Best Practice & Research Clinical Obstetrics and Gynaecology

Vol. 21, No. 3, pp. 451–466, 2007

doi:10.1016/j.bpobgyn.2007.01.005
available online at http://www.sciencedirect.com

Periodontal disease and pregnancy outcomes:

exposure, risk and intervention

B. Clothier
Graduate Student

M. Stringer
Associate Professor and Clinician Educator
School of Nursing, University of Pennsylvania, Philadelphia, PA, USA

Marjorie K. Jeffcoat *
Professor and Morton Amsterdam Dean
University of Pennsylvania, School of Dental Medicine, 240 S. 40th, Philadelphia PA 19104, USA

Despite the many advances in medicine, the rate of preterm birth has not significantly decreased
in the United States over the past several decades. In fact, the rate rose in 2003 to more than
12% of all births in the United States. This equates to over half a million premature births in the
United States alone. Consequently, the identification of risk factors for preterm birth which are
amenable to intervention would have far-reaching and long-lasting effects. There is emerging ev-
idence of a relationship between periodontal health and adverse pregnancy outcomes, particu-
larly preterm birth/preterm low-birth-weight infants. Therefore this chapter explores the
putative association between periodontal disease and infant prematurity, as well as the results
of intervention studies which treated periodontal disease in order to reduce the incidence of
prematurity. Of 31 published studies, 22 show a positive association between premature birth
and periodontal disease. Ongoing studies are addressing the efficacy of periodontal treatment
for decreasing the incidence of infant prematurity.

Key words: periodontal disease; periodontitis; prematurity; preterm birth; low birth weight;
clinical trial.

There is emerging evidence of a relationship between periodontal health and adverse

pregnancy outcomes, particularly preterm birth/preterm low-birth-weight infants. Pre-
term birth is defined as delivering at less than 37 completed weeks of gestation, whereas

* Corresponding author.
E-mail address: jeffcoat@dental.upenn.edu (M.K. Jeffcoat).
1521-6934/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved.
452 B. Clothier et al

preterm low-birth-weight infants are born less than 37 weeks and weigh less than
2500 g.1 Preterm birth is a health-care problem, because it is associated with increased
neonatal morbidity and mortality.1–3 As such, the efforts to decrease the rate of preterm
birth and the associated morbidity and mortality remain research priorities.1,4
Despite the many advances in medicine, the rate of preterm birth has not
decreased significantly in the United States over the past several decades. In fact,
the rate rose in 2003 to more than 12% of all births in the United States.5 This equates
to over half a million premature births in the United States alone.5 Consequently, the
identification of risk factors for preterm birth which are amenable to intervention
would have far-reaching and long-lasting effects. This chapter therefore explores the
risk factors for one such putative risk factor: periodontal disease. First, periodontal
disease and current treatment will be overviewed. Second, the existing literature on
the relationship between periodontal disease and preterm birth, results from interven-
tion studies, and the biologic plausibility for the purported relationship will be
presented. Lastly, we will draw conclusions based on the current state of the science
and outline some of the questions yet to be answered.

PERIODONTAL DISEASE

Periodontal diseases are initiated by bacterial infection but are modified by host
response factors. These factors are discussed below. Periodontal diseases may be di-
vided into two broad categories. Gingivitis is an inflammation of the gingival tissues
without the loss of supporting soft tissue or bone, while periodontitis is characterized
by loss of bone and soft tissue attachment (Figure 1). Gingival health during pregnancy
is compromised by hormonal changes. This condition, called pregnancy gingivitis, pre-
disposes women to gingivitis, the mildest form of periodontal disease.6 Periodontitis
has been further subdivided into specific diseases based primarily on the clinical syn-
dromes and rapidity of bone and attachment loss. Whereas earlier classification sys-
tems in the United States were based on age, the new system is based on rapidity
of disease progression. A world-wide classification is yet to be achieved. Table 1 sum-
marizes the forms of periodontitis according to the most recent categories defined by
the American Academy of Periodontology.7 These classifications of periodontal
diseases are continually evolving in the light of our increasing knowledge of the
pathogenesis of the disease process.7

Figure 1. (a) Clinical photograph of gingivitis. Note the erythematous, edematous gingiva. (b) Clinical
photograph of periodontontitis. Note the subgingival calculus, erythema and edema.
 Periodontal disease and pregnancy outcomes 453

Table 1. Classification system for periodontitis (US).

