Periodontal Disease and Upper Genital Tract
Inflammation in Early Spontaneous Preterm Birth
Alice R. Goepfert, MD, Marjorie K. Jeffcoat, DMD, William W. Andrews, PhD, MD,
Ona Faye-Petersen, MD, Suzanne P. Cliver, Robert L. Goldenberg, MD, and John C. Hauth, MD
OBJECTIVE: To estimate the relationship between mater-
nal periodontal disease and both early spontaneous pre-
term birth and selected markers of upper genital tract
inflammation.
METHODS: In this case-control study, periodontal assess-
ment was performed in 59 women who experienced an
early spontaneous preterm birth at less than 32 weeks of
gestation, in a control population of 36 women who expe-
rienced an early indicated preterm birth at less than 32
weeks of gestation, and in 44 women with an uncompli-
cated birth at term (> 37 weeks). Periodontal disease was
defined by the degree of attachment loss. Cultures of the
placenta and umbilical cord blood, cord interleukin-6 lev-
els, and histopathologic examination of the placenta were
performed for all women.
RESULTS: Severe periodontal disease was more common in
the spontaneous preterm birth group (49%) than in the
indicated preterm (25%, P .02) and term control groups
(30%, P .045). Multivariable analyses, controlling for
possible confounders, supported the association between
severe periodontal disease and spontaneous preterm birth
(odds ratio 3.4, 95% confidence interval 1.57.7). Neither
histologic chorioamnionitis, a positive placental culture,
nor an elevated cord plasma interleukin-6 level was signif-
icantly associated with periodontal disease (80% power to
detect a 50% difference in rate of histological chorioamnio-
nitis, 0.05).
CONCLUSION: Women with early spontaneous preterm
birth were more likely to have severe periodontal disease
From The Center for Research in Womens Health and the Department of
Obstetrics and Gynecology, The University of Alabama at Birmingham, Birming-
ham, Alabama; Department of Periodontology, The University of Pennsylvania
School of Dental Medicine, Philadelphia, Pennsylvania; and Department of
Pathology, The University of Alabama at Birmingham, Birmingham, Alabama.
This study is supported by the National Institute for Child Health and Human
Development, grants P01 HD 33927 and K12 HD01258.
Presented at the 22nd Annual Meeting of the Society for Maternal-Fetal Medicine,
January 14 19, 2002, New Orleans, Louisiana.
The authors thank Nico C. Geurs, DMD, and Janatha Grant, RN, for their work
on this project.
VOL. 104, NO. 4, OCTOBER 2004
2004 by The American College of Obstetricians and Gynecologists.
Published by Lippincott Williams & Wilkins.
than women with indicated preterm birth or term birth.
Periodontal disease was not associated with selected mark-
ers of upper genital tract inflammation. (Obstet Gynecol
2004;104:777 83. 2004 by The American College of
Obstetricians and Gynecologists.)
LEVEL OF EVIDENCE: II-2
Preterm birth complicates 12% of all pregnancies in the
United States and is one of the leading causes of infant
morbidity and mortality.12 Evidence indicates that ma-
ternal infection and inflammation of the lower and upper
genital tract, as well as at sites distant from the pelvis,
play a major role in the etiology of preterm birth in some
women.35
Periodontal disease is a chronic anaerobic inflamma-
tory condition that affects as many as 50% of pregnant
women in the United States.6 8 Emerging evidence sup-
ports a relationship between periodontal disease and
other systemic conditions, including cardiovascular dis-
ease and diabetes mellitus.9 11 Recent studies in the
United States have demonstrated an association between
maternal periodontal disease and multiple adverse preg-
nancy outcomes, including preterm birth, low birth
weight, fetal growth restriction, preeclampsia, and peri-
natal mortality.6 8,1216 The mechanisms by which peri-
odontal disease and preterm birth are associated are not
clear. It has been hypothesized that in the presence of
severe periodontal disease, oral organisms can dissemi-
nate hematogenously to target the placenta, membranes,
and fetus.1718 This bacterial challenge may result in
increased cytokine expression and precipitate preterm
labor.
We sought to determine if women who have a sponta-
neous preterm birth at less than 32 weeks of gestation are
more likely to have periodontal disease than women who
have either an indicated preterm birth at less than 32 weeks
of gestation or a term birth. In addition, we sought to
determine whether selected markers of upper genital tract
inflammation were associated with periodontal disease in
these women.
0029-7844/04/$30.00 777
doi:10.1097/01.AOG.0000139836.47777.6d
MATERIALS AND METHODS
This case-control study was approved by the Institutional
Review Board at the University of Alabama at Birming-
ham. Women delivering at our institution at between 24
0/7 and 31 6/7 weeks of gestation, as well as women
following spontaneous vaginal delivery at term ( 37
weeks) who were enrolled in an ongoing study of risk
factors for preterm birth at our institution (Perinatal Em-
phasis Research Center at the University of Alabama at
Birmingham) were eligible for the study. The study
population for this periodontal disease supplement to
Perinatal Emphasis Research Center was a sample of
convenience, in that women were recruited only when
delivered during daytime business hours on weekdays.
Spontaneous preterm birth was defined as delivery following
spontaneous preterm labor or spontaneous preterm pre-
