Uticaj faktora inflamacije na tok i ishod trudnoća komplikovanih preeklampsijom

Preeclampsia is a common disorder of pregnancy characterized by disturbed placentation and hemodynamic response to pregnancy. It remains to be a leading cause of maternal morbidity and mortality and is associated with a significant increase in perinatal mortality, a clear etiology and pathophysiology is still unknown. It occurs in 3-14% of all pregnancies in the world and to moderate pre-eclampsia by 75% and 25% severe preeclampsia. Early prediction and prevention of pre-eclampsia is a dream of many obstetrician during generations. We used the number of tests (biophysical, biochemical ...) during the years of testing (more than 60 tests), but none of them gave the expected results of reliability as the sole test. More markers of inflammation and inflammatory responses has been studied in pre-eclampsia, in order to define their role in the pathogenesis and disease prediction. Many studies have addressed the role of inflammation in the pathogenesis of preeclampsia. However, little is known about the relationship between the severity of inflammation and severity of preeclampsia due to insufficient testing on this topic. Aim Since prevention is not possible to estimate severity of disease intensive supervision during the further course of pregnancy should be the target. 1. To determine the effect of the levels of cytokines on the clinical parameters of pregnant women with preeclampsia. 2. Define the demographic and socio-economic characteristics of pregnant women with the risk of pre-eclampsia in Macedonia,. 3. Assessment the impact factors of inflammation in certain biophysical and biochemical markers for prediction of severe preeclampsia in relation to women in the general obstetric population. 4. Evaluate the diagnostic and prognostic test options concentration levels of inflammation factors in maternal serum as a test to assess the severity of preeclampsia in the third trimester of pregnancy. 5. Determinate the dependence of pregnancy, mode of completion and perinatal outcomes in relation to inflammatory response Materials and methods The study was conducted as prospective study at the University Clinic of Gynecology and Obstetrics, University "Ss. Cyril and Methodius" in Skopje, Macedonia. The study included 50 pregnant women with singleton pregnancies between 28 and 40 gestational weeks hospitalized with symptoms of pre-eclampsia, determined by standard clinical laboratory analysis. The control group consisted of 50 normotensive pregnant women of the same gestational age (+ / - 1 Week), parity (primapara, parity 1 to 4 and parity> 4) and maternal age ( 35 years). After obtaining consent for participation in the examination of every pregnant woman, we took a detailed history, perform cardiotocography, ultrasound biometry and Doppler of fetomatemal unit, we took a blood sample to determine the appropriate serum concentrations of appropriate markers. Clinical laboratory testing to assess the severity of pre-eclampsia (moderate or severe). Inflammatory cytokines were analyzed from peripheral blood 1-1,5ml by enzymatic amplification chemiluminescence on the device Immulite 1000, Siemens Healthcare Diagnostics, USA. The duration of pregnancy, method of delivery, birth weight and length of the child at birth, Apgar score, are also analyzed. The data were digitized and all statistical tests were performed using SPSS version 13.0. We used descriptive statistical analysis that we would display the following parameters: mean, standard deviation, coefficient of variation, variation interval. Categorical variables were tested using Chi square and Fisher exact tests and quantitative variables were analyzed with independent sample test and Mann-Whiteney's U test to determine the correlation between the variables we used Spearman Rank Correlation Orded test and Pearson's linear correlation coefficient. We used binary logistic regression to determine the predictive role of the parameters analyzed. Results The average age of pregnant women included in the study was 32.06 ± 4.8 in the range of 20 to 40 years. Our data indicate a significant relationship between nulliparity, age, pregnant women, their nutritional status assessed by BMI and their religious convictions. History pregnant women about previous obstetric complications associated with hypertension, diabetes and smoking are important predictors of preeclampsia in our study. Multiple analysis of this study as independent significant factors for severe pre-eclampsia, confirms the ages of pregnant women: a systolic blood pressure of 160 mmHg and higher diastolic blood pressure of 100 mmHg and higher, the existing proteinuria, serum LDH values of 450 and above, and reduced serum concentrations of IL-4 and IL-tenth. Preeclampsia has a significant impact on the mode of delivery and newborn weight. The results of our study show that the birth by caesarean section is indicated in 10% of normotensive pregnant women and 46% in pregnant women with preeclampsia (52% severe, moderate 40%). Pregnancy ended with preterm delivery at 20% of normotensive pregnant women and insignificantly higher percentage of 36% in the group with preeclampsia. Tested differences between the analyzed groups in relation to the fetus (IUGR and SGA) show that pregnant women with preeclampsia often give birth with SGA, regardless of the severity of the disease, compared to normotensive pregnant women. Conclusion Comparison of changes in the profile of cytokines with increasing severity of preeclampsia may allow us to determine the level of compensation of pathological conditions that reflects the level of implementation and functional reserves of various mechanisms to maintain homeostasis. This happens in the background of increased concentrations of other proinflammatory cytokines and decreased levels of anti-inflammatory cytokines IL-4 and IL-10. 1. Multiple analysis of this study as independent significant factors for severe pre-eclampsia confirms: age ≥ 35 years, nulliparity and ethnicity, and as insignificant factors confirms smoking, Diabetes gestationes and preeclampsia in prior preegnancy. 2. In pregnant women with mild preeclampsia there is increase of IL 1β, IL 2, IL 4, IL 8, IL 10, TNF and IL 6 (statistically significant) compared with normotensive pregnant woman. 3. In pregnant women with severe preeclampsia significantly reduces the levels of IL 4 and IL 10, and increasing the levels of IL 2, IL 6, IL 8, IL 1β, and does not change significantly the level of TNF compared with normotensive pregnancies. 4. Preeclampsia has a significant impact on the way of delivery and newborns weight. In pregnant women with preeclampsia and low levels of factors of inflammation significantly higher percentage of deliveries were by Caesarean section, a significantly smaller percentage of vaginaldelivery.Preterm births insignificantly is in higher percentage in pregnant women with preeclampsia compared to control group. 5. The best statistical model for predicting the severity of preeclampsia is the correlation of the levels of serum interleukin (IL-4 and IL-10) with indicators of pre-eclampsia: LDH, creatinine, uric acid, and platelet count. However, the study is only the beginning of this type of research in our population. Further research is needed in terms of evaluating the costs and benefits of using such a test in order to prevent subsequent unnecessary interventions in groups with low risk, and realizing the benefits of such interventions in high-risk groups, the patient is given

