J Clin Periodontol 2014; 41: 869874 doi: 10.1111/jcpe.

12281

Association between
periodontitis and preeclampsia in
never-smokers: a prospective
study

Jung-Eun Ha1,2, Jong-Kwan Jun3,

Hyun-Joo Ko3, Dai-Il Paik1,2 and
Kwang-Hak Bae1,2
1

Department of Preventive and Public Health

Dentistry, School of Dentistry, Seoul National
University, Seoul, Korea; 2Dental Research
Institute, School of Dentistry, Seoul National
University, Seoul, Korea; 3Department of
Obstetrics and Gynecology, Seoul National
University College of Medicine, Seoul, Korea

Ha J-E, Jun J-K, Ko H-J, Paik Dai-Il, Bae K-H. Association between periodontitis
and preeclampsia in never-smokers: a prospective study. J Clin Periodontol 2014;
41: 869874. doi: 10.1111/jcpe.12281.

Abstract
Aim: The aim of this prospective study was to investigate the relationship
between periodontitis and preeclampsia in never-smokers.
Materials and Methods: Pregnant women were recruited at 21 to 24 weeks of gestation from March 2009 to June 2013. Information on demographics, health
behaviours, obstetric history, and systemic diseases that can influence periodontal
status and preeclampsia was collected. Full-mouth periodontal probing was performed by two trained examiners. The inter-examiner Kappa value was 0.822 for
clinical attachment loss (CAL). Periodontitis was defined as clinical periodontal
attachment loss (CAL) of 4.0 mm or greater on 2 or more sites not on the same
tooth. Information on the occurrence of preeclampsia was collected by five obstetricians.
Results: We studied a total of 283 subjects, comprised of 67 subjects with periodontitis and 216 subjects without periodontitis. Of these, 13 (4.6%) women were
diagnosed with preeclampsia. After adjusting for all confounders, the adjusted
odds ratio of periodontitis for preeclampsia was 5.56 (95% confidence interval of
1.4920.71).
Conclusions: There was a significant relationship between periodontitis and the
occurrence of preeclampsia among never-smokers.

Preeclampsia (PE) is a pregnancyspecific disease characterized by the

occurrence of hypertension and significant proteinuria in previously
Conflict of interest and source of
funding statement
The authors declare no conflicts of
interest related to this study.
This research was supported by Basic
Science Research Program through
the National Research Foundation of
Korea (NRF) funded by the Ministry
of Education (NRF-2012R1A1A2038
458).

healthy women. This disease occurs

in about 28% of pregnant women
and remains as one of the major
causes of maternal and neonatal
mortality and morbidity throughout
the world (Villar et al. 2004, Lo
et al. 2013). Despite being widely
studied, the aetiology and physiopathology of PE remains unclear (Roberts & Gammill 2005, Widmer et al.
2007). Current theories include
abnormal placentation, cardiovascular maladaptation to pregnancy,
genetic and immune mechanisms,
an enhanced systemic inflammatory
response, and nutritional, hormonal,

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Key words: epidemiology; periodontitis;

preeclampsia; prospective study; relationship
Accepted for publication 9 June 2014

and angiogenic factors (Lam et al.

2005, Redman & Sargent 2005), but
several authors hypothesize that
inflammation plays an important
role in the occurrence of PE (Trogstad et al. 2001, Conde-Agudelo et al.
2008).
Periodontitis is one of the most
common chronic inflammatory disorders. Since it may indicate a
chronic burden of endotoxin and
inflammatory cytokines, it has been
considered as a risk factor of systemic illnesses including cardiovascular disease, atherosclerosis, and
cerebrovascular ischaemia (Beck

869

870

Ha et al.

