Screening performances of abnormal first-trimester ductus venosus blood flow and increased nuchal translucency thickness in detection of major heart defects.

OBJECTIVE: The aim of this study was to evaluate the screening performances of abnormal ductus venosus (DV) blood flow for the detection of heart defects in chromosomally normal fetuses with increased nuchal translucency (NT) thickness at 11-13 + 6 weeks' gestational in a population of singleton pregnancies. METHODS: During an 8-year period, all singleton pregnancies from 11 + 0 to 13 + 6 weeks were scanned for NT and DV blood flow assessment. Two groups of cases with abnormal NT were evaluated: NT ≥ 95th and NT ≥ 99th centile. DV waveforms were considered to be abnormal if the a-wave was reversed or absent (R/A). RESULTS: Addition of DV R/A a-wave to either NT ≥ 95th or NT ≥ 99th percentile increased specificity (p < 0.001 and p < 0.001, respectively), but not screening performances in detection of major heart defects (p = 0.73 and p = 0.91, respectively). Combination of DV R/A a-wave with NT ≥ 95th or NT ≥ 99th centile correlated with right heart defects (p = 0.024 and p = 0.013, respectively). CONCLUSIONS: In chromosomally normal fetuses, addition of abnormal DV a-wave to increased NT does not improve screening performances of NT in detection of major hearts defects in first trimester. However, there is correlation of such parameter with right heart defects and AV septal defects.

Improved diagnostic accuracy by using secondary ultrasound markers in the first-trimester screening for trisomies 21, 18 and 13 and Turner syndrome.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: The addition of secondary ultrasound markers (NB, DV and TR) to combined first-trimester screening showed a tendency toward improved accuracy of the screening.

Use of FMF algorithm for prediction of preeclampsia in high risk pregnancies: a single center longitudinal study.

OBJECTIVE: This study aimed to assess the accuracy of The Fetal Medicine Foundation (FMF) screening algorithm for the prediction of preeclampsia.METHODS: Out of 138 women with high-risk pregnancies prospectively followed, 30 developed preeclampsia. The clinical examination and biochemical measurements were performed at first, second, early and late third trimester.RESULTS: A lower PAPP-A levels were found in the first trimester, while sFlt/PlGF was increased in the second and early third trimester in preeclampsia (p>0.05). FMF algorithm presented higher specificity (>70%), but had a drawback of lower sensitivity (35-77%).CONCLUSION: FMF algorithm had modest performance in the prediction of preeclampsia for high-risk pregnancies.

Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in Serbian population.

BACKGROUND: Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. METHODS: The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. RESULTS: Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). CONCLUSIONS: This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.

Placenta-specific plasma miR518b is a potential biomarker for preeclampsia.

INTRODUCTION: MicroRNAs have a significant role in the pathogenesis of preeclampsia. Circulating microRNAs could represent a potential biomarker for preeclampsia. The aim of this study was to evaluate plasma miR210-3p and miR518b in preeclampsia and healthy pregnancy for the first time by digital droplet PCR (ddPCR). METHODS: Thirty-six pregnant women (seventeen healthy pregnancies, nineteen preeclampsia patients) were involved from the Clinic for Gynaecology and Obstetrics "Narodni front" in Belgrade, Serbia. Plasma miR210-3p, miR518b and cel-miR-39 as a spike-in control were measured by ddPCR. RESULTS: MiR518b was significantly elevated in preeclampsia compared to a healthy pregnancy (P = 0.034; 0.302(0.217-0.421) vs. 0.171(0.110-0.266)). MiR210-3p showed no significant difference between the two groups (P = 0.951). The adjustment of miR518b was made for a gestational age and smoking status and the difference between the preeclampsia and healthy pregnancy group was more significant (P = 0.026; 0.300(0.216-0.419) vs. 0.172(0.121-0.245)). Plasma miR-518b was significantly higher in the group of preeclampsia patients with proteinuria above the 75th percentile for the group (P = 0.033), in women who smoked (P = 0.039), and was positively related to uric acid in preeclampsia (P = 0.018, r = 0.536). Plasma miR518b was able to significantly discriminate between preeclampsia and healthy pregnancy, yielding AUC of 0.712 (95%CI:0.539-0.891), P = 0.028. CONCLUSIONS: In this study plasma microRNA were measured for the first time in preeclampsia and healthy pregnancies with ddPCR. Placenta-specific miR-518b could serve as a potential biomarker for discriminating preeclampsia and healthy pregnancy, which should be confirmed on a larger study population. This study has failed to confirm the same potential for miR210-3p.

