Volume 87 Number 12

Changes in Periodontal Parameters and

C-Reactive Protein After Pregnancy
Luca Gil Raga,* Ignacio Mnguez, Raul Caffesse, and Fernando Llambes

Background: This study assesses hormonal, inflammatory, and periodontal changes in pregnant women and postpartum in the absence of periodontal treatment, and seeks to
determine any correlations among these parameters.
Methods: A longitudinal, observational study of 117 pregnant women (aged 23 to 42 years) was undertaken in a private
gynecologic center between weeks 32 and 35 of pregnancy
and 6 to 8 weeks after delivery. Levels of progesterone and
C-reactive protein (CRP) in plasma were determined, as well
as periodontal indices, including: 1) plaque index (PI); 2)
bleeding on probing (BOP); 3) probing depth (PD); and 4)
clinical attachment level (CAL).
Results: Postpartum progesterone and CRP declined
sharply from 90.85 42.51 ng/mL and 3.73 4.01 mg/L to
0.77 1.43 ng/mL and 1.43 1.67 mg/L, respectively. There
was also a significant improvement in all periodontal indices
(P <0.05) with the exception of PI. During pregnancy mean
BOP was 21.03%, mean PD 2.62 mm, and mean CAL
1.20 mm. After delivery mean BOP was 13.25%, mean PD
2.39 mm, and mean CAL 1.14 mm. Percentage of 1- to
3-mm pockets increased (P <0.05), while 4- to 5-mm pockets
and pockets >6 mm decreased significantly (P <0.001). Reduction in CRP correlated significantly with decrease in BOP
(P <0.001).
Conclusions: Postpartum, there was a dramatic reduction in
progesterone and CRP, together with an improvement in BOP,
PD, and CAL in the absence of periodontal treatment. Decrease in CRP was related to an improvement in periodontal
bleeding. J Periodontol 2016;87:1388-1395.
KEY WORDS
Anti-inflammatory agents; gynecology; obstetrics;
periodontitis; pregnancy.
*

Department of Odontology, CEU Cardenal Herrera University, Valencia, Spain.

Department of Oral Surgery, CEU Cardenal Herrera University.
Department of Periodontics, Complutense University of Madrid, Madrid, Spain.
Medically Compromised Patients Department, School of Dentistry, University of Valencia,
Valencia, Spain.

regnancy is a condition where hormonal changes produce systemic

multiorgan effects, influencing the
cardiovascular, respiratory, dermal, genitourinary, digestive, and nervous systems
and even the oral cavity.1,2
The first report studying the relation
between pregnancy and periodontal disease dates to 1946.3 Since then, many
authors4-6 have maintained that hormonal
changes, together with plaque, were responsible for alterations produced during
pregnancy in periodontal tissues. Research has demonstrated an increase in
progesterone at the oral level produced
changes in oral bacteria.7 This would be
responsible for clinical periodontal alterations detected during pregnancy. The
possibility has been raised, however, that
progesterone and plaque may not be the
only factors involved.8
During pregnancy there are specific
gingival alterations such as pregnancy
gingivitis,9 characterized by hypervascularity and non-specific cellular inflammatory infiltration. Another alteration
is pyogenic granuloma which is an exaggerated proliferative fibrovascular inflammatory reaction located in the
gingiva.10 These periodontal alterations
may trigger an immune response and
provoke release of inflammatory mediators. Bacteria and their toxins activate
macrophages and other cells to synthesize and secrete a broad spectrum of
molecules, among them C-reactive protein (CRP).11 Research has suggested
periodontitis during pregnancy may have
repercussions at a systemic level and
doi: 10.1902/jop.2016.160093

