (NS)††P = 0.0006P = 0.0006

A Predictable Event – A Predictable Event – Edematous tissue will shrink Edematous tissue will shrink after the teeth are cleaned.after the teeth are cleaned.

Gingivitis (Pretreatment)Gingivitis (Pretreatment) • • RednessRedness • • Swelling (edema)Swelling (edema) • • Bleeding on probingBleeding on probing

Health (Post-treatment)Health (Post-treatment) • • Absence of inflammationAbsence of inflammation • • Improved architectureImproved architecture • • Better tissue toneBetter tissue tone

23 y.o. WF23 y.o. WF

BaselineBaseline 3 Months post-treatment3 Months post-treatment

Periodontal therapy may reduce the Periodontal therapy may reduce the risk of preterm low birth weight in risk of preterm low birth weight in women with periodontal disease: A women with periodontal disease: A randomized controlled study. – I. randomized controlled study. – I.

(López et al. (López et al. J PeriodontolJ Periodontol 2002;73:911-924.) 2002;73:911-924.) • • Purpose was to determine if periodontal therapy in pregnantPurpose was to determine if periodontal therapy in pregnantwomen with periodontal disease reduces the risk of pretermwomen with periodontal disease reduces the risk of pretermlow birth weight (PLBW).low birth weight (PLBW).• • 400 pregnant women were enrolled, with 200 assigned to a400 pregnant women were enrolled, with 200 assigned to aperiodontal Treatment Group and 200 were used controls.periodontal Treatment Group and 200 were used controls.• • Treatment consisted of oral hygiene instructions, SRP, andTreatment consisted of oral hygiene instructions, SRP, andonce daily rinsing with 0.12% chlorhexidine; completed beforeonce daily rinsing with 0.12% chlorhexidine; completed before28 weeks of gestation. The Control Group was not treated28 weeks of gestation. The Control Group was not treateduntil after delivery.until after delivery.• • 163 women in the Treatment Group and 188 in the Control 163 women in the Treatment Group and 188 in the Control Group completed the study.Group completed the study.

Periodontal therapy may reduce the risk Periodontal therapy may reduce the risk of preterm low birth weight in women with of preterm low birth weight in women with

periodontal disease: periodontal disease: A randomized controlled study. – II. A randomized controlled study. – II.

(López et al. (López et al. J PeriodontolJ Periodontol 2002;73:911-924.) 2002;73:911-924.) Incidence of Preterm Births (PTB), Low Birth Weight (LBW), Both (PLBW)

Treatment Group Control Group (n = 163) (n = 188) N% N % P ValueIntention-to-treat analysis PTB 21.10 12 6.38 0.017 LBW 10.55 7 3.72 0.083 PLBW 31.63 19 10.11 0.001Protocol analysis PTB 21.22 12 6.38 0.001 LBW 10.61 7 3.72 0.11 PLBW 31.8431.84 19 10.11 0.003 Odds Ratio = 5.49 (C.I. 1.65 to 18.22); P = 0.001Odds Ratio = 5.49 (C.I. 1.65 to 18.22); P = 0.001

PLBW = Preterm/Low Birth Weight

– – Large Intervention Large Intervention Studies –Studies –

“Does Periodontal Therapy Reduce “Does Periodontal Therapy Reduce the Risk of Adverse Pregnancy the Risk of Adverse Pregnancy

Outcomes?”Outcomes?”

Obstetrics & Periodontal Therapy Study

Enrollment = 823Enrollment = 8234 Centers4 Centers University of Minnesota (2 sites)University of Minnesota (2 sites) University of MississippiUniversity of Mississippi Columbia UniversityColumbia UniversityBrian Michalowicz (PI)Brian Michalowicz (PI)

Enrollment Target = 1,800Enrollment Target = 1,8003 Centers3 Centers University of North CarolinaUniversity of North Carolina University of AlabamaUniversity of Alabama University of Texas (San Antonio)University of Texas (San Antonio)Steven Offenbacher & James Beck (PIs)Steven Offenbacher & James Beck (PIs)

COMPLETEDCOMPLETED

Treatment of Periodontal DiseaseTreatment of Periodontal Diseaseand the Risk of Preterm Birthand the Risk of Preterm Birth(Michalowicz et al. (Michalowicz et al. N Engl J MedN Engl J Med2006;355:1885-1984.2006;355:1885-1984.