et al. 1996, Hung et al. 2003, Janket

et al. 2003, Seymour et al. 2007).
Given the similarity between placental vascular damage and atherosclerosis, the potential for chronic oral
infection to affect PE has been considered (Boggess et al. 2003). Specifically, Boggess et al. (2003) suggested
that women with periodontal disease
progression during pregnancy may
translocate oral organisms to the
uteroplacental unit, inciting placental
inflammation or oxidative stress
early in pregnancy, which ultimately
produces placental damage and the
clinical manifestations of PE.
Several recent epidemiological
studies have shown that periodontitis
is associated with a higher risk of
PE (Canakci et al. 2004, Contreras
et al. 2006, Cota et al. 2006, Kunnen
et al. 2007, Siqueira et al. 2008,
Shetty et al. 2010, Moura da Silva
et al. 2012). One cohort study
showed that active maternal periodontal disease during pregnancy
was associated with an increased risk
of development of PE (Kumar et al.
2013). Several casecontrol studies
also revealed that a significant relationship between active periodontitis
detected within 48 h before delivery
or 328 months postpartum and the
occurrence of PE (Canakci et al.
2004, Contreras et al. 2006, Cota
et al. 2006, Kunnen et al. 2007,
Siqueira et al. 2008, Shetty et al.
2010, Moura da Silva et al. 2012).
Conde-Agudelo et al. (2008) reported
that women with evidence of periodontal disease during pregnancy
had a 76% increased risk of PE
compared with women without periodontal disease in a meta-analysis.
In Korea, Ha et al. (2011) demonstrated an adjusted odds ratio 4.79
of localized periodontitis and 6.60 of
generalized periodontitis for preeclampsia in a hospital-based case
control study. Yet, despite efforts to
understand the risk factors through
epidemiologic research in the past
decade, there are few prospective
studies on the causal relationship
between periodontal disease and the
occurrence of PE.
There are several risk factors
common to both periodontitis and
PE, of which smoking is potentially
the most important shared risk factor (Haber et al. 1993, Conde-Agudelo et al. 1999, Albandar et al. 2000,
Perni et al. 2012). Thus, smoking

may confound the association

between periodontal disease and PE
(Hujoel et al. 2002).
Therefore, the aim of this prospective study was to investigate the
relationship between periodontitis
and the occurrences of PE in neversmokers.
Materials and Methods
Study participants and study design

The study was conducted in compliance with the principles of the Helsinki Declaration. Ethical clearance
of the study was approved by the
Institutional Review Board of Seoul
National University Hospital (Institutional Review Board no. H-0808003-252).
This study was designed as a hospital-based prospective cohort study,
which was performed from March
2009 to June 2013. This study population consisted of outpatients in the
Department of Obstetrics and Gynecology, Seoul National University
Hospital in Seoul, South Korea. Criteria for inclusion in the study population were (1) Age: 2540 years; (2)
Gestational age: 2124 weeks; (3)
Women with at least 20 teeth; (4)
Women with a single live pregnancy;
(5) Never-smokers. Pregnant women
were excluded for systemic conditions such as chronic hypertension
before pregnancy, pre-gestational
diabetes, active hepatic disease, and
any infectious disease requiring antibiotic treatment including PE. Study
population was 756 pregnant women
(in matrimony) in the Department of
Obstetrics and Gynecology, Seoul
National University. The number of
pregnant women who agreed to participate in this study was 283 women
(response rate: 37.4%). Among 473
women who were excluded, 167
women did not satisfy the inclusion
criteria. And, 306 women refused
participation because of a shortage
of time and indifference.
After ultrasonography in obstetric
clinic, obstetricians informed pregnant women about the purpose and
procedure of this study. Pregnant
women agreed to participate after
signing an informed consent. Once
enrolled, a health behaviour interview
and periodontal examination were
performed by a trained interviewer
and examiner at 2124 weeks of

gestation.
Pregnancy
outcomes,
obstetric history and general health
information were collected by five
obstetricians from hospital records
after delivery.
Sample size estimation

For a prospective study with 5%

Type I error and 80% power, 51 subjects with periodontitis (exposed
group) were required based on 10%
PE among the subjects with no periodontitis (Ha et al. 2011), and an
odds ratio of three between periodontitis and PE (Canakci et al. 2004).
Assuming 10% loss to follow-up, 56
subjects with periodontitis were
needed for the exposed group. We
needed to screen 280 subjects to get
the required 56 subjects with periodontitis, based on a 20% prevalence of periodontitis among the
target population. We studied 283
subjects, resulting in a cohort of
67 subjects with periodontitis and
216 subjects without periodontitis.
Demographic and health information

