Gestational Diabetes and Risk Assessment of Adverse Perinatal Outcomes and Newborns Early Motoric Development.

Background and Objectives: The aim of this study was to analyze the presence of gestational diabetes mellitus (GDM) on maternal and fetal perinatal parameters, as well to evaluate the influence of GDM on neonatal early motoric development. Materials and Methods: In this prospective study, we evaluated 203 eligible participants that were admitted to obstetrics department for a labor. GDM was assessed by evaluation of maternal parameters, fetal parameters, as well its impact on infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Presence of GDM was significantly positively associated with: pre-pregnancy weight, obesity degree, weight at delivery, gestational weight gain (GWG), body mass index (BMI) at delivery, GWG and increased pre-pregnancy BMI, glucose levels in mother's venous blood after the delivery, positive family history for cardiovascular disease, pregnancy-related hypertension, congenital thrombophilia, drug use in pregnancy, large for gestational age (LGA), mode of delivery (Cesarean section and instrumental delivery). Likewise, GDM association was detected for tested ultrasound parameters (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femoral length (FL)), length at birth, birth weight, newborn's head circumference, newborn's chest circumference, AIMS supination and pronation at three months, AIMS supination, pronation, sitting and standing at six months. Only Amniotic Fluid Index and AIMS supination at three months of infant's age remained significantly associated in multivariate regression model. Conclusions: The presence of significant positive association of numerous tested parameters in our study on perinatal outcomes and early motoric development, points to the necessity of establishing appropriate clinical decision-making strategies for all pregnant woman at risk and emphasize the importance of providing adequate glycaemia control options and further regular follow ups during the pregnancy.

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.

Can Thyroid Screening in the First Trimester Improve the Prediction of Gestational Diabetes Mellitus?

This study aimed to evaluate the clinical utility of the subclinical hypothyroidism (SCH) marker, elevated thyroid-stimulating hormone (TSH) and thyroid antibodies in their ability to predict subsequent gestational diabetes mellitus (GDM). In a prospective clinical trial, 230 pregnant women were screened for thyroid function during the first trimester of pregnancy. Increased TSH levels with normal free thyroxine (fT4) were considered SCH. The titers of thyroid peroxidase antibody (anti TPO Ab) at >35 IU/mL and thyroglobulin antibody (anti Tg Ab) at >115 IU/mL were considered as antibodies present. According to the OGTT results, the number of pregnant women with GDM showed the expected growth trend, which was 19%. Two groups of pregnant women were compared, one with GDM and the other without. Increased TSH levels and the presence of thyroid antibodies showed a positive correlation with the risk of GDM. TSH levels were significantly higher in pregnant women with GDM, p = 0.027. In this study, 25.6% of pregnant women met the diagnostic criteria for autoimmune thyroiditis. Hashimoto's thyroiditis was significantly more common in GDM patients, p < 0.001. Through multivariate logistic regression, it was demonstrated that patient age, TSH 4 IU/mL, and anti TPO Ab > 35 IU/mL are significant predictors of gestational diabetes mellitus that may improve first-trimester pregnancy screening performance, AUC: 0.711; 95% CI: 0.629−0.793.

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.

The Influence of Increased Prepregnancy Body Mass Index and Excessive Gestational Weight Gain on Pregnancy Course and Fetal and Maternal Perinatal Outcomes.

Background: The aim of our study was to assess the influence of prepregnancy Body Mass Index (BMI) changes as well as excessive gestational weight gain (GWG) on maternal and fetal perinatal parameters. Furthermore, we aimed to analyze the influence of increased prepregnancy BMI values and excessive GWG on neonatal early motoric development. Methods: The 203 eligible female participants were evaluated. Prepregnancy Body Mass Index (BMI) and excessive gestational weight gain (GWG) defined according to Institute of Medicine 2009 guidelines in the USA were assessed with tested maternal and fetal perinatal parameters and infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Significant predictors of increased prepregnancy BMI in perinatal period include: weight at delivery (p = 0.001), GWG (p = 0.002) and BMI at delivery (p < 0.001), while significant predictors of excessive GWG in perinatal period are: prepregnancy BMI (p = 0.029) and BMI at delivery (p < 0.001). In the group of participants with both increased prepregnancy BMI and excessive GWG versus others, significant predictors were: hypertension (HTA) (p = 0.019), amniotic fluid index (AFI) (p = 0.047), Pronation (AIMS) (p = 0.028) and Supination (AIMS) (p = 0.029). Conclusion: Increased prepregnancy BMI and excessive GWG are significantly associated with numerous perinatal factors that could alter the pregnancy course, pregnancy outcome and early motoric development of newborn. Moreover, increased prepregnancy BMI is shown to be a significant predictor of excessive GWG; thus, early selection of pregnant women for close monitoring of weight gain during pregnancy will have positive effects on reducing the risk of less favorable pregnancy course and early motoric development of newborn.