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J Periodontol December 2016

alter levels of inflammatory markers such as CRP.12

Other studies also stress that alteration of this marker
could be an indicator of complications during pregnancy, such as preeclampsia, premature birth, and low
birthweight.13-15
Soon after childbirth, production of estrogen and
progesterone decreases and reaches values comparable to those present in non-pregnant women.16,17
Literature is scarce on behavior of CRP and periodontal changes that women sustain postpartum. For
this reason, the aim of the present study is to assess
variations which take place postpartum with reference
to hormonal levels, periodontal parameters, and plasma
inflammatory mediators in the absence of periodontal
treatment. It was hypothesized that hormonal, inflammatory, and periodontal changes would take place after
delivery, and variations in these parameters may possibly be correlated.
MATERIALS AND METHODS
Study Population
A longitudinal, observational study of 117 pregnant
women (aged 23 to 42 years; mean age: 33.16 3.64
years) was undertaken. Women between weeks 32
and 35 of their pregnancy were included because the
highest increase of progesterone levels occurs in
the last trimester.18,19 The study was performed in
a private gynecologic and dental care center, Valencia,
Spain, from January 2014 to January 2015. A specific
database was created where all values recorded were
included in accordance with the Spanish Data Protection Law. The investigation proposal was approved by the Research and Ethics Committee of
CEU Cardenal Herrera University, Valencia, Spain.
All participants gave written informed consent in
which the objectives of the study were detailed.
Inclusion and Exclusion Criteria
The study excluded patients who were at risk for
preterm delivery, with twin pregnancies, and with
obstetric pathology prior to pregnancy such as uterine
malformation or cervical incompetence. Patients with
fewer than 15 teeth (excluding third molars) and
having periodontal treatment during pregnancy were
also excluded. Patients were treated and removed
from the study if they had any gynecologic complication or dental or periodontal acute infection during
the observation period.
A total of 140 pregnant women were screened, with
117 selected. Twenty-three patients were excluded for
not meeting the inclusion criteria, of these 12 had
periodontal treatment during pregnancy, four had
a twin pregnancy, three reported spontaneous gynecologic bleeding, and four refused to participate in the
study. No pregnant women had to be excluded during
the study due to gynecologic complications or urgent
dental or periodontal infection.

Gil Raga, Mnguez, Caffesse, Llambes

Furthermore, analysis of CRP was not carried out in

women with chronic systemic diseases such as diabetes mellitus, hyperthyroidism, hypothyroidism, or
cardiovascular problems;20-22 nor in those who experienced systemic acute infections of a non-periodontal
nature which could alter levels of CRP.14,23 Consequently, the sample on which statistical analyses for
the CRP variable was performed was reduced to 96,
because 21 patients had chronic systemic diseases or
non-periodontal acute infections which could modify
the value of CRP.
Laboratory and Periodontal Examination
A fasting blood sample was collected to detect levels of
CRP and progesterone in plasma. Baseline levels of CRP
were determined by turbidimetry in an auto-analyzeri
with a range of detection between 0.2 to 40 mg/L, in
accordance with instructions provided by the manufacturer. To detect progesterone an auto-analyzer was
used, applying the technique of competitive chemiluminescent enzyme immunoassay in solid phase with
a range of calibration between 0.8 to 80 mg/L.
Periodontal evaluation was performed by one calibrated examiner (LGR) using a North Carolina probe.
The OLeary plaque index (PI)24 was recorded for each
tooth at four different areas: 1) mesio-buccal, 2) midbuccal, 3) disto-buccal, and 4) mid-lingual. Probing
depth (PD), clinical attachment level (CAL), and
bleeding on probing (BOP) were recorded at six locations per tooth: 1) mesio-buccal, 2) mid-buccal, 3)
disto-buccal, 4) mesio-lingual, 5) mid-lingual, and 6)
disto-lingual). Mean PD, mean CAL, percentage of sites
with plaque, and percentage of BOP areas were calculated for each patient before statistical tests. Percentages of pockets 6 mm; 4 to 5 mm; and 1 to 3 mm
were also calculated for each patient.
Study Design
The study was divided into two observational periods.
The first was carried out between weeks 32 and 35
of pregnancy and was performed by one examiner
(LGR). Data collection included: 1) demographics; 2)
medical conditions; 3) obstetric care; 4) all periodontal
parameters (PI, BOP, PD, CAL); and 5) oral habits.
Patients with PD 4 mm; CAL 1 mm; and BOP 30
seconds after periodontal probing were diagnosed as
having periodontal disease. Baseline levels of CRP and
progesterone were also recorded.
Neither dental nor periodontal treatment were provided during the observational period unless an infection
was detected which needed urgent attention in the final
phase of pregnancy or immediately postpartum.
The second phase of the study took place between
6 and 8 weeks postpartum. At that time, progesterone
i AU 5400 IZASA Chemistry-analyzer, Beckman Coulter, Brea, CA.
IMMULITE 2000, Siemens Healthcare, Erlangen, Germany.