mature rupture of membranes. Indicated preterm birth was
defined as delivery for maternal or fetal indications
excluding chorioamnionitis. All patients enrolled in this
periodontal disease supplement to the Perinatal Empha-
sis Research Center provided informed consent before
participation.
Study participants underwent a dental examination by
a periodontist from the School of Dentistry within 72
hours postpartum. Eighteen of the women had a dental
examination performed at 24 weeks of gestation as part
of the larger Perinatal Emphasis Research Center obser-
vational study, and the dental examination was not
repeated at the postpartum visit for these women. The
dental examination technique used was a modification of
the Community Periodontal and Treatment Index, also
known in the United States as the Periodontal Screening
and Recording Index.19 Briefly, the oral cavity and den-
tition were divided into 6 standard regions or sextants.
At least 6 areas of each tooth were examined using a
periodontal probe. The highest score in millimeters for
any tooth in each sextant was recorded for probing depth
and clinical attachment level. To perform the dental
examination, a 0.5-mm diameter probe is slipped be-
tween the gingiva and the tooth until resistance is met by
the probe. The distance from the cemento-enamel junc-
tion and pocket base was defined as attachment loss. Any
evidence of gingival inflammation, defined as bleeding on
periodontal probing of any tooth, was recorded for each
sextant. Periodontal health was defined as no evidence of
attachment loss or gingival inflammation. Periodontal dis-
ease was defined as 1) gingival inflammation and no
attachment loss (gingivitis); 2) 35 mm (mild periodontitis);
or 3) 5 mm (severe periodontal disease) in any one sextant.
The extent of periodontal disease was classified using an
index. This Extent Index describes the proportion of
sextants with a threshold attachment level (ie, the Extent
778 Goepfert et al Periodontal Disease and Upper Genital Tract
5 Index is the proportion of sextants with an attachment
loss of 5 mm).20 In reporting the index, the denomi-
nator is sextants in any group of women, not an individ-
ual score for each woman.
At the time of delivery, the placenta and a sample of
neonatal umbilical cord blood were collected using asep-
tic technique, refrigerated, and processed for culture
within 12 hours of delivery. Placental culture included
swabs and placental tissue for aerobic and anaerobic
culture and culture for Mycoplasma species and Ureaplasma
urealyticum obtained using aseptic technique. The swabs
were taken between the chorion and amnion in 3 sepa-
rate sites. The placental tissue was taken just beneath the
chorion. All placentas were then placed in formalin and
underwent histologic examination by a single patholo-
gist. Umbilical cord blood was cultured for Mycoplasma sp
and U urealyticum, and the remaining fetal cord serum was
aliquoted and stored at 70C for batched analysis.
Interleukin-6 (IL-6) levels in the cord serum were deter-
mined by commercially available enzyme-linked immu-
nosorbent assay (ELISA) kits (R&D Systems, Inc, Min-
neapolis, MN). The lower limit of sensitivity of the assay
was 0.7 pg/mL. The intra-assay and interassay coeffi-
cients of variation were 2.6% and 4.5%, respectively.
Concentrations of cord IL-6 greater than or equal to the
95th percentile for the combined indicated preterm and
term control groups of the larger Perinatal Emphasis
Research Center study were considered elevated. The
periodontists, laboratory personnel, and pathologist
were blinded to delivery outcome.
Maternal demographic, intrapartum, delivery, and
postpartum information was recorded by a trained ob-
stetric research nurse. Neonatal outcome data through
hospital discharge or death was also recorded. Neonatal
systemic inflammatory response syndrome was defined as the
presence of negative cerebrospinal fluid and blood cul-
tures plus clinically suspected sepsis and/or a band/band
plus polymorphonuclear cell ratio of 0.15 or greater.
Composite neonatal morbidity was defined as any one
or more of the following complications: neonatal sys-
temic inflammatory response syndrome, intraventricu-
lar hemorrhage (grades 3 or 4), periventricular leukoma-
lacia, respiratory distress syndrome, bronchopulmonary
dysplasia, necrotizing enterocolitis, and/or neonatal
death.
Based on prior studies in our pregnant patient popu-
lation,6 we estimated the baseline rate of severe peri-
odontal disease to be 20%. Using a 2-sided test of signif-
icance with an level of 0.05 and power of 80%, we
estimated needing 45 cases and 45 term controls, assum-
ing a 50% exposure rate in cases versus a 20% exposure
rate in controls (an odds ratio of 4.0). However, because
spontaneous preterm deliveries accounted for two thirds
OBSTETRICS & GYNECOLOGY
Table 1. Demographic Factors for the Study Population
P
Spontaneous preterm birth Indicated preterm birth Term birth
(n 59) (n 36) (n 44) a vs b* a vs c
Maternal age (y) 24.4 5.8 25.0 6.7 22.3 3.8 .605 .032
African American (%) 63 42 80 .046 .065
Nulliparous (%) 47 56 43 .444 .667
Previous SPTB (%) 24 6 0 .025 .002
Smoker (%) 15 8 2 .526 .041
Education 12 y (%) 36 17 43 .056 .501
Private insurance (%) 10 28 2 .026 .234
Gestation age at delivery (wk) 28.7 2.1 29.0 1.9 39.5 1.1 .537 .001
SPTB, spontaneous preterm birth.
Data are presented as percentage or mean standard deviation.
* a vs b spontaneous compared with indicated preterm birth; 2 and Student t test.