Reliability, Consistency and Temporal Stability of Alberta Infant Motor Scale in Serbian Infants.

Our study aimed to analyze the reliability, consistency, and temporal stability of the Alberta Infant Motor Scale (AIMS) in Serbian infants. Additionally, we aimed to present a percentile distribution of AIMS in the tested population. The prospective study included 60 infants that were divided into three age groups: 0-3 months, 4-7 months, and 8-14 months. The Serbian version of AIMS was tested by two raters on two different occasions (test/retest) with a five day period between tests. The observed inter-rater reliability (intraclass correlation coefficient (ICC)) was more than 0.75 for all AIMS scores, except for standing (ICC 0.655 = moderate) in the age group of 4-7 months on retest between raters. The observed intra-rater reliability (ICC) was more than 0.75 for all AIMS scores except standing (ICC 0.655 = moderate) in the age group 4-7 months in test-retest for Rater One, and for sitting (ICC 0.671 = moderate) and standing (ICC 0.725 = moderate) in the age group between 0-3 months on test-retest for Rater Two. The Serbian version of AIMS was shown to have high consistency and high reliability with good to high temporal stability. Thus, it can be used in the evaluation of infants' motor development in Serbia.

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.

The value of sentinel lymphadenectomy in radical operative treatment of cervical cancer.

BACKGROUND/AIM: Therapy of the early stages of cervical carcinoma is surgical or radiation therapy, and for advanced stages chemoradiotherapy. Pelvic and paraaortic lymphadenectomy in early stages offers the most important prognostic factor for survival. To evaluate the method and possible influence on surgical and therapy of the disease, we performed sentinel node (SN) identification and excision during open radical hysterectomy and lymphadenectomy in stage Ib-IIa cervical carcinoma. METHODS: Fifty patients initially diagnosed with invasive squamous-cell cervical cancer stage Ib-IIa were included in the study. Only blue dye was used for sentinel node mapping. During the surgery sentinel nodes were identified and sent to histopathology separately from the other lymph nodes. After lymphadenectomy, radical hysterectomy was performed. RESULTS: The mean age of our fifty patients was 49.10 years (SD = 5.92), and the mean number of extracted lymph nodes per patient was 25.78 (SD = 5.58). The number of sentinel nodes identified per patient was between 0 and 5, mean 2.60 (SD = 1.54). There were no inframesenteric paraaortic sentinel nodes found among the patients. The dominant tumor grades were 1 and 2, 40% and 50% respectively, and 37 out of 50 patients (74%) had tumor diameter less than 2 cm. In four patients (8%) SN were not identified. In the rest of 46 patients the presence of SN was bilateral (19 patients, 38%) or unilateral (27 patients, 54%). Positive SN were found in 17 patients (34%), and negative in 29 patients (58%). Out of the whole group of patients (50), 21 of them (42%) had positive lymph nodes (LN). In the crosstab statistics, no differences were noticed in the group without SN found, in comparison with tumor grade and diameter. Finally, our test showed sensitivity of 85% (SE = 8%), specificity 100%, positive predictive value of 100%, negative predictive value of 89.6% (SE = 5.60%), and effectiveness of 93% (SE = 3.6%) regarding sentinel lymphadenectomy. CONCLUSION: This method of sentinel lymph node identification is simple, but not reliable enough to support further laparoscopic SN excision in order to make the final decision about the treatment of cervical cancer.

[Central venous catheter-related infections: risk factors and effects of glycopeptide antibiotics].

