Zeljko Mikovic

University of Belgrade, Beograd, Central Serbia, Serbia

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Publications (38)54.06 Total impact

  • Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: Abstract Objective: To determine if there is any difference in amniotic fluid erythropoietin (EPO) concentration between fetuses small for gestational age (SGA) and appropriate for gestational age (AGA), and between the constitutionally small (CSF) and growth-restricted (GRF) fetuses. Methods: EPO concentrations in the amniotic fluid samples were determined by EpoELISA test in 38 pregnancies with SGA and 15 pregnancies with AGA fetuses. In SGA group we measured ponderal index (Pi) and skin-fold thickness (SFT). If PI and/or SFT were below 10(th) percentile the neonate was GRF. If both PI and SFT were above 10(th) percentile the neonate was CSF. Results: Higher levels of EPO were detected in the SGA in comparison to the AGA fetuses (p<0.01). EPO concentration was higher in GRF compared to CSF (p<0.05). The EPO cut-off level between SGA and AGA was 6.81 IU/L (sensitivity 92.3%; specificity 73.3%), and between GRF and CSF was 9.8 IU/L (sensitivity 81%; specificity 80%). Conclusion: The preliminary results of this study suggest that amniotic fluid erythropoietin concentration is elevated in growth-restricted fetuses and could potentially be used for distinction between growth restricted and constitutionally small fetuses. Confirmation of these results on a larger group of pregnant women is needed.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2013; · 1.36 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this study was to investigate the importance of aPL type and level for non-criteria-related events in APS patients. METHODS: Our study included 374 patients: 260 with PAPS and 114 with APS associated with systemic lupus erythematosus (SLE). RESULTS: We discovered significant connection between migraine and LA absence, livedo reticularis and aCL-IgG, skin ulcerations with aCL-IgG and anti-β2GPI-IgM, pseudovasculitis lesions with aCL-IgG, aCL-IgM and anti-β2GPI-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG and anti-β2GPI-IgG. Thrombocytopenia occurred more frequently in patients with more than one aPL. In PAPS, epilepsy correlated with ß2GPI-IgM, migraine with aCL-IgM, and thrombocytopenia with aCL-IgM, aCL-IgG, anti ß2GPI-IgG and LA. Skin ulcerations occurred more frequently in IIc category patients and in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Livedo reticularis was more prominent in PAPS with high levels of aCL-IgG. Significantly higher prevalence of thrombocytopenia was observed in patients with high levels of aCL-IgG and anti ß2GPI-IgG. Epilepsy was related to high levels of anti ß2GPI-IgM and thrombocytopenia in the SAPS was correlated with aCL-IgG. Skin ulcerations were more prevalent in aCL-IgM positive SAPS patients and epilepsy more frequently in SAPS patients with high levels of anti ß2GPI-IgG. CONCLUSIONS: Our study showed that certain aPL type with certain level correlated with non-criteria manifestations, suggesting their predictive role.
    Clinical and experimental rheumatology 01/2013; · 2.66 Impact Factor
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    ABSTRACT: The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.
    Clinical and Applied Thrombosis/Hemostasis 12/2012; · 1.02 Impact Factor
  • Thrombosis Research 09/2012; 130(5):826-9. · 3.13 Impact Factor
  • Clinical Neurophysiology. 07/2012; 123(7):e85–e86.
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    ABSTRACT: Abstract Background: Pregnancy is a stressful condition linked with altered lipid profile, increased oxidative stress and increased inflammation processes. The purpose of the present study was to determine the associations between those alterations with increased weight gain during pregnancy. Methods: The atherogenic index of plasma (AIP) and oxidative stress status parameters were determinated in 50 healthy and 172 pregnant women with non-complicated pregnancy. Pregnant women were divided in four groups according to body mass index (BMI) values (BMI quartiles). Results: Oxidative stress parameters were significantly lower in the control group compared with all the pregnant women quartiles. Unexpectedly, differences in oxidative stress parameters between BMI quartiles groups were not significant. The antioxidant defence parameters remained quite similar in the different BMI quartiles. Weight gain and paraoxonase-1 (PON1) activities were independently associated with increased AIP while weight gain and triglyceride concentration were found to be significant predictors of PON1 activities. Conclusions: The results of our current study indicate the association of maternal weight gain during pregnancy and altered lipid profile, elevated oxidative stress and changed antioxidative capacity of PON1. Taken together all these facts indicate possible increased risk of cardiovascular disease (CVD) development in later life if the weight gain during pregnancy is excessive.
