O A RIGINAL RTICLE

2732
Advances in Environmental Biology, 5(9): 2732-2735, 2011
ISSN 1995-0756
This is a refereed journal and all articles are professionally screened and reviewed
ORIGINAL ARTICLE
Is Serum Creatine Kinase a Reliable Indicator for Early Diagnosis of Ectopic
Pregnancy?
1
4
Parvin Mostafa-Gharabaghi, 2Seddigheh Abdollahi-Fard, 3Manizheh Mostafa-Gharabaghi,
Nadereh Rashtchizadeh, 5Morteza Ghojazadeh, 6Arash Khaki, 6Elham Ghadamkheyr
1
Associate professor of Ob & Gyn, Women's Reproductive Health Research Center, Tabriz University of
Medical Sciences, Tabriz, Iran
2
Associate professor of Ob & Gyn, Tabriz University of Medical Sciences, Tabriz, Iran
3
Associate professor of pediatrics, Tabriz University of Medical Sciences, Tabriz, Iran
4
Associate professor of Biochemistry, Tabriz University of Medical Sciences, Tabriz, Iran
5
PhD of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.
6
Associate professor of Pathology, Tabriz Branch, Islamic Azad University, Iran
7
MD student, Tabriz Branch, Islamic Azad University, Iran.
Parvin Mostafa-Gharabaghi, Seddigheh Abdollahi-Fard, Manizheh Mostafa-Gharabaghi, Nadereh
Rashtchizadeh, Morteza Ghojazadeh, Arash Khaki, Elham ghadamkheyr; Is Serum Creatine Kinase a
Reliable Indicator for Early Diagnosis of Ectopic Pregnancy?
ABSTRACT
Background: To determine the sensitivity of serum creatine kinase level in diagnosis of unruptured ectopic
pregnancy. Methods: This descriptive prospective case control study was performed in Alzahra and Taleghani
teaching hospitals in Tabriz Iran from 2006 to 2008 on 88 women with ectopic pregnancy (44 case of ruptured
and 44 case of unruptured ectopic pregnancy). The control group was consisted of 44 women with normal
intrauterine pregnancy. The serum cretine kinase level was measured by Eliza method in blood samples.
Results: the results were compared by variance analysis and t-test. SPSS.14 statistical software were used for
analyzing the data. By determining cut-off level of 45 Iu/L the specificity and sensitivity was estimated. The
mean of creatine kinase level was 48.24±14.97 iu/l in intrauterine pregnancy and 54.40±20.40 iu/l and
87.00±45.42 iu/l in unruptured and ruptured ectopic pregnancies, respectively. The difference in creatine kinase
level between ectopic pregnancy and normal intrauterine pregnancy was significant (p=0.001). The difference
between serum creatine kinase level in rupture and unrupture ectopic pregnancy also was significant p=0.04.
Creatine kinase levels above 45u/l was 65% sensitive and 79% specific for diagnosis of ectopic pregnancy from
intrauterine pregnancy and 78% sensitive and 84% specific for diagnosis of unruptured ectopic pregnancy from
ruptured ectopic pregnancy. Conclusions: Transvaginal sonography and quantitative bHCG measurment are the
optimal and most effective strategy for diagnosis of ectopic pregnancy.
Key words: ruptured ectopic pregnancy, unruptured ectopic pregnancy, intrauterine pregnancy, serum creatine
kinase.
Introduction
Ectopic pregnancy is a potentially life-threatening
condition in which the fertilized egg implants outside
the uterus. About 2 percent of all pregnancies is
ectopic, it is the most common cause of pregnancy
related mortality in the first trimester [5,2,6]. For
reducing maternal mortality and morbidity, early
Corresponding Author
Parvin Mostafa-Gharabaghi, Associate professor of Ob & Gyn, Women's Reproductive Health
Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
E-mail: [email protected]
Tel: 098 914 1153694
Fax: 098 411 5541221
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Adv. Environ. Biol., 5(9): 2732-2735, 2011
diagnosis is critical [7,10]. It is possible by
measurement of serum βHCG and vaginal
ultrasonography [4,8]. Despite their efficacy,
diagnosis can be uncertain below discriminative zone
of βHCG.
Other new diagnostic markers are also described
for diagnosis as progesterone, creatine kinase, CA125
and pregnancy specific β glycoprotein (PSBS)[5,6].