Biochemical Indicators as Predictive Markers by Combining Clinical Signs in Pre-eclampsia

AIM: To determine whether previously identified risk factors are associated with the development of a severe form of pre-eclampsia in a heterogeneous cohort of women, and the predictive values of these risk factors when combined with certain biochemical indicators. MATERIALS AND METHODS: Systematic review of data collected for a doctoral case-control study plus an examination of the indicators of pre-eclampsia and maternal IL10 levels. This examination was conducted in 100 women with pregnancies complicated by varying degrees of pre-eclampsia and in 80 normotensive patients hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. Patients with pre-eclampsia were categorized into moderate (m PE) and severe (s PE) pre-eclampsia group according to the degree of pre-eclampsia. The severity of pre-eclampsia was determined according to the definition of the World Health Organization, Handbook for guideline development from 2010. RESULTS: The regression analysis applied in this study showed that elevated systolic blood pressure of 160 mmHg or higher, diastolic blood pressure of 100 mmHg or higher, pregnancy at an older age, nulliparity, persistent proteinuria in pregnancy, the serum lactate dehydrogenase concentration of 450 U/L or higher, and reduced serum concentrations of IL10 as significant predictors of severe pre-eclampsia in pregnant women. While other variables predicted a higher likelihood for the development of severe pre-eclampsia, IL10 decreased such likelihood. IL10 was also found to be negatively correlated with proteinuria and positively correlated with blood platelets. Significantly higher concentration of IL10 was confirmed in patients with a higher number of platelets in the blood and vice versa. On the other hand, the serum concentration of IL10 was significantly lower in patients with a higher amount of proteins in the urine and vice versa. CONCLUSIONS: Examination of clinical risk factors combined with biochemical markers can improve the predictive success of pre-eclampsia and has important clinical values in improving the prognosis of pregnant women and fetuses

