J Clin Periodontol 2013; 40 (Suppl. 14): S164–S169 doi: 10.1111/jcpe.

12083

Periodontitis and adverse Mariano Sanz1, Kenneth Kornman2

and on behalf of working group 3 of
the joint EFP/AAP workshop*

pregnancy outcomes: consensus 1

2
University Complutense of Madrid, Spain;
Interleukin Genetics, Waltham, MA, USA

report of the Joint EFP/AAP

Workshop on Periodontitis and
Systemic Diseases
Sanz M, Kornman K, and on behalf of working group 3 of the joint EFP/AAP
workshop. Periodontitis and adverse pregnancy outcomes: consensus report of the Joint
EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol 2013;
40 (Suppl. 14): S164–S169. doi: 10.1111/jcpe.12083.

Abstract
Background: Pregnancy sometimes has adverse outcomes including low birthweight
(<2500 g), pre-term birth (<37 weeks), growth restriction, pre-eclampsia, miscarriage
and/or stillbirth. Maternal periodontitis directly and/or indirectly have potential to
influence the health of the foetal–maternal unit.
Aims: To assess the epidemiological evidence for the impact of periodontal disease
on adverse pregnancy outcomes and to identify potential underpinning mechanisms.
Epidemiology: Low birthweight, pre-term birth and pre-eclampsia have been
associated with maternal periodontitis exposure. However, the strength of the
observed associations is modest and seems to vary according to the population stud-
ied, the means of periodontal assessment and the periodontal disease classification
employed. Key words: adverse pregnancy outcomes;
Biological mechanisms: Two major pathways have been identified, One direct, in complications; intervention; low birthweight;
which oral microorganisms and/or their components reach the foetal–placental unit mechanisms; periodontal disease;
and one indirect, in which Inflammatory mediators circulate and impact the foetal– periodontitis; pre-eclampsia; pre-term birth;
placental unit. still birth
Interventions: Although periodontal therapy has been shown to be safe and leads
to improved periodontal conditions in pregnant women, case-related periodontal Accepted for publication 14 November 2012
therapy, with or without systemic antibiotics does not reduce overall rates of
The proceedings of the workshop were jointly
pre-term birth and low birthweight.
and simultaneously published in the Journal
Guidelines: Given the current evidence, various treatment strategies could be evaluated of Clinical Periodontology and Journal of
that consider specific target populations, as well as timing and intensity of treatment. Periodontology.

Conflict of interest and source of funding statement

Group participants declare no conflict of interest. The workshop was funded by an unrestricted educational grant from Colgate-
Palmolive to the European Federation of Periodontology and the American Academy of Periodontology.

*Working group participants: Mariano Sanz, Spain; Kenneth Kornman, USA; Mark Ide, UK; Anders Gustafsson, Sweden; Phoebus
Madianos, Greece; Panos Papapanou, USA; Steve Offenbacher, USA; Bryan Michalowicz, USA; Lior Shapira, Israel; Leo Trom-
belli, Italy; Gernot Wimmer, Austria; Bjorn Klinge, Sweden; Tellervo Tervonen, Finland; Michael Reddy, USA; Ricardo Teles,
USA; James Katancik, USA; Michael Rethman, USA; Yiping Han, USA; Laurie McCauley, USA; Manuel Voegtli, Switzerland.
S164 © 2013 European Federation of Periodontology and American Academy of Periodontology
 Adverse pregnancy outcomes and periodontitis S165

