Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

C-Reactive Protein Level as a Diagnostic Tool for

Assessment of Adverse Pregnancy Outcomes in
Females with Periodontal Disease – A Randomized
Clinical Trial
First Author Second Author
Dr Rambhika Thakur Dr. Vikas Jindal
Reader Professor
Dept. of Periodontics Dept. of periodontics
MN DAV Dental College, Solan, Himachal Dental College, Sundernagar,
Himachal Pradesh, India Himachal Pradesh, India

Third Author Fourth Author

Dr Saroj Thakur Corresponding Author
Reader Dr. Pavan Kumar Gujjar
Dept. Of conservative dentistry and endodontics Prof and HOD
MN DAV Dental College, Solan Dept. of Oral pathology and microbiology
Himachal Prasesh, India Yogita Dental College and hospital
Khed, Maharashtra
India

Fifth Author Sixth Author

Dr. Jyoti Zingade Dr. Ajay Mahajan
Senior Lecturer Professor
Dept. Oral medicine and radiology Department of periodontics
Yogita Dental College and hospital HPGDC, Shimla
Khed, Maharashtra Himachal Pradesh
India India

Abstract:- Background: An acute-phase protein found in sent for laboratory analysis. CRP levels were determined
plasma that reflects a measure of acute phase response to using Immuno Turbidometry method on an autoanalyzer.
inflammation is C-reactive protein (CRP). Early detection Result It was found that the mean value of CRP levels is
of periodontal disease and its prediction can be used by correlated with high incidence of preterm delivery.
CRP. There is an association of C-reactive protein with Subjects with preterm delivery have high mean CRP
adverse pregnancy outcomes, including pre-eclampsia values as compared to subjects with normal delivery.
intrauterine growth restrictions, and preterm delivery. Conclusion Increased CRP levels in early pregnancy is
The present study endeavor to evaluate serum C-reactive associated with periodontal disease in pregnant women. In
protein level in pregnant women with and without healthy normal controls the incidence of preterm delivery
periodontal disease and to compare incidence of pre-term is lesser comparative to pregnant women with periodontal
delivery in pregnant women with and without periodontal disease.
disease .Material and methods This study was undertaken
in 40 pregnant women, divided into 2 equal groups of 20 Keywords: C-Reactive Protein, Periodontal Disease, Preterm.
pregnant women within 22nd weeks of gestation; group I
(study group) with periodontal disease and group II
(control group) without periodontal disease. Blood samples
were taken for estimation of C-reactive protein levels from
both the groups within 22nd weeks of gestation and were

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Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
I. INTRODUCTION An Informed consent was obtained from all the patients.

C-reactive protein (CRP) is 120,000-140,000 molecular All the patients were followed through a post partum
weight pentameric protein. Tillett and Francis in 1930 visit to evaluate the incidence of preterm delivery.
discovered that , substance in the serum of patients exhibiting
acute inflammation, was found reacting with pneumococcus  Laboratory analysis
capsular polysaccharide.[1] CRP is an acute phase reactant Estimation of C-reactive protein levels from both the
synthesized by liver in response to the inflammatory cytokines groups within 22nd weeks of gestation were done and sent for
like interleukin (IL)-6, IL-1, and tumor necrosis factor- laboratory analysis after blood samples were taken. CRP
alpha.[2] Systemic inflammation and periodontal diseases are levels were determined using Immuno Turbidometry method
indicated by circulating C-reactive protein [3],[4] There is a on an autoanalyzer. The detection limit of the test was 2.9
proportional increase of inflammation with increase in high mg/L and the biological reference interval was <5 mg/L.
sensitivity CRP levels[5] therefore the prediction and early
detection of periodontal disease is possible by the use of CRP  Measurement of periodontal status
.[6]
 Gingival inflammation [12]
[7]
Increased risk of preterm low birth weight, low birth Loe & Silness Gingival Index was used to know the
weight,[8] and preterm birth [9] has been associated with severity of gingivitis
periodontal disease. Therefore, C-reactive protein level can be
used as a diagnostic tool as a plausible mediator of association  Probing depth
between periodontitis and adverse pregnancy outcomes. [10] The probing depth measurement was assessed by means
of University of Michigan “O” probe with Williams’s
Thus the aim and objective of the present study were to markings. Except third molars probing depth measurements
assess serum C-reactive protein level in pregnant women with were made at the mesio-buccal, buccal, disto-buccal, disto-
and without periodontal disease and to compare incidences of lingual, lingual, and mesio-lingual positions of every tooth.
preterm delivery.
 Clinical attachment level
II. MATERIAL AND METHODS The distance between the base of the pocket and a fixed
point on the crown, such as the cementoenamel junction (CEJ)
Study was conducted in the Department of Obstetrics and was made to measure the clinical attachment level. Except
Gynaecology, Kamla Nehru state hospital for Mother and third molars Clinical attachment level measurements were
Child, Shimla and at Civil Hospital, Sundernagar, Himachal made at the mesio-buccal, buccal, disto-buccal, disto-lingual,
Pradesh. lingual, and mesio-lingual positions of every tooth.