Disease Age Progression Replaces old terminology
Chronic periodontis Any Slow Adult periodontitis
Aggressive periodontitis Any Rapid Juvenile, prepubertal, rapidly progressive
periodontitis
Necrotizing ulcerative periodontitis Any Rapid Necrotizing ulcerative periodontitis
Periodontitis as a manifestation Any Any rate Not in older classifications
of systemic disease

SCREENING AND TREATMENT

Periodontal evaluation includes review of a person’s medical and dental history, fol-
lowed by a clinical examination.8 The clinical exam includes ascertaining probing
depths, defined as ‘the distance from the gingival margin to the base of the probeable
crevice’, and clinical attachment loss, defined as ‘the distance from the cementoenamel
junction to the base of the probable crevice.’9 Figure 2 provides an illustration of prob-
ing to determine the status of the periodont. Severity of disease is quantified as absent,
mild, moderate, or severe.7 Treatment for periodontal disease includes surgical as well
as non-surgical interventions (Table 2). Initial treatment for periodontal disease is
a procedure called scaling and root planing. Scaling and root planing involve mechan-
ically cleaning the roots (i.e. below the gum) to remove plaque.10 Once periodontal
health has been restored, maintenance is an important component of treatment.

PERIODONTITIS AND PREGNANCY

The early warning signs of periodontitis – namely persistent swollen, red or bleeding
gums, tooth sensitivity, and bad breath – mirror many of the symptoms of pregnancy

Figure 2. (a) Schematic of the tooth anatomy. The periodontal pocket is defined as the distance between
the gingival margin and the attachment level. (b) Clinical photograph of the use a periodontal probe to
measure probing or pocket depth.
454 B. Clothier et al

Table 2. Treatment for periodontal disease.10

Prevention
Non-surgical
Scaling and root planing
Maintenance
Surgical
Pocket reduction procedures
Regenerative procedures

gingivitis. Oftentimes, these symptoms are not signals that patients recognize as health
problems needing preventative dental care, as evidenced by the wide incidence (30–
90%) of periodontal disease in the United States.10 Based on the 2003 National Vital
Statistics Report for live births in the United States, this equates to the potential an-
nual exposure of between 1,226,985 and 3,680,955 mother/baby pairs to periodontal
disease.5 To better appreciate the potential influence of periodontal disease on preg-
nancy outcomes, it is helpful to understand the risk factors for periodontal disease.

RISK FACTORS FOR PERIODONTAL DISEASE

Health history, age, gender, and genetics are risk factors for periodontal disease.
Health history includes behavior, coexisting conditions, and disease progression. For
example, smoking is one of the most significant risk factors in the development and
progression of periodontal disease.10–15 Furthermore, this behavior is a well-known
risk factor for preterm birth. In addition to smoking, poor oral hygiene and clenching
or grinding of the teeth are additional behaviors that promote gum disease by increas-
ing inflammation and placing excessive force on the supporting tissues.10,11,15 Oral hy-
giene habits, including lack of periodontal maintenance, are associated with poor
periodontal conditions during pregnancy.16–18 Along with pregnancy, coexisting health
conditions that contribute toward periodontal disease and its progression include
stress, diabetes, autoimmune disorders, and previous periodontal disease.10,11,15
In a report entitled ‘Oral Health in America: A Report to the Surgeon General’19, the
proportion of adults with periodontal attachment levels of at least 2 mm doubled be-
tween the ages of 18 and 44 years. This finding is concerning because 2 mm defines
the upper limit of mild periodontal disease.7 Furthermore, this time frame encompasses
most of the childbearing years for women. During pregnancy, the correlation between
age and gingivitis is well documented, and more severe periodontal disease – defined
as deeper probing depths – is reported among pregnant women >30 years old.14,16,17,20
Gender is another individual risk factor for periodontal disease. Over the life span,
men are more likely than women to have periodontal disease.19 The hormonal changes
associated with pregnancy and oral contraceptive use increase a woman’s susceptibility
to periodontal disease during pregnancy.10,15,21 In fact, the literature consistently de-
fines the second trimester, which corresponds to the time when there are increased
levels of circulating estrogen and progesterone, as the period when gingival tissue
demonstrates the greatest amount of deterioration.22–24 The final risk factor that is
currently not amenable to change is an individual’s inherited risk of developing peri-
odontal disease. Approximately 30% of the population may be genetically susceptible,
placing them at a six-fold risk for developing periodontal disease.10,15
 Periodontal disease and pregnancy outcomes 455