A trained interviewer asked all the

enrolled subjects about demographic
information, health behaviours such
as the frequency of drinking and
exercise per week, the experience of
periodontal care such as scaling and
the regular use of floss or inter-dental brush before and during pregnancy. According to the frequency
of drinking, the subjects were
divided to three groups (Non-drinking; 13 times per month; more than
1 time per week). Also, height and
weight before pregnancy were asked
for evaluation of body mass index
(BMI). Obstetric history such as history of preterm birth, abortion, the
experience of delivery, and medical
history were collected by five obstetricians from hospital records.
Periodontitis

Periodontal examination was performed by two trained examiners

during the study period using dental
mirrors, the University of North
Carolina 15 periodontal probes,
and a flashlight of headset type with
the patient lying on a mobile dental
chair. The full-mouth periodontal
examination included determining
clinical attachment loss (CAL) at six

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Periodontitis and preeclampsia

sites (mesio-buccal, mid-buccal, disto-buccal, disto-lingual, mid-lingual,
and mesio-lingual surfaces) on of all
the teeth except the third molars and
the distal sites of the second molars.
The kappa value of inter-examiner
reproducibility for determining periodontitis based on CAL 4 mm as
cut-off value was estimated for fifteen women. The kappa value for
inter-examiner reliability was 0.822
for CAL.
To obtain the highest validity in
predicting the occurrence of PE
according to the severity of periodontitis, a receiver operating characteristic (ROC) curve analysis was used.
Four parameters (the number of sites
with CAL 3.0 mm, 4.0 mm, 5.0 mm,
and 6.0 mm) for predicting PE were
assessed by computing the area under
the curve (AUC). The AUC was 0.761
for the number of sites with CAL
3.0 mm, 0.787 for the number of
sites with CAL 4.0 mm, 0.654 for
the
number
of
sites
with
CAL 5.0 mm, and 0.538 for the
number of sites with CAL 6.0 mm.
In addition, the cut-off value of two
sites with CAL 4.0 mm had the
highest validity in predicting the
occurrence of PE. The sensitivity and
specificity for this value was 0.692 and
0.785, respectively. Therefore, periodontitis was defined as a CAL of
4.0 mm and over on two or more sites
on different teeth.
Preeclampsia

After the patient delivered, data on

the occurrence of PE and the method
of delivery were obtained by five
obstetricians from hospital records.
PE was defined as blood pressure
greater higher than 140/90 mmHg on
two separate occasions, and at least
1+ proteinuria on a random urine
screen after the 20th week of pregnancy (Boggess et al. 2003).
Data analysis

All analyses were performed using

the PASW statistical package (Version 18.0) (SPSS, Chicago, IL,
USA). Statistical significance was
determined at p < 0.05. The exposure was periodontitis and the
explanatory variables consisted of
age, health behaviours including
drinking and exercise, obstetric
information and oral health behav-

iours related to periodontitis and

preeclampsia were selected as confounders (Joles & Poston 2010, Ha
et al. 2011, Salihu et al. 2011). Comparison between the exposed and
unexposed groups for the explanatory variables was performed by chisquare test for categorical variables
and independent samples t-test for
normally distributed continuous
variables. The odds ratios and 95%
confidence intervals of periodontitis
for PE was calculated by multivariate logistic regression analysis. To
adjust for confounders, all variables
with a p value 0.20 were selected
and the entering procedure was used
for selecting variables. Age, BMI,
health behaviours (drinking before
pregnancy and weekly exercise during pregnancy), oral health behaviours (use of floss or inter-dental
brush), obstetric history (history of
preterm and delivery mode) were
also considered as confounders in
the multivariable logistic regression
model.
Results

Table 1 compares demographic characteristics and health behaviours

between the periodontitis and the

871

control (no periodontitis) groups.

BMI was significantly different
between the groups. Exposed group
had significantly more over weight
subject (32.8%) compared to 12.5%
in unexposed group (p < 0.001). The
proportion of no drinking before
pregnancy was 49.3% in the periodontitis group and 54.6% in the
control group, which was a significant difference between the groups
(p = 0.011). Table 2 indicates differences in obstetric history and pregnancy
outcomes
between
the
periodontitis and control groups.
The periodontitis group had significantly more history of preterm birth
(p = 0.013). In 283 subjects, PE
occurred in 13 women (4.6%).
Table 3 compares number of teeth
and dental history between the periodontitis and control groups. Within
the periodontitis group, 20.9% regularly used floss or an inter-dental
brush for oral hygiene compared to
39.4% in the control group
(p = 0.006). In the final multivariate
logistic regression model, periodontitis was significantly associated with
the occurrence of PE, with an
adjusted OR of 4.51 and a 95% confidence
interval
of 1.1317.96
(Table 4).