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Periodontal Disease and Pregnancy

returns to preovulation levels (1 ng/mL);25 hence,

postpartum gynecologic and periodontal check-ups
were performed during those weeks. The same examiner (LGR) performed a new periodontal assessment (PI, BOP, PD, CAL), and a new blood test was run
to detect levels of progesterone and CRP postpartum.
Statistical Analyses
A statistical program# was used for data analyses.
Descriptive analyses, means, and their standard deviations were calculated for each variable of interest.
Several inferential tests were performed. Women were
assessed at two time points, and those values were
analyzed applying two different approaches. Means of
Time 1 and Time 2 were compared using paired t tests
for each variable to establish if there was a significant
change at group (mean) level. Statistical conditions
for use of paired t test were assessed and were adequately met. Additionally, the Pearson correlation
coefficient was used to correlate quantitative variables
of interest. Reduction in CRP was correlated with
postpartum changes in periodontal parameters. Significance level was evaluated at P <0.05.
Scatterplot diagrams were also constructed to
analyze changes in BOP, PD, and CRP after delivery,
establishing a cut-off point which separates the 15%
of patients with the most significant improvements.
RESULTS
Daily brushing frequency of the sample was 2.20
0.89 times, with a maximum of four and a minimum
of zero. Periodontal disease was moderate to severe
in 22 patients (18.8% of the total), who had five or
more areas with PD 5 mm and CAL 3 mm. BOP
was frequent, with 50% of the women having 20%.
Mean level of progesterone in the third trimester of
pregnancy was 90.85 42.51 ng/mL. Levels of CRP
in the last trimester of pregnancy were measured in
96 pregnant women as 21 were excluded because
of a chronic systemic disease or an acute nonperiodontal infection. CRP demonstrated a mean
value of 3.73 4.01 mg/L (normal value during pregnancy: <4 mg/L).
Postpartum mean progesterone level was 0.77
1.43 ng/mL. This dramatic reduction of 90.08 ng/mL
was statistically significant (P <0.05), and meant
a 99% reduction of initial progesterone. CRP was also
sharply reduced postpartum in the absence of periodontal treatment. It decreased to 1.43 mg/L, representing a significant decrease of approximately
42% (P <0.001) (Table 1).
Periodontal examination before childbirth showed
mean PI was 21.61% 2.149%, mean BOP was 21.03%
15.60%, mean PD was 2.62 0.61 mm, and mean
CAL 1.20 0.29 mm. Descriptive analysis showed
81.12% for 1- to 3-mm pockets, 16.06% for 4- to 5-mm
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Volume 87 Number 12