Intrauterine treatment of large fetal neck lymphangioma with OK-432.

Lymphangiomas are benign vascular malformations of the lymphatic system and most commonly present in the neck area. Large lymphangiomas may compress and/or displace the larynx, trachea and esophagus and cause serious respiratory and feeding problems in neonates. Prenatal therapy could eliminate the risks of the mentioned complications. Prenatal therapy may include the EXIT (ex utero intrapartum treatment) procedure. As this procedure has certain risks for both the neonate and mother, the introduction of a safer method is justified. The use of OK-432, as a sclerosing agent, has shown positive results in several published cases of cystic hygroma, but there is no study about the prenatal use of this agent in the treatment of lymphangioma. The aim of this study was to present our experience with intrauterine intralesional injection of OK-432 in the treatment of neck lymphangiomas. Two cases of large multicystic neck lymphangiomas that were closely situated to the fetal airway were treated by single intralesional injection of OK-432. We noticed a progressive decrease in tumor volume throughout gestation. We did not experience any complications and there were no respiratory or feeding problems in the neonates. The esthetical appearance was satisfactory and both children were normal at the age of 2 years and 6 months, respectively. This report suggests that prenatal intralesional injection of OK-432 might be a safe and effective treatment in selected cases with large fetal neck lymphangiomas.

Screening performance of congenital heart defects in first trimester using simple cardiac scan, nuchal translucency, abnormal ductus venosus blood flow and tricuspid regurgitation.

OBJECTIVE: The objective of this study was to analyze if the addition of simple cardiac scan in cases with increased nuchal translucency (NT) and/or abnormal ductus venosus (DV) blood flow, and/or tricuspid regurgitation (TCR) can improve detection of congenital heart defects (CHD) in chromosomally normal fetuses without non-cardiac defects at 11-13 + 6 gestational weeks in a population of singleton pregnancies. METHODS: During the 10 years period, all singleton pregnancies at 11-13 + 6 weeks were routinely scanned for NT, DV blood flow and TCR assessment and, if a single of these parameters was abnormal, simple cardiac scan with 2D gray scale and color and/or directional power Doppler in 4-chamber (4-CV) and 3 vessel and trachea views (3VTV) was performed. RESULTS: The sensitivity and specificity of NT ≥ 95th + DV R/A a-wave + TCR in detecting CHD were 77% and 97%, respectively, and of simple cardiac scan, 67% and 98%, respectively. Area under the curve of receiver operating characteristic curve of NT ≥ 95th + DV R/A a-wave + TCR was 0.838, and of NT ≥ 95th + DV R/A a-wave + TCR + simple cardiac scan was 0.915. CONCLUSIONS: In chromosomally normal fetuses without non-cardiac anomalies, addition of simple cardiac scan to the combined first trimester screening parameters improves detection of major CHD during first trimester.

Increased oxidative stress and cytokinesis-block micronucleus cytome assay parameters in pregnant women with gestational diabetes mellitus and gestational arterial hypertension.