Table 1. Demographic characteristics and health behaviours between the periodontitis and
no periodontitis groups
Total
32.8  3.4 (2540)
Age (range)
Body Mass Index (kg/m2)
Low weight
50 (17.7)
(<18.5)
Normal
184 (65.0)
(<23.0)
Over weight
49 (17.3)
(23.0)
Drinking before pregnancy
No
151 (53.4)
13 times a
104 (36.7)
month
1 times a
28 (9.9)
week
Weekly exercise before pregnancy
No
176 (62.2)
12 times
73 (25.8)
3 times
34 (12.0)
Weekly exercise during pregnancy
No
155 (54.8)
12 times
89 (31.4)
3 times
39 (13.8)

Periodontitis
(n = 67)

No periodontitis
(n = 216)

p*

33.3  3.4 (2540)

32.7  3.3 (2640)

0.142
<0.001

12 (17.9)

38 (17.6)

33 (49.3)

151 (69.9)

22 (32.8)

27 (12.5)

33 (49.3)
21 (31.3)

118 (54.6)
83 (38.4)

13 (19.4)

15 (6.9)

42 (62.7)
17 (25.4)
8 (11.9)

134 (62.0)
56 (25.9)
26 (12.0)

0.995

40 (59.7)
14 (20.9)
13 (19.4)

115 (53.2)
75 (34.7)
26 (12.0)

0.064

0.011

Number (%) was presented except for age.

*By chi-square test for categorical variables and by independent samples t-test for continuous variables.

Mean and standard deviation.

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

872

Ha et al.

Table 2. Obstetric history and pregnancy outcomes between the periodontitis and no periodontitis groups
Total
31.3  3.2 (2440)
Age at first delivery
(range)
Delivery experience
Yes
132 (46.6)
No
151 (53.4)
History of preterm birth
Yes
69 (24.4)
No
214 (75.6)
History of abortion
Yes
107 (37.8)
No
176 (62.2)
Preeclampsia
Yes
13 (4.6)
No
270 (95.4)
Delivery mode
Vaginal
182 (64.3)
Caesarean
101 (35.7)

Periodontitis
(n = 67)

No periodontitis
(n = 216)

p*

31.7  3.7(2539)

31.2  3.1 (2440)

0.321

33 (49.3)
34 (50.7)

99 (45.8)
117 (54.2)

0.624

24 (35.8)
43 (64.2)

45 (20.8)
171 (79.2)

0.013

29 (43.3)
38 (56.7)

78 (36.1)
138 (63.9)

0.290

9 (13.4)
58 (86.6)

4 (1.9)
212 (98.1)

<0.001

34 (50.7)
33 (49.3)

148 (68.5)
68 (31.5)

0.008

Number (%) was presented except for age at first delivery.

*By chi-square test for categorical variables and by independent samples t-test for continuous variables.

Mean and standard deviation.

Table 3. Dental status and oral health behaviours between the periodontitis and no periodontitis groups
Total
27.6  1.1 (2328)
Number of teeth
(range)
Scaling within 1 year before pregnancy
Yes
93 (32.9)
No
190 (67.1)
Scaling during pregnancy
Yes
25 (8.8)
No
258 (91.2)
Use of floss or inter-dental brush
Regular use
99 (35.0)
No or irregular
184 (65.0)
use

Periodontitis
(n = 67)
27.6  0.9 (2428)

No periodontitis
(n = 216)
27.6  1.2 (2328)

p*
0.969

22 (32.8)
45 (67.2)

71 (32.9)
145 (67.1)

0.996

7 (10.4)
60 (89.6)

18 (8.3)
198 (91.7)

0.594

14 (20.9)
53 (79.1)

85 (39.4)
131 (60.6)

0.006

Number (%) was presented except for number of teeth.

*
By chi-square test for categorical variables and by independent samples t-test for continuous variables.