Periodontitis and Adverse Pregnancy individual-level behavioural and explain the observed association
Outcomes psychosocial factors, neighbourhood and review the evidence,
Pregnancy is normally a healthy characteristics, environmental expo- (d) Review and interpret the evidence
physiological process that sometimes sures, medical conditions, infertility from periodontal intervention
has adverse outcomes including treatments, biological factors and trials, summarizing the overall
low birthweight (<2500 g) or very genetics. Many of these factors interpretation of the combined
low birthweight (<1500 g), pre-term occur in combination, particularly evidence from epidemiological,
birth (<37 weeks or very pre-term in those who are socio-economi- mechanism and intervention stud-
<32 weeks), growth restriction (weight cally disadvantaged or are members ies and Identifying key issues for
for gestational age), pre-eclampsia of racial and ethnic minority future research,
(commonly defined as maternal hyper- groups. (e) Provide general recommendations
tension and proteinuria after the 20th Adverse pregnancy outcomes are for the general oral health profes-
gestational week), miscarriage and/or generally associated with elevated sional and the medical profession.
still birth. Some of these outcomes local and systemic inflammatory
occur together, and it is unclear whether mediators and intra-uterine infec-
tions. Current evidence suggests that Epidemiological evidence
they share common mechanisms.
Every year, 1
1 million babies die adverse outcomes primarily originate Are the currently used periodontal
from prematurity, and many survi- from ascending infections from the case definitions suitable in the study
vors are disabled. Worldwide, 15 mil- vagina or cervix or from haematoge- of the epidemiological association
lion babies are born pre-term with nous spread from known or between periodontal infections and
two decades of increasing rates in unknown non-genital sources. adverse pregnancy outcomes?
almost all countries with reliable Maternal periodontitis represents
one potential source of microorgan- The currently used case definitions
data. Pre-term birth is now worldwide may not be deemed suitable for such
the second most common cause of isms that are known to routinely
enter the circulation, and directly investigations of potential associa-
death in children younger than tions. The majority of studies inves-
5 years after pneumonia, and is and/or indirectly have mechanistic
potential to influence the health of tigating this association have used a
decreasing at a much slower rate than dichotomous definition based on the
pneumonia, even increasing in several the foetal–maternal unit.
number of teeth or sites with pre-
countries. In addition, pre-term birth The scope of this Working Group defined levels of probing depth and
is the leading risk factor for deaths will be: attachment loss.
due to neonatal infections and con- These definitions do not capture
(a) Review current evidence for a
tributes to long-term growth impair- “cases” with profound gingival
role of periodontal diseases in
ment and substantial long-term inflammation in the absence of clinical
adverse pregnancy outcomes,
morbidity such as cognitive, visual attachment loss and associated pock-
(b) Review the epidemiological evi-
and learning impairments (Chang eting, and may exclude individuals
dence for an association between
et al. 2013) with significant oral inflammatory
periodontal diseases and adverse
Adverse pregnancy complications burden exacerbated during pregnancy.
pregnancy outcomes,
have been associated with a variety Other studies have employed a range
(c) Identify the currently known
of general risk factors including of continuous variables to reflect peri-
potential mechanisms that may
© 2013 European Federation of Periodontology and American Academy of Periodontology
S166 Sanz and Kornman

