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OBJECTIVE: The goal was to estimate whether maternal CONCLUSION: The OCAP study demonstrates that ma-
periodontal disease was predictive of preterm (less than ternal periodontal disease increases relative risk for pre-
37 weeks) or very preterm (less than 32 weeks) births. term or spontaneous preterm births. Furthermore, peri-
METHODS: A prospective study of obstetric outcomes, odontal disease progression during pregnancy was a
entitled Oral Conditions and Pregnancy (OCAP), was predictor of the more severe adverse pregnancy out-
conducted with 1,020 pregnant women who received come of very preterm birth, independently of traditional
both an antepartum and postpartum periodontal exami- obstetric, periodontal, and social domain risk factors.
nation. Predictive models were developed to estimate (Obstet Gynecol 2006;107:2936)
whether maternal exposure to either periodontal disease LEVEL OF EVIDENCE: II-2
at enrollment (less than 26 weeks) and/or periodontal
disease progression during pregnancy, as determined by
comparing postpartum with antepartum status, were
predictive of preterm or very preterm births, adjusting for R ecently, both case-control and cohort studies have
reported that maternal oral infections, as indexed by
clinical measures of acute gingival infections (gingivitis)
risk factors including previous preterm delivery, race,
smoking, social domain variables, and other infections. and chronic periodontal infections (periodontitis) may
RESULTS: Incidence of preterm birth was 11.2% among be an independent contributor to abnormal pregnancy
periodontally healthy women, compared with 28.6% in outcomes, including preterm births, growth restriction,
women with moderate-severe periodontal disease (ad- and preeclampsia.1 8 However, not all case-control re-
justed risk ratio [RR] 1.6, 95% confidence interval [CI] ports support an association between these clinical con-
1.12.3). Antepartum moderate-severe periodontal dis- ditions,9 raising the possibility of potential confounding
ease was associated with an increased incidence of of the association by established risk factors, such as
spontaneous preterm births (15.2% versus 24.9%, ad- smoking, or other factors that may underlie both condi-
justed RR 2.0, 95% CI 1.23.2). Similarly, the unadjusted tions. Both gingivitis and periodontitis are relatively
rate of very preterm delivery was 6.4% among women
common concomitant clinical conditions among preg-
with periodontal disease progression, significantly higher
nant women, although prevalence estimates during
than the 1.8% rate among women without disease pro-
gression (adjusted RR 2.4, 95% CI 1.15.2). pregnancy vary considerably (gingivitis 30 100% and
periodontitis 520%).10 The potential mechanisms un-
derlying the reported association between periodontal
From the Departments of Periodontology and Dental Ecology, Center for Oral
conditions and preterm delivery have not been estab-
and Systemic Diseases, University of North Carolina School of Dentistry, Chapel
Hill, North Carolina; Department of Obstetrics and Gynecology, University of lished. It has been demonstrated in humans that peri-
North Carolina, Chapel Hill, North Carolina; Department of Obstetrics and odontal pathogens within dental plaque are capable of
Gynecology, Duke University, Durham, North Carolina; and National Institutes
invading host periodontal tissues, eliciting recurrent
of Allergy and Infectious Diseases, Bethesda, Maryland.
bacteremias, translocating to distant tissues, and activat-
This study was supported by the following grants: RO1-DE-12453, P-60-DE-
13079, T-32-DE-07310, M01-RR-00046. ing the hepatic acute phase response, especially during
Corresponding author: Steven Offenbacher, DDS, PhD, MMSc, OraPharma
periods of disease progression.11
Distinguished Professor of Periodontal Medicine, Director, Center for Oral and Because periodontal health generally worsens
Systemic Diseases, UNC School of Dentistry, CB #7455, DRC Room 222, during pregnancy, and when periodontal disease is
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7455;
e-mail: steve_offenbacher@dentistry.unc.edu.
present, it is characterized by periods of exacerbation
2005 by The American College of Obstetricians and Gynecologists. Published
and remission, it is possible that the onset of new
by Lippincott Williams & Wilkins. disease or periodontal progression during pregnancy
ISSN: 0029-7844/05 may pose greater risk to the pregnancy than just the
VOL. 107, NO. 1, JANUARY 2006 Offenbacher et al Periodontitis Increases Very Preterm Births 31
Kaplan-Meier curves were generated for gesta- gestation) was 186 (18.2%) of 1,020. Preterm birth was
tional age at delivery for 1,020 live births based upon significantly associated with maternal age, race, mar-
3-level antepartum periodontal status or gingivitis/ ital status, use of public assistance, insurance status,
periodontal disease progression. Statistical signifi- prior preterm birth, and clinical chorioamnionitis at
cance between groups in this unadjusted survival delivery. The 169 women who either withdrew or
function were determined by the Mantel Haenszel test. delivered elsewhere did not significantly differ from
the 1,020 study population with regard to baseline
RESULTS characteristics shown in Table 1.13
The results of the bivariate analyses are shown in Maternal periodontal health status at enrollment/
Table 1. The preterm birth rate ( 37 weeks of baseline/antepartum and active clinical disease pro-
Table 1. Baseline Characteristics, Exposures, and Behaviors of OCAP Subjects During Pregnancy for
Term and Preterm Delivery Outcomes
Gestational Age Outcome
P .005.