Measurement of serum levels of creatine kinase , an
intracellular metabolic enzyme with high
concentrations in the brain, the myocardium and
skeletal and smooth muscle, have first been
supported by lavie et al in ectopic pregnancy [3]. So
far its measurement only been used in the evaluation
of acut myocardial infarction [11].
In ectopic pregnancy the trophoblast can invade
the muscular layer of the fallopian tube and the
damaged muscle cells release creatine kinase in the
maternal blood stream through the tubal blood
vessels [12].
There is increasing concern that rising maternal
creatine kinase activities could be an early biological
index of tubal nidation, but there is no general
agreement about using it [14].
The aim of this study was to determine the
sensitivity and specificity of serum creatine kinase
level in diagnosis of unruptured ectopic pregnancy.
Methods:
This descriptive study was carried out at Alzahra
and Taleghani teaching hospitals in Tabriz,Iran from
2006 to 2008. The study group included 88 women
from population of ectopic pregnancy who were
admitted with signs and symptoms of ectopic
pregnancy. Ectopic pregnancy was confirmed by
laparoscopy or laparatomy in all cases.
The study group were divided into two groups
ruptured(44 cases) and unruptured(44 cases) based on
surgical findings.
The control group consist of 44 intrauterine
pregnancies with similar gestational age, based on
LMP and ultrasound findings who were randomly
selected from population of normal pregnancy.
All study group gave informed consent to be
included to study, which had been approved by
Regional Research Ethics Committee.
Blood samples were obtained with consent, from
all cases upon admission before any invasive
procedure for the measurement of creatine kinase
levels, another one just before surgery.
In control group the blood sample was obtained
at the prenatal care clinic for measurement of creatin
kinase.
Serum level of creatine kinase was measured by
Eliza method( pars Azmon ck-203 kit made in Iran).
Sample size calculations, assuming 90% power,
q=0.05 and p=0.5 indicated the need for at least 44
patients in each group.
Data management and analysis was performed
using SPSS14.
Analysis of Variance (ANOVA) test was used to
analyze the creatine kinase levels between three
groups and chi –squre test was used to compare
differences between two groups.
Data were presented as mean±standard deviation.
Significance levels were set at the p<0.05.
The efficiency and sensitivity of creatine kinase
in prediction of ectopic pregnancy and differentiation
of ruptured and unruptured ectopic pregnancy was
estimated by ROC for determination of best cut off
point.
Results:
Table 1 shows there was no significant
differences in demografic characterstics of patients
between two groups.
As shown in table 2 no significant difference
was found in the site of ectopic pregnancy between
two groups (p=0.83, df=1, x2=0.046).
Ampular pregnancy was the most common type
of ectopic pregnancy.
As table 3 shows no significant difference was
found in serum level of creatin kinase between
normal intrauterine and ruptured ectopic
pregnancies(p=0.998) but it was significantly different
between normal intrauterine and unruptured ectopic
pregnancies(p=0.11)and also between ruptured and
unruptured ectopic pregnancies(p=0.04).
There was a significant difference in serum level
of creatine kinase between three groups(p=0.009)
(Table 4).
A significant difference was found in serum
level of creatine kinase between ruptured(54.50±4.22)
and unruptured (66.15±7.19) ectopic pregnancies in
second measurement (p=0.04 r=0.72).
The difference between ampular and isthmus
pregnancies was significant (45.57±11.36 and
58.38±12.48 respectively, p=0.048).
Discussion:
As mentioned in the literature review ,the
diagnosis of ectopic pregnancy can be difficult
because of the wide spectrum of clinical
findings,from asymptomatic cases to acute abdomen
and hemodynamic shock [5].
The findings from this study indicated that 15%
of patients with ruptured ectopic pregnancy and
27.5% of unruptured cases were asyptomatic(p=0.45).
The present study was designed to determine the
sensitivity of serum creatine kinase level in dignosis
of unruptured ectopic pregnancy.
Gestational age as a determining factor for
placental tissue volume, a known source of cratine
kinase [13] was the same in all cases and control
group (p=0.67).
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Adv. Environ. Biol., 5(9): 2732-2735, 2011
Table 1: Demographic characters of patients.
