maternal periodontal disease as a fetal stressor

Steven Offenbacher DDS, PhD, MMScJames D Beck, PhD

Center for Oral and Systemic DiseaseComprehensive Center for Inflammatory

DisordersUniversity of North Carolina at Chapel Hill

2001 Frances Glenn Mayson Symposium

“Pre-term Labor: Is the Fetus Trying to Tell Us Something November, 2001

What are the major pregnancy complications?

Preterm : <37 wks completed gestational age

Low birth weight <2500g

PPROM : Preterm premature rupture of membranes

PTL : Preterm labor Preeclampsia : Pregnancy

induced hypertension and proteinuria

Key Terms (outcomes)Partus & Neonate

Obstetric

Why is this important?

About 10% all births are preterm low birth weight

Preterm birth accounts for two-thirds of all infant mortality

Each gram of fetal weight under 2500g costs 75$ in neonatal unit expenses

USA NICU costs in excess of 5.5 billion dollars a year as consequence of preterm births

Preterm Births

Infant Health Issues Improvements in perinatal

care have dramatically improved survival rates of premature births

This has resulted in improvement in neonatal mortality

BUT There has been no decrease in the rate of preterm births.

Actual costs and number of low birth weight survivors with disabilitites has increased.

Low-birthweight live births(Percent of live births less than 2,500g in US during

selected years according to maternal race)

0

2

4

6

8

10

12

14

1970 1980 1990 1994 1998

All racesWhiteBlack

Infant Health Issues

Since 1981, percent born (survivors) < 37 weeks has increased 17%

Significant disparities by race and ethnicity

Preterm infants are–7x more likely to die prior to 1st birthday – at increased risk for: neuro-developmental, respiratory

disorders, learning disabilities, delayed development, cerebral palsy

KNOWN RISK FACTORS

Tobacco, drug or alcohol usage. Previous preterm delivery Concurrent genitourinary tract infection: Bacterial vaginosis, chorioamnionitits, STDs

MAJOR

KNOWN RISK FACTORS

Maternal age, weight, stature, cervical length

Nulliparous Stress – physical & social, familial

support, SES Familial history Level of prenatal care

MINOR

25-50% of preterm births occurin absence of significant risk factors

Cervicaldilation

Fetus

Amnion

Cervix

Vagina

Fetus

AmnionAmnion

Vaginal Infection[BV, bacterial vaginosis]

Uterine contraction

Pathogenesis of bacterial vaginosis induced

prematurity

?Fetus

AmnionAmnion

UterusPlacenta & Membranes

IL-1, TNF, PGE2

M

PGE2, IL-1b, TNFa, IL-6,

MMPs

Lymphocytes

Monocytes

Gram- Flora

Leukocyte

Wall

Epithelial Ulceration

Bacterial Invasion,Bacteremia

Periodontitis: Intra-Oral toExtra-Oral Pathway

Biochemical Mediators of Prematurity

ILIL-1

PGEPGE22

IL-1IL-1

TNF

TNF

LPS Can induce uterine contraction, cervical dilation, labor or abortion, placenta damage, inhibit fetal growth, mediate preterm delivery, low birth weight and neonatal morbidity.IL-6IL-6

ILIL-6

Biochemical mediators and indicators of fetal stress

Fetal antibody to bacteria : e.g. Rubella IgM

sICAM: soluble Intracellular adhesion molecule, a marker of vascular (endothelial) stress

Fetal CRP (C-reactive protein), acute phase response

Prospective Study of Pregnant Mothers

MaternalPeriodontitis

•Models that adjust for obstetric risk factors: e.g. Demographic, smoking, SES, infection, parity•Clinical periodontal disease as exposure for abnormal pregnancy outcome

Risk

Prematurity(gestational age <37 weeks)

Low Birth Weight(<2500g)

Impaired Fetal Growth(low weight for getational age)


Prematurity

Low Birth Weight

Impaired Fetal Growth


Biological Mechanisms

Microbial InfectionMaternal Antibody

Fetal Exposure

PregnancyOutcome

OCAP- Oral Conditions and Pregnancy- NIDCR

funded

Preliminary Analyses• Prospective study of pregnant women to

determine contribution of periodontal disease to pregnancy complications.

• Exclusions included HIV, drug abuse, diabetes, hypertension, STD

• Currently enrolled over 1200 subjects, expected total of about 1500.

