PKISSN 0006 – 3096 (Print)
ISSN 2313 – 206X (On-line)
BIOLOGIA (PAKISTAN)
December, 2015, 61 (2), 307-311
Elevated Levels of C - reactive protein in Preeclamptic Women Following 20th
Week of Pregnancy
YASMIN ASHRAF, *NABILA ROOHI, AASIA SHARIF, SAMINA ASHRAF, & SADAF ILYAS
Department of Zoology, University of the Punjab, Lahore Pakistan
ABSTRACT
The aim of the current study was to evaluate the high sensitive C-reactive protein (hsCRP) level in
th
primigravida and multigravida preeclamptic and normotensive pregnant women following 20 week of
pregnancy. It was a cross sectional study conducted in different hospitals of Lahore from June 2012 to May
2014. Study included 140 participants with 70 preeclamptic cases and equimumeral normotensive pregnant
th
women after 20 week of pregnancy. Preeclamptic cases were further categorized as primigravida and
multigravida. All of the participants were in the age group of 18-40 years and BMI was in the range of 18-27
2
kg/m . hsCRP levels were measured by Enzyme Link Immunosorbent Assay. Levels of hsCRP were
significantly high in preeclamptic patients compared to normotensive pregnant group. Further the elevation
in hsCRP levels was more intensified in primigravida preeclamptic women compared to multigravida
preeclamptic women. Determination of serum C – reactive protein levels may be used as potential indicator
for the severity of preeclampsia.
Key words: C – reactive protein, Preeclampsia, Primigravida, Multigravida
INTRODUCTION
Hypertensive disorders of pregnancy,
gestational diabetes and premature birth are
common pregnancy disorders. Maternal and foetal
health as well as pregnancy outcome is markedly
affected by preeclampsia, eclampsia or HELLP
(hemolysis, elevated liver enzymes and low platelet
volume) disorders. These disorders significantly
contribute to maternal morbidity and mortality
(Tavana et al., 2010).
Preeclampsia, a complication of the late
pregnancy, develops in 7% of all pregnancies. It is
characterized by high blood pressure equal to or
above 140/90 mmHg with manifestation of
proteinuria after 20 weeks of pregnancy. It is one of
the leading causes of maternal and foetal morbidity
and mortality and currently there is no treatment
other than cessation of the pregnancy. About
50,000 mothers die due to pregnancy induced
hypertension per year all over the word. It is
responsible for 25% of all foetal growth retardation
and 15% preterm birth in developed countries
(Kameswaramma, 2014).
Preeclampsia may result in eclampsia if
seizure develops or exhibits as hemolysis, elevated
liver enzymes and low platelet volume (HELLP)
syndrome. Eclampsia and HELLP disorders have
been linked with severe complications like cerebral
hemorrhage, renal failure, lung edema and liver
hemorrhage. The recent postulate about the
etiology of preeclampsia focuses on mal-adaptation
*Corresponding author: nabilaruhi@gmail.com
of the immune responses and malfunctioned
trophoblast invasion. Thus, a life-threatening
maternal inflammatory response, perhaps directed
against foreign foetal antigens, results in a series of
activities
including
imperfect
spiral
artery
remodeling, shallow trophoblast attack, placental
infarction and discharge of pro-inflammatory
cytokines in the general circulation (Tavana et al.,
2010).
Complete pathogenesis of the disease is
still not clear, emphasizing a multifactorial etiology.
Endothelial cell dysfunction and inflammation are
considered to have a critical role in the
pathogenesis
of
preeclampsia.
A
general
inflammatory response includes both the clotting
and fibrinolytic system and immune system (Murthy
et al., 2012).
C – reactive protein is synthesized in
hepatocytes as a result of infection and tissue
damage (Halder et al., 2013). It is a part of inborn
immune system and takes part in the systemic
response to inflammation (Brown et al., 2013). CRP
was revealed in Oswald Avery's laboratory during
the development studies of patients with
Streptococcus pneumonia infection. In humans,
plasma levels of CRP may rise rapidly and
markedly, as much as 1000-fold or more, after an
acute inflammatory stimulus, largely reflecting
augmented synthesis by hepatocytes (Black et al.,
2004).