Patients who participated in the study are of age group  Community periodontal index of treatment needs (cpitn) [13],[14]
between 18-34 years, systemic healthy, Singleton pregnancy, It was noted using a CPITN probe. The ten specified
pregnant females within 22nd week of gestation were included. index teeth were recorded. These teeth have been identified as
History of antibiotic intake during pregnancy, periodontal the best estimators of the worst periodontal condition of the
therapy in the past six months, other risk factors like alcohol mouth and only one score, the highest is recorded.
consumption, smoking or drug use, multiple pregnancy,
pregestational diabetes, previously diagnosed uterine The obtained results were compiled and subjected to
anomalies, patients with medical history of cardiac disease and statistical analysis using SPSS software by a qualified
chronic renal disease, without access for communication and statistician.
correspondence address, having less than 18 teeth were
excluded. III. RESULTS

The 40 subjects who met the selection criteria were In this study, an attempt was made to evaluate the CRP
divided into study group (Group I) and the control group levels in pregnant women with and without periodontal
(Group II). A questionnaire was administered by the examiner. disease in subjects within a defined age group and similar
Information was obtained regarding socioeconomic status of body mass index. In group I (Study) the mean age of the
the patients from this questionnaire. Modified Kuppuswamy’s subjects was 24.8±4.66 years. In group II (Control) the mean
socioeconomic scale [11] was utilized in this study for the age was 25.3±2.29 years. In group I (Study) mean BMI of the
stratification of the patients. Five classes were stratified subjects was 20.70±2.95 kg/m2. In group II (Control) the mean
comprising of upper, upper-middle, lower-middle, upper- BMI was 20.86±2.95 kg/m2. There was a difference in mean
lower and lower. age of subjects in both the groups which were statistically
insignificant (p=0.67, p>0.05). The difference in mean BMI in

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Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
the group I (Study) and the group II (Control) was statistically insignificant (p=0.86, p>0.05) (Table 1).

Table 1 Comparison of age and body mass index between group I (Study) and group II (Control).
Std.
Groups N Mean SD
Variable Error Mean
Cases 20 24.8 4.66 1.04
Age Controls 20 25.3 2.29 0.51
Cases 20 20.70 2.95 0.66
BMI (Kg/m2) Controls 20 20.87 2.95 0.66
Age: p=0.67, p>0.05 BMI: p=0.86, p>0.05

The majority of subjects enrolled in the study were from upper middle, 18 (45.0%), followed by lower middle, 14(35.0%), upper
lower, 7(17.50%) and 1(2.5%) from upper class. There was statistically significant (p=0.024, p<0.05) with the difference in
socioeconomic status between group I (Study) and group II (Control) (Table 2).

Table 2: Comparison of socioeconomic status between group I (Study) and group II (Control)
Cases Controls Total
Socioeconomic status
N (%) N (%) N (%)
Upper 1 (5.0%) 0 (0.0%) 1 (2.5%)
Upper middle 5 (25.0%) 13 (65.0%) 18 (45.0%)
Lower middle 9 (45.0%) 5 (25.0%) 14 (35.0%)
Upper lower 5 (25.0%) 2 (10.0%) 7 (17.5%)
Total 20 (100.0%) 20 (100.0%) 40 (100.0%)
 2 = 14.6 & p=0.024, p<0.05

The incidence of preterm and term delivery in group I (Study) was 11(55.0%) and 9 (45.0%) respectively. The incidence of
preterm and term delivery in group II (controls) was 3(15.0%) and 17(85.0%) respectively. A statistically significant difference was
found in incidence of preterm and term delivery in the Study and Control group. The incidence of preterm delivery between group I
(Study) and group II (Control) was statistically significant (p=0.033, p<0.05). The incidence of term delivery between group I (Study)
and group II (Control) was statistically significant (p=0.05) (Table 3).

Table 3: The incidence of preterm and term delivery between group I (Study) and group II (Control).
Cases Controls Total
Incidence
N (%) N (%) N (%)
2 P value
Number of preterm% of Total 11 (55.0) 3 (15.0) 14 (35.0) 4.57 0.033**
Number of term % of Total 9 (45.0) 17 (85.0) 26 (65.0) 3.84 .05**
Total number % of Total 20 (50.0) 20 (50.0) 40 (100.0)
** Significant at 0.05 level of significance

The mean value of C-reactive protein level in group I (Study) was 13.2±10.0 mg/L. The mean value of C-reactive protein level
in group II (Control) was 5.5±4.2 mg/L. The difference in mean CRP level was statistically significant (p=0.002, p<0.05) (figure 1).

The mean value of C-reactive protein level of group I (Study) with normal (Term) delivery was 4.94±3.24 mg/L. The mean value
of C-reactive protein level of group I (Study) with preterm delivery was 20.02±8.32 mg/L. The difference in mean value of CRP level
in term and preterm delivery in group I (Study) was found to be statistically significant (p=0.00, p<0.01) (Table 4).