a vs c spontaneous preterm compared with term birth; 2 and Student t test.

of the preterm births at our institution, we calculated the
sample size for the preterm birth groups using a 2:1 ratio
of cases to controls. We estimated needing 57 spontane-
ous cases versus 38 indicated controls for the same
comparison as described for the term control group. We
therefore attempted to recruit 57 cases of spontaneous
preterm birth, 38 indicated preterm controls, and 45
term controls for our study.
Statistical analyses were performed using SAS 8.2
software (SAS Institute, Inc, Cary, NC). Analyses were
performed for cases and the 2 separate control groups,
not across all 3 groups. Unadjusted odds ratios (ORs)
and their 95% confidence intervals (CIs) were calculated
separately for spontaneous cases compared with indi-
cated and term controls. For demographic characteris-
tics, groups were compared using 2 tests or Fisher exact
test, where appropriate. Means of continuous variables
were compared using Student t test. Distribution of IL-6
between groups was compared using a Wilcoxon rank
sum test. Logistic regression analysis, adjusting for pos-
sible confounding factors, was used to calculate adjusted
ORs for spontaneous preterm birth.
RESULTS
From October 1998 through May 2001, 139 maternal-
infant pairs were enrolled: 59 following a spontaneous
preterm birth, 36 following an indicated preterm birth,
and 44 following uncomplicated spontaneous labor at
term. The indicated preterm births included 31 (86%) for
severe preeclampsia and 5 (14%) for nonreassuring fetal
status. There were no significant differences in birth
group among the 18 women with a periodontal exami-
nation at 24 weeks (n 10 term, n 6 spontaneous
preterm, n 2 indicated preterm; P .053). Selected
maternal demographics are presented in Table 1. Most
of the differences noted among the birth groups reflect
the demographics of our patient population. Our local
patient population (those receiving prenatal care and
delivering in our hospital) is predominantly African
American, funded by Medicaid, and younger, whereas
maternal transfers (from across the state with an expect-
ant preterm delivery) are more likely to be older, have
private insurance, and a higher percentage of white
women.
We evaluated the potential association between peri-
odontal disease and spontaneous preterm birth in several
ways. The extent or the number of regions (sextants)
with mild-to-severe attachment loss is reported using the
Extent Index.20 With a threshold attachment loss of
more than 3 mm and more than 5 mm, the Extent 3 and
5 Index for each study group are presented in Table 2.
Using either threshold for periodontal disease, the spon-
taneous preterm birth group had significantly more
extensive periodontal disease than the term birth group,
ie, more areas of the mouth were affected. The sponta-
neous preterm birth group also had more extensive
periodontal disease than the indicated preterm birth
group, but the more than 5 mm threshold was not
statistically significant.
We also evaluated whether women had evidence of
severe disease in at least one area of the mouth in relation
Table 2. Extent of Periodontal Disease for Each Study
Group
Extent index* SPTB IPTB Term
Extent 3 (%) 48.0
33.8 29.2
Extent 5 (%) 18.4 13.2 9.1
SPTB, spontaneous preterm birth 32 weeks of gestation; IPTB,
indicated preterm birth 32 weeks of gestation; Term, birth 37
weeks of gestation.
* Extent index is the proportion of sextants with 3 mm or 5 mm
attachment loss. The denominator is sextants in each group, not each
individual.
P .001 compared with IPTB, and P .001 compared with term;
2
test.
P .116 compared with IPTB, and P .001 compared with term;
2 test.