• Data presented reflect 814 deliveries

19

Flow Chart of Oral Conditions and Pregnancy Study (OCAP)University of North Carolina Chapel Hill and Duke University Medical Center

Presentation at Prenatal Clinic Refuse

Ineligible

EligibleWomen < 26 weeks

gestation

Refer for dental cleaning at UNC School of Dentistry

Obtain samples at initial prenatal or enrollment visit

Consent

Monitor for PTL, PROM, bacterial vaginosis and other infections

Obtain samples during immediate postpartum period

OCAP Measurements

OB Risk profile: Demographic, obstetric, medical, behavioral & socioeconomic parameters

Maternal Blood

Antepartum

IgG & IgM to Periodontal & Vaginal Organisms

Inflammatory MediatorsIL-1, TNFa, CRP, sICAM, IL-6, total 8-iso PGF2a

Interleukin SNPs

Vaginal & Cervical Vaginal and Periodontal Organisms

Inflammatory MediatorsIL-8, IL-1, TNFa, IL-6

Periodontal PlaqueGingival Crevicular FluidPeriodontal Exam

OCAP Measurements

OB Risk profile: Patient interview, chart abstraction

Repeat: Maternal Blood

Postpartum

Periodontal Plaque Gingival Crevicular Fluid Periodontal examFetal cord bloodNeonatal data

IgM to Periodontal Organisms (and vaginal)

Inflammatory MediatorsIL-1, TNFa, CRP, sICAM, IL-6, total 8-iso PGF2a

OCAP Pregnancy Outcomes

1. Prematurity (Gestational Age <37 weeks). Excluding elective abortion

2. Birth weight (<2500g)3. Weight for gestational age (small for

gestational age, growth restriction)

Weight

Gestational Age (weeks)37 3938 40

Prematurity

2500gGrowth Restriction

(lowest 10%)

OCAP Baseline characteristics and exposures

Term Preterm TotalSubjects

624 (76.9%) 188(23.1%) 812

275 (67.6%) 132 (32.4%)a 407 (50.1%)

311 (86.2%) 50 (13.9%) 361 (44.5%)

38 (86.4%) 6 (13.6%) 45 (5.4%)

27.6 + 6.63 25.8 + 6.07b

186 (29.8%) 56 (29.8%) 242 (29.8%)

98 (15.7%) 38 (20.2%) 136 (16.8%)

142 (22.8%) 50 (26.6%) 192 (23.7%)

Race Black

White

Other

Age (mean+SD)

Married

Smoke

WIC food stamps

P values

a)<0.0001

b) 0.0017

OCAP Baseline characteristics and exposures

Term Preterm TotalSubjects

624 (76.9%) 188(23.1%) 812

275 (67.6%) 132 (32.4%)a 407 (50.1%)

311 (86.2%) 50 (13.9%) 361 (44.5%)

38 (86.4%) 6 (13.6%) 45 (5.4%)

27.6 + 6.63 25.8 + 6.07b

186 (29.8%) 56 (29.8%) 242 (29.8%)

98 (15.7%) 38 (20.2%) 136 (16.8%)

142 (22.8%) 50 (26.6%) 192 (23.7%)

Race Black

White

Other

Age (mean+SD)

Married

Smoke

WIC food stamps

P values

a)<0.0001

b) 0.0017

OCAP Baseline characteristics and exposuresTerm Preterm Total

Subjects 624 (76.9%) 188(23.1%) 81289 (14.3%) 56 (29.8%)a 145 (17.9%)259 (41.5%) 80 (42.6%) 339 (41.8%)33 (5.3%) 14 (7.5%) 47 (5.8%)4 (0.6%) 12 (6.4%)a 16 (2.0%)

163 (26.1%) 38 (18.9%) 201 (24.8%)434 (69.6%) 132 (70.2%) 566 (69.7%)27 (4.3%) 18 (9.6%)c 45 (5.5%)180(33.1%) 75 (47.2%)d 255 (36.3%)

Previous PretermFirst Time BirthBV TreatmentChorioamnionitisPeriodontal StatusHealthMildMod-severeIncidence/Progression

P values

a)<0.0001

b) 0.0017

c) 0.013

d) 0.0012

OCAP Baseline characteristics and exposuresTerm Preterm Total

Subjects 624 (76.9%) 188(23.1%) 81289 (14.3%) 56 (29.8%)a 145 (17.9%)259 (41.5%) 80 (42.6%) 339 (41.8%)33 (5.3%) 14 (7.5%) 47 (5.8%)4 (0.6%) 12 (6.4%)a 16 (2.0%)

