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Introduction. Although uterine myomas are becoming more common in pregnancies due to advanced maternal age, the literature lacks reports on complications, such as hysterectomy following cesarean myomectomy (CM). The aim of this work was to describe when CM is inevitable, complicated by severe intrapartum hemorrhage and requiring a hysterectomy. Case outline. A pregnant, with a term pregnancy and large multiple myomas, was referred for elective cesarean section (CS). During the CS, forced enucleation of a 100 mm anterior and left myoma previa (pre-fetal extraction) was necessary, and a 2,800 g neonate was delivered through the lower uterine segment incision. After the delivery and another CM, it was necessary to stop a massive hemorrhage from the myometrial myoma bed. Following provisory suturings of the hysterotomies, an urgent hysterectomy was performed with left salpingo-oophorectomy, due to a large hematoma in the left retroperitoneal space. The patient?s further recovery was uneventful and she was discharged with her baby on the sixth postoperative day. The histopathology report revealed a 135 ? 190 ? 150 mm uterus, weighing together with the enucleated myomas and left adnexa 5,000 g in total. The weight of the enucleated myomas was 1,670 g. The histopathological examination also showed 12 intramural and subserous myomas in the myometrium, ranging 30?190 mm. Conclusion. Large myomas, especially previa, may present a serious problem for fetal extraction during a CS. Therefore, the authors suggest an informed consent for CM, in patients who should undergo a CS. Additionally, such patients should be counseled about the possibility of an intrapartum hysterectomy.

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.

Endometriosis is characterized by endometrial tissue found outside of the uterus (primarily in the pelvic cavity), causing chronic inflammatory reaction, infertility, and pain. The impact of endometriosis on different aspects of women?s life is important, including family and social life, work, and reproduction. The usual way of examining endometriosis is history taking, recognition of typical symptoms, clinical examination, and the use of imaging techniques, but the diagnosis is made by histopathology findings, usually after laparoscopy. The aim is to represent current recommendations and guidelines referring to endometriosis diagnostics and therapy, proposed by two major societies dealing with reproductive medicine: European Society for Human Reproduction and Embryology (ESHRE) and American Society of Reproductive Medicine (ASRM). The recommendations refer primarily to the therapeutic modalities in infertility and pain problems caused by endometriosis, and represent the basis of appropriate strategy for overcoming numerous problems linked with this chronic illness.

The ideal agent for prevention and treatment of uterine abnormal contractility has not been found. The polyphenol resveratrol possesses a wide spectrum of pharmacologic properties, but its influence on the contractility of human myometrium is not defined. The present study evaluated the effect of resveratrol on the oxytocin-induced contractions of human term pregnant myometrium in vitro and the contribution of different K(+) channels to resveratrol action. Resveratrol induced a concentration-dependent relaxation of myometrium contractions (pD2 value and maximal responses were 4.52 and 82.25%, respectively). Glibenclamide, a selective blocker of ATP-sensitive (KATP), iberiotoxin, a selective blockers of big-calcium sensitive (BK(Ca)) and 4-aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced a significant shift to the right of the concentration-response curves of resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all K(+) channel blockers. A K(+) channel opener, pinacidil, inhibited oxytocin-induced contractions of pregnant myometrium with comparable potency and efficacy to resveratrol (pD2 values and maximal relaxation were 4.52 and 83.67%, respectively). Based on K(+) channel opener/blocker affinities, it appears that the inhibitory response of resveratrol involves different myometrial K(+) channels. When applied in high concentrations, resveratrol has an additional K(+)-channel-independent mechanism(s) of action. Furthermore, immunohistochemistry staining and western blot analyses detected the presence and distribution of KATP, BK(Ca) and Kv channel proteins in pregnant myometrium.