Анализа на етиолошки фактори за појава на ендометријална хиперплазија во перименопаузa

The aim of this study was to evaluate the possible reasons for the emergence of endometrial hyperplasia in perimenopause. Material and methods: A total of 71 patients with irregular bleeding were analyzed, at the age of 40-50 years, who should have undergone diagnostic curettage. Depending on the histopathological findings, we divided them into 2 groups: group 1-findings for endometrial hyperplasia, group 2 - atrophic or endometrium with deficient secretory changes. Body mass index (BMI) was determined (obesity defined with BMI >30 kg/m2); we measured blood pressure (cut-off value was 135/90 mmHg), waist circumference (cut-off value was 88 cm) as well as data of anamnesis (age, physical activity, type of diet, smoking cigarettes). All these data were analyzed as etiological factors in the emergence of endometrial hyperplasia.Results: The mean age of patients was 47 years, and the results obtained were very similar in both examined groups. BMI and waist circumference were increased, more than 60% of patients had hypertension, but not all had a statistical significance. Most of them were with completed secondary education, and city living statistically significantly increases the risk of endometrial hyperplasia (p <0.05). As for the lifestyle (physical activity, caloric diet, smoking), the results have shown that a small number of patients are active, almost half of them consume caloric food and smoke, but without a statistical significance.Conclusion: Increased body weight and elevated blood pressure have a major impact on the onset and progression of pathological changes in the endometrium. As clinicians, we should always think of hyperplasia in obesity and patients with hypertension who are irregularly bleeding. At the same time, we should educate them to change the lifestyle in order to prevent gynecological and internistic morbidity.Целта на оваа студија беше да се евалуираат можните причини  за појава на ендометријална хиперплазија во перименопауза. Материјал и методи: Беа анализирани 71  пациентка  со неправилно  крвавење, на возраст од 40-50 години, кај кои беше индицирана фракционирана киретажа. Зависно од хистопатолошкиот наод ги поделивме  во 2 групи : група 1- со наод за ендометријална хиперплазија , група 2- атрофичен или ендометриум со дефициентни секреторни промени. Одредивме  индекс на телесна маса (БМИ), обезитет дефиниран со БМИ > 30 kg/m2, измеривме  крвен притисок (cut-off вредност 135/90 mmHg), обем на струк (cut-off вредност 88 см), како и податоци од анамнезата (возраст, физичка активност, тип на исхрана, пушење цигари).  Сите овие податоци беа анализирани  како етиолошки фактори во појавата на ендометријална хиперплазија. Резултати: Средна возраст на пациентките беше околу 47 години, а добиените резултати беа многу слични во двете испитувани групи. БМИ и обем на струк беа зголемени, хипертензија имаа повеќе од 60% од пациентките, но не беше утврдена статистичка значајност.  Најголем дел беа со средно образование, а живеењето во град статистички значајно го зголемува ризикот за ендометријална хиперплазија (p< 0,05). Што се однесува до животниот стил (физичка активност, калорична исхрана, пушење), резултатите покажаа дека мал дел се активни, речиси половина од нив конзумираат калорична храна и пушат, но без статистичка сигнификантност. Заклучок: Зголемената телесна тежина и покачениот крвен притисок  имаат големо влијание врз започнување и прогресија на патолошки промени на ендометриумот. Како клинички доктори секогаш треба да помислиме на хиперплазија  кај обезни и пациентки со хипертензија, кои неправилно крвават. Воедно треба и да ги едуцираме за промена на животниот стил, со цел спречување на гинеколошки и интернистички морбидитети