Mean and standard deviation.

Table 4. Adjusted odds ratios and 95% confidence intervals of periodontitis for
preeclampsia
Variables
Periodontitis
(Reference:
No periodontitis)

Model 1

Model 2

Model 3

8.54 (2.5228.97)

7.31 (2.0526.00)

4.51 (1.1317.96)

Model 1 was adjusted for age.

Model 2 was adjusted for age, body mass index, obstetric history (history of preterm and
delivery mode).
Model 3 was adjusted for age, body mass index, obstetric history, health behaviours (drinking before pregnancy, weekly exercise during pregnancy, and use of floss or inter-dental
brush).

Discussion

This prospective study was conducted to evaluate the association

between periodontitis and the occurrence of PE. Our results showed that
periodontitis defined by the presence
of CAL of 4.0 mm and over on two
or more sites not on the same tooth
is associated with an increased risk
of PE. Those who had periodontitis
were nearly five times more likely to
have PE. These results are consistent
with previous findings. Canakci et al.
(2004) carried out a matched case
control study with 41 preeclamptic
women and 41 control women who
were matched with for age, parity,
and smoking. The result of that
study showed that periodontal disease during pregnancy is associated
with PE (adjusted OR = 3.47, 95%
CI = 1.0711.95) after adjusting for
maternal body weight, serum triglyceride level, and serum cholesterol
level. Shetty et al. (2010) also demonstrated that periodontitis at 26
32 weeks of gestation was associated
with an increased risk of PE
(adjusted OR = 5.78, 95% CI 2.41
13.89) in Indian women. In addition,
Kunnen et al. (2007) confirmed that
women with early onset PE has
more severe periodontal conditions
than women without PE taking into
consideration the effects of age,
smoking, educational level, and body
mass index (adjusted OR = 7.9).
Kumar et al. (2013) found that periodontitis was significantly associated
with PE (adjusted OR = 7.5) among
2035 year old women (n = 340) in
a prospective study. Ha et al. (2011)
revealed that those who had generalized periodontitis defined as CAL
3.5 mm on 4 teeth were nearly
six times more likely to have PE
while those who had localized periodontitis
defined
as
CAL
3.5 mm on 2 or 3 teeth were
nearly five times more likely to do
so.
The periodontitis group had significantly more history of preterm
birth (Table 2). Since previous preterm birth was considered as a
strong predictor of preterm birth,
the history of preterm birth should
be considered as main confounder in
the epidemiological study for periodontitis and preterm birth (Agueda
et al. 2008, Baskaradoss et al. 2011).
Some studies suggested that the

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Periodontitis and preeclampsia

treatment of periodontal disease during pregnancy may represent a novel
approach to the prevention of
preeclampsia (Boggess et al. 2003,
Kunnen et al. 2007). However,
Newnham et al. (2009) revealed that
there was no difference between the
control group and the treatment of
periodontitis group in preeclampsia
(OR = 0.82, 95% CI = 0.441.56).
In our result, within the periodontitis
group, 20.9% regularly used floss or
an inter-dental brush for oral
hygiene compared to 39.4% in the
control group (Table 3). Therefore,
it is suggested that oral health
behaviours before pregnancy such as
inter-dental plaque control, which
can decrease the level of periodontal
pathogen, may be more important as
a new approach to prevent preeclampsia than the treatment of periodontal disease during pregnancy.
Although there were positive
associations in the previous studies,
the odds ratio has varied across
studies. The difference between previous studies may be due to ethnic
factors, study sample size, control
matching variables, and, in particular, the definition of periodontitis.
Ide & Papapanou (2013) showed
that the substantial variation in the
definition of periodontal disease
across studies has an impact on
observed relationships between periodontal disease and pregnancy outcomes. Furthermore, Siqueira et al.
(2008) suggested that the extent and
severity of periodontal parameters
were strongly related to the occurrence of PE. To establish a definition
for periodontal disease, the threshold
values for CAL or PD need to be
determined among the number of
sites that must be involved to diagnose disease (Page & Eke 2007).
Page & Eke (2007) pointed out that
minor changes in the threshold values for CAL, PD, and the number
of affected sites used in the case definitions result in major changes in the
prevalence scores. Therefore, selection of a threshold value is critical.
In this study, the ROC curve analysis was conducted for the highest
validity to predict the occurrence of
PE. Among the four parameters (the
number of sites with CAL 3.0 mm,
4.0 mm, 5.0 mm, and 6.0 mm), the
AUC was 0.787 for the number of
sites with CAL 4.0 mm, and the
threshold value of two sites with