odontal status, including probing tory markers and serum antibodies (myometrium, membranes, amniotic
depth, attachment loss and bleeding to oral microorganisms fluid, placenta, foetal circulation and
on probing. These variables have been tissues).
What are the adverse pregnancy out-
expressed either as mean values or as (1) Direct pathway
comes that are currently associated with
total numbers/percentages of sites
maternal periodontitis exposure? What
involved. This approach allows an (a) Oral microorganisms and/or
is the strength of the association?
exposure–response relationship analy- their components reaching
sis, and provides greater insight Low birthweight, pre-term birth and foetal–placental unit via hae-
into the effects of a range of periodon- pre-eclampsia have all been associ- matogenous dissemination
tal conditions that may be involved. ated with maternal periodontitis from oral cavity,
However, in situations where there is exposure. However, the strength of (b) Oral microorganisms and/or
a low extent of disease, mean values the observed associations based on their components reaching
of probing depth or attachment loss clinical parameters is modest and foetal–placental unit by an
may not fully reflect periodontal sta- seems to vary according to the popu- ascending route via genitouri-
tus and associated exposure. lation studied, the means of periodon- nary tract.
Regardless of the choice of dichot- tal assessment and the periodontal
omous or continuous classification, disease classification employed (Ide & (2) Indirect pathway
these studies have involved either Papapanou 2013).
full-mouth or partial mouth record- (a) Inflammatory mediators locally
ing protocols. While the latter are Are there identifiable potential produced in periodontal tissues,
known to underestimate/misclassify confounders, which may influence the for example, PGE2, TNFa, cir-
periodontal disease status, they have association between periodontitis and culate and impact the foetal–
been adopted due to logistical chal- adverse pregnancy outcomes placental unit,
lenges (e.g. recruitment of adequate demonstrated in epidemiological (b) Inflammatory mediators and/or
numbers of women attending medical studies? microbial components circulate
clinics). This is disadvantageous when Studies have identified a range of to the liver, enhancing cytokine
assessing periodontal status in a pop- relevant exposures, which include: production (e.g. IL-6) and acute
ulation of younger adults with low phase protein responses (e.g.
prevalence/extent of periodontitis. (a) Socio-economic status, CRP), which then impact the
(b) Race and ethnicity, foetal–placental unit.
What are the features of periodontal (c) Smoking and use of recreational
infections that may be relevant to drugs.
pregnancy outcomes? The strongest evidence from both
animal and human studies supports
Most epidemiological studies have Attempts have been made to try the concept that periodontal infections
thus far focused on clinical measures to compensate for the potential provide a portal for haematogenous
of periodontal disease, which may impacts of these exposures in some dissemination of oral microorganisms
not adequately reflect the infectious/ analyses in high-quality studies. In and their products, which reach the
inflammatory burden present in preg- addition, it has been postulated that foetal–placental unit. This direct path-
nant women. Importantly, the record- several other exposures may have a way is associated with inflammatory/
ing of bleeding following probing has role, although these have not been immune responses in the foetal–
often been omitted. In addition, these confirmed, and these may include: placental unit that induce a range
measures have generally been assessed (a) Maternal age and weight, and of adverse outcomes, which are
at a single time point, and hence do weight gain during pregnancy, dependent on timing and severity of
not allow determination of the (b) Behavioural and lifestyle factors exposure. Lower exposures may
impact of changes in and duration of including alcohol use, nutritional induce hyper contractility of the
exposures during gestation related to status, exercise and stress, uterus, cervical dilation and loss of
bacterial biofilm, and maternal and (c) Other medical conditions includ- membrane integrity leading to pre-
foetal inflammatory states. At least ing obesity, metabolic syndrome term delivery. Growth restriction and
two assessments, carried out early in/ and diabetes. earlier pre-term delivery are associated
preceding pregnancy and again close with higher and/or earlier exposures.
to parturition, are desirable. Even higher exposures may lead to
Additional relevant features Biological mechanisms spontaneous abortion, late miscar-
include: riage and stillbirth (Madianos et al.
What are the most likely mechanisms 2013).
that may mediate an association
(a) An assessment of the microbial What are the variables that provide
between periodontal infections and
composition of the oral biofilm, an assessment of oral infectious
adverse pregnancy outcomes?
(b) Measures of host inflammatory exposure to the foetal–placental unit?
response, including. Two major pathways have been pro-
posed to trigger an inflammatory/ The main variables are presence and
Biological markers of microbial immune response and/or suppression levels of microorganisms and micro-
challenge or maternal and foetal of local growth factors (such as bial components in amniotic fluid,
response, such as systemic inflamma- IGF-2) in the foetal–placental unit placental cord blood, neonatal respi-

© 2013 European Federation of Periodontology and American Academy of Periodontology