INTRODUCTION: Central venous catheters (CVC) are used in the treatment of critically ill patients. Indications for placement of CVCs include hemodynamic monitoring, administration of intravenous fluids, medications and total parenteral nutrition. MATERIAL AND METHODS: We investigated risk factors and effects of glycopeptide antibiotics on the development of central venous catheter-related injections in 300 patients treated in intensive care units. A semiquntitative culture technique was used. The investigation included: age, diagnosis on admission, catheter insertion site, catheter duration, the first or next catheter and using of glycopeptide drugs. RESULTS: 91 catheters (30.3%) were colonised, catheter-related infection was found in 50 catheters (16.7%). Infections were more frequent in catheters inserted through the internal jugular vein than in subclavian venous catheters, they were also more frequent if duration of catheterization was longer than seven days, but less frequent in patients who received glycopeptide antibiotics. The isolated microorganism was Staphylococcus aureus. Discussion According to the literature, a number of catheter-related risk factors for infections include: insertion site, type of catheter, the number of manipulations, inadequat asepsis, lumen number, type of antiseptic. The relative importance of one risk factor over another is difficult to assess, given that studies have no priority report. CONCLUSION: The duration of catheterization and the insertion site were the most frequent risk factors for infection. The use of glycopeptide antibiotics during catheterization has protective effects.

[Assessment of maternal cerebral blood flow in patients with preeclampsia].

INTRODUCTION: Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. MATERIAL AND METHODS: A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if p<0.05. RESULTS: Significantly increased Pi, Ri and all velocities were established in the group of patients with severe preeclampsia compared with the other two groups. In the group with severe preeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. DISCUSSION: In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that blood vessels changes are most prominent in severe preeclampsia. Cerebral blood flow meassurements can be used as a clinical test for the prediction of eclampsia. Magnesium-sulfate (MgSO4) has a signifficant role in prophylaxis and treatment of eclampsia, and, therefore, positive influence on reduction of cerebral ishemic lesions can be expected. CONCLUSION: We can conclude that changes of the cerebral blood flow can be evaluated by evaluating blood flow velocities in the medial cerebral artery. Velocities tend to increase in severe preeclampsia, especially with signs of threatening eclampsia, and decrease after treatment with mgnesium sulfate. Serial measurements of blood flow in medial cerebral artery in patients with severe preeclampsia may be used in prediction of eclampsia and in evaluation of magnesium sulfate therapy effects.

[Noninvasive diagnosis of fetal anemia in Rh-alloimmunized pregnancies by color Doppler].

UNLABELLED: INTRODUCTION Fetal anemia is usually diagnosed by invasive procedures, such as amniocentesis and cordocentesis. As these procedures carry a substantial risk for pregnancy loss, a nonivasive method for diagnosing fetal anemia is needed. Doppler allows measurement of blood flow velocity in fetal vessels. In anemic fetuses increased velocities in medial cerebral artery (MCA) are registered. The aim of our study was to evaluate if there were changes in blood flow waveforms in anemic fetuses' MCA, and if these changes correlated with values of fetal hematological parameters. MATERIAL AND METHODS: A clinical study evaluated 172 pregnancies of gestational age between 28 and 32 weeks, in which cordocentesis was performed due to maternal Rh-alloimmunization. During sonographic examination we evaluated blood flow velocities and pulsatility index (Pi) in MCA. We registered hematological parameters such as hemoglobin and hematocrit. Based on hemoglobin levels, all fetuses were divided into four groups: nonanemic (140 g/l); mild anemia (120-139.9 g/l); moderate anemia (100-119.9 g/l) and severe anemia requiring intrauterine transfusion (99.9 g/l). We compared mean systolic velocities and Pi between groups and studied the correlation between MCA mean systolic velocities and hemoglobin and hematocrit values. Statistical analysis was done using ANOVA test and parameter linear correlation. The difference was considered to be significant if p < 0. 05. RESULTS: Out of 172 fetuses, 60 (34.09%) were nonanemic, 56 (31.82%) showed mild anemia, 56 (31.82%) moderate anemia and 24 (13.64%) fetuses had severe anemia. Anemic fetuses had significantly higher MCA flow velocities compared to nonanemic fetuses. Values of Pi decreased in severe forms of fetal anemia, but the difference wasn't significant. Levels of hemoglobin and hematocrit showed inverse correlation with the values of MCA mean systolic velocities, while correlation with the values of Pi wasn't observed. DISCUSSION: Cerebral blood flow velocity in medial cerebral artery was assessed to diagnose fetal anemia. MCA mean systolic velocity is increased in anemic fetuses and correlates with the degree of anemia. The main advantage of this parameter is that advanced software programs are not necessary. We can conclude that in cases of Rh-alloimmunization in anemic fetuses increased MCA mean systolic velocities are registered. There is an inverse correlation between MCA mean systolic velocities and hemoglobin and hematocrit values. We suggest that measurements of MCA mean systolic velocities should be used in fetuses at risk for anemia and in selection of fetuses requiring invasive procedures.

[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.

[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.