163 (26.1%) 38 (18.9%) 201 (24.8%)434 (69.6%) 132 (70.2%) 566 (69.7%)27 (4.3%) 18 (9.6%)c 45 (5.5%)180(33.1%) 75 (47.2%)d 255 (36.3%)

Previous PretermFirst Time BirthBV TreatmentChorioamnionitisPeriodontal StatusHealthMildMod-severeIncidence/Progression

P values

a)<0.0001

b) 0.0017

c) 0.013

d) 0.0012

Health= no PD>3mm or CAL>2mmHealth= no PD>3mm or CAL>2mm

Mod-severe= 4+ sites 5+mm PD and 2+mm C ALMod-severe= 4+ sites 5+mm PD and 2+mm C AL

Incidence/Progression = 4+ sites with PD Incidence/Progression = 4+ sites with PD increase 2+mmincrease 2+mm

Figure 1A. Adjusted distribution of maternal antepartum periodontal status by GA at delivery among 812 pregnant women

Gestational Age (weeks)

% of

Mothers

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<28 <32 <35 <37 term

Mod-SevereMildHealth

a)p=0.06b)p=0.01c)p=0.006d)p=0.002

ab

cd

Figure 1A. Adjusted distribution of maternal antepartum periodontal status by GA at delivery among 812 pregnant women


% of

Mothers

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<28 <32 <35 <37 term

Mod-SevereMildHealth

a)p=0.06b)p=0.01c)p=0.006d)p=0.002

ab

cd

Maternal Periodontitis and Gestational Age

Adjusted for race, smoking, food stamps, marital status, previous

preterm birth, first time birth,

bacterial vaginosis,

chorioamnionitis,

Maternal Periodontitis and Birth Weight

Figure 1B. Adjusted distribution of maternal antepartum periodontal status by BW at delivery among 812 pregnant women

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Mod-SevereMild

Health

Birth weight (grams)

% of

Mothers

>2500<1000 <1500 <2000 <2500

a)p=0.06b)p=0.004c)p=0.007d)p=0.0004

ab

cd

Figure 1B. Adjusted distribution of maternal antepartum periodontal status by BW at delivery among 812 pregnant women

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Mod-SevereMild

Health

Birth weight (grams)

% of

Mothers

>2500<1000 <1500 <2000 <2500

a)p=0.06b)p=0.004c)p=0.007d)p=0.0004

ab

cd

Adjusted for race, smoking, food stamps,

marital status, previous preterm

birth, first time birth, bacterial

vaginosis, chorioamnionitis

,

Distribution of time to premature delivery among 767 births based upon maternal antepartum periodontal status


% Pregnant

40

50

60

70

80

90

100

110

26 27 28 29 30 31 32 33 34 35 36 37 38

HealthMildMod-Severe

Health = absence of any PD>3mm and no sites with AL>2mm

Mod-Severe = 5mm PD and 2mm AL at 4 or more sites

Adjusted* Prevalence of Gestational Age at Delivery by Antepartum Maternal Periodontal

Disease Status

0%10%20%30%40%50%60%70%80%90%

100%

Health Mild Mod/Severe

< 2828 to <3535 to <37Term

% ofBirths

Maternal Antepartum Periodontal Status

* Maternal age, race, smoking, marital status, food stamps, bacterial vaginosis, and chorioamnionitis. Health = absence of any PD>3mm and no sites with

CAL>2mmMod-Severe = 5+mm PD and 2+mm CAL at 4 or more sites

Adjusted* Prevalence of Birth Weight at Delivery by Antepartum Maternal

Periodontal Disease Status

% ofBirths

Maternal Antepartum Periodontal Status

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<1000

1000-1999

2000-2499

>2500

* Maternal age, race, smoking, marital status, food stamps, bacterial vaginosis , and chorioamnionitis.