The Connection of the Level of Estradiol in Serum and Obesity with the Endometrial Bleeding in Postmenopausal Women

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times

Indicators of Moderate and Severe Preeclampsia in Correlation with Maternal IL10

AIM: The purpose of the actual study was to evaluate the relationship between the formation of anti-inflammatory cytokine IL10 and several indicators of moderate and severe preeclampsia in the third trimester of pregnancy.MATERIAL AND METHODS: Examination of the indicators of preeclampsia and maternal IL10 levels was conducted in 50 women with pregnancies complicated by varying degrees of preeclampsia in the third trimester of gestation as well as in 50 normotensive patients, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. The levels of IL10 were determined with a commercial test developed by Orgenium Laboratories (Finland), using reagents from AviBion ELISA research kits. Patients with preeclampsia were categorized into moderate and severe preeclampsia group according to the degree of preeclampsia. Logistic regression analysis was used to determine the predictive value of different parameters for the occurrence of severe preeclampsia. Odds ratios and 95% Confidence Intervals were calculated in order to quantify independent associations.RESULTS: The regression analysis detected systolic blood pressure (160 mmHg or higher), diastolic blood pressure (100 mmHg or higher), persistent proteinuria in pregnancy, serum LDH concentration (450 U/L or higher) and reduced serum concentrations of IL10 as significant predictors of severe preeclampsia in pregnant women after adjusting for age. CONCLUSION: The findings of significantly lower serum IL10 concentrations in patients with severe preeclampsia in comparison with respective concentrations in patients with moderate preeclampsia can be considered as major pathognomonic laboratory sign of severe preeclampsia

Indicators of Preeclampsia in Correlation with Maternal Cytokines in Pregnancy

Aim: the purpose of the actual study was to evaluate, in the third trimester of pregnancy, the relationship between the formation of anti-inflammatory IL-10 cytokine and several indicators of moderate and severe preeclampsia. Materials and methods: in the third trimester of gestation, examination of the biochemical markers of preeclampsia (PE) and maternal IL-10 levels was conducted in 100 women with pregnancies complicated by varying degrees of preeclampsia and in 100 normotensive patients, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. Patients with preeclampsia were categorized into moderate and severe preeclampsia groups according to the degree of preeclampsia. Logistic regression of the different parameters for the occurrence of severe preeclampsia analysis was used to determine the predictive value. Results: the regression analysis detected systolic blood pressure of 160 mmHg or higher, diastolic blood pressure of 100 mmHg or higher, persistent proteinuria in pregnancy, serum LDH concentration of 450 U/L or higher, and reduced serum concentrations of IL-10 as significant predictors of severe preeclampsia. Conclusion: significantly, lower IL-10 concentrations in maternal serum in patients with severe preeclampsia in comparison with respective concentrations in patients with moderate preeclampsia can be considered as major pathognomonic laboratory sign of severe form of preeclampsia

Улогата на некои инфламаторни маркери, цитокини и тумор маркери во дијагноза на ендометриозата