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Y. ASHRAF ET AL
BIOLOGIA (PAKISTAN)
C – Reactive protein has been shown to be
linked with several diseases, which includes
endothelial dysfunction and systemic inflammation
such as metabolic syndrome, type II diabetes and
cardiovascular disease. Both of the endothelial
dysfunction and inflammation have been associated
with the pathogenesis of preeclampsia and other
important pregnancy complications, including
gestational diabetes mellitus and foetal overgrowth.
Estimation of CRP level as a marker of inflammation
has been of great interest in such complications.
Hence, the purpose of the present study was to
investigate
the
hsCRP
concentrations
in
th
preeclamptic patients after 20 week of gestation
and to find out the role of C – reactive protein in the
pathogenesis of preeclampsia.
the Ethical review committee, participants were
informed about the study and consent was taken
from the subjects. Data about all of the participants
of the study was taken on a prestructured proforma
designed for the study. For measuring C- reactive
protein level, venous blood samples were collected
using sterilized disposable syringes during the
regular antenatal checkup at OPD or in the
antenatal ward patients. Blood was centrifuged and
serum was separated and preserved at -80C. CRP
was estimated by using commercially available
ELISA kit. The data was analysed using graph pad
prism version 5. Mean values were compared
between two groups using student t-test.
MATERIALS AND METHODS
Results are shown in Mean ± SEM. Mean ±
SEM of age of preeclamptic group is 27.04 ± 0.5931
and that of control group 25.36 ± 0.3606. hsCRP
level measured in preeclamptic group were
significantly higher 14.80 ± 0.679 mg/l compared to
control group 4.978 ± 0.336 mg/l with p-value
0.0001. Further preeclamptic group was divided into
two groups i.e., primigravida and multigravida. Level
of
hsCRP
was
significantly
high
in
primigravida16.58 ± 0.7438 mg/l than in
multigravida 12.29 ± 1.115 mg/l with p-value 0.001.
No significant difference was observed in hsCRP
level in primi and multigravida of control group.
Preeclamptic multigravida group was also divided
into two groups on the basis of history of
hypertension in previous pregnancy and it was
found that the multigravida preeclamptic women
with positive history of hypertension in pregnancy
showed significantly high level of hsCRP level 20.64
± 0.952 mg/l as compared to those multigravida
preeclamptic women without any history of
hypertension 8.795 ± 1.111 mg/l with p-value
<0.0001. p<0.05 is taken as significant.
It was a cross sectional study conducted in
two different hospitals of Lahore from June 2012 to
May 2014. In this study CRP level was measured in
th
140 pregnant women following 20
week of
gestation, divided into two groups: group A
consisted of 70 women (ages 18-40 years, BMI
2
ranges 18-27 kg/m ) having peeclampsia with blood
pressure 140/90 mmHg or greater, proteinuria
300mg in 24 hours and edema. group B included 70
pregnant women of parallel ages and BMI with
normal blood pressure and without proteinuria.
Group A and B were further subcategorized as
st
primigravida (a woman who is pregnant for the 1
time) and multigravida (a woman who has been
pregnant one or more times previously).
Multigravida preeclamptic women were also sub
grouped on the basis of positive and negative
history of pregnancy hypertension. Subjects using
any drugs, smoking or having diabetes mellitus,
renal disease, cardiovascular disease, chronic
hypertension or symptomatic infectious diseases of
upper respiratory tract were excluded from the
study. After getting approval from the hospitals and
RESULTS
Table I: Inter group comparison of age (years) and CRP (mg/l) level
Age (years)
Preeclamptic group
(n= 70)
27.04 ± 0.593
Control group
(n= 70)
25.36 ± 0.360
CRP mg/l
14.80 ± 0.679***
4.978 0± 0.336
*** Significant at P< 0.001
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C-REACTIVE PROTEIN IN PREECLAMPTIC WOMEN
309
Table II: Inter group comparison for obstetric index with reference to
CRP (mg/l) value
Preeclampsia (n=70)
Mean±SEM
CRPmg/l
Control (n=70)
Mean±SEM
Primigravida
n=41
Multigravida
n=29
Primigravida
n=34
Multigravida
n=36
16.58 ± 0.743
12.29 ± 1.115
5.12 ± 0.515
4.843 ± 0.443
Table III: Level of CRP (mg/l) in multigravida preeclamptic patients with and without history of
hypertension in pregnancy
History
of
pregnancy
hypertension
in
Multigravida
subjects
Preeclamptic
Mean ± SEM
Positive
17
20.64 ± 0.952
Negative
12
8.79 ± 1.111
DISCUSSION
Preeclampsia is a multisystem disorder of
human pregnancy. It is characterized by high blood
pressure, proteinuria, platelet aggregation and
edema. Pathophysiologically, the hallmark of
preeclampsia is vasoconstriction which causes
maternal hypertension and reduced uteroplacental
blood flow resulting in disturbed vascular endothelial
integrity with increased vascular penetrability and
activation of hyper coagulation (Nanda et al., 2012).
