abies born prematurely are at a significant

risk of developing serious and lasting health

problems. Preterm delivery, or PTD, is the
major cause of neonatal mortality and of nearly one-half of all serious long-term neurological morbidity.1 In the United States, approximately 10
percent of women deliver before term (defined as 37
weeks gestational age), and PTDs at less than 32 weeks
gestation constitute 1 to 2 percent of all
Pre-existing births. PTD accounts for more than 60
periodontal percent of all neonatal mortality and for
50 percent of all perinatal health care
disease in
costs in this country. While substantial
the second strides have been made in the treattrimester of ment of babies born prematurely, the
pregnancy incidence of prematurity continues to
increases the rise. Data from the National Center for
risk of preterm Health Statistics and the March of
Dimes show a 0.6 percent increase in
birth.
preterm births between 1986 and 1990
and a 0.4 percent increase from 1990 to
1996 (Figure 1).2
Table 1 lists some of the major known risk factors for
preterm births. Several characteristics are known to be
associated with an elevated risk of experiencing PTD.3
Rural, poor and minority women have more preterm
labor and deliveries than do middle-class women; those
who have had a previous spontaneous PTD and those
whose pre-pregnancy weight is less than 50 kilograms
(110 pounds) are at the greatest risk. As often is the
case with risk factors, however, the causal links between
these observable characteristics and the PTD itself are
not at all clear.
When using a risk factor to guide patient assessment

MARJORIE K. JEFFCOAT, D.M.D.; NICO C. GEURS,

D.M.D.; MICHAEL S. REDDY, D.M.D., D.M.SC.;
SUZANNE P. CLIVER, B.S.; ROBERT L. GOLDENBERG, M.D.; JOHN C. HAUTH, M.D.

Results of a prospective study

CON

Periodontal infection
and preterm birth

Background. Previous studies have suggested that chronic periodontal

infection may be associated
A D A
J
with preterm births. The

authors conducted a prospective study to test for

this association.
N
C
U
Methods. A total of
A ING EDU 1
R
1,313 pregnant women were
TICLE
recruited from the Perinatal
Emphasis Research Center at the University of Alabama at Birmingham. Complete
periodontal, medical and behavioral assessments were made between 21 and 24 weeks
gestation. After delivery, medical records
were consulted to determine each infants
gestational age at birth. From these data,
the authors calculated relationships between periodontal disease and preterm
birth, while adjusting for smoking, parity
(the state or fact of having born offspring),
race and maternal age. Results were expressed as odds ratios and 95 percent confidence intervals, or CIs.
Results. Patients with severe or generalized periodontal disease had adjusted odds
ratios (95 percent CI) of 4.45 (2.16-9.18) for
preterm delivery (that is, before 37 weeks
gestational age). The adjusted odds ratio
increased with increasing prematurity to
5.28 (2.05-13.60) before 35 weeks gestational age and to 7.07 (1.70-27.4) before 32
weeks gestational age.
Conclusions. The authors data show
an association between the presence of
periodontitis at 21 to 24 weeks gestation
and subsequent preterm birth. Further
studies are needed to determine whether
periodontitis is the cause.
Clinical Implications. While this large
prospective study has shown a significant
association between preterm birth and periodontitis at 21 to 24 weeks gestation, neither it nor other studies to date were designed to determine whether treatment of
periodontitis will reduce the risk of preterm
birth. Pending an answer to this important
question, it remains appropriate to advise
expectant mothers about the importance of
good oral health.

IO
N

COVER STORY

ABSTRACT

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875

PERCENTAGE
CHANGE FROM 1986

D E N T I S T R Y

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by Kramer,4 in which he reviewed the determinants of low birthweight based on an extensive

meta-analysis of more than 800 articles. Kramer
classified the etiology of PTD into three major
1.2
categories according to whether the causal factor
is established, its contribution is of major impor1.0
tance and the characteristic is modifiable and, if
0.8
so, over how long a period.
Early evidence of periodontal disease as
0.6
a potential risk factor for preterm birth.
0.4
Chronic periodontitis has been proposed as a risk
0.2
factor for preterm birth. Offenbacher and colleagues5 conducted a case-control study of 124
0.0
pregnant or postpartum women. Those with
1986 1988 1990
1992 1994 1996
preterm or low-birthweight babies had signifiYEAR
cantly worse periodontal disease than did the
control subjects who delivered babies at full term.
Multivariate logistic regression models, controlling for other risk factors and covariates, indiFigure 1. Percentage change in preterm birth rate. Note
the increase in the preterm birth rate. The National
cated that periodontal disease is a significant risk
Center for Health Statistics/March of Dimes baseline perfactor, with impressively high odds ratios of 7.9
centage was 10 percent preterm births in 1986.
for mothers of preterm low-birthweight babies
and 7.5 for mothers giving birth for the first time.
and treatment planning, it is important to know
The odds ratio is a customary way to express the
whether the risk factor can be modified by either
risk of an undesirable outcome (such as PTD) in
the patient or the clinician. Smoking, for
patients who have a condition (such as periodonexample, is a known risk factor that clearly is
titis) relative to patients who do not have the conmodifiable (Table 1). A past history of preterm
dition. An odds ratio of 1.0 means that the risk of
an adverse outcome in a patient with periodonlabor is just as clearly not modifiable, whereas a
titis is the same as the risk for a subject without
genetic tendency toward preterm labor (none has
periodontitis. When the outcome may result from
been identified yet) might be modifiable by appromultiple causes, odds ratios need to be adjusted
priate therapy.
for other known risk factors, such as smoking, to
Characteristics that affect pregnancy outthe extent that data concerning these risks are
comes, either directly or indirectly through
available. Confidence intervals, or CIs, indicate
health behaviors, are well-covered in an article
the range of odds ratios that are
TABLE 1
explained by the data.
Retrospective vs. prospective
study
designs. In a case-control
RISK FACTORS FOR PRETERM BIRTH.
study, patients who have experienced
preterm labor (cases) are recruited
MODIFIABLE
RISK FACTOR
after the births and are matched with
Yes
Smoking
patients (controls) whose deliveries
were normal but who otherwise have
Yes
Alcohol
similar personal and medical profiles.
Yes
Weight
Periodontal examinations usually are
No (usually)
Multifetal Pregnancies
performed after the birth, allowing for
a clear comparison of the influence of
Variable
Mothers Medical Problems
this factor on outcome.
No
Abnormal Placenta, Uterus
The major drawback of case-control
or Cervix
and
other cross-sectional studies is
No
Previous Preterm Birth
that they cannot show that the risk
Unknown
Periodontal Disease
factor and the outcome occurred in a
876

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D E N T I S T R Y

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logical temporal order6; for example, that periof study results. Since antibiotics could modify
odontitis was present before the preterm birth.
the risk factors being tested, patients taking antiCase-control studies can present another problem
biotics would complicate both this observational
in that both a patients willingness to participate
study and a future planned intervention study.
in a study and her postpartum health behaviors
Medical data collection. After obtaining
can be biased by the outcome being studied. A
informed consent from the patient, a research
prospective study, in which all evaluations are
nurse administered a study questionnaire covconducted before delivery, overcomes these limiering the patients behavior and oral health histations.
tory. We reviewed the patients prenatal medical
Such a prospective study is under way at the
record to obtain data not provided by the interUniversity of Alabama at Birmingham, or UAB,
view, including the patients age, race, parity (the
and is being conducted jointly by clinical restate or fact of having born offspring), pre-pregsearchers from the department of periodontics
nancy weight, height, medical diagnoses and
and the department of obstetrics and gynecology.
blood pressure. After the babys birth, abstracted
It draws its patient volunteers from a research
information concerning pregnancy complications
program in perinatal health, from which we
and delivery information (including preterm
can efficiently abstract extensive medical
labor, premature rupture of membranes and type
information.
of delivery) from the labor and delivery record
This article describes the design of this onand computerized it. Trained and standardized
going study and presents our results
study nurses were responsible for
to date, linking periodontal disease
collecting, recording and maintaining
The best advice
to preterm birth. In addition, we
all medical data.
to give a woman
offer some guidelines to practitioners
Oral examination. Each subject
contemplating
on treating and advising their
received an oral examination to
patients in the light of our current
check for dental caries and periopregnancy is to try
state of knowledge.
to prevent periodontal dontal disease. We measured pocket
depth and recession and calculated
disease from
METHODS
attachment loss. Full-mouth periodeveloping.
dontal examinations also were perOverall experimental design. We
formed, as partial recordings tend to
designed our study to correlate the
underestimate the prevalence of disease and
presence of periodontitis in pregnant women
could have biased the results of the study.7 We
assessed at 21 to 24 weeks gestation with the
presence and severity of subsequent preterm
did not take any radiographs, in the interest of
births. Subjects were drawn from among subjects
patient safety.
being studied by the Perinatal Emphasis ReCalibration of examiners. All dental examsearch Center, or PERC, at UAB. In this article,
inersa team of calibrated dental hygienists
we report the results we obtained from the first
received training using a series of standardized
1,313 subjects to have delivered their babies.
procedures, demonstrations and one-on-one tutoEligibility criteria. To be eligible for particirials. To assess intraexaminer and interexaminer
pation in this study, a pregnant woman must
error, we performed a calibration study in the
have attended one of the PERC study health
periodontal research clinic after receiving full
clinics as an obstetric patient and have reached
IRB approval and written informed consent from
21 to 24 weeks gestation. We obtained informed
the subjects. Each examiner performed duplicate
consent from each subject and, when possible,
examinations of probing depth and attachment
from the father. The study was reviewed and aplevel in eight patients who had moderate periproved by UABs institutional review board, or
odontitis; none of the patients was pregnant. The
IRB.
examiners calculated error (defined as the mean
Exclusion criteria. We excluded subjects
of the absolute value of the difference between
who required antibiotic prophylaxisfor
examinations) and the correlation between values
example, for mitral valve prolapse with regurgiat successive examinations. No examiner whose
tation. This exclusion was primarily in the inerror exceeded 0.5 millimeter was allowed to parterest of patient safety, but it also eliminated one
ticipate further in the study.
potential source of confusion in the interpretation
Statistical analysis. We defined three levels
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TABLE 2