 Adverse pregnancy outcomes and periodontitis S167

ratory aspirates, placenta, foetal Intervention studies pregnancy outcomes. However,

membranes, foetal tissues (still born), Based on the available evidence, do based on epidemiological and plausi-
titres of antibodies to oral microor- periodontal interventions improve bility studies that have associated
ganisms in maternal serum (all iso- adverse pregnancy outcomes? periodontitis with adverse pregnancy
types) and foetal cord blood (IgM). outcomes various treatment strate-
Although periodontal therapy has gies could be evaluated that consider
What are the variables that currently been shown to be safe and leads to specific target populations, as well as
provide an assessment of inflamma- improved periodontal conditions in timing and intensity of treatment.
tory exposure or response relevant to pregnant women, scaling and root
a potential foetal–placental effect? surface debridement, with or without
Inflammatory biomarkers in the adjunctive care including systemic Recommendations for future research
maternal serum may include IL-6, antibiotics, does not reduce overall
TNFa, CRP, 8-isoprostane (oxida- rates of pre-term birth and low birth- The association of maternal peri-
tive stress), sICAM1 weight. Because some trials have odontitis with adverse pregnancy
Inflammatory biomarkers in foetal shown an overall positive effect, there outcomes has been investigated for
cord blood may include IL-6, PGE2, may be distinct patient populations the past 20 years. As reviewed
TNFa, 8-isoprostane, sICAM1 that benefit from treatment. Previous above, epidemiological studies identi-
Inflammatory biomarkers in pre-term birth history and baseline fied a modest but statistically signifi-
amniotic fluid may include MMPs periodontal conditions may be associ- cant association between maternal
(2,3,8,9,13), fibronectin, a-fetopro- ated with a treatment effect (Micha- periodontitis and pre-term birth, low
tein, IL-6, TNFa, IL-1, 8-isoprostane lowicz & Gustafsson 2013). birthweight and pre-eclampsia, inde-
pendent of other exposures.
Is there evidence of specific oral In the context of improved pregnancy In parallel, several studies in ani-
microorganisms being implicated in outcomes, which periodontal mals and humans contributed to a
the pathobiology of adverse pregnancy conditions should be targeted for better understanding of the biological
outcomes? intervention studies? plausibility and the mechanisms that
Based on the amount of evidence Oral health, and periodontal health are involved in these associations.
such as frequency of detection of in particular, should be maintained On the other hand, several well-
the microorganism and/or their or re-established in pregnant conducted, adequately powered
respective antibodies in cases of women, with specific attention to intervention studies over the past
adverse pregnancy outcomes and reduction of the periodontal micro- decade demonstrated that non-surgi-
animal studies, the following bacte- bial infection and related inflamma- cal periodontal therapy delivered
rial species have been more strongly tory responses. However, available during the second trimester does not
associated with adverse pregnancy evidence does not provide clinical, improve pregnancy outcomes.
outcomes: Fusobacterium nucleatum, microbiological or immunological It would be inappropriate to con-
Campylobacter rectus, Porphyromon- parameters (or combinations of the clude that these seemingly contradic-
as gingivalis and Bergeyella sp. Fur- above) that define patient subgroups tory findings from observational/
thermore, additional oral bacterial whose pregnancy outcomes would mechanistic versus interventional
species have been associated with be improved with periodontal treat- studies indicate a lack of rationale
adverse pregnancy outcomes in ment. for further research in this field that
human and animal studies, but with continues to have high public health
less evidence. What clinical and other end points importance. Experiences in medical
In humans, Fusobacterium nuclea- should be targeted with treatment research (notably the early trials on
tum has been detected in amniotic flu- protocols in intervention studies? hypercholesterolaemia treatment and
ids in cases of pre-term birth and in cardiovascular disease risk) under-
In the absence of clinical, inflam- score the possibility that interven-
the amniotic fluid and foetal tissues in matory or microbiological thresh-
cases of stillbirth. Anti-F. nucleatum tional studies may still fail despite
olds that convey an increased risk targeting true risk/causative factors.
IgM antibodies have also been for adverse pregnancy outcomes,
detected in cord blood from cases of This could be due to several reasons
intervention studies should strive to related to the complexities of the
pre-term birth. Campylobacter rectus: eliminate clinical signs of periodon-
approximately 1/3 of foetuses harbour clinical condition and of the interven-
tal inflammation, which reflects tions, including inappropriate timing
positive IgM antibodies to oral bacte- control of the microbial biofilm
ria. Anti-C. rectus IgM titres in foetal and/or type of intervention, or inclu-
load. sion of patients whose risk was not
cord blood were the best predictor of
adverse pregnancy outcomes. Porphy- modifiable. These observations indi-
What would be the recommended oral cate that a more thorough under-
romonas gingivalis has been detected health interventions for reducing
in placental tissues from pre-term standing of the effects of treatment
adverse pregnancy outcomes? on the pathophysiology of the condi-
deliveries and anti-P. gingivalis IgM
antibodies have been frequently Given the existing intervention trials, tion under study will provide impor-
detected in foetal cord blood. Bergey- non-surgical periodontal therapy, tant insights relevant to the design of
ella sp. have been detected in amniotic delivered during the second trimester future clinical trials. For example,
fluids and cord blood in cases of pre- of pregnancy, cannot be recom- knowledge that mechanical instru-
term birth. mended as a means of improving mentation of the periodontal tissues