CAL 4.0 mm had the highest

validity in predicting the occurrence
of PE. This definition of periodontitis is similar to that proposed by the
Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) (Page &
Eke 2007) for moderate periodontitis
(two or more sites with attachment
loss 4.0 mm, not on the same
tooth, or two or more sites with
pocket depths 5.0 mm, not on the
same tooth) as well as the definition
adopted by some epidemiological
studies to associate systemic disease
and periodontitis (Moura da Silva
et al. 2012). Establishment of the
proper periodontal parameters using
the ROC curve analysis may be a
useful method to achieve the highest
validity while predicting the incidence of adverse pregnancy outcomes and PE (Al Habashneh et al.
2013).
We studied the influence of periodontitis on the occurrence of PE
through a prospective study on
never-smokers. Hujoel et al. (2002)
suggested that the comparison of
the occurrence of systemic disease
between subjects with and without
periodontal disease may be biased
because of the unequal distribution
of smoking among the two groups.
Smoking spuriously inflates the
association between periodontal disease and smoking-related diseases,
because it is causally related to
both regardless of whether periodontal disease and the systemic
disease are causally related to each
other. Several studies revealed that
there was an association between
past or current smoking and PE
(Conde-Agudelo et al. 1999, Perni
et al. 2012). Therefore, the subjects
of this study were limited to neversmokers to evaluate the association
between PE and periodontitis without the confounding influence of
smoking.
This study has some limitations.
First, this study used only clinical
attachment loss as clinical periodontal parameter. CAL could accompany non-inflammatory gingival
recession, use of CAL as a periodontal parameter might overestimate the
periodontal inflammation. However,
as pregnant women having gingival
recession were few due to young age,
the overestimation would be little in
this study. Because one parameter

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

873

may not sufficiently assess the

inflammatory burden of periodontitis, further studies could potentially
consider the other periodontal
parameters such as microbiological
data. Second, socio-economic status,
which could be associated with the
prevalence of periodontitis and PE,
was not considered as a confounder.
Even though we did not consider
SES as a confounding factor, we
may obtain more valuable results if
SES was considered as a confounder
in our study. However, the multivariate model used in this study took
into consideration more potential
confounders than any other previous
study.
Above all, this prospective study
is valuable because studies on the
relationship between periodontal
condition and the occurrence of PE
have been relatively rare worldwide.
In addition, this study limited subjects to healthy never-smokers to
analyse this relationship without the
confounding effect of smoking. Since
PE and periodontal disease may
share common risk factors such as
socio-economic status, genetics, and
health behaviours, future research
should include prospective studies
with a large sample size and include
more comprehensive confounders.
Ultimately, randomized controlled
trials will be required to confirm a
clear causal relationship between
periodontal condition and onset of
PE.
In conclusion, this study revealed
that periodontitis increased the risk
of preeclampsia among never-smokers. As periodontitis can be associated with the increased risk of
preeclampsia, oral health care for
periodontitis need to be recommended before and during pregnancy.
References
Agueda, A., Ramon, J. M., Manau, C., Guerrero,
A. & Echeverria, J. J. (2008) Periodontal disease as a risk factor for adverse pregnancy outcomes: a prospective cohort study. Journal of
Clinical Periodontology 35, 1622.
Al Habashneh, R., Khader, Y. S., Jabali, O. A. &
Alchalabi, H. (2013) Prediction of preterm and
low birth weight delivery by maternal periodontal parameters: receiver operating characteristic (ROC) curve analysis. Maternal and
Child Health Journal 17, 299306.
Albandar, J. M., Streckfus, C. F., Adesanya, M.
R. & Winn, D. M. (2000) Cigar, pipe, and cigarette smoking as risk factors for periodontal

874

Ha et al.

disease and tooth loss. Journal of Periodontology 71, 18741881.

