
ASSOCIATION BETWEEN INHERITED THROMBOPHILIA
IN PREGNANCY AND MICRONUCLEUS FREQUENCY
IN PERIPHERAL BLOOD LYMPHOCYTES Šošić GM1,*, Jović N2,5, Rakić B3, Dimitrijević A2,4, Varjačić M2,5 *Corresponding Author: Gordana M. Šošić, B.Sc., Department of Cytogenetic Diagnosis, Obstetrics and Gynecology
Clinic, Clinical Center “Kragujevac,” 30 Zmaj Jovina Street, 3400 Kragujevac, Serbia. Tel: +381-63-835-66-24.
Fax: +381-34-37-00-73. Email: gordana.sosic.2011.02@gmail.com page: 11
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RESULTS
The examined women included in the study (n = 74)
were 21 to 39 years old, median 30 years old. The average
age of women included in this study was 29.93 ± 4.51.
Within this group, the first trimester combined aneuploidy
screening test was applied to 62 women below the age of 35. Pregnancy associated plasma protein-A (PAPPA),
free β human chorionic gonadotropin (fbHCG) and
fetal nuchal translucency (NT) were compared between
healthy pregnant women (n = 33) and pregnant women
with thrombophilia (n = 29). The PAPP-A (mLU/L) values
were significantly higher (p = 0.028), whereas fbHCG
(IU/L) levels were lower and fetal NT (mm) measurements
were higher in women with thrombophilia, but these differences
were not statistically significant.
The average MN frequency in the examined population
of pregnant women was 6.09 ± 4.78 MN/1000BN. The
obtained median of 4.50 MN/1000BN for the whole population
was used as a limit for forming examination case
and control groups (≤4MN/1000BN cells and >4MN/1000
BN cells). In this model, we investigated the influence of
the predictor variables on the outcome.
The average age in the control group was not significantly
different from the one in the case group (29.49 ± 4.58
vs. 30.38 ± 4.46; t = 0.848, p = 0.399). In the case group,
there were more cases of thrombophilia (p = 0.000) and
miscarriages (p = 0.002), an increased number of miscarriages
(p = 0.010) and of pregnancies (p = 0.023) (Table 1).
Table 2 shows the exogenous risk factors and risk factors
related to family anamnesis. It can be observed that most
of the pregnant women did not smoke (81.1%), or use alcohol
(90.5%) during pregnancy. Pregnant women who consumed
alcohol did it irregularly. It was determined that most of
them did not have relatives with malignant diseases, venous
thromboembolism and CADs or T2DM (Table 2). In the
group of pregnant women with frequency >4MN/1000BN,
there were more women who used alcohol compared to the
control group (18.9 vs. 0.0%; p = 0.017). In the group with
higher MN frequency, we also noticed statistically significant
increased alcohol consumption compared to the control
group with lower MN frequency (p = 0.021) (Table 2).
The prediction of all the studied risk factors in our
model for the percentage of pregnant women with frequency
>4MN/1000BN was determined by univariate
binary logistic regression analysis (Table 3). Using the
goodness-of-fit test, it showed how well our model (a set
of predictor variables shown in Tables 1 and 2) predicted
results. It was shown that with a given set of predictor
variables our model anticipated the results of the univariate
binary logistic regression analysis (p <0.005, with an indicator χ2 from 64,356,589 for 19 degrees of freedom).
The Hosmer and Lemeshow test supported the claim that
the model was good (p = 0.980>0.05). The given set of
variables in our models explained between 58.1% (Cox
& Snell R Square) and 77.5% (Nagelkerke R Square) of
variance in MN frequency.
Significant risk factors in the univariate model were
thrombophilia (p = 0.000), miscarriages (p = 0.002), the
number of miscarriages (p = 0.004) and the number of pregnancies
(p = 0.005). The significant risk factors from the
univariate model were included in the multivariate logistic
regression analysis, which showed that hereditary or combined
thrombophilia during pregnancy (OR = 76.06; 95% CI
= 7.97-724.39; p = 0.000) had a significant partial influence
on the frequency of >4MN/1000BN occurrence (Table 3).
In the examined group, the pregnant women who
consumed alcohol had frequencies of >4MN/1000BN.
The analysis showed that there was a lack of statistically
significant difference in the mean values of the MN frequency
between the groups of women who did not use
alcohol and those who consumed alcohol during pregnancy
(5.87 ± 4.18 vs. 7.36 ± 7.50; p = 0.939). There was also no
statistically significant difference between the mean MN
frequency in the groups concerning an increased intake of
alcohol (p = 0.246). These results are consistent with the
univariate analysis in which alcohol consumption and an
increased alcohol intake do not represent a significant risk
factor for the increased frequency of MN.
By analyzing the given results it can be concluded
that pregnant women with thrombophilia are 26.69-times
more likely to have the frequency of >4MN/1000BN than
pregnant women without thrombophilia. Pregnant women
who had previous miscarriages or recurrent miscarriages
and a higher number of pregnancies, are 4.92, 2.85 and
2.05 more likely to have the frequency of >4MN/1000BN
than pregnant women with no present risk factors (Table 3).
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