    Clinical Chemistry and Laboratory Medicine 06/2012; · 3.01 Impact Factor
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    ABSTRACT: The aim of this study was to examine the effectiveness of a combination of parameters at first-trimester screening for fetal aneuploidies, including ultrasound assessment of the nasal bone (NB), blood flow in the ductus venosus (DV) and flow across the tricuspid valve. Screening for aneuploidy was carried out in 4172 singleton pregnancies between January 2006 and December 2010. Diagnostic accuracy of combined screening [inclusive of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A] and of secondary ultrasound markers [NB, tricuspid regurgitation (TR) and Doppler studies of the DV] obtained at the same visit was assessed using the receiver operating characteristic (ROC) curve analysis. The individual areas under the ROC curves of NT, NB, DV or TR ranged between 0.7 and 0.8, representing acceptable discrimination. The area under the ROC curve of combined first-trimester screening was 0.87, whereas the addition of secondary ultrasound markers increased the area under the curve to 0.92, which represents excellent discrimination. At a risk cutoff of 1 : 275, the detection rate for aneuploidy increased from 87% to 92% (z statistic = 1.78, P = 0.076), and the false positive rate decreased from 5.3% to 4.8%. The addition of secondary ultrasound markers (NB, DV and TR) to combined first-trimester screening showed a tendency toward improved accuracy of the screening.
    Prenatal Diagnosis 05/2012; 32(7):638-43. · 2.68 Impact Factor
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    ABSTRACT: Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.
    Maternal and Child Health Journal 04/2012; · 2.24 Impact Factor
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    ABSTRACT: The purpose of the present study was to determine changes in plasma paraoxonase-1 activity (an indicator of paraoxonase phenotype) throughout normal pregnancy and its relationship with maternal oxidative stress status. The frequencies of the paraoxonase-1 phenotype in the studied population were determined using a two-substrate (paraoxon/diazoxon) activity method. As a parameter of oxidative stress status we measured the redox balance. Paraoxonase-1 activity significantly decreased at gestational week 32. In addition, the lipid profile was more atherogenic. Redox balance was significantly increased across gestational weeks. There were independent direct associations between maternal smoking habits before pregnancy, glucose concentrations and redox balance with PON1 activity in the third trimester. This study shows that pregnancy is followed by a decrease in PON1 activity and increased risk for development of cardiovascular diseases. We conclude that changes in paraoxonase-1 status during pregnancy are associated with maternal oxidative stress status and smoking habits.
    Reproductive Toxicology 10/2011; 33(1):20-6. · 3.14 Impact Factor
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    ABSTRACT: Presence of inherited thrombophilia is an additional risk factor for maternal thromboembolism and certain adverse pregnancy outcomes, including recurrent fetal loss, placental abruption, intrauterine growth restriction and early-onset severe preeclampsia. Pregnant women with thrombophilia, especially those with antithrombin (AT) deficiency, are at high risk of both kinds of complications. We presented a pregnant women with congenital antithrombin deficiency in the first pregnancy, whose mother had had four times pregnancy-related deep vein thrombosis, and antithrombin deficiency. With the regular laboratory monitoring of hemostatic parameters and gynaecology surveillance including the follow-up of placental vascular flow, the whole pregnancy proceeded without complications. The prophylactic therapy with low molecular weight heparin was introduced from the 20th week of gestation and one dose of substitution therapy with antithrombin concentrate was administrated before delivery. Pregnancy and labour were terminated without complications at the 37th week of gestation, resulting in the delivery of a healthy male newborn of 3.6 kg body weight, 52 cm long, and with the Apgar scores of 9/10. A timely made diagnosis of thrombophilia, accompanied with regular obstetrics check-ups and follow-ups of hemostatic parameters during pregnancy, as well as the use of adequate prophylactic and substitution therapy, are the successful tools for the prevention of possible maternal complications and pregnancy itself in our patient with congenital AT deficiency.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 02/2011; 68(2):175-7. · 0.21 Impact Factor