pockets, and 2.62% for >6-mm pockets. A significant

statistical improvement (P <0.001) was observed in all
parameters postpartum, except for PI. Postpartum,
mean PI registered was 21.63%, mean BOP 13.25%,
mean PD 2.39 mm, and mean CAL 1.14 mm. One- to
3-mm pockets represented 84.04% of the total, 4- to
5-mm represented 12.85%, and >6-mm represented
1.05%. These reductions represent a decrease in
bleeding of 38%, in PD of 8.8%, and in CAL of 5% from
initial values. Pockets >6 mm decreased by 60%, 4- to
5-mm pockets by 20%, and, 1- to 3-mm pockets
increased 3.6% from initial values (Table 2).
Scatterplots were constructed for variations in BOP,
PD, and CRP, establishing a cut-off point separating
the 15% of patients with the most significant improvements.
Figure 1 shows the decrease in BOP. The horizontal line marks the 15% of pregnant women (n =
17) with greatest reduction in bleeding. Pattern of
decrease is not linear because those who experienced
the most reduced bleeding postpartum did not correspond with those who had most bleeding at the
beginning.
In Figure 2 each patient is represented and arranged according to mean PD in the third trimester of
pregnancy. The horizontal line separates the 15% of
pregnant women who experienced the most reduced
initial PD (n = 17). Reduction in PD postpartum did
not follow a linear pattern since those with most reduced mean PD did not correspond with those who
had a greater PD before childbirth.
Figure 3 shows a decrease in CRP postpartum in all
women arranged according to mean CRP before
childbirth. The horizontal line separates the 15% of
women (n = 14) with the greatest reduction of CRP
after pregnancy. This reduction was greater the more
CRP was registered before childbirth. Furthermore,
this 15% group presented a CRP level during pregnancy higher than the values considered normal,
oscillating between 0.2 to 4 mg/L.
Reduction of CRP postpartum and improvement in
periodontal indices (BOP, PD, CAL) demonstrated
a positive, significant correlation between decrease in
CRP and reduction of BOP (P <0.001). However, no
relation was found between decrease in CRP and
improvement in the remaining periodontal parameters (Table 3).
DISCUSSION
The first phase of the study was carried out between
weeks 32 and 35 of pregnancy. Progesterone levels
throughout pregnancy will reach concentration levels
of up to 30 times the luteal phase, with the highest
increase occurring in the last trimester, when levels
# SPSS Statistics for Windows, Version 22.0, IBM, Armonk, NY.

Gil Raga, Mnguez, Caffesse, Llambes

J Periodontol December 2016

Table 1.

Postpartum Changes in Analytic Values

Parameters
Progesterone (ng/mL) (n = 117)
CRP (mg/mL) (n = 96)

Pregnancy

Postpartum

Reduction

P Value

90.85 42.51

0.77 1.43

-90.08

<0.001

3.73 4.01

1.43 1.67

-2.3

<0.001

Table 2.

Postpartum Changes in Periodontal Parameters (n 5 117)

Parameters

Pregnancy

Postpartum

Difference

P Value

Mean PI (%)

21.61 2.149

21.63 2.148

+0.02

0.48

Mean BOP (%)

21.03 15.6

13.25 12.85

-7.78

<0.001

Mean PD (mm)

2.62 0.61

2.39 0.56

-0.23

<0.001

Mean CAL (mm)

1.20 0.29

1.14 0.29

-0.06

<0.001

Sites with PD 1 to 3 mm (%)

81.12 17.07

84.04 20.70

+2.9

0.08

Sites with PD 4 to 5 mm (%)

16.06 13.86

12.85 15.83

-3.21

<0.001

2.62 4.78

1.05 2.32

-1.57

<0.001

Sites with PD 6 mm (%)

reach rates of 250 to 300 mg/day. Therefore, progesterone levels should have a higher influence in the
periodontium of patients during weeks 32 to 35 of
pregnancy.18,19 There is also existing documentation
which substantiates the highest peak of periodontal
inflammation being reached during the third tri e and Silness6 demonstrated that the
mester.26,27 Lo
first clinical signs of gingivitis appeared in the second
month of pregnancy and continued increasing until
the eighth month, when it reached its highest levels.
The second phase of this study was carried out 6 to
8 weeks postpartum when progesterone returns to
preovulation phase levels (1 ng/mL). Figuero et al.28
detected a significant reduction of gingival bleeding
two months postpartum. The present study was performed in a short period of time to evaluate the effect of
progesterone changes in periodontal parameters and
CRP, without influence of other factors.
The sample studied had low obstetric risk because
they were treated in a private clinical center with
regular pregnancy control sessions. Most had good
oral hygiene as indicated by the average brushing
frequency of 2.20 times a day, with a maximum of
four and a minimum of zero. It would be interesting to
repeat the study with pregnant women in gynecologic
centers from different social strata.
In the third trimester of pregnancy, 18.8% of the
sample presented moderate to severe periodontitis
with five or more areas with PD 5 mm and CAL