Ectopic pregnancy
(ruptured, unruptured)
Age
28.54±5.73 (18-40)
Gravid
1.99±0.77 (1-5)
Pariety
0.86±0.09 (0-5)
Abortion
20%
Number of abortion
0.35±0.06 (0-2)
Smoking
6.3%
Gestational age
7.95±0.10 (6-10 weeks)
Normal pregnancy
P value
26.98±5.96 (16-40)
1.78±0.57 (1-3)
0.68±0.11 (0-3)
30%
0.33±0.10 (0-2)
5%
7.88±0.14 (6-10)
0.16
0.12
0.33
0.25
0.83
0.78
0.67
Table 2: Site of ectopic pregnancy.
Ruptured
Unruptured
Ampula
82.4%
80%
Isthmus
17.6%
20%
Table 3: Comparison of the serum level of βHCG in three groups.
Mean ± SD
Normal pregnancy
3515±2150.10
Ruptured ectopic pregnancy
1016.9±142.58
Unruptured ectopic pregnancy
1041.08±163.23
Lowest level
56
44
84
Highest level
78689
2900
4987
Table 4: Comparison of the serum level of cretin kinase in three groups.
Mean ± SD
Normal intrauterine pregnancy
48.28±14.97
Ruptured ectopic pregnancy
54.40±20.40
Unruptured ectopic pregnancy
87±45.43
Lowest level
7
19
15
Highest level
89
107
482
Table 5: Correlation between creatin kinase and Βhcg.
P
Intrauterine pregnancy
0.21
Ruptured ectopic pregnancy
0.102
Unruptured ectopic pregnancy
0.84
N
44
44
44
r
0.2
0.26
0.03
Lavie et al showed that serum creatine kinase
would increase in ectopic pregnancy as a result of
the trophoblastic invasion and insuing damage to the
mascularis layer of the tube [3,9]. They found
creatine kinase level in all cases of ectopic pregnancy
is higher than normal intrauterine pregnancies ,and
suggested that creatine kinase level is an useful
diagnostic tool for diagnosis of ectopic pregnancy
[3,9].
Though we did not find any significant
difference of creatine kinase level between normal
intrauterine pregnancy and ruptured ectopics
(p=0.889) but the difference between normal
intrauterine pregnancy and unruptured ectopic
pregnancy was significant. The difference between
ruptured and unruptured ectopic was significant
(p=0.04) .This result may be explained by the fact
that half life of creatin kinase is short [1].
By determining the cut off level of 45 the
sensivity and specificity of creatine kinase
measurement in diagnosis of ectopic and nomal
intrauterine pregnancies was 65% and 79%
respectively,while it was 78% and 84% in dignosis
of ruptured and unruptured ectopic pregnancies. This
is the same as the results of Jenn Rene Zorn,s study.
Done on 20 cases of intrauterine and 14 cases of
ectopic pregnancies and gaining 65% specificity and
50% sensitivity for creatine kinase in the diagnosis
of ectopic pregnancy.
Osman, H. [11] estimated the sensivity of 65%
and specivity of 87% for creatine kinase by using cut
off point of 120 iu/lit in the diagnosis of ruptured
and unruptured ectopic pregnancies [3].
The current study found that the amount of
creatine kinase in unruptured ectopic pregnancy was
higher than ruptured. It seems possible that this result
is due to muscular damage that precede rupture of
the tube.
There was no correlation between the serum
level of βHCG an indicator of the amount of viable
trophoblastic tissue and creatin kinase in present
study (Table 5). In second measurement the level of
creatin kinase in ruptured ectopic pregnancy were
lower than unruptured one. It may be due to short
half-life of creatin kinase [1].
Another important finding was that the level of
creatine kinase in isthmus ectopic pregnancy was
higher than ampular (58.38±12.48 and 48.57±11.26
respectively) (p=0.48). The reason for this result is
not clear but it may be due to more mascular
damage in isthmus pregnancy.
Conclusions:
In conclusion, risk factors assessment and
physical examination are the initial steps in the
dignosis of ectopic pregnancy. Transvaginal
sonography and quantitative bHCG measurment are
the optimal and most effective strategy for diagnosis.
The findings of this study suggest a role for
measurment of creatine kinase in differentiation of
ruptured and unruptured ectopic pregnancies but not
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Adv. Environ. Biol., 5(9): 2732-2735, 2011
for diagnosis. Further studies with more cases are
therefore recommended.
8.
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