The next level of risk factors for periodontal disease incorporates those classified
as microcultural. These risk factors include the subcategories of race/ethnicity, class,
and household management.25 All races are affected by periodontal disease; however,
a higher prevalence is observed among certain groups. For example, in the United
States the poorest oral health is noted among non-Hispanic Blacks, Hispanics,
American Indians and Alaskan natives.19 In addition to race/ethnicity, socioeconomic sta-
tus indicators – such as low income, lack of comprehensive insurance coverage, and less
education – are also correlated with poor periodontal outcomes.13,14,17–19,26,27 The
translation of these racial, ethnic, and socioeconomic findings to different international
populations and concomitant environment is unknown. It is important to note, however,
that these barriers ‘emphasize larger social forces and not the cumulative effects of
individual behaviors per se as the ultimate causes of bad health’.28

PRETERM LABOR

Idiopathic preterm labor (PTL) is defined as uterine contractions with progressive

cervical change in the absence of identifiable cause.4,29–31 In the United States the treat-
ment for idiopathic preterm labor typically consists of a medical intervention to arrest
uterine contractions with a tocolytic agent (such as magnesium sulfate, terbutaline and/
or indomethacin) in addition to antenatal steroid administration to promote fetal lung
maturity.29–32 However, the use of these agents has not reduced the rates of PTL and
preterm birth, although the use of adjuvant antenatal steroids and the advances in
neonatal medicine have improved the survival rate for infants born prematurely.1,29,33
Consequently, the Clinical Management Guidelines for Obstetrician-Gynecologists de-
clared that ‘There are no clear ‘‘first-line’’ tocolytic drugs to manage preterm labor’.34
The frustration with the efficacy of preterm labor management has resulted in at-
tempts to better identify women at risk of preterm labor (prior to a need for medical
intervention). Epidemiological studies have identified factors associated with preterm
labor and subsequent birth. These studies have indicated multiple risk factors such as
age, race, multiple gestation, low pre-pregnancy weight, vaginal bleeding, inadequate
prenatal care, maternal substance abuse, smoking, cervical length, and stress as asso-
ciated with preterm labor.1,35–43 Moreover, women with previous preterm labor re-
sulting in preterm birth have a recurrence risk of 17–40%.42,44–48 Unfortunately,
existing preterm prediction models and interventions have variable degrees of reliabil-
ity and success, respectively.32,33,36,38,49 For example, some studies have focused on
the positive predictive value of uterine contraction frequency and preterm birth.
Although contraction frequency is significantly related to preterm birth, contraction
frequency measurement has low sensitivity and poor positive predictive power.49–51

RELATIONSHIP BETWEEN PERIODONTAL DISEASE

AND PRETERM BIRTH

The hypothesized connection between periodontal infection and adverse pregnancy

outcome is not recent. Galloway52 is credited with suggesting a deleterious relationship
between periodontal disease and pregnancy. After a study in which he had full-mouth
x-rays on all prenatal patients and subsequently treated those who demonstrated radio-
graphic symptoms of chronic infection, he concluded that ‘routine care of pregnancy
should include a full-mouth x-ray of the patient’s teeth as a part of the first examination’.52
After a 65-year hiatus, interest in periodontal disease and pregnancy outcomes
456 B. Clothier et al

Table 3. Periodontal disease and preterm birth/low-birth-weight infant.