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    ABSTRACT: Twin reversed arterial perfusion syndrome (TRAP) or acardiac anomaly presents a rare and severe complication affecting monochorionic multiple pregnancies occurring in 1 per 35,000 pregnancies or 1 per 100 of monozygotic twins. We report four cases of multiple pregnancies with TRAP diagnosed over the last 2 years, which were under check-up and treatment during the entire pregnancy course finalized by delivery. In two cases pregnancies were trigeminal, and other two geminal, with acardia of one foetus, by anceps type in three and acephalus in one. Expectant management was initially done in all cases. The relation of acardiac and donor abdominal circumference was below 50% and negative signs of the donor's cardiac failure were detected in two cases, so that expectative management was continued until delivery. Due to obstetric indications, a cesarean section was performed on the 33rd and 34th gestational week, and healthy newborns were delivered. Another two acardiac twins had abdominal circumference ratio between the acardiac fetus and the donor of over 50%, and signs of congestive heart failure in the donor, which indicated invasive therapeutic procedure with absolute alcohol chemisclerosis; it was done by alcohol injection into the acardiac abdominal aorta which interrupted the retrograde blood-flow into the acardiac umbilicus. In the first case a successful intervention was performed at 29th gestational week, but after 12 hours distress signs were registered. The delivery was finalized by a cesarean section, and a live donor was delivered. In the second case the intervention was successfully done at the 20th gestational week, and after 96 hours from the intervention lethal ending of the donor was registered. Bearing in mind that the occurrence of TRAP is rare, it is necessary to sum-up experiences from a larger number of centres to determine efficient therapeutic procedure.
    Srpski arhiv za celokupno lekarstvo 01/2011; 139(3-4):233-8. · 0.23 Impact Factor
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    ABSTRACT: More recently, the regions of increased abdominal echogenicity such as echogenic bowel, meconium ileus and meconium peritonitis have been associated with an increased prevalence of a variety of unfavourable outcomes including chromosomal abnormalities, cytomegalovirus infection, intestinal obstruction, anorectal malformations and cystic fibrosis. Earlier prenatal examinations of these severe autosomal recessive diseases had been suggested only to families with history of cystic fibrosis. Recently, systemic examination has been introduced by ultrasound with bowel hyperechogenicity where the fetus is the index case for genetic disease. Risk for cystic fibrosis with this ultrasonography findings ranges from 0-33%. Two patients are presented, aged 24 and 29 years, both primigravide. The first one had ultrasonography finding of meconium peritonitis revealed at the 37th week of gestation and the other meconium ileus revealed on ultrasonography at the 29th week of gestation. Both patients had prenatal testing of foetal blood obtained by cordocenthesis, both had normal kariotype and were negative for cytomegalovirus infection. Parental DNA testing for the 2nd patient showed that parents were not carriers for the 29 most frequent mutations. Both neonates had intestinal obstruction, underwent surgery and early postoperative course was normal. Hystopathological finding suggested a possibility of cystic fibrosis for the 1st patient, but parents did not want to be tested and for the 2nd one congenital bowel stenosis as a cause of intestinal obstruction. Ultrasonographic echogenic bowel is an indication for invasive procedures for foetal blood testing for chromosomal abnormalities, congenital infections and parental testing for cystic fibrosis. Only if parental heterozygosity is proven foetus should be tested.
    Srpski arhiv za celokupno lekarstvo 01/2011; 139(7-8):527-30. · 0.23 Impact Factor
  • Thrombosis Research - THROMB RES. 01/2011; 127.
  • Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):28. · 3.56 Impact Factor
  • Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):234. · 3.56 Impact Factor
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    ABSTRACT: We reported a case of a child with neurodevelopment delay induced by long-term amiodarone exposure due to a treatment of fetal supraventricular tachycardia (FSVT), subtype permanent junctional reciprocating tachycardia (PJRT) with the normal thyroidal function. Refractory persistent FSVT was treated intrautero with digoxin (0.5 mg QD) until delivery and amiodarone (100 mg QD) from 26 to 35 weeks of gestation. A baby weighing 3550 g with normal acid-base status was delivered at 38 weeks of gestation. The PJRT recurred 28 hours after delivery and reverted to sinus rhythm with amiodarone and propranolol for another 24 months. The neurological disturbances were manifested at the age of 12 months, when hypotonia and delayed motor milestones were recognised. At the age of 18 months, the child had mildly neurological development delay with hypotonia, ataxia and foot deformities. At the age of 24 months, motor milestones were mildly delayed with the usage of a few words without the ability to connect them into the sentence. The developmental quotient (DQ) was 68. Electroencephalogram and magnetic resonance imaging of the central nervous system were all normal. At the age of 30 months, motor milestones were still delayed together with speech development and language delay, only some words were used, not distinctly, DQ was 78. Thyroid function was normal on each examination. All blood and urine analyses were in normal ranges. Chromosome analysis did not show any abnormalities. Since we excluded all possible reasons, we could only bring an indirect link between the long-term amiodarone exposure during fetal and postnatal life and neurodevelopment delay.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2010; 64(6):396-8. · 2.24 Impact Factor
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    ABSTRACT: Existing data regarding the prevalence of thrombophilia in women with pregnancy complications are conflicting. To investigate the relationship between pregnancy-associated complications and the presence of thrombophilia, we studied the records of 453 women with pregnancy-associated complications. In 55 women, intrauterine fetal death (fetus mortus in utero, FMU) after 20 weeks of gestation was recorded, in 231 two or more consecutive recurrent fetal losses (RFL) were recorded, while 167 had a venous thromboembolism (VTE) during one of their pregnancies. The control group consisted of 128 healthy women, with no previous history of thrombotic events or miscarriages. In the FMU group we found 54.5% of women had thrombophilia, in the RFL group 38%, and in the VTE group 52.7%. The most frequent thrombophilia in the VTE group was the FV Leiden (OR 17.9, 95% CI 4.2-75.9). The most frequent thrombophilia in the FMU group was the FII G20210A (OR 7.09, 95% CI 1.8-27.9). Statistical difference between RFL and the control group was observed only for FV Leiden (OR 6.8, 95% CI 1.6-29.7). Thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the women with normal pregnancies, most frequently in patients with VTE or FMU.
    Gynecologic and Obstetric Investigation 01/2010; 69(4):233-8. · 1.10 Impact Factor
  • V Parovic, Z Mikovic, V Mandic
    Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):136. · 3.56 Impact Factor
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    ABSTRACT: D-dimer testing has an important role in the exclusion of acute venous thromboembolism (VTE) in the nonpregnant population. Establishing D-dimers role in the diagnosis of VTE in pregnancy is hampered because of the substantial increase of D-dimer throughout gestational age. In a prospective study we followed 89 healthy pregnant women to establish the reference range of D-dimer for each trimester. D-dimer testing was also performed in 12 women with clinical suspicion of VTE and their results were compared with the established new reference range of D-dimer, and with the recorded ultrasound findings. In the first trimester, 84% women from reference group had normal D-dimer, in the second 33%, and by the third trimester only 1%, which suggests that D-dimer has no practical diagnostic use in ruling out VTE if the threshold of 230 ng/mL for abnormal is used. All pregnant women with thrombosis who had positive ultrasound findings also had statistically significant elevation of the D-dimer level, considering the established reference range of the corresponding trimester. We found 100% sensitivity of D-dimer test. A women developed thrombosis in the first trimester had 6.7-7.6 time higher level of D-dimer than the mean value in the reference group, and in the third trimester thrombotic women had 2.0-3.8 time higher level of D-dimer, p<0.0001. D-dimer test with the new threshold for: the first of 286, the second of 457 and the third trimester of 644 ng/mL can be useful in diagnosis of pregnancy related VTE.
    European journal of obstetrics, gynecology, and reproductive biology 10/2009; 148(1):27-30. · 1.97 Impact Factor

Publication Stats

58 Citations
54.06 Total Impact Points


  • 2010–2014
    • University of Belgrade
      • • Institute of Molecular Genetics and Genetic Engineering
      • • School of Medicine
      • • Faculty of Pharmacy
      Beograd, Central Serbia, Serbia
    • Institut za transfuziju krvi Srbije
      Beograd, Central Serbia, Serbia