Endometriosis is a multifactorial disease which etiopathogenesis has not been elucidated. One of the theories of etiopathogenesis is the inflammatory theory. Aims of the study: To develop a practical non-invasive test for the diagnosis of endometriosis by examining some inflammatory markers and cytokines; to compare the highly sensitive C-reactive protein (hsCRP), cytokines (interleukin-6-IL-6 and tumor necrotizing factor alpha) and the tumor marker cancer antigen 125 (CA-125) among healthy patients and patients with endometriosis; to determine the sensitivity and specificity of each biomarker separately in the diagnosis of endometriosis and to determine their role in the diagnosis of endometriosis. Materials and methods: In a prospective study conducted at the University Clinic for Gynecology and Obstetrics, Ss. Cyril and Methodius University in Skopje, North Macedonia 138 patients were included of a reproductive age between 18-50 years (83 with diagnosis endometriosis operated laparoscopically or with laparotomy) and a control group of 55 healthy women, in a period between 01.09.2018 to 01.05.2021. Serum levels of IL-6, TNF-α, hs-CRP and tumor marker CA-125 were evaluated in both groups. Results: Serum levels of CA-125, IL-6 and TNF-α and hs-CRP were significantly higher in patients with endometriosis compared to the control group. The surface under the ROC curve (AUC) for IL-6, CA-125, hs-CRP, and TNF-α has shown that as individual markers they all have a discriminatory capacity to diagnose patients with endometriosis. Conclusions: Results obtained in our study showed statistically significantly higher serum concentrations of CA-125, IL-6 and TNF-α and hs-CRP in patients with endometriosis compared to the control group of patients. However, none of these biomarkers showed a high sensitivity for diagnosis of endometriosis. It is necessary to find a panel combination of biomarkers with a high sensitivity of about 100% that will enable early diagnosis of endometriosis.Ендометриозата е мултифакторно заболување, чија етиопатогенеза не е разјаснета. Една од теориите за етиопатогенезата е инфламаторната теорија. Цели на истражувањето: Да се развие практичен неинвазивен тест за дијагноза на ендометриозата со иследување нанекои инфламаторни маркери и цитокини; да се направи споредба на  високосензитивниот Ц-реактивен протеин  (hsCRP), цитокините (интерлеукин 6 –IL-6 и тумор-некротизирачки фактор алфа - TNF-α) и туморскиот маркер cancer antigen 125 (CA-125) кај здрави пациентки и пациентки со ендометриоза; да се утврди сензитивноста и специфичноста на секој биомаркер посебно во дијагнозата на ендометриозата и да се утврди нивната улога во дијагноза на ендометриозата. Материјал и методи: Во проспективна студија спроведена на Универзитетската клиника за гинекологија и акушерство, Универзитет „Св. Кирил и Методиј“ во Скопје, Северна Македонија беа вклучени 138 испитанички на репродуктивна возраст помеѓу 18-50 години (83 со дијагнозa ендометриоза, оперирани со лапароскопија или лапаротомија) и контролна група од 55 здрави жени, во период од 01.09.2018 година до 01.05.2021. Серумските вредности на интерлеукин 6 (IL-6), тумор-некротизирачки фактор алфа (TNF-α), високоспецифичен Ц-реактивен протеин (hsCRP) и туморскиот маркер CA-125 беа евалуирани во двете групи. Резултати: Серумските вредности на CA-125, IL-6 и TNF-α и hsCRP беа сигнификантно повисоки кај пациентките со ендометриоза во споредба со оние во контролната група. Површината под ROC кривата (AUC) за IL-6, CA-125, hs-CRP и TNF-α покажа дека како поединечни маркери сите имаат дискриминаторен капацитет за дијагноза на пациентки со ендометриоза. Заклучоци: Иследувањата во нашата студија покажаа статистички сигнификантно повисоки концентрации на CA-125, IL-6 и TNF-α и hs-CRP кај пациентките со ендометриоза во однос на контролната група пациентки. Меѓутоа, ниту еден од овие биомаркери не покажа висока сензитивност за дијагноза на ендометриозата. Потребно е да се најде панел комбинација на биомаркери со висока сензитивност од околу 100% кои ќе овозможат  рана дијагноза на ендометриозата

KONCENTRACIJA JODA U MOKRAĆI: PREDSKAZATELJ POROĐAJNE TEŽINE ILI BIOLOŠKI BILJEG ZA PROCJENU JODNOG STATUSA SAMO U ZDRAVIH TRUDNICA?

Introduction: This study determined urine iodine concentration (UIC) during gestation, assessed the maternal iodine nutrition status and correlated it with gestational age at birth (GAB) and birth weight (BW).The measurement of UIC provides the best single measurement of the iodine nutritional status in population. Objective: Determination of UIC in pregnant women in North Macedonia. Methods: This prospective study assessed the iodine nutrition status during the course of pregnancy with reference of median UIC among 364 healthy pregnant women in different gestational age (in trimester and 5-week intervals). Results: The overall and the 1st to the 3rd trimester median UIC were: 183.7, 207, 189.75 and 169.28 [μg/L], respectively. The median UIC (μg/L) results according to 5-week interval in advancing gestation were: 232.34, 200.13, 152.81, 194.39, 181.28, 160.28, 169.41 and 175.24, respectively. We detected 5.22% (19/364) and 74.72% (272/364) with the median UIC < 50 μg/L and UIC ≥ 100 μg/L, respectively. In multiple regression, the median UIC (β = 0.0000767, P = 0.929) had no statistically signifi cant prediction to the GAB. Disease prevalence results for mean UIC in detecting BW had no statistical signifi cance: area under curve (AUC) = 0.521, z-statistic (0.340), sensitivity (45.83%), specifi city (66.27%), predictive (6.59%) and P value (0.734). Conclusion: Iodine status of pregnant women in our study is generally suffi cient by World Health Organization recommendations. The median UIC in each trimester and 5-week interval has statistically insignifi cant decrease in accordance to the advancing gestation. The median UIC has no signifi cance in predicting GAB and BW.Uvod: Ova je studija utvrdila koncentraciju joda u mokraći (UIC) tijekom trudnoće, procijenila prehrambeni status joda kod majke i povezala ga s gestacijskom dobi pri rođenju (GAB) i porođajnom težinom (BW). Mjerenje UIC-a omogućava najbolje pojedinačno mjerenje prehrambenog statusa joda u populaciji. Cilj: Određivanje UIC-a trudnicama u sjevernoj Makedoniji. Metode: Ova prospektivna studija procjenjivala je prehrambeni status joda tijekom trudnoće, pozivajući se na medijan UIC 364 zdrave trudnice u različitoj gestacijskoj dobi (u intervalima tromjesečja i 5 tjedana). Rezultati: Ukupna i prosječna UIC od 1. do 3. tromjesečja bila su: 183,7, 207, 189,75 i 169,28 [μg / L]. Srednji rezultati UIC (μg / L) prema intervalu od 5 tjedana u napredovanju trudnoće bili su: 232,34, 200,13, 152,81, 194,39, 181,28, 160,28, 169,41 i 175,24. Otkrili smo 5,22 % (19/364) i 74,72 % (272/364) s medijanom UIC <50 μg / L, odnosno UIC ≥ 100 μg / L. U višestrukoj regresiji, medijan UIC (β = 0,0000767, P = 0,929) nije imao statistički značajno predviđanje za GAB. Rezultati prevalencije bolesti za srednji UIC u otkrivanju BW nisu imali statističku značajnost: područje ispod krivulje (AUC) = 0,521, z-statistika (0,340), osjetljivost (45,83 %), specifi čnost (66,27 %), prediktivna (6,59 %) i P vrijednost (0,734). Zaključak: Jodni status trudnica u našem istraživanju u pravilu je dovoljan prema preporukama Svjetske zdravstvene organizacije. Medijan UIC-a u svakom tromjesečju i intervalu od 5 tjedana statistički je beznačajno smanjen u skladu s napredovanjem trudnoće. Medijan UIC nema značenje u predviđanju GAB i BW