VOL. 104, NO. 4, OCTOBER 2004 Goepfert et al Periodontal Disease and Upper Genital Tract 779
Table 3. Rates of Severe Periodontal Disease by Birth
Group
Severe periodontal
disease*
Birth group Yes (%) No (%)
Spontaneous preterm birth (n 59) 49
51
Indicated preterm birth (n 36) 25 75
Term birth (n 44) 30 70
* Severe periodontal disease is defined as an attachment loss of 5 mm
in any one oral sextant.
P .02 versus periodontal disease in the indicated preterm birth
group, and P .045 versus periodontal disease in the term birth group;
2
test.
to birth group. None of the women had completely
healthy gums. Women with a spontaneous preterm birth
at less than 32 weeks of gestation had higher rates of
severe periodontal disease than both the indicated pre-
term birth or term birth groups (Table 3). Multivariable
analyses were performed, controlling for maternal age,
race, education, insurance status, parity, history of a
spontaneous preterm birth, and smoking. The unad-
justed and adjusted ORs for spontaneous preterm birth
in women with periodontal disease compared with
women without severe periodontal disease are presented
in Table 4. Each regression model included the sponta-
neous preterm birth group as well as one or both of the
control groups. Severe periodontal disease was associ-
ated with an almost 3-fold risk for spontaneous preterm
birth compared with the combined controls, indicated
preterm birth, and term birth (OR 2.6, 95% CI 1.1 6.2).
Because periodontal disease may be in the causal path-
way in each of a womans pregnancies, we repeated the
logistic regression adjusting for the same factors but
excluding history of preterm birth. Again, severe peri-
odontal disease was associated with a 3-fold risk for
spontaneous preterm birth (OR 3.4, 95% CI 1.57.7;
Table 4).
The association between markers of upper genital
tract inflammation at the time of delivery and periodon-
tal disease is presented in Table 5. Women with and
without severe periodontal disease had similar rates of
positive placental cultures, positive umbilical cord cul-
tures for U urealyticum and Mycoplasma species, histologic
chorioamnionitis, funisitis, median cord IL-6 level, and
an elevated umbilical cord IL-6 level ( 95% or 41.2
pg/mL). These findings were true in the overall popula-
tion as well as within each birth group (Table 5, data for
indicated preterm and term birth not shown). Using the
number of participants in the overall population with
and without periodontal disease (n 51 and n 88,
respectively), we determined that we had 80% power
( 0.05) to detect a significant difference between
groups (baseline rate of histological chorioamnionitis of
50% in the group with periodontal disease, compared
with 25% in the group without periodontal disease).
Organisms that are known periodontal pathogens were
identified by placental culture in only 5 of the women (2
women with spontaneous preterm birth and 3 women
with a term birth) and included Peptostreptococcus micros,
Streptococcus constellatus, and Eubacterium species.21
None of the infants delivered at term had any of the
adverse neonatal outcomes assessed in this study. Neo-
natal outcome and presence or absence of severe peri-
odontal disease in the preterm population (spontaneous
and indicated) are presented in Table 6. All of the
adverse neonatal outcomes evaluated were represented
similarly among women with and without periodontal
disease.
DISCUSSION
The results of our study demonstrate an association
between severe periodontal disease and spontaneous
preterm birth at less than 32 weeks of gestation. Others
have shown an association between periodontal disease
and preterm birth.6 8,1216 In a case-control study of 124
women, Offenbacher and colleagues12 found that pre-
term low birth weight cases had significantly worse
periodontal disease than control women with normal
birth weight infants. Cases were defined as women with