3 mm. BOP was frequent and 50% of patients had

a BOP 20%. Ziskin et al.3 in 1946 were the first to
relate levels of progesterone during pregnancy with
changes in gingival tissue.
Progesterone levels increased during pregnancy
from 9 to 47 ng/mL in the first trimester, to 17 to 147
ng/mL in the second trimester, and 55 to 200 ng/mL in
the third.29 After delivery, progesterone decreases
rapidly to normal values (1ng/mL).30 Periodontal
effects of the increase are diverse, and may affect
vascularization, microbiology, and immunologic reaction. These alterations give rise to: 1) development of periodontal pockets; 2) edema; 3) gingival
bleeding; and 4) increase in pathogenic bacteria and
its immunologic response.31
Raber-Durlacher et al.32 reported that microbiologic changes in periodontal tissues produced an increase in BOP, whereas postpartum there was no
increase in microorganisms and gingival bleeding was
reduced with respect to prebirth without carrying out
any treatment. These results coincide with those of the
current study, and its authors share the hypothesis
that increase in gingival inflammation is related to
increase in progesterone. Progesterone increases
vascular permeability and gives rise to microbiologic
changes during pregnancy, with an increase in periodontal pathogenic species such as Porphyromonas
gingivalis, Prevotella intermedia, or Aggregatibacter
actinomycetemcomitans.7,33
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Periodontal Disease and Pregnancy

Figure 1.
BOP scatterplot. Each patient is represented as a dot. Dots above the
horizonal line represent the 15% of patients with the greatest
postpartum reduction in BOP. BOP1 = BOP in pregnancy (%); BOP3 =
BOP reduction after delivery (%).

Volume 87 Number 12

CRP level in healthy non-pregnant women is

<1 mg/L, but in the third trimester of pregnancy CRP
ranges from 0.2 to 4 mg/L, and some systemic diseases may increase this value even more.35 Miller36
corroborated levels of CRP were higher in healthy
pregnant women than in non-pregnant women. Forty
percent of healthy pregnant women had high levels of
CRP. They concluded that in some women pregnancy
with a sharp increase of progesterone could alter the
immune system and, as a result, provoke an increase
in levels of CRP unrelated to periodontitis.
Reduction in CRP postpartum could be more pronounced in women with more hyperreactive and
hypersensitive immunologic systems which, in the
presence of certain stimuli, respond by producing
greater amounts of inflammatory mediators, just as in
other groups of the population.37,38 This can be corroborated in Figure 3 which shows some patients had
more improvement in CRP values than others after
delivery. Similarly, results showed an improvement in
periodontal parameters postpartum (BOP, PD, CAL),
with the exception of PI, without performing any
periodontal treatment, which could have altered
quantity of periodontal pathogens present.
The present study gives the opportunity to analyze
accurately the role played by progesterone on the
periodontium since progesterone is the only factor
which varies significantly during this period. On the
contrary, other factors which could have an influence
on the periodontium, such as PI, remained stable.
Several studies have used a similar design.39,40 In
2008, Gu
rsoy et al.39 examined periodontal changes
during pregnancy and postpartum in a longitudinal

Figure 2.
PD scatterplot. Each patient is represented as a dot. Dots above the
horizontal line represent the 15% of women with the greatest
postpartum reduction in PD. PD1 = mean PD in pregnancy (mm);
PD3 = mean PD after delivery (mm).

The present study showed a dramatic decrease of

progesterone (90%) and CRP (50%) postpartum which
was accompanied by reduction of periodontal inflammation. It should not be forgotten that progesterone
has other systemic effects that may also activate
inflammatory mechanisms.34 Hence, if this hormone
stops functioning systemically, as is the case postpartum, it will also trigger a reduction of CRP.
1392

Figure 3.
CRP scatterplot. Each patient is represented as a dot. Dots above the
horizontal line represent the 15% of women with the greatest
postpartum reduction in CRP levels. CRP1 = CRP in pregnancy (mg/L);
CRP3 = CRP reduction after delivery (mg/L).

Gil Raga, Mnguez, Caffesse, Llambes

J Periodontol December 2016

Table 3.