“Treatment of periodontitis in pregnantwomen improves periodontal disease and is safe but does not significantlyalter rates of preterm birth, low birthweight, or fetal growth restriction.”

Kaplan-Meier curves for cumulative incidence Kaplan-Meier curves for cumulative incidence of pregnancies ending before 37 weeks.of pregnancies ending before 37 weeks.

(Michalowicz et al. (Michalowicz et al. N Engl J MedN Engl J Med 2006;355:1885-1894 ) 2006;355:1885-1894 )

5 spontaneous abortions or stillbirths in5 spontaneous abortions or stillbirths intreatment group versus 14 in the controltreatment group versus 14 in the controlgroup (P = 0.08)group (P = 0.08)

““We have hypothesized that once the inflam-We have hypothesized that once the inflam-matory cascade is activated during pregnancy,matory cascade is activated during pregnancy,interventions targeting this pathway may beinterventions targeting this pathway may beineffective in reducing the rate of preterm birthineffective in reducing the rate of preterm birth((Arch Pediatr Adolesc MedArch Pediatr Adolesc Med 2005;159:89-90.). 2005;159:89-90.). Treatment during pregnancy may be too late; Treatment during pregnancy may be too late; it is possible that treatment either before preg-it is possible that treatment either before preg-nancy (in nulliparous women) or in the period nancy (in nulliparous women) or in the period between pregnancies (for multiparous women, between pregnancies (for multiparous women, especially those with a history of preterm birth) especially those with a history of preterm birth) may yield more promising results.”may yield more promising results.”

Goldenberg RL, Culhane JF. Goldenberg RL, Culhane JF. N Engl J MedN Engl J Med 2006;355:1925-1927. 2006;355:1925-1927.

Comparison of Baseline & Post-treatment Bleeding on Probing (BOP) in

the Obstetrics & Periodontal Therapy (OPT) Study

69 66.9 69.6

45.9

0

10

20

30

40

50

60

70

80

1

69%69% 66.9%66.9% 69.6%69.6%

45.9%45.9%

NO TREATMENT

PERIODONTALTREATMENT

BASELINE(CONTROL)

CONTROL(After Delivery)

BASELINE(EXPERIMENTAL)

EXPERIMENTAL(After Delivery)

(Data from: Michalowicz et al. (Data from: Michalowicz et al. N Engl J MedN Engl J Med 2006;355:1885-1894. ) 2006;355:1885-1894. )

[University of Minnesota, University of Kentucky, University of Mississippi, Columbia University]

N = 410N = 410 N = 413N = 413

Decrease in BOP After Scaling & Root Planing in Two Populations

with Chronic Periodontitis

81.7

10.4

68

10

0

10

20

30

40

50

60

70

80

90

1

81.7%81.7%

10.4%10.4%

68%68%

10%10%

BASELINE BASELINE7 MONTHS 6 MONTHS

Apatzidou & Kinane. Apatzidou & Kinane. J ClinJ ClinPeriodontolPeriodontol 2004;31:132-140. 2004;31:132-140.

Badersten et al. Badersten et al. J Clin Perio-J Clin Perio-dontoldontol 1981;8:57-72. 1981;8:57-72.

UNIVERSITY OF LUND (SWEDEN) UNIVERSITY OF GLASGOW (SCOTLAND)

N = 15N = 15

N = 20N = 20

Should the Periodontal Therapy in the OPT Study Have Been More Rigorous?