We investigated whether gestational diabetes mellitus (GDM) and gestational arterial hypertension (GH) are associated with increased oxidative stress and DNA damage. Study included 3 groups of pregnant women (GDM, GH and control). DNA damage biomarkers (micronuclei MNi, nucleoplasmic bridges NPBs and nuclear buds NBUDs) were assessed by cytokinesis-block micronucleus cytome assay. Oxidative stress levels were evaluated by analyzing malondialdehyde equivalents (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Genotoxic effect of methyldopa, drug used to treat GH, was evaluated in in vitro experiment. TBARS levels, MNi, NPBs and NBUDs frequencies were significantly increased in both GDM and GH group. Concentrations of 8-OHdG were significantly higher in GDM than in other groups. Since methyldopa did not affect MNi, NPBs and NBUDs frequencies, nor TBARS and 8-OHdG levels, we concluded that methyldopa has no genotoxic effect. Thus, even when hyperglycemia or hypertension are present only during pregnancy they induce oxidative stress, DNA damage and chromosomal aberrations.

Major risk factors of maternal adverse outcome in women with two or more previous cesarean sections.

Background/Aim: Maternal morbidity is defined as any condition that is attributed to or aggravated by pregnancy and childbirth that has a negative impact on the woman's wellbeing. In recent years, a growing trend of cesarean section rates can be seen throughout the world. The aim of this study was to assess factors that might have major impact on maternal adverse outcome in women with two or more previous cesarean sections. Methods: This retrospective study included women with single term pregnancy after two or more cesarean deliveries in a 10-year period (2004−2013) in the University Clinic "Narodni front" in Belgrade, Serbia. Medical records were reviewed for clinical data for maternal intraoperative and early postoperative complications regarding gestational age at delivery, the number of previous cesarean sections and mode of surgery (elective or emergency). Results: A total of 551 patients were included in the study. At 37 completed weeks delivered 14.1%, at 38 delivered 45.2% and at 39 completed weeks 40.7% patients. Women younger than 35 years more often delivered after 39 completed weeks compared with those over 35 years (69.2% vs 30.8%, p < 0.05). The overall rate of maternal complications in the study group was 16.5% with no statistical difference by gestational age at delivery. The overall rate of maternal adverse outcome was significantly less in the patients with three as compared with those with four or more cesareans (10.4% vs 66.7%, p < 0.05). There was a statistically significant difference between these groups of women regarding complications: scar dehiscence, the presence of adhesions, blood transfusion and admission in intensive care unit. Elective cesarean delivery was with less maternal complications compared with emergency cesarean deliveries (12.9% vs 27.3%, p < 0.05). Conclusion: Termination of pregnancy before completed 39 weeks does not decrease maternal morbidity. The major impact on maternal complications has the number of previous cesarean deliveries (≥ 3), as well as emergency cesarean section. Patients should be informed about potential risks for maternal health with increasing number of cesarean deliveries, especially after the first cesarean section when counseling in elective repeat cesarean vs trial of labor.

Degree and rate of growth discordance in dichorionic twins conceived by in vitro fertilization.

Objective. Our objective was to estimate degree and rate of discordant growth and its impact on perinatal outcome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF) compared to those conceived spontaneously. Study Design. Growth discordance was defined as 90th percentiles for the study population. Adverse perinatal outcome was defined as 5-minute Apgar score <7 and/or admission to neonatal intensive care unit. Results. In the total study population of dichorionic twins (176 conceived by IVF and 215 spontaneously), 30% discordant growth represented the 90th percentile. After adjusting for gestational age, discordant twins conceived by IVF or spontaneously were at higher risk for adverse perinatal outcome (hazard ratio 4.4; 95% CI 2.4-8.3, P < 0.0001; hazard ratio 2.5; 95% CI 1.5-4.4, P = 0.001, resp.). Similar rates of 5-minute Apgar score <7, admission to neonatal intensive care unit, and delivery <34 weeks were found between discordant twins conceived by IVF and those conceived spontaneously. Conclusion. Dichorionic twins conceived by IVF are at similar risk for the rate and degree of discordant growth and adverse perinatal outcome compared to dichorionic twins conceived spontaneously.

Screening for aneuploidies by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-13+6 gestational weeks.