Correlation (r) Among Changes in CRP and Changes in Periodontal Parameters After
Delivery (n 5 96)
6 to 8 Weeks Postpartum Change

Reduction in CRP

BOP

P Value

PD

P Value

CAL

P Value

0.386

<0.001

0.152

0.14

0.041

0.69

study to assess if pregnancy could produce permanent changes in the periodontium. Results showed
that BOP and PD increased during pregnancy without
relation to plaque, and they improved during postpartum. Gu
rsoy et al.39 concluded gingival changes
during pregnancy could be reversible indicating gingivitis did not necessarily lead to periodontitis during
pregnancy.
As also indicated in the literature,41,42 results of the
present study showed a major periodontal improvement postpartum, in the absence of periodontal
treatment. Hence, it can be concluded that an increase
in progesterone during pregnancy is the main cause
for increase in periodontal inflammation, as all periodontal parameters, with the exception of PI, improved postpartum without periodontal treatment,
and were accompanied by a dramatic decrease in
levels of progesterone in blood. What cannot be
determined is the mechanism through which progesterone acts to increase gingival inflammation. It
does not seem that the effect of progesterone on
plaque bacteria is the main factor because for this to
be so, periodontal pathogens would have to decrease
postpartum to levels which did not irritate the periodontium. The hypothesis of effect of progesterone on
the immune system increasing production of inflammatory mediators becomes more robust when
explaining the present results: CRP and periodontal
parameters decreased postpartum as progesterone
reduced. This periodontal improvement, however, did
not occur homogeneously throughout the sample. It
can be observed in the scatterplots (Figs. 1 and 2) that
the 15% of patients who most reduced their BOP and
PD did not correspond with those with greater periodontal inflammation during pregnancy, but rather
included patients with differing severities of periodontal disease before childbirth. These individual
variations could not depend on the magnitude of reduction of progesterone, since it was dramatically
reduced postpartum in all pregnant women. Perhaps
there are individuals with a more hyperreactive immunologic system than others, with greater periodontal
sensitivity to increases in progesterone. It would be
important to be able to detect these individuals in

advance so stricter periodontal supervision during pregnancy could be instituted.

There are limited data analyzing evolution of CRP
postpartum, as well as its relation with periodontal
disease. In the present study there was a significant
decrease in levels of CRP 2 months after pregnancy,
and this improvement correlated statistically with reduction in BOP. In 2009, Sharma et al.43 observed
periodontal treatment during pregnancy reduced CRP
plasma levels. As a result, they related serum levels
of the CRP marker with severity of periodontal disease
and its treatment.43 However, others have not found
changes in CRP in pregnant women after periodontal
treatment,44 suggesting periodontal inflammation may
not be closely linked to an increase in CRP. More studies
are necessary to assess CRP as a source of periodontal
inflammation both in pregnant and non-pregnant patients to clarify its relation with periodontitis.
It would be interesting in future investigations to
increase sample size and assess other possible influential factors. Microbial testing of periodontal bacteria
would indicate which microbes grow during pregnancy
and how they affect the periodontium. Assessment of
saliva would depict any salivary changes during
pregnancy, and effect of saliva in reducing oxidative
stress produced by periodontal infection. Other factors, such as different types of cytokines, should be
assessed to discover their relationship with progesterone levels and periodontal disease.
In essence, proper periodontal control during
pregnancy will significantly reduce effects of progesterone on the periodontium, avoiding destruction
of supporting tissues45 as well as production of inflammatory mediators which could enter the bloodstream affecting the fetus.45 It is therefore paramount
to provide periodontal supervision during pregnancy,
together with gynecologic control.
CONCLUSION
Within the limits of this study, it can be concluded that
postpartum, there is a dramatic reduction in progesterone and CRP, together with an improvement
in BOP, PD, and CAL in the absence of periodontal
treatment and a decrease in CRP is related to an
improvement in periodontal bleeding.
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Periodontal Disease and Pregnancy

ACKNOWLEDGMENTS
The study was self-funded by the authors and their
institutions. The authors report no conflicts of interest
related to this study.
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Correspondence: Dr. Luca Gil Raga, Gran Va Marques del
Turia 40-1 46005 Valencia, Spain. E-mail: luciagilraga@
yahoo.es.
Submitted February 17, 2016; accepted for publication
June 21, 2016.

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