Health Mild Mod/Severe

500

1000

1500

2000

2500

3000

3500

4000

<28 28 to <32 32 to <35 35 to<37 Term

No Incidence/Progression

Incidence/ Progression

Gestational Age in Weeks

Mean BirthWeight(grams)

a

a) p=0.01b) p=0.007c) p=0.09d) p=0.03e) p=0.12 _

b

c

d

e

Effects of maternal periodontal disease incidence/ progression * during pregnancy

on mean birth weight by gestational age adjusting for maternal race, sex of baby and

parity* 4+ sites with 2+mm PD increase

Table 2A. Logistic Regression Model* for Prematurity of GA<37 weeks (total n=672, n=148 for GA<37 )

0.98-2.191.47Incid/ProgrPeriodontal Disease

1.34-6.873.03Moderate-Severe Periodontal Disease

1.32-4.772.51BV & Chorioamnionitis

1.02-2.601.63First time birth

1.54-4.392.60Previous Preterm

0.70-2.001.18Smoking

1.75-4.552.82Race (African American)

0.83-2.211.35Mild Periodontal Disease

*Also adjusted for age, food stamps and marital status

OddsRatio 95% CI

Table 2B. Logistic Regression Model* for Prematurity of GA<35 weeks (total n=672, n=64 for GA<35)






0.45-2.441.05Smoking




OddsRatio 95% CI

Table 3. Logistic Regression Model* for Low Birth Weight of <2500 g (total n=664, n=96 for BW<2500g)






0.60-2.121.12Smoking




OddsRatio 95% CI

Table 4. Logistic Regression Model for Fetal Growth Restriction(lower 10th percentile of weight for gestational age, adjusting for maternal race, parity and baby sex)

0.95-4.091.97Smoking


0.41-2.240.96Ethanol

0.52-4.601.54Drugs

0.90-1.000.95Age

0.79-2.851.50Food Stamps

0..72-3.921.68Mild Periodontal Disease

OddsRatio 95% CI

Table 4. Logistic Regression Model for Fetal Growth Restriction(lower 10th percentile of weight for gestational age, adjusting for maternal race, parity and baby sex)

0.95-4.091.97Smoking


0.41-2.240.96Ethanol

0.52-4.601.54Drugs

0.90-1.000.95Age

0.79-2.851.50Food Stamps

0..72-3.921.68Mild Periodontal Disease

OddsRatio 95% CI

Perinatal MortalityHealth: 1.97%Mild: 3.16%

Mod-severe: 16.3%34/ 967, (p<0.0001)

Table 3. Effects of maternal periodontal disease progression during pregnancy on risk for FGR** (total n=680, n=39 for FGR )

1.72-7.243.52Incid/ Progrof Periodontal Disease



1.37-5.932.85Smoking

0.88-1.000.94Age

*Also adjusted for food stamps and marital status**Using Berkowitz FGR lower 10th percentile weights for GA based upon parity, baby sex and race

OddsRatio 95% CI

Antepartum maternal periodontal disease status and progression on birth weight for

all births of GA<37 weeks


Prematurity

Low Birth Weight

Impaired Fetal Growth


Biological Mechanisms

Microbial InfectionMaternal Antibody

Fetal Exposure

PregnancyOutcome

YES P.g. placental infection

NO P.g. placentalinfection

Runted fetusNormal weight fetus

MWFetal

Memb.Placenta

Liver

Positive control

Fetal Memb.

PlacentaSpleen

1,500 bp

400 bp

1,000 bp

Fetus #63-L3 Fetus #63-R2P.g. PCR signal in pregnant mouse with 2 small/5 normal fetus

P. gingivalisB. forsythusT. denticola

E. corrodensC. gingivalisC. sputigenaC. ochraceaA. actino. a

S. mitisS. oralis

S. sanguis

S. gordoniiS. intermedius

V. parvulaA. odontolyticus

P. intermediaP. nigrescens

P. microsF. nucleatum

F. periodonticum

E. nodatumS. constellatus

C. showae

C. rectusC. gracilis

S. noxia

A. actino. b

Socransky et al. 1998Socransky et al. 1998

**

********

**

********

****

**

**

****

P.g.

P.n.

P.i.

B.f.

C.r

.

A.a

.

E.c

.F

.n.

T.d.

P.m

.

C.o

.V

.p.

S,s.

S.o.

S.s.

A.v

.

Plaquesamples

Pooledbacterial

standards106

105

Maternal PlaqueMaternal Plaque

Plaque lanes

Maternalserum

Maternalserum

Human IgG(200-50ng/ml)

Pro

tein

A

Maternal IgG P.g

. P.n

.P.i.

B.f

.

C.r

.

A.a

. E.c

.F.n

. P.

m.C.o

.V.p

.S.s

.

T.d

. E.n

. S.i.