Baskaradoss, J. K., Geevarghese, A. & Kutty, V.
R. (2011) Maternal periodontal status and preterm delivery: a hospital based case-control
study. Journal of Periodontal Research 46, 542
549.
Beck, J. D., Garcia, R., Heiss, G., Vokonas, P. S.
& Offenbacher, S. (1996) Periodontal disease
and cardiovascular disease. Journal of Periodontology 67, 11231137.
Boggess, K. A., Lieff, S., Murtha, A. P., Moss,
K., Beck, J. & Offenbacher, S. (2003) Maternal
periodontal disease is associated with an
increased risk for preeclampsia. Obstetrics and
Gynecology 101, 227231.
Canakci, V., Canakci, C. F., Canakci, H., Canakci, E., Cicek, Y., Ingec, M., Ozgoz, M.,
Demir, T., Dilsiz, A. & Yagiz, H. (2004) Periodontal disease as a risk factor for pre-eclampsia: a case control study. Australian and New
Zealand Journal of Obstetrics and Gynaecology
44, 568573.
Conde-Agudelo, A., Althabe, F., Belizan, J. M. &
Kafury-Goeta, A. C. (1999) Cigarette smoking
during pregnancy and risk of preeclampsia: a
systematic review. American Journal of Obstetrics and Gynecololgy 181, 10261035.
Conde-Agudelo, A., Villar, J. & Lindheimer, M.
(2008) Maternal infection and risk of preeclampsia: systematic review and meta-analysis.
American Journal of Obstetrics and Gynecololgy
198, 722.
Contreras, A., Herrera, J. A., Soto, J. E., Arce,
R. M., Jaramillo, A. & Botero, J. E. (2006)
Periodontitis is associated with preeclampsia in
pregnant women. Journal of Periodontology 77,
182188.
Cota, L. O., Guimaraes, A. N., Costa, J. E., Lorentz, T. C. & Costa, F. O. (2006) Association
between maternal periodontitis and an
increased risk of preeclampsia. Journal of Periodontology 77, 20632069.
Ha, J. E., Oh, K. J., Yang, H. J., Jun, J. K., Jin,
B. H., Paik, D. I. & Bae, K. H. (2011) Oral
health behaviors, periodontal disease, and
pathogens in preeclampsia: a case-control study
in Korea. Journal of Periodontology 82, 1685
1692.
Haber, J., Wattles, J., Crowley, M., Mandell, R.,
Joshipura, K. & Kent, R. L. (1993) Evidence
for cigarette smoking as a major risk factor for
periodontitis. Journal of Periodontology 64, 16
23.
Hujoel, P. P., Drangsholt, M., Spiekerman, C. &
DeRouen, T. A. (2002) Periodontitis-systemic
disease associations in the presence of smok-

Clinical Relevance

Scientific rationale for the study:

Although an association between
periodontitis and preeclampsia has
been reported in some casecontrol
studies, a prospective cohort study
is needed to draw a more valid
causal inference. In particular, few