Author Type of study Sample size Periodontal variable(s) Association

Obstetrical variable(s)
72
Boggess et al, 2006 Cohort 1017 1. Periodontal status 1. Yes
1. SGA
Buduneli et al, 200558 Caseecontrol 181 1. Periodontal disease: 1. No
postpartum assessment
1. Preterm low birth weight
Carta et al, 200459 Caseecontrol 92 1. Status of periodontal 1. Yes
disease: postpartum
assessment
1. Low birth weight
Dasanayake, 199860 Caseecontrol 110 1. Poor oral health: 1. Yes
postpartum assessment
1. Low birth weight
Davenport et al, 200261 Caseecontrol 743 2. Periodontal disease: 1. No
postpartum assessment
1. Preterm low birth weight
Dortbudak et al, 200573 Cohort 36 1. Periodontitis 1. Yes
1. Premature delivery
Farrell et al, 200674 Cohort 1793 1. Periodontal disease 1. No
1. Preterm birth
Goepfert et al, 200462 Caseecontrol 139 1. Periodontal disease: 1. Yes
postpartum assessment
1. Spontaneous preterm birth
Holbrook et al, 200475 Cohort 96 1. Periodontal disease 1. No
1. Preterm birth
Jarjoura et al, 200563 Caseecontrol 203 1. Clinical measurement: 1. Yes
postpartum assessment
1. Preterm birth
Jeffcoat et al, 200176 Cohort 1313 1. Periodontal disease 1. Yes
1. Preterm birth
Jeffcoat et al, 200385 RCT 366 1. Treatment of periodontitis1. Trend
randomized (P < 0.06)
723 in 1. Spontaneous preterm birth
untreated
reference
group
Khader and Meta-analysis Five studies 1. Periodontal disease 1. Yes
Ta’ani, 200599 1. Preterm birth 2. Yes
2. Preterm low birth weight
Konopka et al, 200364 Caseecontrol 128 1. Periodontal disease: 1.Yes
postpartum assessment
1. Preterm low birth weight
Lopez et al, 200284 Clinical trial 639 1. Periodontal disease 1. Yes
and treatment
1. Preterm low birth weight
Lopez et al, 200286 RCT 400 1. Periodontal disease and 1. Yes
treatment
1. Preterm low birth weight
 Periodontal disease and pregnancy outcomes 457

Table 3 (continued )
Author Type of study Sample size Periodontal variable(s) Association
Obstetrical variable(s)
Lunardelli and Peres, Cross-sectional 449 1. Periodontal disease: 1. No
200555 postpartum assessment
1. Low birth weight 2. No
2. Prematurity 3. No
3. Low birth weight
and/or prematurity
Marin et al, 200556 Cross-sectional 152 1. Periodontal disease 1. Yes
1. Birth weight
Mitchell-Lewis et al, Cohort 164 1. Periodontal disease 1. No
200177 and effect of intervention
1. Preterm low birth weight
Mokeem et al, 200465 Caseecontrol 90 1. Periodontal infection: 1. Yes
postpartum assessment
1. Preterm low birth weight
Moliterno et al, 200566 Caseecontrol 151 1. Periodontitis: postpartum 1. Yes
assessment
1. Low birth weight
Moore et al, 200478 Cohort 3738 1. Periodontal disease 1. No
1. Preterm birth 2. No
2. Low birth weight
Moore et al, 200567 Caseecontrol 154 1. Severity of periodontal 1. No
disease: postpartum
assessment
1. Preterm birth
Moreu et al, 200579 Cohort 96 1. Periodontal disease 1. No
1. Gestational age 2. Yes
2. Birth weight
Noack et al, 200568 Caseecontrol 101 1. Periodontal status: 1. No
postpartum assessment
on controls
1. Preterm low birth weight
Offenbacher et al, 199669 Caseecontrol 124 1. Prevalence of periodontal 1. Yes
infection: ante- or
postpartum assessment
1. Preterm low birth weight
Offenbacher et al, 200180 Cohort 812 1. Periodontal disease 1. Yes
2. Progression 2. Yes
1. Preterm birth 3. Yes
2. Low birth weight 4. Yes
Offenbacher et al, 200681 Cohort 1020 1. Periodontal disease 1. Yes
and/or progression of disease
1. Preterm birth (<37 weeks) 2. Yes
2. Very preterm birth
(<32 weeks)
Oittinen et al, 200582 Cohort 130 1. Periodontal disease 1. Yes
(before pregnant)
(continued on next page)
458 B. Clothier et al