Table 4: Comparison of mean C-reactive protein level (mg/L) in subjects of group I (Study) with normal (Term) and preterm delivery
(Unpaired t-test).
Cases N Mean SD Std. Error Mean t df P value
CRP level in term delivery 9 4.94 3.24 1.08
CRP level in preterm delivery 11 20.02 8.32 2.51 5.11 18 0.00*
* Significant at 0.01 level.

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Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
The mean value of C-reactive protein level of group II (Control) with normal (Term) delivery was 4.85±3.07 mg/L. The mean
value of C-reactive protein level of group II (Control) with preterm delivery was 8.23±9.97 mg/L. The difference in mean value of
CRP level in term and preterm delivery in group II (Control) was found to be statistically significant (p=0.03, p<0.05) (Table 5).

Table 5: Comparison of mean C-reactive protein level (mg/L) in subjects of group II (Control) with normal (Term) and preterm
delivery (Unpaired t-test).
Std. Error
Controls N Mean SD t df P value
Mean
CRP level in term
17 4.85 3.07 0.74
delivery
CRP level in preterm 2.23 18 0.03**
3 8.23 9.97 5.10
delivery
** Significant at 0.05

The results of this cohort study demonstrate the elevated to Mokeem et al [19],Cruz et al [20]. There was a positive
CRP levels in pregnant women with periodontal disease association between periodontal disease and low birth weight.
compared to healthy controls and preterm delivery rate is The correlation between periodontitis and PTB/LBW were
higher in women with periodontal disease compared to control reported in several cross sectional studies. According to study
group. which was published in 2016 where women with PTB were
found to have worse periodontal parameters [21]. PTB is a
IV. DISCUSSION multifactorial condition and that periodontitis and the presence
of periodontal pathogens are not sufficient to trigger PTB
Even though there is advancement in obstetrical which was suggested in the year 2016 by Martinez- Martinez
prevention, diagnostics, and therapy preterm birth (birth et al. [22]. CRP levels exceeding the threshold that are
before 37 weeks of gestation) is still considered to be a major associated with increased risk of preterm delivery. [23] In the
problem and remains the leading cause of morbidity and present study, the mean value of reported CRP levels was
mortality [15]. An effort was made to assess the CRP levels in correlated with high incidence of preterm delivery. Subjects
pregnant women with and without periodontal disease in this with preterm delivery have high mean CRP values as
study. The elevated CRP levels in pregnant women with compared to subjects with normal delivery.
periodontal disease compared to healthy controls and preterm
delivery rate is higher in women with periodontal disease In this study, the association observed between CRP
compared to control group as a result of this cohort study. level and periodontal disease in pregnancy may or may not be
causal. Periodontal infection and inflammation may cause
The potential risk factors for preterm low birth weight elevated CRP levels. CRP amplifies the inflammatory
are estimated at the age less than 17 and more than 34. response through complement activation, tissue damage, and
However the subjects who participated in the present study are induction of inflammatory cytokines in monocytes [2] and
between 19-34 years of age, the mean age being 24.8 years, therefore may mediate the association between periodontitis
yielding no significant difference in mean ages in both the and adverse pregnancy outcomes.
groups. Mean age of the present study is compared with the
mean age of subjects in studies done by Offenbacher et al [7], This raises the possibility that CRP may mediate
Hasegawa et al [16] and Dongming et al [17] The difference in association between periodontal disease and preterm delivery.
mean BMI in both the groups was statistically insignificant However, during the interpretation of data one has to be
(p>0.05). There was a statistically insignificant relationship cautioned, as there is multi-factorial etiology of both
between preterm birth and body mass index between the periodontal disease and preterm delivery, in addition the role
present study as well as the study done by Hasegawa et al [16] of confounding effect can’t be completely excluded.
.
Our present study had several strengths. First, as the
The difference in mean socioeconomic status between relationship between multiple gestations and preterm labor is
the cases and the controls is found to be statistically well established subjects with only singleton gestation were
significant (p<0.05). According to the study done by Radnai included.[24] Second, there is a free access to all the
et al [18] the data showed insignificant difference as the preterm participants in medical and prenatal medical care. Third, the
birth was more common amongst women who were less temporal relationship between elevated maternal serum CRP
educated and had lower social status.Delivering a premature, concentrations and subsequent risk of preterm delivery was
low weight baby increases fourfold increase of periodontal determined by CRP status using serum collected in early
disease prevalence, regardless of the control of other risk pregnancy. However, our study also had some limitations.
factors such as age, smoking, and social extraction according First, based on the social factors the subjects in our study were

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Volume 8, Issue 4, April – 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
relatively non-homogenous. Second, a single measurement of [11]. Newman JF, Gift HC. Regular pattern of preventive
serum CRP is not likely to provide a time-integrated measure dental services: A measure of access. Soc Sci Med
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[13]. Ainamo J, Barmes D, Beagrie G, Cutress T, Martin J,
At the end of the study the association of CRP with Infirri JS. Development of the world health organization
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Preterm delivery and periodontal disease: a case-control
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