The outcome of Pregnancy with Fetal Primitive Neuroectodermal Tumor

BACKGROUND: Fetal intracranial tumours are very rare. The overall incidence is 0.34 per one thousand live birth newborns. According to the new classification of central nervous system tumour (2016), a primitive neuroectodermal tumour of (PNETs) is an embryonal tumour group; these are tumours with high malignancy and belong to group IV (WHO). In our case, we will present a case of PNETs in 28 gestation week old fetus, diagnosed antenatally and confirmed postnatally.CASE REPORT: We present the third pregnancy in 29 years old patient, with two previous term deliveries of healthy newborn. She came to University clinic at 27+3 gestational week for fetal hydrocephalus. After an ultrasound and MRI scan, possibilities were explained to the parents. During the medico-ethical counselling, explain to the parents the need for operation and the possibility of postoperative adjuvant therapy, quality of life with potential future disabilities. They choose to terminate the pregnancy. Postmortem the diagnosis was PNETs. Summary of analysis: peripheral neuroectodermal tumour with ganglion and neuronal differentiationCONCLUSION: Antenatal management depends on the gestational week in the time of diagnosis and the decision of parents. If the lesion is before viability fetus, it should be offered termination of pregnancy. Another important factor is the mode of delivery, because of increased intracranial pressure although this aggressive combined modality of treatment, recurrence is often. Tree year of survival is between 53% and 73% when the adjuvant radiotherapy is included. For that, they should be diagnosed as soon as possible before achieving fetal viability. Only 18% of those tumours presenting in the first year of life are diagnosed before or at delivery