Table 3 (continued)
Author Type of study Sample size Periodontal variable(s) Association
Obstetrical variable(s)
2. Periodontal disease 2. Yes
and bacterial vaginosis
1. Adverse pregnancy
outcomes
Radnai et al, 200457 Cross-sectional 85 1. Periodontitis: postpartum 1. Yes
assessment
1. Adverse pregnancy
outcome (PTB and LBW)
Rajapakse et al, 200583 Cohort 227 1. Periodontal disease/ 1. No
1. Preterm low birth weight
Romero et al, 200270 Caseecontrol 69 1. Periodontal disease: 1. Yes
postpartum assessment
1. Birth weight
Sadatmansouri RCT 30 1. Periodontal treatment 1. Yes
et al, 200687 1. Preterm low birth weight
Scannapieco et al, Meta-analysis 12 1. Prevention or control 1. Analysis
2003100 of periodontal disease not possible
1. Initiation or progression
of adverse pregnancy
outcomes
Skuldbol et al, 200671 Caseecontrol 60 1. Periodontal status: 1. No
postpartum assessment
1. Preterm birth
Xiong et al, 2006101 Meta-analysis 25 studies 1. Periodontal disease 1. Yes
1. Low birth weight 2. No
2. Preterm birth

resurfaced, as evidenced by the number of studies published during the last decade. Most
of the literature on periodontal health and pregnancy outcomes is concentrated on pre-
term birth and preterm low-birth-weight infants. A review of the literature focusing on
periodontal disease and preterm birth/low-birth-weight infants is summarized in Table 3.
The articles included in this summary are restricted to studies that provide parameters re-
lated to probing depths and/or clinical attachment loss and preterm outcomes.
The quality of studies is often graded according to the manner in which the subjects
were selected for study participation and exposure to intervention.53,54 The studies in
Table 3 encompass a variety of study designs, including: cross-sectional55–57, case–
control58–71, cohort72–83, clinical trial84, and randomized clinical trial.85–87 The majority
of the published studies meeting the criteria for this review support a relationship
between periodontal disease and preterm birth/low birth weight. Furthermore, all of
the published randomized clinical trials report a trend or statistical significance in favor
of periodontal treatment reducing the rate of preterm birth/low birth weight. Because
the benefits of this methodology include improved validity of statistical tests of signifi-
cance, the creation of comparable groups, and the removal of allocation bias between
intervention and control groups, the randomized clinical trial is often regarded as
providing the highest level of evidence.53,54,88
 Periodontal disease and pregnancy outcomes 459

In addition to study design, there are other areas that contribute to the strength of the
evidence regarding periodontal disease and preterm birth/low birth weight. Many of the
studies in Table 3 have been criticized for the homogeneity of the intra-study population,
yet results have been replicated in different parts of the world (Table 4). Therefore, the
generalizability of the study results is strengthened since the relationship has been con-
sistent worldwide. Another criticism is the sample size of the various studies that report
statistical significance. This ranges from 30 subjects in a randomized trial by Sadatman-
souri and colleagues87 to 1313 in a cohort study by Jeffcoat et al76 The largest published
randomized trial to date investigating treatment for periodontal disease and preterm
birth/low-birth-weight infants enrolled 400 women86, whereas the same investigators
enrolled 870 women with gingivitis, not periodontal disease, in a different study.89
Although the diversity in study designs and the significant findings favor an associ-
ation between periodontal disease and preterm birth/low-birth-weight infants, a review
of the literature would not be complete without addressing factors which could con-
tribute to the findings. Publication bias (the tendency for studies with positive results
to be accepted for scholarly publication) could be responsible for a majority of the
studies supporting a relationship. There are design and analysis issues that could
also affect this trend. For example, the sample selection may favor a hypothesis.
Many of the studies in Table 3 collected periodontal measurements postpartum
(i.e. after the outcome of interest had occurred).55,57–67,70,71 This approach can lead
to ‘selection bias’. Another factor that may contribute to positive results is the
repeated use of data collected from the same population. For example, the Oral Con-
dition and Pregnancy (OCAP) study is represented three times in Table 3.72,80,81 Lastly,
reporting significant results found in a subgroup of the study sample also inflates the
positive results in the literature as a result of publication bias.56,57,62,64