P .05.
VOL. 107, NO. 1, JANUARY 2006 Offenbacher et al Periodontitis Increases Very Preterm Births 33
Table 2. Risk FactorAdjusted Relative Risk for Preterm Births According to Antepartum Maternal
Periodontal Disease Status
Spontaneous
Variable Preterm* Preterm*
Periodontal health 1.0 (referent) 1.0 (referent)
Mild periodontal disease 1.2 (0.91.7) 1.5 ( 1.02.2)
Moderate-severe periodontal disease 1.6 (1.12.3) 2.0 (1.23.2)
Age (5-y increment) 0.9 (0.81.04) 0.9 (0.81.04)
Race (white) 0.5 (0.40.7) 0.5 (0.40.8)
First birth 0.9 (0.61.2) 0.9 (0.61.2)
Previous preterm 2.0 (1.42.7) 2.4 (1.73.4)
Smoking 1.2 (0.91.6) 1.2 (0.81.7)
Married 1.1 (0.81.5) 1.2 (0.81.7)
WIC or food stamps 1.0 (0.71.4) 1.1 (0.81.6)
Insurance 1.1 (0.81.6) 1.2 (0.81.8)
Chorioamnionitis 3.1 (1.75.4) 4.3 (2.28.4)
WIC, Supplemental Food Program for Women, Infants, and Children.
Data are expressed as relative risk (95% confidence interval).
* Predictive risk models for preterm births (gestational age 37 weeks, 187 cases) and spontaneous preterm births (spontaneous gestational
age 37 weeks, 170 cases).
Table 3. Risk FactorAdjusted Relative Risk for Periodontal disease is a chronic infection, and
Very Preterm Births* for Mothers With when present, the natural history of the disease is
Periodontal Disease Progression During characterized by episodic periods of quiescence and
Pregnancy progression14 Furthermore, pregnancy increases the
Relative Risk onset of new periodontal disease.10 These patterns
(95% Confidence would suggest that, if the preexisting periodontal
Variable Interval) disease becomes active during the pregnancy, it may
Periodontal disease, no progression 1.0 (referent) pose a significant concomitant infectious or inflamma-
Periodontal disease, progression 2.4 (1.15.2) tory exposure during the current pregnancy, as would
Race (white) 0.1 (0.020.5) the onset of new disease. In this context the OCAP
First birth 0.3 (0.10.9)
Previous preterm 3.4 (1.39.1)
investigation provides novel information to demon-
Smoking 0.6 (0.22.1) strate that active clinical periodontal disease progres-
Chorioamnionitis 9.5 (3.724.2) sion during pregnancy conveys significant risk for
* Very preterm births: gestational age 32 weeks; n 27. very preterm birth, independently of preexisting peri-
odontal disease.
odontal status is not included in the model shown in The results of our study should be considered in
Table 3. All but 2 of the very preterm births were light of previously published data on maternal peri-
spontaneous deliveries, limiting our ability to stratify odontal disease and preterm birth.15 The magnitude
association of active clinical periodontal disease pro- of the association between maternal periodontal dis-
gression based on type of very preterm birth. ease and preterm birth in our study is lower than that
reported by Jeffcoat et al.5 In a prospective study of
DISCUSSION 1,313 pregnant women, Jeffcoat and colleagues re-
Our findings demonstrate that maternal periodontal ported that severe periodontal disease is associated
disease, identified either early in pregnancy or pro- with an odds ratio of 5.28 (95% CI 2.0513.6) for
gressing during pregnancy, is a risk factor for preterm preterm birth at less than 37 weeks and an odds ratio
and very preterm birth, respectively, independent of of 7.07 (95% CI 1.727.4) for preterm birth at less
other risk factors. Antepartum moderate-severe peri- than 32 weeks, adjusting for age, race, smoking, and
odontal disease increased the risk for spontaneous parity. The differences in magnitude of association
preterm birth 2-fold in fully adjusted models, and the between our study and the data of Jeffcoat et al may
effect of active periodontal disease on very preterm be due to differences in baseline maternal oral health
delivery was even larger (adjusted RR 2.4, 95% CI between our study cohort and the cohort in the
1.15.2). Jeffcoat et al Alabama study population because the
VOL. 107, NO. 1, JANUARY 2006 Offenbacher et al Periodontitis Increases Very Preterm Births 35
as described by Romero and Mazor22 and Williams et 7. Romero BC, Chiquito CS, Elejalde LE, Bernardoni CB. Rela-
tionship between periodontal disease in pregnant women and
al.23 For example, it is not unreasonable to suggest
the nutritional condition of their newborns. J Periodontol
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secretion of inflammatory mediators and cytokines, 8. Boggess KA, Lieff S, Murtha AP, Moss K, Beck J, Offenbacher
such as prostaglandin E2, interleukin (IL)-6, or IL-1, S. Maternal periodontal disease is associated with an increased
may be simultaneously at risk for both periodontal risk for preeclampsia. Obstet Gynecol 2003;101:22731.
disease and abnormal pregnancy outcomes. The pres- 9. Davenport ES, Williams CE, Sterne JA, Murad S, Sivapatha-
sundram V, Curtis MA. Maternal periodontal disease and
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