S.o

.M.c

.P.b

.

B.v

.G

.v.Vaginal Oral

FetalIgM

FetalIgM

Human IgM(200-50ng/ml)

P.g

. P.n

.P.i.

B.f

.

C.r

.

A.a

. E.c

.F.n

. P.

m.C.o

.V.p

.S.s

.

T.d

. E.n

. S.i.

S.o

.M.c

.P.b

.

B.v

.G

.v.Vaginal Oral

Pro

tein

A

Prevalence of Orange and Red Organisms in Maternal Plaque From 337 Term and 106 Preterm

Deliveries

Organism

C. rectusF. nucleatumP. microsP. nigrescensP. intermedia


Term Preterm

18.1 12.347.5 40.649.3 45.329.1 27.435.3 30.2

7.42 4.72 8.90 7.5516.0 14.2

Orange

Red

Prevalence Orange>Red MicrobesPrevalence of O&R for Term ~

Preterm

(n=337) (n=106)

Maternal Plaque

0

20

40

60

0 1 2 3 4 5

# Orange Cluster Organisms Present

% Distribution of

Red Cluster

(1+ Positive)

Frequency Distribution of Red Microbial Cluster Organisms as Function of Orange

Cluster Organisms within Maternal Plaque

DNA Microbial Macroarray “Checkerboard”

Red cluster organism detection is enhanced by or “requires”

Orange cluster organisms

0

10

20

30

40

0 1 2 3 4 5

# Orange Cluster Organism IgG Positive

% Distribution of

Red Cluster

Positive IgG

Frequency Distribution of Maternal IgG Antibody Responses to Red Microbial Cluster Organisms as

Function of Orange Cluster IgG Responses Maternal IgG (n=390)

Red seropositity is enhanced by or “requires” Orange

seropositivity

Prevalence of Orange and Red Organism Positive IgG in Maternal Sera from 289 Term and 101

Preterm Deliveries

Organism



Term Preterm

58.1 43.620.4 9.966.4 53.574.7 62.471.3 52.5

40.1 28.721.8 8.939.5 22.8

Orange

Red

Prevalence of positive maternal IgG responses for O&R Organisms among preterm has a non-significant trend to be generally less than that

of full term

(n=289) (n=101)

Maternal IgG (n=390)

Prevalence of Orange and Red Fetal IgM responses among 271 Term and 80 Preterm

Neonates

Organism



Term Preterm

6.3 20.0 2.2 7.5 1.1 8.8 1.5 6.3 1.1 8.8

16.2 16.310.7 20.0 8.1 17.5

Orange

Red

(n=271) (n=80)

Fetal IgM (n=351)

P=0.0002

P=0.02

NS

0.018

0.0003

NS

P=0.03

P=0.015

Prevalence of Fetal IgM seropositive responses to Orange and Red Cluster

organisms is signficantly higher among preterm newborns

0

20

40

60

80

0 1 2 3 4 5# Orange Cluster Organism IgM Positive

% Distribution of

Red Cluster

Positive IgM

Frequency Distribution of Fetal IgM Responses to Red Microbial Cluster

Organisms as Function of Fetal Orange Cluster IgM Responses

Fetal Red cluster IgM response appears in absence of Orange

cluster organisms, [Orange IgM requires Red IgM response]

Rate of Prematurity as related to Maternal and Fetal Seropositivity to

Orange and Red Cluster Microbes (n=287)

Maternal IgGRed Cluster

Seroreactivity

Fetal IgMOrange ClusterSeroreactivity

++ -

-A-C, P=0.03B-C, P<0.0001D-C, P=0.0002

53.3% 20.9%

17.5%

32.8%

33.3% 16.2%

66.7% 27.3%

A B

C D

Column test: P<0.0001, OR=4.3, (2.11-8.90)Row test: P=0.0003, OR=2.37, (1.48-3.79)

Combined: OR=10.3

Incident Periodontal Disease Progression (% mothers with 4+ sites, 2+mm PD increase) as related to

Maternal and Fetal Seropositivity to Orange and Red Cluster Microbes (n=287)