© 2013 European Federation of Periodontology and American Academy of Periodontology

S168 Sanz and Kornman

results in a transient bacteraemia/ evaluation should include peri- bacterial load and the signs of
increased systemic inflammation may odontal probing and evaluation inflammation,
partly negate the longer term poten- of the periodontal inflammatory (c) Once periodontal health is
tial benefits of periodontal treatment status (bleeding on probing). re-instituted, frequent monitoring
associated with reduced maternal of the periodontal status should
infectious and inflammatory burden. The result of this periodontal be maintained throughout preg-
Therefore, additional research is examination will render as periodon- nancy and recurrence occurs, a
needed to better understand the tal diagnosis: similar intervention should be
pathophysiology and risk profile that (a) Healthy, indicated.
underlie these associations, to (b) Gingivitis,
develop the most appropriate treat- (c) Periodontitis.
ment modalities with respect to type, In presence of a pregnant female with
time and intensity, as well as to iden- These are the specific recommen- Periodontitis
tify subpopulations of pregnant dations according to the obtained
women that will benefit most from diagnosis: (a) The same health promotion mea-
these interventions. sures as discussed above
(b) The professional intervention aimed
In presence of a pregnant female with to treat periodontitis should be the
Recommendations for the Dental healthy periodontium standard non-surgical periodontal
Profession therapy with the goal of reducing
(a) Health Promotion: In addition to the subgingival biofilm and the signs
Pregnancy is a unique period during a
providing pregnant women with of periodontal inflammation. If pos-
woman’s life and is characterized by
oral health care, educating them sible, extensive traumatic interven-
complex physiological changes, which
about preventing and treating tions should be avoided.
may affect oral health. At the same
periodontal diseases is critical, (c) In presence of localized gingival
time, oral health is key to overall health
both for women’s own oral health enlargements, surgical excision
and well-being. It is therefore essential
and for the future oral health of should be delayed if possible until
for oral health professionals (OHP) (e.g.
their children. The OHP should the inflammation has been con-
dentists, dental hygienists, periodontists)
inform the patient on the peri- trolled. Recommend supportive
to provide pregnant women with appro-
odontal physiological events usu- measures (oral hygiene instruction)
priate and timely oral health care, which
ally occurring during pregnancy and re-evaluation after delivery.
includes oral health education.
(increase in vascularity, possibility
These are the preventive, diagnos-
of higher incidence of bleeding
tic and therapeutic recommendations
and gingival enlargement). The Recommendations for the Medical
for the oral health professionals in
OHP should also undertake a Profession
regards to periodontal health and
general health assessment empha-
periodontal treatment. It is important Health professionals as part of their
sizing the history of hypertension,
to emphasize that all oral preventive, regular care should provide oral
diabetes, cardiovascular disease,
diagnostic and therapeutic procedures health care to pregnant women. At
etc. The OHP should try to
are safe throughout pregnancy and the same time, pregnant women,
include as part of the general
these measures are usually effective in should have the knowledge of the
patient examination the evaluation
improving and maintaining oral obvious signs of oral disease and try
of blood pressure and in case of
health. General obstetric guidelines, to seek or receive the appropriate
perceived medical risk the patient
however, suggest that elective proce- oral care.
should be referred to the physi-
dures should be avoided in the first The health professionals (HP)
cian,
trimester due to the possible stress to should include an oral health history
(b) An important component in oral
the foetus and preferably rendered as part of the patient’s general
health education should be train-
during the second trimester. health history. These types of ques-
ing and motivation in periodontal
Every OHP evaluating a female tions should always be asked: do
self-assessment and in oral
patient in childbearing age should you have swollen gums? Do you
hygiene practices, with special
always ask whether they are currently have problems eating or chewing
emphasis on inter-dental cleaning,
pregnant or are trying to become food? Are you suffering from oral
(c) The patient should be scheduled
pregnant and if the patient responds pain or other oral problems? The
for a re-evaluation at a later
affirmatively, the OHP should always health professionals should inform
stage during pregnancy
consider this pregnancy status before the pregnant females that periodon-
any oral health intervention is recom- tal disease is associated with a higher
In presence of a pregnant female with
mended. risk for adverse pregnancy outcomes
Gingivitis:
With regards to periodontal and therefore recommend them to
health the OHP should: (a) The same health promotion mea- visit an oral health professional for a
(a) Identify the stage of pregnancy, sures as discussed above, check-up early during gestation.
(b) Perform a comprehensive oral (b) The professional intervention The HP should include an oral
evaluation including a periodon- aimed to treat gingivitis should examination as part of their regular
tal examination. The periodontal have the goal of reducing the initial examination. This examina-