ingcausal or coincidental?. Periodontology

2000 30, 5160.
Hung, H. C., Willet, W., Merchant, A., Rosner,
B. A., Ascherio, A. & Joshipura, K. J. (2003)
Oral health and peripheral arterial disease. Circulation 107, 11521157.
Ide, M. & Papapanou, P. N. (2013) Epidemiology
of association between maternal periodontal
disease and adverse pregnancy outcomes-systematic review. Journal of Clinical Periodontology 40, 181194.
Janket, S. J., Baird, A., Chuang, S. & Jones, J. A.
(2003) Meta-analysis of periodontal disease and
risk of coronary heart disease and stroke. Oral
Surgery, Oral Medicine, Oral Pathology, Oral
Radiology, and Endodontology 95, 559569.
Joles, J. A. & Poston, L. (2010) Can exercise prevent preeclampsia? Journal of Hypertension 28,
23842385.
Kumar, A., Basra, M., Begum, N., Rani, V., Prasad, S., Lamba, A. K., Verma, M., Agarwal, S.
& Sharma, S. (2013) Association of maternal
periodontal health with adverse pregnancy outcome. Journal of Obstetrics and Gynaecology
Research 39, 4045.
Kunnen, A., Blaauw, J., van Doormaal, J. J., van
Pampus, M. G., van der Schans, C. P., Aarnoudse, J. G., van Winkelhoff, A. J. & Abbas,
F. (2007) Women with a recent history of
early-onset pre-eclampsia have a worse periodontal condition. Journal of Clincal Periodontology 34, 202207.
Lam, C., Lim, K. H. & Karumanchi, S. A. (2005)
Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension 46, 10771085.
Lo, J. O., Mission, J. F. & Caughey, A. B. (2013)
Hypertensive disease of pregnancy and maternal mortality. Current Opinion in Obstetrics and
Gynecology 25, 124132.
Moura da Silva, G., Coutinho, S. B., Piscoya, M.
D., Ximenes, R. A. & Jamelli, S. R. (2012)
Periodontitis as a risk factor for preeclampsia.
Journal of Periodontology 83, 13881396.
Newnham, J. P., Newnham, I. A., Ball, C. M.,
Wright, M., Pennell, C. E., Swain, J. & Doherty, D. A. (2009) Treatment of periodontal disease during pregnancy: a randomized
controlled trial. Obstetrics and Gynecology 114,
12391248.
Page, R. C. & Eke, P. I. (2007) Case definitions
for use in population-based surveillance of periodontitis. Journal of Periodontology 78, 1387
1399.
Perni, U. C., Wikstrom, A. K., Cnattingius, S. &
Villamor, E. (2012) Interpregnancy change in
smoking habits and risk of preeclampsia: a

studies have examined the relationship between preeclampsia and periodontitis based on a prospective
design.
Principal findings: This study found
that periodontitis is associated with
an increased risk of preeclampsia
among never-smokers.

population-based study. American Journal of

Hypertension 25, 372378.
Redman, C. W. & Sargent, I. L. (2005) Latest
advances in understanding preeclampsia. Science 308, 15921594.
Roberts, J. M. & Gammill, H. S. (2005) Preeclampsia: recent insights. Hypertension 46,
12431249.
Salihu, H. M., Kornosky, J. L., Lynch, O., Alio,
A. P., August, E. M. & Marty, P. J. (2011)
Impact of prenatal alcohol consumption on
placenta-associated syndromes. Alcohol 45, 73
79.
Seymour, G. J., Ford, P. J., Cullinan, M. P., Leishman, S. & Yamazaki, K. (2007) Relationship
between periodontal infections and systemic
disease. Clinical Microbiology and Infection 13,
310.
Shetty, M., Shetty, P. K., Ramesh, A., Thomas,
B., Prabhu, S. & Rao, A. (2010) Periodontal
disease in pregnancy is a risk factor for preeclampsia. Acta Obstetricia et Gynecologica
Scandinavica 89, 718721.
Siqueira, F. M., Cota, L. O., Costa, J. E., Haddad, J. P., Lana, A. M. & Costa, F. O. (2008)
Maternal periodontitis as a potential risk variable for preeclampsia: a case-control study.
Journal of Periodontology 79, 207215.
Trogstad, L. I., Eskild, A., Bruu, A. L., Jeansson,
S. & Jenum, P. A. (2001) Is preeclampsia an
infectious disease? Acta Obstetricia et Gynecologica Scandinavica 80, 10361038.
Villar, J., Say, L., Shennan, A., Lindheimer, M.,
Duley, L., Conde-Agudelo, A. & Merialdi, M.
(2004) Methodological and technical issues
related to the diagnosis, screening, prevention,
and treatment of pre-eclampsia and eclampsia.
International Journal of Gynaecology and
Obstetrics 85, 2841.
Widmer, M., Villar, J., Benigni, A., Conde-Agudelo, A., Karumanchi, S. A. & Lindheimer, M.
(2007) Mapping the theories of preeclampsia
and the role of angiogenic factors: a systematic
review. Obstetrics and Gynecology 109, 168
180.

Address:
Kwang-Hak Bae
Department of Preventive and Public Health
Dentistry
School of Dentistry
Seoul National University, 28, Yeongeuondong, Jongno-gu
Seoul 110-749, Korea
E-mail: baekh@snu.ac.kr

Practical implications: Periodontitis

during pregnancy is associated with
preeclampsia in the prospective
study, and further randomized clinical trials are needed to determine
if there is a cause and effect relationship between these two conditions.

2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd