Successful pregnancies in a patient with Takayasu arteritis and antiphospholipid syndrome, maintained on infliximab corticosteroid-free regimen: case-based review.

Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen.

Clinical and ultrasonographic parameters in assessment of labor induction success in nulliparous women.

Purpose: Evaluation of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.Methods: Prospective cohort study included 146 nulliparous women with singleton pregnancy and indications for labor induction. Prior to labor induction, cervicometry and Bishop score were determined. Upon delivery, patients were classified as those delivered vaginally and by cesarean section (CS) after unsuccessful labor induction.Results: Bishop score >5 was found in 47.95% of vaginally delivered women and 12.33% of patients delivered by CS (p < .01). Cervicometry had appropriate findings in 34.2% of vaginally delivered women and 75.3% of those delivered by CS (p < .01). Bishop score (>5 versus ≤5) had lower sensitivity (52.05%) and specificity (12.33%) than cervicometry (good versus unfavorable findings) (sensitivity 65.75%, specificity 75.34%) for prediction of labor induction success. If Bishop score was ≤5, cervicometry had 50.0% sensitivity and 78.13% specificity, while if Bishop score was >5, 82.86% sensitivity and 55.56% specificity. Obtained model for predicting labor induction outcome in nulliparous women based on their clinical and ultrasonographical characteristics identified the Bishop score as the most important predictor.Conclusions: Study confirmed the usefulness of simplified Bishop score and ultrasound cervicometry in the assessment of labor induction success in nulliparous women.

Biochemical Markers for Prediction of Hypertensive Disorders of Pregnancy.

BACKGROUND: Gestational hypertension (GH) and pre eclampsia (PE) are the most common gestational complications. Several placental biochemical markers are used to predict GH/PE, but with conflicting results. METHODS: The study aim was to estimate the biochemical markers' ability to predict hypertensive disorders in pregnancy. On the first ultrasonographic examination, 104 healthy pregnant women were recruited. At the regular pregnancy check-ups, BMI, blood pressure, occurrence of gestational hypertension (early or late onset), preeclampsia, eclampsia and other complications were recorded. Serum concentrations (in multiples of median - MoM) of human chorionic gonadotropin (HCG) and pregnancyassociated plasma protein A (PAPPA) were measured from the 11th to 14th gestational week, while HCG, alpha feto protein (AFP), estriol and inhibin were determined between the 16th and 19th gestational week. RESULTS: Hypertensive disorders throughout pregnancy were diagnosed in 20.2% women. Early-onset GH was registered in 7 and PE in 6 patients, while 14 had late-onset GH and 10 additional women PE. There were no significant differences (p≥0.05) in biochemical markers concentrations between women with and without GH/PE. PAPPA levels in the first and HCG in the second trimester correlated with early and late GH/PE. Moreover, higher AFP concentrations were registered in women with preeclampsia signs/symptoms. According to ROC analysis, AFP>1.05 MoM properly identified 80% of GH/PE cases. Obtained models imply that HCG, PAPPA and AFP should be used for GH/PE prediction. CONCLUSIONS: Biochemical markers HCG, PAPPA and AFP could be useful in predicting gestational hypertension and preeclampsia. However, different markers should be used for early and late onset GH/PE.

Maternal glycoregulation in pregnancies complicated by diabetes mellitus in the prediction of fetal echography findings and perinatal outcomes.

AIM: We aimed to determine maternal hemoglobin A1c (HbA1c) levels and pregestational body mass index (BMI) as the predictors of glycemic control and its importance for fetal echography findings and perinatal outcomes in pregnancies complicated by diabetes mellitus (DM). METHODS: Our intention was to evaluate how BMI and HbA1c levels might be used to predict fetal interventricular septum (IVS) thickness, atrioventricular inflow early diastole (E)/ atrial systole (A) velocity ratio, and perinatal outcomes. Patients in the 38th gestational week were divided into three groups according to their insulin therapy: (i) patients with gestational diabetes mellitus (GDM) treated only with dietary changes (GDM group, n = 32); (ii) patients with GDM treated with insulin therapy (DM2 group, n = 27); and (iii) patients with type 1 DM (DM1 group, n = 22). RESULTS: In the DM1 group, we found statistically significant correlations between BMI and IVS thickness (P = 0.036), HbA1c and IVS thickness, as well as the mitral E/A velocity ratio (P = 0.013 vs P = 0.007). In this group, HbA1c showed a statistically significant correlation to neonatal birth weight (P = 0.037) and BMI influenced on appearance respiratory distress syndrome in neonates in DM1 group (P = 0.027). The values of HbA1c predict neonatal respiratory distress syndrome in DM2 and GDM groups (P = 0.036). CONCLUSION: As good predictors of maternal glycoregulation, BMI and HbA1c levels determine fetal echography findings as well as neonatal outcomes in pregnancies complicated by DM.

Correlation between maternal anxiety, reactivity of fetal cerebral circulation to auditory stimulation, and birth outcome in normotensive and gestational hypertensive women.

This study investigated the correlation between maternal anxiety and blood flow changes through the fetal middle cerebral artery (MCA) after defined acoustic stimulation in 43 normotensive (C) and 40 gestational hypertensive (GH) subjects. Neonatal outcomes (gestational age at birth, Apgar score, birth weight) in the C and GH groups were analyzed. State (STAI-S) and trait (STAI-T) anxiety was assessed using Spielberger's questionnaire. The MCA blood flow was assessed once between 28 and 41 weeks of gestation using color Doppler ultrasound before and after application of defined acoustic stimulus. Relative size of the Pulsatility index (Pi) change (RePi) was calculated. The general hypotheses were: (1) women in GH group would have higher anxiety; (2) higher anxiety correlates with higher RePi change and poorer neonatal outcome; (3) fetuses from the GH group would have poorer neonatal outcome. Subjects from the GH group had higher STAI-T and RePi compared to the C group. A positive correlation between RePi and STAI-S, STAI-T, and systolic/diastolic blood pressure was found in both groups. There were more preterm deliveries in the GH group compared to the C group. A significant effect of STAI-T on body weight was observed in the C and GH group. There was a predictive effect of STAI-T and RePi on the C group, and STAI-S, STAI-T, diastolic blood pressure, and RePi on the GH group in terms of neonatal body weight. This study demonstrates an association between antenatal anxiety in GH women and increased fetal cerebral circulation in response to defined auditory stimulation.

First trimester ultrasonographic parameters in prediction of the course and outcome of monochorionic twin pregnancies.

BACKGROUND/AIM: The aim of the study was to evaluate the association and the potential predictive value of first trimester ultrasonographic parameters on the course and outcome of monochorionic diamniotic twin pregnancies. MATERIALS AND METHODS: A prospective cohort study was undertaken of 39 healthy women with consecutive monochorionic diamniotic twin pregnancies. During first-trimester screening, crown-rump length (CRL) and nuchal translucency (NT) were measured. The intertwin discordance in CRL and NT was determined. As pregnancy outcomes we assessed twins' live-born rates, Apgar scores, birth weight, pregnancy complications, and gestational week of delivery. RESULTS: None of the assessed pregnancy outcomes significantly correlated with standard CRL discordance ≥10%. The newly established cut-off was 3.75 mm for CRL and 1.3 mm for NT. Monochorionic diamniotic twins were delivered in a later gestational week and had better chance of survival if CRL intertwin difference was <3.75 mm. Apgar scores significantly negatively correlated only with NT of corresponding twins. When intertwin NT difference was ≥1.3 mm, twins had lower birth weight and pregnancy complications were more frequent. Regression models show that intertwin CRL difference <3.75 mm is a significant predictor of live-born monochorionic diamniotic twins. CONCLUSION: CRL and NT in monochorionic diamniotic twin pregnancies could indicate pregnancy complications and outcomes.

Follow-Up Imaging of Inflammatory Myofibroblastic Tumor of the Uterus and Its Spontaneous Regression.

Inflammatory myofibroblastic tumor (IMT) is an aggressive benign mass that may arise from various tissues and organs with a great variability of histological and clinical appearances. Due to variable and nonspecific imaging findings, diagnosis of IMT is not obtained before surgery. The aim of this paper is to present CT and MRI findings during four-year follow-up of complete, spontaneous regression of IMT of the uterus. The diagnosis was made by histology and immunohistochemistry analysis of the open excisional biopsy specimen. At that time, the organ of origin was not specified. After analysis of the follow-up imaging findings and the mode of tumor regression, the uterus was proclaimed as the probable site of origin. IMT of the uterus is extremely rare and has been reported in ten cases up to now. The gradual, complete regression of uterine IMT documented by CT and MRI may contribute to understanding of its nature.

Direct intramuscular fetal or maternal antenatal corticosteroid therapy: short-time effects on fetal behavior and oxygenation: a comparative study.

OBJECTIVE: To compare the effects of antenatal administration of corticosteroids used in two different regimens, on fetal biophysical profile (BPP), baseline fetal heart rate (BFHR), nonstress test (NST) and perinatal outcomes. STUDY DESIGN: We evaluated the effects of single direct intramuscular (i.m.) fetal dose of dexamethasone (4 mg/kg), or four doses of 6 mg dexamethasone given to the mother 12 hours apart on the parameters of fetal BPP 0-4 hours before and after antenatal contraction stress (ACST). We evaluated two groups of 41 fetuses in the 31st gestation week at risk of fetal hypoxia at the Department of Gynecology/Obstetrics, Clinical Center of Serbia in 2013. RESULTS: In fetal ACST group, we found significantly different changes in fetal breathing movement before (D0-f) and after therapy (D1-f), p = 0.019 (-11.75; -1.12), 95% confidence interval (CI), as well as in the maternal ACST group, p = 0.001; (-11.75; -1.12), 95% CI. We found significant difference between BPP 0-m and BPP1-m in the maternal group, p = 0.000. Neonatal asphyxia occurred more often with the increased frequency of fetal breath movements after both ACST (p = 0.04 versus p = 0.07). CONCLUSION: Fetal ACST results in increased fetal breathing movements. Maternal ACST can result in changes to BPP. The increase in fetal breathing movements determinates neonatal asphyxia regardless of the ACST.

Vaginal delivery or cesarean section at term breech delivery--chance or risk?

AIM: The aim of the study was to examine maternal age, parity, and estimated neonatal birth weight (BW) depending on the mode of a full-term breech presentation (BP) birth delivery and neonatal outcomes. MATERIAL AND METHODS: One hundred and forty-six singleton term breech presentation pregnancies were included in a retrospective study conducted at the Department of Gynecology/Obstetrics, Clinical Center of Serbia in Belgrade in 2013. Statistical analysis: Student's-t test, χ(2) likelihood ratio, and the Fisher's exact test. The level of statistical significance was set at p <0.05. RESULTS: An ECS was the most common mode of delivery in (81.2%) nulliparous older than 35 years and most of the neonates (66.67%) with an estimated birth weight (BW) above 3500 grams were delivered by elective cesarean section (ECS). Perinatal asphyxia remained increased in the successful vaginal delivery (SVD) group (23.8%) compared with the urgent CS (UCS) group (13.3%) (p = 0.035). Birth asphyxia was the most common in neonates were delivered by SVD (23.8%). There were no cases of perinatal deaths. CONCLUSION: ECS remained the recommended mode of breech term delivery in nulliparous women older than 35 years, as well as in neonates with an estimated BW above 3500 grams.

Fetus sound stimulation: cilia memristor effect of signal transduction.

BACKGROUND: This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. METHODS: PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. RESULTS: Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the "memristor" property. CONCLUSION: Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

Nutrition in pregnancy: basic principles and recommendations.

Healthy diet in pregnancy should guarantee proper fetal growth and development, maintain (and promote) maternal health and enable lactation. Nutritional counseling and interventions need to be an integral part of antenatal care and continue during pregnancy in order to reduce the risk of maternal, fetal and neonatal complications, as well as the short- and long-term adverse outcomes. Adverse pregnancy outcomes are more common in women who begin the gestation as undernourished or obese in comparison to pregnant women whose weight is within normal ranges. Increased nutritional and energy needs in pregnancy are met through numerous metabolic adaptations; pregnancy is successfully achieved within wide range of variations in energy supply and weight gain. However, if nutrient restriction exceeds the limits of adaptive responses, evidence indicates that fetus will develop the alternative metabolic competence that might emerge as a disease (type 2 diabetes, hypertension, coronary heart disease and stroke) in adult life.