MATERNAL RACE (SELF-CLASSIFIED) AND AGE.

DEMOGRAPHIC

NUMBER OF SUBJECTS

PERCENTAGE

1,084

82.68

227

17.32

Younger Than 20 Years

317

24.14

20-24 Years

662

50.42

25-29 Years

220

16.76

30 Years and Older

114

8.68

Race
African-American
Caucasian
Age

UNADJUSTED ODDS RATIO

RESULTS

10
9
8
7
6
5
4
3
2
1
0
Less Than
37 Weeks

Less Than
35 Weeks

Less Than
32 Weeks

GESTATIONAL AGE GROUP

Figure 2. Unadjusted odds ratios for preterm birth in

patients with generalized periodontitis.

of periodontal disease: periodontitis (three or

more sites with attachment loss of 3 mm or
more), generalized periodontal disease (90 or
more sites with attachment loss of 3 mm or more)
and no disease (less than three sites with 3 mm
of attachment loss). We used descriptive statistics to characterize the population. We calculated
odds ratios and 95 percent CIs for preterm birth
and adjusted them for smoking, parity, race and
maternal age. To explore the possibility of a
dose effect, we calculated separate adjusted
odds ratios for preterm births before 37, 35 and
32 weeks.
878

The demographic characteristics and age distribution of the study population are shown in
Table 2. We found significantly more periodontal
disease among African-American subjects, who
made up 82.68 percent of the population, than
among Caucasians (2 22.59, P < .001).
Figure 2 shows the unadjusted odds ratios for
patients with generalized periodontal disease.
Interestingly, we found that the odds ratios rise
with increasing prematurity; that is, the association with periodontal disease is strongest when
we focus on the most severe class of prematurity.
It is important to note, however, that these unadjusted odds ratios do not account for other known
risk factors.
Figure 3 again presents results for patients
with generalized periodontal disease, but in
terms of odds ratios that have been adjusted for
maternal smoking, parity, race and age. Among
these first 1,313 subjects, the risk of preterm
birth in subjects with generalized periodontitis
was from 4.45 to 7.07 times higher than that in
periodontally healthy patients. Again, the adjusted odds ratios rise with increasing prematurity. Specifically, subjects with severe or generalized periodontitis had adjusted odds ratios of
4.45 (95 percent CI, 2.16-9.18) for preterm delivery before 37 weeks gestational age. The odds
ratio increased to 5.28 (95 percent CI, 2.05-13.60)
for delivery before 35 weeks gestational age and
increased again to 7.07 (95 percent CI, 1.7027.40) for delivery before 32 weeks gestational
age.