Table 4. Odds Ratios and 95% Confidence Intervals for Spontaneous Preterm Birth in Women With and Without Severe
Periodontal Disease*
OR (95% CI) for spontaneous preterm birth
Control group combined with spontaneous Unadjusted Adjusted OR for Adjusted OR for
preterm birth group OR Model I Model II
Indicated preterm birth 2.9 (1.27.2) 2.6 (0.97.8) 3.2 (1.19.3)
Term birth 2.3 (1.05.3) 2.5 (0.97.4) 3.2 (1.28.8)
Indicated preterm plus term birth 2.5 (1.35.2) 2.7 (1.26.5) 3.4 (1.57.7)
OR, odds ratio; CI, confidence interval.
* Severe periodontal disease is defined as an attachment loss of 5 mm in any one oral sextant.

Model I is adjusted for maternal age 20 years, black race, education level ( 12th grade), type of insurance, parity, prior spontaneous preterm
birth history, and smoking.

Model II is adjusted for the same factors as Model I, excluding history of prior spontaneous preterm birth.

780 Goepfert et al Periodontal Disease and Upper Genital Tract OBSTETRICS & GYNECOLOGY
Table 5. Upper Genital Tract Inflammatory Markers in Women With and Without Severe Periodontal Disease*
Periodontal disease in spontaneous Periodontal disease in overall study
preterm birth group population
Yes No Yes No
Inflammatory marker (n 29) (n 30) P (n 51) (n 88) P
Positive placental culture (%) 69 70 .93 67 58 .31
Positive umbilical cord culture (%) 21 25 .73 14 11 .63
Histological chorioamnionitis (%) 76 73 .82 45 52 .41
Funisitis (%) 38 62 .07 26 29 .65
Elevated cord interleukin 6 (%) 35 37 .85 20 17 .68
Median cord interleukin 6 level 21.9 (5.7, 221.4) 17.1 (4.9, 147) .92 87 (1.6, 26.7) 4.6 (1.6, 18.3) .78
(25%, 75%)
* Severe periodontal disease is defined as an attachment loss of 5 mm in any one oral sextant.

Overall study population included all women (spontaneous preterm, indicated preterm, and term birth).

Chi squared or Fisher exact test for significance used unless otherwise designated.

Cultured for Ureaplasma urealyticum and Mycoplasma species.

Picograms per milliliter, Wilcoxon rank sums.