Change of pulsatility index of the fetal middle cerebral artery after auditory stimulation in no risk pregnancies and in pregnancies with gestational hypertension.

PURPOSE: An aim was to determine the degree and the mode of variation of PI of middle cerebral artery in no risk pregnancies and in pregnancies with gestational hypertension, after the constant sound stimuli. METHOD: Study included 343 patients divided in two groups. Group 1: low risk pregnancies and group 2: gestational hypertension. Ultrasound prenatal auditory screening was performed after the 27th week of gestation. RESULTS: The percentage of fetuses with increase of cerebral blood flow was slightly higher in the pregnancies with hypertension. CONCLUSION: An average change of PI of median cerebral artery was higher in this group.

Correlation of biochemical parameters and neonatal outcome in patients with gestational hypertension.

Hypertensive disorders in pregnancy are one of the leading causes of maternal death in the world and one of the major causes of perinatal mortality. The incidence of hypertensive disorders in pregnancy is 8%-15%. Significant changes of biochemical parameters in cases of hypertensive disorders in pregnancy are increased levels of blood glucose, urea, creatinine, uric acid (hyperuricemia), transaminases, and LDH. The most increased is the level of proteinuria. Bad laboratory results and the intensification of clinical signs, with multiorgan dysfunction, are indications for termination of pregnancy.

Normal vaginal flora, disorders and application of probiotics in pregnancy.

PURPOSE: To assess the effectiveness of vaginal administration of the probiotic Lactobacillus rhamnosus BMX 54 in preventing the occurrence of abnormal vaginal flora and the alteration of parameters relevant to the progression of pregnancy. METHODS: Sixty pregnant women were assigned randomly to the untreated arm of the study (n = 30) or received (n = 30) vaginal application of one tablet containing Lactobacillus rhamnosus BMX 54, once a week for 12 weeks. Every 4 weeks (T0-T3), vaginal and cervical swabs were collected and pH, and quantity and quality of vaginal discharge measured as well as consistency, length and dilatation of cervix, and level of the presenting part of the foetus relative to interspinous diameter. RESULTS: In untreated women, there was a significant trend towards increase in the presence of pathogenic microorganisms in the vaginal and/or cervical swabs (p < 0.05), and in average pH values (p < 0.05), amount (p < 0.05) and "whiff test" positivity (p < 0.05) of vaginal discharge. Significant trend was also found for decrease in length (p < 0.0001) and increase in dilatation (p < 0.05) of cervix, as well as for lower position of the foetus (p < 0.0001). In the group treated with Lactobacillus rhamnosus BMX 54, none of these values significantly changed throughout the observation period, with the exception of cervical length that was significantly decreased at T3 (p < 0.01). CONCLUSIONS: During pregnancy, vaginal administration of Lactobacillus rhamnosus BMX 54 is effective in preventing the development of abnormal vaginal microflora, lowering of the presenting part of the foetus and modifying cervical parameters that could represent risk factors of vulnerability to preterm delivery.

[The influence of direct intramuscular corticosteroid therapy on parameters of venous circulation in hypoxaemic foetuses].