INTRODUCTION: Aneuploidies are the major cause of perinatal death and early psychophysical disorders. OBJECTIVES: In this study, we analyzed detection and false-positive rates of screening for aneuploidies in the first trimester by the combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (beta-hCG), and pregnancy-associated plasma protein-A (PAPP-A) at 11-13+6 weeks of gestation, using the appropriate software developed by the Fetal Medicine Foundation. METHODS: Our screening study for aneuploidies analyzed 4172 singleton pregnancies from January 2006 to December 2010. The sensitivities and false-positive rates using the combined aneuploidies determination for the risk cut-off of 1:275 were evaluated. RESULTS: In the trisomy 21 pregnancies, the fetal NT was higher than 95th centile, in 72.8%, serum free b-hCG concentration it was above the 95th centile in 55% and serum PAPP-A was below the 5th centile in 47% of the cases. In the trisomy 18 and 13, the fetal NT was above 95th centile in 66.6% and 44.4% of the cases, respectively.The serum free b-hCG concentration was above the 95th centile in 0 and 10%, but serum PAPP-A was below 5th centile in 80.9% and 88.8% of pregnancies. In the trisomy 21 pregnancies the median free beta-hCG was 2.3 MoM and the median PAPP-A was 0.45 MoM. Chromosomal abnormalities were detected in 169 fetuses: trisomy 21 (97), Turner syndrome (19), trisomy 18 (28), trisomy 13 (11) and others (14). Detection rate of combined screening for aneuploides were 86.0% with false positive rate of 5.3% (mean age 33 +/- 4.9 years, > 35 years in 35% of pregnancies). CONCLUSION: Our study suggests that the strategy of first-trimester combined screening of biochemical values and ultrasonographic parameters at 12 gestational weeks identifies higher percentage of aneuploidies with a lower false-positive rate than a single parameter strategy.

[Prenatal diagnosis of meconium ileus and meconium peritonitis: indications for cystic fibrosis testing].

INTRODUCTION: 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%. OUTLINE OF CASES: 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. CONCLUSION: 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.

[Multifoetal pregnancies complicated by reversed arterial perfusion: report of four cases].

INTRODUCTION: 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. OUTLINE OF CASES: 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. CONCLUSION: 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.

Developmental delay associated with normal thyroidal function and long-term amiodarone therapy during fetal and neonatal life.

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.

[Birth weight discordance and perinatal mortality among triplets].

INTRODUCTION: The incidence of multiple births has increased in the last decade. Perinatal mortality in triplets is significantly greater than in twin and singleton births. OBJECTIVE: The objective of this study was to describe the extent of birth weight discordance among triplets and to identify its association with an increased risk of perinatal mortality. METHOD: A retrospective analysis of triplet births, for the period 1993-2003, was conducted at the Gynaecological-Obstetric Clinic "Narodni Front" in Belgrade. Birth weight discordance was defined as the difference in birth weight between the largest and the smallest triplet's weight of more than 20%. RESULTS: The rate of triplets has increased by almost 75% between the first (7.7%) and the last (29.6%) 5-year period of the last decade. Triplets are becoming more common because of the frequent use of assisted reproductive technology as a treatment for infertility. In the period 1993-2003, there were a tota of 40 triplet live births (24 weeks and greater) with incidence of 0.06%. There was no clear association between maternal age, parity, method of conception, birth gestational age, and disorders complicating pregnancy with birth discordance more than 20%. Regarding birth weight groups, statistical significance occurred only in the < 999 grams group for discordant and in the 2000-2499 grams group for concordant triplets. Overall, the perinatal mortality rate in the group was 10.8%, the foetal mortality rate was 1.7% (2/120), and the neonatal (0-28 days) mortality rate was 9.1% (11/120). An odds ratio of 95% confidence interval shows 3 times greater risk for adverse perinatal outcome in the discordant group. However, the difference was not significant. CONCLUSION: Increasing birth weight discordance may increase the risk of adverse perinatal outcome. Triplet pregnancies, being high risk, require intensive antenatal care in order to prevent preterm delivery and ultrasound in order to diagnose foetal growth abnormality and discordance, which increase foetal surveillance, through the use of biophysical profiles, non stress tests, and Doppler velocimetry, thus assessing foetal well being and the appropriate moment for obstetric intervention.