Elevated cord interleukin 6 defined as 95th percentile ( 41.2 pg/mL) for combined term and indicated preterm birth groups.

a current or previous history of a birth in which the CI 2.29.2) and less than 32 weeks of gestation (adjusted
infant ( 2,500 g) was delivered after preterm labor or OR 7.1, 95% CI 1.727.4). Our results are consistent
premature rupture of membranes. In their multivariable with these findings, with the added strength of compar-
analysis in that study, the OR for periodontal disease in ing well-defined cases of spontaneous preterm birth at
cases was 7.5 (95% CI 1.9528.8). These investigators less than 32 weeks of gestation and 2 control groups: one
also demonstrated a significant association between peri- of preterm birth following maternal or fetal indications
odontal disease and preterm birth in a larger prospective and one of term birth.
study (n 814) in which 9% of women delivering at less The mechanisms by which periodontal disease and
than 37 weeks and 13.6% of women at less than 32 weeks preterm birth are associated are not clear. It has been
of gestation had moderate-severe periodontal disease, hypothesized that, in the presence of severe periodontal
compared with 4.5% of women delivering at term.8 In a disease, cytokines produced by the infected periodon-
large prospective cohort study of 1,313 women at our tium may appear in the systemic circulation and target
institution, Jeffcoat and colleagues6 showed that women the placenta and fetus, precipitating preterm labor. Alter-
with severe periodontal disease at 2124 weeks of gesta- natively, oral organisms can disseminate hematog-
tion had a higher OR for subsequent spontaneous pre- enously to target the placenta, membranes, and fetus.
term birth at less than 37 weeks (adjusted OR 4.5, 95% This infectious challenge may result in increased cyto-
kine expression and precipitate preterm labor.1718 In the
Table 6. Neonatal Outcome in Women With and Without prospective study by Offenbacher and colleagues8 de-
Periodontal Disease* scribed above, maternal immunoglobulin (Ig)G and fetal
Severe periodontal disease n IgM directed against known periodontal pathogens were
(%) measured at the time of delivery.22 The highest risk for
Outcome Yes (n 38) No (n 57) P preterm birth was observed among mothers without
SIRS 7 (19) 13 (23) .65 evidence of a protective IgG response combined with a
IVH (III or IV) 5 (14) 2 (4) .08 fetus with an IgM response (OR 10.3, P .001).22 These
RDS 19 (50) 36 (63) .20 data would suggest that when the fetal-placental unit is
BPD 9 (24) 9 (16) .34
exposed to the periodontal pathogens in the absence of
NEC 5 (13) 6 (11) .75
Death 3 (8) 3 (5) .68 maternal antibody protection, this may precipitate pre-
Composite morbidity 25 (66) 41 (72) .52 term birth.
SIRS, neonatal systemic inflammatory response syndrome; IVH, in- Previous reports have documented a consistent rela-
traventricular hemorrhage (grade III or IV); RDS, respiratory distress tionship between upper genital tract infection/inflamma-
syndrome; BPD, bronchopulmonary dysplasia; NEC, necrotizing
enterocolitis. tion and preterm birth, particularly early spontaneous
Data are expressed as n (%). preterm birth.35 Previous studies have not evaluated the
* The population for this table includes preterm births only (spon- presence of upper genital tract inflammation at the time
taneous plus indicated preterm birth, n 95).

Chi squared test. of delivery and the potential association with periodontal

Composite morbidity is any one or more of the above outcomes. disease. In our study, we could not demonstrate any