Uticaj faktora inflamacije na tok i ishod trudnoća komplikovanih preeklampsijom

Preeclampsia is a common disorder of pregnancy characterized by disturbed placentation and hemodynamic response to pregnancy. It remains to be a leading cause of maternal morbidity and mortality and is associated with a significant increase in perinatal mortality, a clear etiology and pathophysiology is still unknown. It occurs in 3-14% of all pregnancies in the world and to moderate pre-eclampsia by 75% and 25% severe preeclampsia. Early prediction and prevention of pre-eclampsia is a dream of many obstetrician during generations. We used the number of tests (biophysical, biochemical ...) during the years of testing (more than 60 tests), but none of them gave the expected results of reliability as the sole test. More markers of inflammation and inflammatory responses has been studied in pre-eclampsia, in order to define their role in the pathogenesis and disease prediction. Many studies have addressed the role of inflammation in the pathogenesis of preeclampsia. However, little is known about the relationship between the severity of inflammation and severity of preeclampsia due to insufficient testing on this topic. Aim Since prevention is not possible to estimate severity of disease intensive supervision during the further course of pregnancy should be the target. 1. To determine the effect of the levels of cytokines on the clinical parameters of pregnant women with preeclampsia. 2. Define the demographic and socio-economic characteristics of pregnant women with the risk of pre-eclampsia in Macedonia,. 3. Assessment the impact factors of inflammation in certain biophysical and biochemical markers for prediction of severe preeclampsia in relation to women in the general obstetric population. 4. Evaluate the diagnostic and prognostic test options concentration levels of inflammation factors in maternal serum as a test to assess the severity of preeclampsia in the third trimester of pregnancy. 5. Determinate the dependence of pregnancy, mode of completion and perinatal outcomes in relation to inflammatory response Materials and methods The study was conducted as prospective study at the University Clinic of Gynecology and Obstetrics, University "Ss. Cyril and Methodius" in Skopje, Macedonia. The study included 50 pregnant women with singleton pregnancies between 28 and 40 gestational weeks hospitalized with symptoms of pre-eclampsia, determined by standard clinical laboratory analysis. The control group consisted of 50 normotensive pregnant women of the same gestational age (+ / - 1 Week), parity (primapara, parity 1 to 4 and parity> 4) and maternal age ( 35 years). After obtaining consent for participation in the examination of every pregnant woman, we took a detailed history, perform cardiotocography, ultrasound biometry and Doppler of fetomatemal unit, we took a blood sample to determine the appropriate serum concentrations of appropriate markers. Clinical laboratory testing to assess the severity of pre-eclampsia (moderate or severe). Inflammatory cytokines were analyzed from peripheral blood 1-1,5ml by enzymatic amplification chemiluminescence on the device Immulite 1000, Siemens Healthcare Diagnostics, USA. The duration of pregnancy, method of delivery, birth weight and length of the child at birth, Apgar score, are also analyzed. The data were digitized and all statistical tests were performed using SPSS version 13.0. We used descriptive statistical analysis that we would display the following parameters: mean, standard deviation, coefficient of variation, variation interval. Categorical variables were tested using Chi square and Fisher exact tests and quantitative variables were analyzed with independent sample test and Mann-Whiteney's U test to determine the correlation between the variables we used Spearman Rank Correlation Orded test and Pearson's linear correlation coefficient. We used binary logistic regression to determine the predictive role of the parameters analyzed. Results The average age of pregnant women included in the study was 32.06 ± 4.8 in the range of 20 to 40 years. Our data indicate a significant relationship between nulliparity, age, pregnant women, their nutritional status assessed by BMI and their religious convictions. History pregnant women about previous obstetric complications associated with hypertension, diabetes and smoking are important predictors of preeclampsia in our study. Multiple analysis of this study as independent significant factors for severe pre-eclampsia, confirms the ages of pregnant women: a systolic blood pressure of 160 mmHg and higher diastolic blood pressure of 100 mmHg and higher, the existing proteinuria, serum LDH values of 450 and above, and reduced serum concentrations of IL-4 and IL-tenth. Preeclampsia has a significant impact on the mode of delivery and newborn weight. The results of our study show that the birth by caesarean section is indicated in 10% of normotensive pregnant women and 46% in pregnant women with preeclampsia (52% severe, moderate 40%). Pregnancy ended with preterm delivery at 20% of normotensive pregnant women and insignificantly higher percentage of 36% in the group with preeclampsia. Tested differences between the analyzed groups in relation to the fetus (IUGR and SGA) show that pregnant women with preeclampsia often give birth with SGA, regardless of the severity of the disease, compared to normotensive pregnant women. Conclusion Comparison of changes in the profile of cytokines with increasing severity of preeclampsia may allow us to determine the level of compensation of pathological conditions that reflects the level of implementation and functional reserves of various mechanisms to maintain homeostasis. This happens in the background of increased concentrations of other proinflammatory cytokines and decreased levels of anti-inflammatory cytokines IL-4 and IL-10. 1. Multiple analysis of this study as independent significant factors for severe pre-eclampsia confirms: age ≥ 35 years, nulliparity and ethnicity, and as insignificant factors confirms smoking, Diabetes gestationes and preeclampsia in prior preegnancy. 2. In pregnant women with mild preeclampsia there is increase of IL 1β, IL 2, IL 4, IL 8, IL 10, TNF and IL 6 (statistically significant) compared with normotensive pregnant woman. 3. In pregnant women with severe preeclampsia significantly reduces the levels of IL 4 and IL 10, and increasing the levels of IL 2, IL 6, IL 8, IL 1β, and does not change significantly the level of TNF compared with normotensive pregnancies. 4. Preeclampsia has a significant impact on the way of delivery and newborns weight. In pregnant women with preeclampsia and low levels of factors of inflammation significantly higher percentage of deliveries were by Caesarean section, a significantly smaller percentage of vaginaldelivery.Preterm births insignificantly is in higher percentage in pregnant women with preeclampsia compared to control group. 5. The best statistical model for predicting the severity of preeclampsia is the correlation of the levels of serum interleukin (IL-4 and IL-10) with indicators of pre-eclampsia: LDH, creatinine, uric acid, and platelet count. However, the study is only the beginning of this type of research in our population. Further research is needed in terms of evaluating the costs and benefits of using such a test in order to prevent subsequent unnecessary interventions in groups with low risk, and realizing the benefits of such interventions in high-risk groups, the patient is given