There is strong evidence that preeclampsia is a
systemic inflammatory disease associated with
endothelial cell damage or activation and hyper
coagulation. CRP being a sensitive marker of
inflammation and tissue damage has been
suggested to show an important role in the
pathogenesis of preeclampsia. CRP acts as
scavenger and is responsible for the clearance of
membrane and nuclear antigens (Murthy et al.,
2012). Hence, its measurement as a marker for
early detection of preeclampsia has been of
considerable interest.
The present study shows increased level of
CRP in preeclamptic subjects as compared to
normotensive pregnant women. This elevation in Creactive protein level in preeclamptic subjects may
be due to exaggerated systemic inflammation during
pregnancy that may lead to endothelial dysfunction
and preeclampsia (Can et al., 2011; Deveci et al.,
2009; Hwang et al., 2007; Kameswaramma, 2014).
The etiology of preeclampsia is still not clear. The
most common concept is the poor implantation that
causes placental hypoxia and thought to augment
the release of inflammatory stimuli into maternal
circulation which stimulates the production of
proinflammatory cytokines by the placenta as
response (Ertas et al., 2010). It has also been
observed that degree of severity of the disease
relates with the elevated level of CRP protein level,
this elevation can be useful in determining the
severity of preeclampsia (Ertas et al., 2010).
However study of Tavana et al. (2010) showed no
significant difference in various hypertensive
disorders of pregnancy compared to control
pregnant women. This contradiction may be due to
the difference of sample size.
Increased concentrations of C-reactive
protein in preeclampsia also amplify the involvement
of innate immunity in the pathogenesis of
preeclampsia, as it is an important component of
innate immune system (Molvarec et al., 2011).
Serum levels of CRP are higher in healthy pregnant
women as compared to non-pregnant women
because even normal pregnancy is accompanied by
mild systemic inflammatory response (Qiu et al.,
2004).
Moreover, in preeclamptic group mean CRP
level was high in both primigravida and multigravida
preeclamptic subjects but it was more intensified in
primigravida than multigravida showing that
primigravida have high rate of obstetric
complications when compared to multigravida
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Y. ASHRAF ET AL
preeclamptic subjects. No significant difference of
mean CRP level was however, observed in
primigravida and multigravida among control group.
This high risk of obstetric complications in
primigravida might be due to the low age as most of
the primigravida preeclamptic subjects were in the
age of 18-26 years. Young age of primigravida
individuals along with lack of awareness about
importance of antenatal care might have withdrawn
them from taking antenatal care till the progress of
obstetric complication (Jaspinder & Kawaljit, 2012).
Murthy et al. (2012) have also observed raised CRP
level in primigravida than multigravida among
preeclamptic patients. Further, an increased
incidence of pregnancy induced hypertension in
primigravida compared to multigravida preeclamptic
patients has also been reported earlier by
Cunningham et al. (2005).
The present study also reveals that women
with history of hypertension or preeclampsia in
previous pregnancy in multigravida preeclamptic
group showed significantly higher mean CRP level
than those without history of hypertension
suggesting the association of recurrence of
preeclampsia with pre-pregnancy levels of common
cardiovascular and inflammatory markers (Van Rijn
et al., 2014). Elevated CRP level has also been
reported by Brown et al. (2013) in females who have
history of hypertension in pregnancy.
CONCLUSION
Preeclamptic women show high level of C
reactive protein as compared to normotensive
pregnant women in third trimester of pregnancy
suggesting that elevated levels of CRP can be taken
as potential indicator of preeclampsia. Even in
preeclamptic group, primigravida shows higher level
of CRP than multigravida patients. Further,
multigravida preeclamptic women with history of
hypertension in previous pregnancy show
significantly higher level of CRP than those without
a history of hypertension.
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