VOL. 104, NO. 4, OCTOBER 2004 Goepfert et al Periodontal Disease and Upper Genital Tract 781
association between markers of upper genital tract in-
flammation at the time of birth and moderate-to-severe
periodontal disease in cases of spontaneous preterm
birth, indicated preterm birth, or term controls. Our data
would suggest that the potential mechanism of periodon-
tal diseaseassociated preterm birth is not hematogenous
spread of the periodontal organisms to the placenta with
colonization and subsequent inflammation precipitating
preterm labor or premature rupture of membranes.
Periodontal pathogenic organisms may be more diffi-
cult to culture from the placenta. However, we used
meticulous methods and were able to isolate multiple
species of anaerobic and Gram-negative organisms, in-
cluding several known periodontal pathogens. Perhaps
the relative lack of growth of periodontal organisms
represents sampling error. However, we sampled multi-
ple sites of the chorioamnion, as well as placental tissue,
for culture in these women. It is possible that the organ-
isms do spread to the placenta but are not viable and do
not colonize the placenta and membranes. Perhaps more
sensitive tests, such as DNA tests for periodontal patho-
gens, may demonstrate that the presence of the organ-
isms and the antigenic challenge of these few bacteria is
enough to precipitate preterm labor. Regardless, the
inflammation that occurs is not sufficient to be demon-
strated by evidence of higher rates of histological chorio-
amnionitis or elevated umbilical cord levels of the proin-
flammatory cytokine, IL-6. Another possibility to
consider is that periodontal disease and spontaneous
preterm birth are not, in fact, directly associated in a
cause-and-effect manner. Rather, these 2 conditions may
be linked by a third factor that predisposes the pregnant
woman to both adverse outcomes: periodontal disease
and spontaneous preterm birth.
Finally, previous studies of inflammation and preterm
birth have demonstrated an increased risk for neonatal
morbidity, especially neurological morbidity, in the set-
ting of intrauterine infection and inflammation.2328 We
did not see an association between periodontal disease
and adverse neonatal outcome in the preterm infants in
our study. This further suggests that, if the preterm birth
associated with periodontal disease is inflammation-me-
diated, the levels of inflammation are not of the same
magnitude as those seen in infection-mediated preterm
birth previously studied. Further investigation into the
potential etiology of the association between periodontal
disease and preterm birth is warranted.
REFERENCES
1. Hack M, Fanaroff AA. Outcomes of children of extremely
low birthweight and gestational age in the 1990s. Semin
Neonatol 2000;5:89 106.
782 Goepfert et al Periodontal Disease and Upper Genital Tract
2. Martin JA, Hamilton BE, Sutton PD, Ventura SJ,
Menacker F, Munson ML. Births: final data for 2002. Natl
Vital Stat Rep. 2003;52(10):116.
3. Andrews WW, Goldenberg RL, Hauth JC. Preterm labor:
emerging role of genital tract infections. Infect Agents Dis
1995;4:196 211.
4. Hauth JC, Andrews WW, Goldenberg RL. Infection-
related risk factors predictive of spontaneous preterm
birth. Prenat Neonat Med 1998;3:86 9.
5. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine
infection and preterm delivery. N Engl J Med 2000;342:
1500 7.
6. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP, Golden-
berg RL, Hauth JC. Periodontal infection and preterm
birth: results of a prospective study. J Am Dent Assoc
2001;132:875 80.
7. Jeffcoat MK, Geurs NC, Reddy MS, Goldenberg RL,
Hauth JC. Current evidence regarding periodontal disease
as a risk factor in preterm birth. Ann Periodontol 2001;6:
183 8.
8. Offenbacher S, Lieff S, Boggess K, Murtha AP, Madianos
PN, Champagne CM, et al. Maternal periodontitis and
prematurity. Part I: Obstetric outcome of prematurity and
growth restriction. Ann Periodontol 2001;6:164 74.