INTRODUCTION: The influence of glucocorticosteroid therapy on foetal lung maturation is evident but little is known about its effects on parameters of foetal venous circulation. OBJECTIVE: The aim of the study was to assess the influence of direct intramuscular (i.m.) foetal corticosteroid therapy (CST) on parameters of foetal venous circulation which indicates a degree of foetal hypoxia. METHOD: The prospective study was conducted at the Institute of Gynaecology and Obstetrics during 2001. We evaluated the influence of direct i.m. foetal single dose dexamethasone (2 mg/ kg estimated foetal weight by sonographic examination) on foetal ductus venosus (DV) and vena cava inferior (VCI) velocities in 49 foetuses 24 hours before and after therapy. RESULTS: There is positive correlation with the statistical significance in systolic/diastolic ratio (S/D) in DV before and after the corticotherapy r = 0.366; p = 0.018. Reverse flow during contraction of the right atrium in DV was found in 55.6% of foetuses after CST. Reverse flow during the contraction of the right atrium in VCI was found in 3 foetuses before CST and in 4 foetuses after CST. We found positive correlation without statistical significance between the vena cava pre-load indices before and after CST (r = 0.127; p = 0.428). There is positive correlation with the statistical significance between systolic flow in VCI before and after CST (r = 0.478; p = 0.002). CONCLUSION: Corticosteroid therapy influences parameters of foetal venous circulation. Its influence depends on duration of foetal hypoxia. The parameters of foetal venous circulation can be a predictor of the perinatal outcome.

Value of fetal echocardiography in diagnosis of congenital heart disease in a Serbian university hospital.

OBJECTIVE: Ultrasound examination for each and every pregnancy is being accepted as a standard practice worldwide, and prenatal ultrasound diagnosis of congenital heart disease (CHD) is improving due to both staff education and ultrasound equipment modernization. The objective of this study was to estimate the value and accuracy of fetal echocardiography for diagnosis of fetal CHD in a large tertiary referral center for obstetrics and gynecology. METHODS: This study was based on a prospective follow-up of 27,051 consecutive patients at the Institute of Ob/Gyn, Belgrade, during 1999-2003. Out of this population a total of 517 (1.9%) patients were selected for fetal echocardiography. The final diagnosis of congenital heart disease was confirmed or rejected on the basis of autopsy and histopathological findings, for the dead fetuses and newborns, or on the basis of neonatal echocardiography (followed by surgery/invasive diagnostic procedure), for the living neonates. RESULTS: From the total population analyzed, there was 71 gravida (0.26%) with congenital fetal heart disease. In that study group, the most frequent cardiac anomalies were complex congenital heart diseases. Analyzing the outcome, there were 67.6% cases with fetal CHD who delivered live neonates. Out of the 73 fetuses/neonates with CHD, abnormal karyotype was detected in only 9 cases. The parameters of the diagnostic value of fetal echocardiography were as follows: sensitivity 94.4%, specificity 99.8%, positive predictive value 98.5%, negative predictive value 99.1%, and overall diagnostic accuracy 99.0%. CONCLUSION: Fetal echocardiography has a very high diagnostic accuracy, commending referral of suspected patients to large tertiary referral centers.

Anticoagulation therapy during pregnancy of patients with artificial heart valves: fetomaternal outcome.

OBJECTIVES: The major problem is the need for anticoagulant therapy in patient with mechanical heart valves. STUDY DESIGN: The aim of the study was to analyze the course and outcome of pregnancies of patients with artificial mechanical heart valves with anticoagulant therapy. Study included 43 pregnancies leaded and terminated at the Institute of Gynecology and Obstetrics Clinical Center of Serbia in 20 years. We divided the patients in two groups depending on the type of anticoagulation therapy. Group I included 21 patients who were under Ethylbiscumacetate (Pelenthan) during the first 36 weeks of gestation, and intravenous Heparin in the last 4 weeks and after the delivery. Group II included 22 patients who received oral anticoagulant therapy all the time. RESULTS: Worsening of the heart functional status happened in 6 patients (13.9%). The incidence of heart failure during the pregnancy was 13.9% and after the delivery 9.3%. The incidence of hemorrhagic complications was 11.6% during pregnancy and 14% after the delivery. Four patients had thromboembolic events before the pregnancy. The incidence of postpartal thromboembolic complications was 6.9% in group I. Two patients died due to the heart failure 3-7 days after the vaginal delivery. Maternal mortality was 4.6%. One neonatus died of hydrocephalus (2.5%) in group II. In our study there were no fetuses with congenital heart disease. CONCLUSIONS: Pregnancies of patients with mechanical heart valves should be planned. We suggest ethylbiscumacetate in combination with Heparin as anticoagulation therapy during the pregnancy.