ASSOCIATION BETWEEN INHERITED THROMBOPHILIA IN PREGNANCY AND MICRONUCLEUS FREQUENCY IN PERIPHERAL BLOOD LYMPHOCYTES
Šošić GM, Jović N2, Rakić B, Dimitrijević A, Varjačić M
*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: 5

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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