9. Offenbacher S, Beck JD, Lieff S, Slade G. Role of periodon-
titis in systemic health: spontaneous preterm birth. J Dent
Educ 1998;62:852 8.
10. Zeeman GG, Veth EO, Dennison DK. Focus on primary
care: periodontal disease: implications for womens health.
Obstet Gynecol Surv 2001;56:439.
11. Teng YT, Taylor GW, Scannapieco F, Kinane DF, Curtis
M, Beck JD, et al. Periodontal health and systemic disor-
ders. J Can Dent Assoc 2002;68:188 92.
12. Offenbacher S, Katz V, Fertik G, Collins J, Boyd D,
Maynor G, et al. Periodontal infection as a possible risk
factor for preterm low birth weight. J Periodontal 1996;67:
110313.
13. Jeffcoat MK, Hauth JC, Geurs NC, Reddy MS, Cliver SP,
Hodkins PM, et al. Periodontal disease and preterm birth:
results of an intervention study. J Periodontol 2003;74:
1214 8.
14. Lopez NJ, Smith PC, Gutierrez J. Periodontal therapy may
reduce the risk of preterm low birth weight in women with
periodontal disease: a randomized controlled trial. J Peri-
odontol 2002;73:91124.
15. Lopez NJ, Smith PC, Gutierrez J. Higher risk of preterm
birth and low birth weight in women with periodontal
disease. J Dent Res 2002;81:58 63.
16. Dasanayake AP, Russell S, Boyd D, Madianos PN, Forster
T, Hill E. Preterm low birth weight and periodontal dis-
ease among African-Americans. Dent Clin North Am
2003;47:11525.
17. Offenbacher S, Jared HL, OReilly PG, Wells SR, Salvi
OBSTETRICS & GYNECOLOGY
 GE, Lawrence HP, et al. Potential pathogenic mechanisms
of periodontitis associated pregnancy complications. Ann
Periodontol 1998;3:23350.
18. Bearfield C, Davenport ES, Sivapathasundaram V,
Allaker RP. Possible association between amniotic fluid
micro-organism infection and microflora in the mouth.
BJOG 2002;109:52733.
19. Cutress TW, Ainamo J, Sardo-Infirri J. The community
periodontal index of treatment needs (CPTIN) procedure
for population groups and individuals. Int Dent J 1987;37:
22233.
20. Carlos J, Wolfe M, Kingman A. The extent and severity
index: a simple method for use in epidemiologic studies of
periodontal disease. J Clin Periodontol 1986;13:500 5.
21. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent
RL Jr. Microbial complexes in subgingival plaque. J Clin
Periodontol 1998;25:134 44.
22. Madianos PN, Lieff S, Murtha AP, Boggess KA, Auten RL
Jr, Beck JD, et al. Maternal periodontitis and prematurity.
Part 2: Maternal infection and fetal exposure. Ann Peri-
odontol 2001;6:175 82.
23. Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Lev-
eno KJ. Clinical chorioamnionitis and the prognosis for
very low birth weight infants. Obstet Gynecol 1998;91:
7259.
24. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor
for cerebral palsy: a meta-analysis. JAMA 2000;284:
141724.
VOL. 104, NO. 4, OCTOBER 2004
25. Yoon BH, Jun JK, Romero R, Park KH, Gomez R, Choi
JH, et al. Amniotic fluid inflammatory cytokines (interleu-
kin-6, interleukin-1, and tumor necrosis factor-), neona-
tal brain white matter lesions, and cerebral palsy. Am J
Obstet Gynecol 1997;177:19 26.
26. Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH,
et al. Fetal exposure to an intra-amniotic inflammation and
the development of cerebral palsy at age three years. Am J
Obstet Gynecol 2000;182:675 81.
27. Yoon BH, Romero R, Yang SH, Jun JK, Kim IO, Choi JH,
et al. Interleukin-6 concentrations in umbilical cord plasma
are elevated in neonates with white matter lesions associ-
ated with periventricular leukomalacia. Am J Obstet
Gynecol 1996;174:1433 40.
28. Dammann O, Leviton A. Maternal intrauterine infection,
cytokines, and brain damage in the preterm newborn.
Pediatr Res 1997;42:1 8.
Reprints are not available. Address reprint correspondence to:
Alice R. Goepfert, MD, University of Alabama at Birmingham,
Department of Obstetrics and Gynecology, 619 19th Street,
South OHB 450, Birmingham, AL 35249 7333; e-mail:
aliceg@uab.edu.
Received April 29, 2004. Received in revised form June 27, 2004.
Accepted July 1, 2004.
Goepfert et al Periodontal Disease and Upper Genital Tract 783