69.6

45.9

68

10

0

10

20

30

40

50

60

70

80

1

68%68%69.6%69.6%

45.9%45.9%

10%10%

BASELINEBASELINE 6 MONTHS ~ 6 MONTHS

Apatzidou & Kinane. Apatzidou & Kinane. J ClinJ ClinPeriodontolPeriodontol 2004;31:132-140. 2004;31:132-140.

Michalowicz et al. Michalowicz et al. N Engl JN Engl JMedMed 2006;355:1885-1894. 2006;355:1885-1894.

RESULTS OFPERIODONTALTREATMENT

IN OPT STUDY

[Change in % sites with Bleeding on Probing versus Baseline][Change in % sites with Bleeding on Probing versus Baseline]

TYPICAL(EXPECTED)RESULTS OFSCALING &

ROOT PLANING

N = 20N = 20N = 413N = 413

Additional (Speculative) Additional (Speculative) Conclusions that can be made Conclusions that can be made

from the OPT Resultsfrom the OPT Results

1. Although the periodontal treatment that1. Although the periodontal treatment thatwas provided was the standard of care (i.e., was provided was the standard of care (i.e., OHI, SRP, monthly evaluation + additionalOHI, SRP, monthly evaluation + additionalscaling “as needed”), it was scaling “as needed”), it was insufficient to insufficient to control the periodontal diseasecontrol the periodontal disease. The post-. The post-treatment presence of a high % of sites with treatment presence of a high % of sites with BOP means that the patients were still infected.BOP means that the patients were still infected.2. 2. Treatment may have been too lateTreatment may have been too late..3. 3. More frequent treatment may be neededMore frequent treatment may be needed..

_ THE UNIVERSITY OFWESTERN AUSTRALIA

(PERTH)

FACULTY OFMedicine, Dentistryand Health Sciences

King EdwardKing EdwardMemorial HospitalMemorial Hospital

UNIVERSITY OFPENNSYLVANIAHEALTH SYSTEM

Enrollment Goal = 1,080Enrollment Goal = 1,080Periodontal Treatment = OHI + SRP + 0.12% Chlorhexidine rinsePeriodontal Treatment = OHI + SRP + 0.12% Chlorhexidine rinse[540 treated during 1st or 2nd trimesters; 540 treated after delivery][540 treated during 1st or 2nd trimesters; 540 treated after delivery]

Principal Investigator = John P. Newnham, MDPrincipal Investigator = John P. Newnham, MD

Enrollment Goal = 1,800Enrollment Goal = 1,800Periodontal Treatment = OHI + SRPPeriodontal Treatment = OHI + SRP[900 treated during 2nd trimester; 900 treated after delivery][900 treated during 2nd trimester; 900 treated after delivery]

Principal Investigators = James Beck, PhD &Principal Investigators = James Beck, PhD & Steve Offenbacher, DDS, PhDSteve Offenbacher, DDS, PhD

University of North Carolina

University of AlabamaUniversity of Texas (San Antonio)

Enrollment Goal = > 1,000 (Phase III study)Enrollment Goal = > 1,000 (Phase III study)Periodontal Treatment = SRP versus “Superficial Cleaning”Periodontal Treatment = SRP versus “Superficial Cleaning”Principal Investigator = George A. Macones, MDPrincipal Investigator = George A. Macones, MD

““Prevention of Pre-termPrevention of Pre-termBirth by Treatment ofBirth by Treatment ofPeriodontal Disease”Periodontal Disease”

““Periodontal InfectionPeriodontal Infection and Prematurity Study”and Prematurity Study”

SRP = Scaling & Root Planing; OHI = Oral Hygiene InstructionsSRP = Scaling & Root Planing; OHI = Oral Hygiene Instructions

Yellow-eyed Penguin Yellow-eyed Penguin (Megadyptes antipodes)(Megadyptes antipodes)

Otago PeninsulaOtago Peninsula(Dunedin, New Zealand(Dunedin, New Zealand

South Island)South Island)