SURROGATE MARKERS

In addition to the published studies presented in Table 3, the relationship between

a number of surrogate markers for periodontal status and preterm obstetrical out-
comes has been investigated. These surrogates include maternal inflammatory status
(C-reactive protein, CRP; immunoglobulin G, IgG; tumor necrosis factor a, TNFa;

Table 4. Populations with statistically significant relationship between periodontal disease and preterm
birth/preterm low birth weight.
Population studied
Austria73
Brazil55,56,66
Chile84,86
Finland82
Hungary57
Iran87
Italy59
Poland64
Saudi Arabia65
Thailand60
USA (Alabama, New York, North Carolina)62,63,69,72,76,80,81,85
Venezuela70
460 B. Clothier et al

Table 5. Surrogate markers for periodontal disease exposure and preterm birth/low-birth-weight infant.
Author Type of Sample size Periodontal marker Association
study
Obstetrical variable(s)
Boggess et al, Nested 640 1. Fetal CRP, IL-1b, IL-6, 1. Yes
2005102 case control TNF-a, PGE2, and 8-isopropane (8-isoprostane
and TNF-a)
2. Fetal IgM 2. Yes
1. Preterm birth
Boggess et al, Cohort 1017 1. CRP 1. Yes
200672 1. SGA
Boggess et al, Cohort 661 1. Fetal IgM to one of five 1. Yes
2006103 oral pathogens
2. Fetal IgM and vaginal 2. Yes
bleeding
1. Vaginal bleeding
2. Preterm birth
Buduneli et al, Caseecontrol 181 1. Plaque samples 1. No
200558 2. Preterm low birth weight
Carta et al, 200459 Caseecontrol 92 1. GCF PGE2 & IL-1b 1. Yes
1. Low birth weight
Dasanayake et al, Caseecontrol 80 1. IgG porphyromonas gingivalis 1. Yes
2001104 1. Low birth weight
Dasanayake et al, Cohort 297 1. Oral bacteria NOT 1. Yes
2005105 periodontal pathogens
1. Preterm delivery 2. Yes
2. Preterm low birth weight
Dortbudak et al, Cohort 36 1. Bacterial counts in 1. Yes
200573 periodontal pockets
1. Cytokine levels in
amniotic fluid
Hasegawa et al, Cohort 88 1. Serum cytokine levels 1. Yes
2003106 2. Plaque composition 2. Yes
1. Threatened preterm labor
2. Preterm birth
Jarjoura et al, Caseecontrol 203 1. Microbiologic 1. No (but
200563 M micros lower
in cases)
2. Serologic markers 2. No
2. Preterm birth
Konopka et al, Caseecontrol 128 1. GCF PGE2 and IL-1b levels 1. Yes (in
200364 1. Preterm low birth weight subgroup
>28 years)
Madianos et al, Nested 400 1. Maternal IgG 1. Yes
2001107 caseecontrol 2. Fetal IgM 2. Yes
1. Preterm birth
Moore et al, Caseecontrol 130 1. Presence of IL-1bþ3953 and 1. No
2004108 TNF-a308 (serum) (IL-1bþ3953);
Yes (TNF-a308)
2. Severity of periodontal disease 2. Yes
1. Preterm birth
2. Presence of IL-1bþ3953
and TNF-a308
 Periodontal disease and pregnancy outcomes 461

Table 5 (continued )
Author Type of Sample size Periodontal marker Association
study
Obstetrical variable(s)
Noack et al, 200568 Caseecontrol 101 1. Microbiologic status 1. No
2. IL-1b 2. No
1. Preterm low birth weight
Offenbacher et al, Caseecontrol 40 1. GCF PGE2 and IL-1b levels 1. Yes
199897 (GCF PGE2)
2. Plaque composition 2. Yes
1. Preterm low birth weight (four organisms)
Skuldbol et al, Caseecontrol 60 1. Presence of subgingival 1. Yes
200671 bacteria
1. Preterm birth
CRP, C-reactive protein; IL, interleukin; TNF, tumor necrosis factor; PGE, prostaglandin E; SGA, small for
gestational age; GCF, gingival crevicular fluid.

interleukin 1b, IL-1b), oral bacteria counts, plaque composition, and fetal inflammatory
response to exposure including CRP, IL-1b, IL-6, TNF-a, 8-isopropane, prostaglandin E2
(PGE2), and IgM. Studies which investigated surrogate markers for periodontal status
and preterm birth/low-birth-weight infants are summarized in Table 5. Although the
use of different parameters by different studies complicated the interpretation and gen-
eralization of the findings, their use provides additional biologic plausibility for adverse
pregnancy outcomes in the setting of maternal periodontal disease.