Maternal IgGRed Cluster

Seroreactivity

Fetal IgMOrange Cluster

Seroreactivity

+

+ -

-

30.8 % 31.0 %

61.1 % 28.0 %

A B

C D

B-C, OR=3.5, P=0.015

Maternal Periodontal Disease

GA<37 weeksFetal Orange Complex IgM Response

AB

Prevalent, OR=2.44,

95% CI = 1.18, 5.04

Seropositive, OR= 5.0

95% CI = 2.22,11.3 C

Incident Progression, OR=2. 34,

95% CI = 1.001, 5.4

Models of Interrelationships among Maternal Periodontal Disease, Fetal Exposure to Oral Pathogens and Prematurity

Postpartum Maternal Periodontal Disease (4+ sites with PD> 5mm) and Mean Fetal

Cord Serum CRP by Gestational Age (n=186)

0

0.5

1

1.5

2

2.5

3

3.5

Term <37

No Periodontal Disease

Periodontal Disease


Mean Fetal CRP(ug/mL)

Fetal IgM C. rectus and Mean Fetal Cord Serum CRP by Gestational Age

(n=186)

0

1

2

3

4

5

6

Term <37

No CR IgM CR IgM


Mean Fetal CRP(ug/mL)

Patterns of Maternal Colonization, maternal IgG , fetal IgM and

prematurityMaternal Infection

Maternal Antibody


prematurity

Maternal Infection

Maternal Antibody

No protective Red Complex IgG

Fetal Exposure

Fetal IgM to Red

Complex


prematurity

Maternal Infection

Maternal AntibodyNo protective Red Complex

IgG

Fetal IgM to Red & Orange

Complexes

Increased Fetal

CRP

Fetal ExposureRed and Orange

Abnormal Pregnancy Outcome

Maternal Periodontal Disease

Progression ?

Conclusions1. Results suggest that antepartum

periodontal disease as well as incidence/ progression of periodontal disease is a significant independent risk factor for prematurity, low birth weight and fetal growth impairment.

2. Orange & Red complex organisms are similar at post-partum in preterm and full-term mothers.

3. Fetal IgM response to Red complex organisms occurs in absence of orange IgM, indicating early or initial exposure to maternal organims of the red complex

Conclusions

4. Maternal antibody to Red complex appears to “prevent” fetal exposure to maternal oral microbes.

5. Fetal IgM seropositive responses coupled with seronegative maternal red complex IgG confers greatest risk for prematurity OR=10.3.

New findings: University of Alabama Study of Prematurity (Jeffcoat &

Hauth)

0 1 2 3 4 5 6 7 8

Full term

GA<37 wks

GA<35 wks

GA<32 wks

Odds Ratio*

Bar 2Bar 1

*Adjusted for smoking, parity, age and race[p<0.05, as compared to no periodontal disease, full term deliveries]

Mild-moderateSevere

N=1313,Examined 21-24 wks

New findings :Nestor Lopez (Santiago, Chile)

Effects of Periodontal Therapy on rate of prematurity

850 pregnant women <20 weeks 390 women with periodontal disease ( 1

or more sites with PD>4mm and >3mm attachment loss).

Random assignment to 2 groups; periodontal scaling & root planing vs delayed treatment (post-partum).

Attrition low:24 and 15, respectively

Nestor Lopez (Santiago, Chile)

Risk Factor Distribution Untreated

28 (4.5)

1.2 (0.9)

23.7

4.3

13.5

Treated

27 (4.3)

1.4 (1.1)

24

7.4

13.8

Age

Parity

%Primiparous

% previous preterm

%previous miscarriage

P Value

0.04

0.13

0.43

0.21

0.92


Risk Factor Distribution (%) Untreated

25.7

18.4

16.6

25.1

Treated

23.4

14.9

14.4

17

Smokers

UTI

Antibiotic Tx

Vaginosis

P Value

0.60

0.37

0.56

0.06


Results: Untreated

3344(598)

10.1%(n=19)

Treated

3501 (429)

1.8%(n=3)

Mean birthweight

Incident GA<37*

P Value

0.0047

0.001

*Univariate RR =5.49, 95%CI= 1.65-18.22


Results: (logistic regression) Odds Ratio

4.70

3.98

3.70

3.42

95% CI

1.29-17.1

1.11-14.2

1.46-9.38

1.16-10.0

No periodontal Tx

Previous GA<37

Low # Prenatal visits

Mother underweight

P Value

0.018

0.033

0.005

0.024

Variable

Also controlled for age, parity, smoking, vaginosis, first prenatal visit


Conclusion:

Early studies by Lopez,

as well as those reported by Papapanou,

suggest that periodontal therapy

during pregnancy may reduce

the risk of prematurity.