[Longitudinal analysis of arterial Doppler parameters in growth retarded fetuses]. / Longitudinalna analiza arterijskih dopler parametara kod zastoja u rastu ploda.

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery, and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum, MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV), absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n = 26), 2) chronic renal disease (n = 3), 3) primary antiphospholipid syndrome (n = 2), 4) diabetes mellitus (n = 1), 5) cardiac disease (n = 1) and 6) unknown (n = 2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 +/- 2.5); delivery was between 29. to 34. wg (32.2 +/- 1.9); and average body weight was 1327 +/- 245 g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6%, while perinatal mortality was 14.3%. We found high significant difference (P < 0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA--tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn't register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV. Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ischemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ischemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.

[Twin transfusion syndrome--diagnosis and prognosis]. / Transfuzijski sindrom blizanaca--diagnoza i prognoza.

Twin-twin transfusion syndrome is a serious complication of monozygotic, monochorionic, diamniotic twins resulting from transplacental vascular communications. In this syndrome blood is thought to be shunted from one twin--donor, who develops anaemia, growth retardation and oligoamnios, to the other twin--recipient, who becomes plethoric, macrosomic and develops polyhydroamnios. The incidence of twin-twin transfusion syndrome ranges from 5-15% of all twin pregnancies. If this condition develops in the second trimester, it is usually associated with spontaneous abortion and death of one or both fetuses before viability. Developing the syndrome in the third trimester has better perinatal outcome. Mortality rates ranging from 56%-100%, depending on gestational age and severity of the syndrome. The ultrasound criterias for diagnosis, in this study, were the presence of twins of the same sex with discordant growth, with oligohydroamnios in one twin sac and polyhydroamnios in the other one, one placenta and thin membrane between twins. The present study shows clinical course of 14 cases and value of Doppler ultrasound to analyze the usefulness of umbilical artery blood flow velocimetry for predicting the risk of twin-twin transfusion syndrome. 14 twin pregnancies with twin-twin transfusion syndrome were diagnosed during the last four years period and prospectively followed. 9 cases were diagnosed before the completion od 28 weeks of gestation. The mean gestational age was 21.6 _+ 4.2 weeks at diagnosis and 23.2 +_ 3.6 weeks at delivery. 5 cases were diagnosed after 28 weeks of gestation. The mean gestational age in this group was 29.6 +_ 2.1 weeks at diagnosis and 33 +_ 3.3 weeks at delivery. The survival rate in this study was 29% (8/28). 9 cases ended in spontaneous abortion between 18th and 27th weeks of pregnancy (table 1) and 5 in premature labor (table 2). There were 7 intrauterine death (5 at admission and 2 few days after admission) and 13 neonatal deaths. Overall mortality rate was 71% (20/28). Up to 28th weeks mortality rate was 100% and after 28th weeks mortality rate was 20% (2/10). 9 cases had "stuck" twin phenomenon. The differences in the Doppler indexes from twin-twin transfusion syndrome cases significantly exceeded those without this syndrome. This difference seemed to predict the risk of twin-twin transfusion syndrome, but the number of cases is too small for general conclusions. Treatment regimens for twin-twin transfusion syndrome have included bed rest, tocolytic agents and serial amniocenthesis for decompression in some cases. Neither serial amniocenthesis nor tocolytic agents use were associated with an improved survival rate in our study. Twin-twin transfusion syndrome can be diagnosed early in second trimester of pregnancy, but the survival rate remains low with the current methods of treatment. Survival was related to gestational age at delivery and birth weight. Twin-twin transfusion syndrome diagnosed before 28th weeks of gestation represents one of the most lethal conditions in perinatal medicine today.