BIOLOGICAL PLAUSIBILITY

It is important to understand the underlying biologic mechanisms for the relationship

between periodontal disease and adverse pregnancy outcome such as preterm birth in
order to provide a rationale for therapeutic interventions and exploration of other
methods that may be used as adjuncts to standard treatment. Several pathways have
been proposed to be responsible for contributing to poor perinatal sequelae of un-
treated periodontal disease. The first link draws upon the proximity of periodontal in-
fection to the vascular system. Zeeman et al15 describe the human gingiva as an
estrogen target tissue, and the elevated concentration of sex steroids found during
pregnancy changes the microvascular topography and permeability of the gums. This
change results in an increased risk of bacteremia from the Gram-negative organisms
typically associated with periodontal disease, followed by ‘placental seeding’.90,91
This pathway is supported by case reports where organisms exclusively associated
with periodontal infection have been cultured from amniotic fluid and neonates.92–96
In addition to the hematogenous introduction and spread of bacteria, there appears
to be initiation of an inflammatory cascade. Endotoxins associated with periodontal
disease are responsible for triggering cytokine production (primarily locally and also
systemically). Cytokines stimulate prostaglandin production, particularly PGE2, which
is an inflammatory marker that is common to both periodontal disease and parturition
at term and preterm.90,97 Figure 3 depicts a model of periodontal disease and preterm
low birth weight, illustrating the hypothesized relationship between periodontal dis-
ease and preterm birth/low birth weight.
462 B. Clothier et al

Health

Genetics

Environment Pathogenic Bacteria Susceptible Host

Metabolic Change

Increased cytokines,
PGE2 etc

Periodontitis

Figure 3. Schematic representation of the etiology of periodontal disease.

CONCLUSIONS AND FUTURE DIRECTIONS

The following statement was released by the American Academy of Periodontology in

2004: ‘.all women who are pregnant or planning a pregnancy should undergo peri-
odontal examination. Appropriate preventative or therapeutic services, if indicated,
should be provided’.98 Current treatment for periodontal disease begins with oral hy-
giene instruction and scaling and root planing. Acceptance and implementation of this
parameter of care, however, is dependent upon the strength of the evidence support-
ing the purported relationship and overcoming socio-political barriers.
The risk factors for both periodontal disease and adverse perinatal outcomes are
multifactorial and include risks that are and are not amenable to risk reduction. There-
fore, the proposed relationship between periodontal health and pregnancy outcomes
presents challenges to providers of both prenatal health care and dental health care.
Cross-sectional, case–control and prospective studies support a relationship be-
tween periodontal health and adverse pregnancy outcomes. The literature also points
to a role for inflammation in both infant prematurity and periodontal disease. The lim-
ited numbers of published randomized intervention trials show a trend toward fewer
preterm births (especially before 35 weeks) in the subjects that received periodontal
treatment.
Currently, there are three ongoing randomized clinical trials exploring the effect of
periodontal treatment on pregnancy outcomes.
Additional questions still need to be answered. These include: why do scaling and
root planing decrease preterm birth? The answer to this question will provide reassur-
ance that periodontal disease is the direct contributing factor rather than a surrogate
marker or confounding variable for the actual cause of the correlation. Another ques-
tion is: who is most responsive to treatment? If treatment is effective among certain
subgroups, screening and treatment programs may be targeted toward those groups.
Furthermore, additional lines of investigation including identification of adjunct treat-
ment, and exploration of alternative therapies may answer the question of which treat-
ments work best. Finally, when is treatment most effective in improving perinatal
 Periodontal disease and pregnancy outcomes 463

outcomes? It is important to establish whether there is a point during pregnancy at

which treatment compromises favorable perinatal outcomes.

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