Clinical Implications of OCAP Findings

Antepartum mild or moderate-severe periodontal disease and increases in PD during pregnancy appear to increase the risk for fetal exposure and pregnancy problems.

The magnitude of periodontal disease impact is significant with Odds ratios 2-10 depending on baseline status and worsening of condition during pregnancy

Evidence of fetal exposure to periodontal pathogens raises bacteremia risk questions

Maternal antibody appears to be protective

Prevention would appear to be prudent clinical management strategy

Implications for Health Care

Association may not be causal in nature. The potential benefits of treatment have

not yet been established. Periodontitis is both preventable and

treatable. Periodontal health is necessary for

overall health and periodontal disease may be as deleterious to pregnant mother as smoking, or alcohol consumption.

We need to educate the public, our patients and health care professionals to promote the need for good oral health as an important part of a healthy lifestyle.

OCAP Team UNC Epidemiologists

Susi Lieff (Ecol) Rosemary McKaig (Ecol) Pierre Beukins (SPH) Gary Slade (Ecol)

UNC Clinical Researchers Heather Jared (Hyg) Tracy Kachold (Hyg) Marsha Black (Tech) Sally Timlin (Nurse) Karen Dorman (Nurse) Sacha Singh (Perio)

UNC Clinical Scientists Ken Moise (MFM) Kim Boggess (MFM) Bob Strauss (MFM) Carl Bose (Ped) Phoebus Madianos

(perio) John Gilmore (Psych) Janet Southerland (Ecol)

Duke Clinical Scientists Phil Heine (MFM) Amy Murtha (MFM) Rick Auten (Ped) Ricki Goldstein (Ped)

OCAP Team UNC Lab Scientists

Catherine Champagne Estelle Riche

UNC Lab Technicians Frances Smith Russ Levy Sandra Elmore Jeremy Eissens Jermaine Fuller Christine Downey

UNC Computer Specialists Kevin Moss Morris Worley

UNC Students & Fellows Mark Suttle Dongming Lin Alvin Yeo Julie Hofheimer

UNC Administrative Gail Plaisance

Colleagues Epidemiologists

Sam Arbes Jim Beck Paul Eke John Elter Susi Lieff Rosemary McKaig Jim Pankow Gary Slade

Basic Scientists Catherine Champagne Sara Geva Sid Kalachandra Estelle Riché Chitpol Siddhivarn

Clinical Scientists Kim Boggess Elisa Ghezzi Alison Lohman Phoebus Madianos Sally Mauriello Steve Offenbacher David Paquette Rocio Quinonez Janet Southerland Ray Williams

Behavioral Scientists Julie Hofheimer

Clinical Research Peggy Allen Marsha Black Heather Jared Tracy Kachold Sue Riggsbee Barbara Oliver Betsi Petway

Research Students Nadine Brodala Waka Kadoma Dongming Lin Nora Rooney Diane Sitki Mark Suttle

Valuable Assistants Administration

Gail Plaisance

Computer Specialists Kevin Moss Morris Worley

Laboratory Christine Downey Jeremy Eissens Kendra Floyd Jermaine Fuller Russ Levy Frances Smith

Collaborators UNC Epidemiology

Gerardo Heiss Jim Pankow HA Tyroler

UNC Cardiology Wayne Cascio Efthymios

Deliargyris Alan Hinderliter Sid Smith

UNC Ob/Gyn Kim Boggess Karen Dorman Bob Strauss Steve Wells

UNC Psychiatry John Gilmore

UNC Biostatistics Woody Chambless David Couper Gary Koch

UNC Pediatrics Carl Bose Diane Marshall

Duke Ob/Gyn Elizabeth

Livingston Amy Murtha

Duke Pediatrics Rick Auten

AcknowledgementsNIH & NIDCR Grants :

DE R01HD26652, DE08289, DE012435 Contracts from NHLBI R01 DE 11551, P60 DE 13079

Dental Organizations : AAP, ADA

Corporate sponsors : Procter and Gamble, Block Drug,

Colgate, Orapharma, Interleukin Genetics, Sunstar, Merck, Glaxo-Wellcome, Phillips

Steven

Offenbacher &

James BeckSteven

Offenbacher &

James Beck

maternal periodontal disease as a fetal stressor

Documents

phd center

fetal stressor

mmsc james d beck

frances glenn mayson

term labor

steven offenbacher dds

major pregnancy complications