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D E N T I S T R Y

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Two main points regarding periodontal disease

and preterm birth may be drawn from our data.
First, periodontal disease was present before the
preterm births. While this does not prove a causeand-effect relationship, it is a necessary condition.
Second, in subjects with generalized or severe
periodontitis, the odds of preterm births were
greatest for women who gave birth to the most
premature babies.
In other analyses,6 we have shown that the risk
of experiencing preterm birth increases with increasing severity of periodontal disease.
This study also illustrates the importance of
adjusting odds ratios for known risk factors. For
example, smoking is a known risk factor for both
preterm birth and periodontal disease; in the
absence of adjusted odds ratios, the association
between smoking and preterm birth and periodontitis could lead to a greatly exaggerated estimate of the importance of periodontal disease as
a risk factor for preterm birth. Before applying
risk data in a clinical context, one should always
ask whether the odds ratios are adjusted and, if
so, for what other factors.
While our data show that various patient subpopulations exhibit different patterns of both
periodontal disease and preterm birth, it is not
clear whether the causal linkages themselves
vary among groups. We plan to study these
effects in more detail in future analyses, so we
can understand better the implications of such
differences for diverse patient populations.
Explaining the biological mechanisms linking
periodontal infection and preterm birth was beyond the scope of our study. One plausible mechanism begins with endotoxins resulting from gramnegative bacterial infections (such as periodontal
disease). These endotoxins stimulate the production of cytokines and prostaglandins. It is known
that prostaglandins and certain cytokines (interleukin-1, interleukin-6 and tumor necrosis
factor-), in appropriate quantities, stimulate
labor.8-15 Our laboratory currently is studying
these factors.
The weight of the evidence. Probably the
central question for the dental practitioner is
whether we have convincing evidence that treatment of periodontal disease will reduce the risk of
preterm birth. The answer, on the basis of
existing case-control studies and prospective and
uncontrolled intervention studies, clearly is no.

ADJUSTED ODDS RATIO

DISCUSSION

10
9
8
7
6
5
4
3
2
1
0

Less Than
37 Weeks

Less Than
35 Weeks

Less Than
32 Weeks

GESTATIONAL AGE GROUP

Figure 3. Adjusted odds ratios for preterm births in

patients with generalized periodontitis. Note that the
odds ratios rise with increasing prematurity. The odds
ratios have been adjusted for smoking, parity, race and
maternal age.

Only a controlled intervention study is capable

of unequivocally establishing a causal link between a treatment and an outcome. For this
reason, randomized, placebo-controlled, doubleblind studies are essential to test the efficacy, if
any, of periodontal treatment in reducing the incidence of preterm birth. While opinions differ as to
which treatments (for example, aggressive vs.
minimal) should be tested, at least a test and a
control group must be studied. A recent study by
Mitchell-Lewis16 showed a prevalence of 19.9 percent preterm births without periodontal treatment and 13.5 percent with treatment. Its lack
of randomization, however, makes interpretation
difficult. As a next step, we are conducting a randomized, placebo-controlled, blinded intervention
trial.
Advising the patient. For the present, in the
absence of definitive intervention data, the best
advice to give a woman contemplating pregnancy
is to try to prevent periodontal disease from developing. Regardless of what may be discovered,
this strategy has the sure and immediate benefit
of minimizing treatment when mother and fetus
are most vulnerable.
CONCLUSION

This study provides additional evidence that preexisting periodontal disease in the second tri-

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879

D E N T I S T R Y

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mester of pregnancy increases the risk of preterm

birth. The odds of increased prematurity were increased 4.5- to 7.0-fold.
Ongoing studies are addressing the question
as to whether preterm births can be reduced by
treating the periodontal disease.
Dr. Jeffcoat is the Rosen professor and the chair, Department of Periodontics, University of Alabama School of Dentistry, 1530 3rd Ave.
South, SDB 412, Birmingham Ala. 35294-007, e-mail majorie_
jeffcoat@cs1.dental.uab.edu. Address reprint requests to Dr. Jeffcoat.
Dr. Geurs is an assistant professor, Department of Periodontology,
University of Alabama at Birmingham.
Dr. Reddy is a professor, Department of Periodontology, University of
Alabama at Birmingham.
Ms. Cliver is a statistician, Department of Obstetrics and Gynecology, University of Alabama at Birmingham.
Dr. Goldenberg is a professor, Department of Obstetrics and Gynecology, University of Alabama at Birmingham.
Dr. Hauth is a professor, Department of Obstetrics and Gynecology,
University of Alabama at Birmingham.
This study was supported by National Institutes of Health grant IH
HDP50 1HD33927.
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preterm_new.htm. Accessed May 23, 2001.
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5. Offenbacher S, Katz V, Fertik G, et al. Periodontal infection as a
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