© 2013 European Federation of Periodontology and American Academy of Periodontology

 Adverse pregnancy outcomes and periodontitis S169

tion may consist of the use of a ton- (2013) Preventing preterm births: analysis of Michalowicz, B. S., Gustafsson, A., Thumbigere-
trends and potential reductions with Math, V. & Bulin, K. (2013) The Effects of
gue depressor assessing for presence
interventions in 39 countries with very high Periodontal Treatment on Pregnancy Out-
of bleeding in the margin between human development index. Lancet 381, 223– comes. Journal of Clinical Periodontology, 40
the teeth and the gingiva and overt 234. (Suppl 14), 195–208.
gingival inflammation. In presence of Ide, M. & Papapanou, P. (2013) Epidemiology of
these signs, the physician should association between maternal periodontal dis- Address:
ease & adverse pregnancy outcomes – system- Mariano Sanz
refer to an oral health professional atic review. Journal of Clinical Periodontology, Facultad de Odontologia
for seeking diagnosis and care. 40 (Suppl 14), 181–194. Universidad Complutense de Madrid
Madianos, P. N., Bobetsis, Y. A. & Offenbach-
Ciudad Universitaria
er, S. (2013) Adverse Pregnancy Outcomes
(APOs) and Periodontal Disease:Pathogenic 28040 Madrid
References
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Chang, H. H., Larson, J., Blencowe, H., Spong, odontology, 40 (Suppl 14), 170–180. E-mail: [email protected]
C. Y., Howson, C. P., Cairns-Smith, S., et al.

Clinical Relevance studies have shown a significant vant to fully understand the extent
Adverse pregnancy outcomes are association between chronic perio- of these associations, their possible
the most common cause of death dontitis and prematurity and low biological mechanisms and the
in babies. Several epidemiological birth weight. It is therefore very rele- implications for healthcare.

© 2013 European Federation of Periodontology and American Academy of Periodontology

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