Preclinical Research Potassium (K+ ) channels have a key role in the maintenance of smooth muscle tone; a variety of agonists can modify the tone by altering K+ -channel activity. The aim of this study was assess the effects of the phenols, resveratrol, and naringenin on K+ -channels of the vascular smooth muscle. Segments of human umbilical vein (HUV) without endothelium were precontracted using serotonin (100 μM) or 100 mM K+ to derive cumulative concentration-response curves using increasing concentrations of resveratrol or naringenin. K+ -channel inhibitors were added in the bath before resveratrol (1-100 μM) or naringenin (0.01-1 mM) in assess the role of K+ -channels in their effects on HUV precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM), a nonselective blocker of Ca2+ -dependent and inward rectifier K+ -channels (respectively) induced significant shifts to the right (P < 0.05) of resveratrol. concentration-response curves. The effect of naringenin was antagonized by 4-AP (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K+ -channels are probably involved in the resveratrol vasodilatatory effect, while naringenin seems to affect 4-AP-sensitive K+ -channels. However, other mechanisms of vasodilation induced by polyphenols could not be excluded. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.

The term ?poor respond (POR) patients? is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7). The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-M?llerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol - GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time.

The blood flow from the placenta to the fetus depends on human umbilical vein (HUV) vascular tone. ATP-sensitive K+ (KATP) channels link the metabolic state of the cell to membrane potential, and their activation in the HUV represents protection against hypoxia. The aims of our study were to assess the effects of resveratrol and naringenin on the HUV and to define the roles of KATP channels in their effects. Serotonin or 100 mM K+ were used for precontraction of the HUV without endothelium. The cumulative concentration–response curves were obtained by adding increasing concentrations of resveratrol or naringenin. Glibenclamide was used, in order to test the role of KATP channels in its effect. Resveratrol induced more potent vasodilatation of serotonin- and 100 mM K+-precontracted HUV than naringenin. Glibenclamide induced significant shift to the right of the concentration–response curves of resveratrol and P1075 (a specific opener of KATP channels). Western blotting showed that HUV expressed protein Kir6.1. Thus, resveratrol and naringenin produce dilatation of HUV. It seems that KATP channels are involved in the relaxation of HUV induced by resveratrol, while naringenin seems to interact with other ion channels. The K+ channel-independent mechanism(s) of these polyphenols could not be excluded. Copyright © 2014 John Wiley & Sons, Ltd.

Fetuses from mothers with autoimmune thyroid disease (AITD) may be affected by antithyroid antibodies, antithyroid drugs, and iodine.The study correlated fetal free T(4) (fT4) with fetal ultrasound parameters and maternal thyroid function, thyroid antibodies, and medication dose from mothers with AITD.The study was designed as a prospective cohort study and conducted in an academic referral center.Eighty-three of 85 women with AITD completed the study; 38 were treated for hyperthyroidism and 25 for hypothyroidism, and 20 were euthyroid.Outcomes were as follows: 1) fetal-fT4, TSH, ultrasound parameters (morphology, biometrics, heart rate); and 2) maternal-fT4, TSH, antithyroid drug dose, and antithyroid antibodies, thyroid peroxidase and TSH receptor (TRAK). Parameters were determined at the same time, between the 22nd and 33rd wk gestation.A total of 48.3% of fetuses from hyperthyroid mothers, 60% of fetuses from hypothyroid mothers, and 10% of fetuses from euthyroid mothers had elevated fT4 levels (P = 0.006). In hypothyroid mothers, the presence of both thyroid antibodies was related to fetal hyperthyroidism, whereas absence was related to fetal euthyroidism (P = 0.019). Hyperthyroid mothers (TRAK-positive, thyroid peroxidase-negative) with hyperthyroid fetuses had significantly higher mean TRAK than hyperthyroid mothers with euthyroid fetuses (13.7 vs. 3.7 IU/liter; P = 0.02). Fetal fT4 correlated weakly negatively with maternal TSH within the normal range, but not with ultrasound parameters or with antithyroid drug dose.High fetal fT4 levels were unexpectedly frequent in women with AITD, including maternal autoimmune hypo- and hyperthyroidism. Further studies are needed, as well as noninvasive methods to assess fetal thyroid function.

Dear Editor, With great interest I read the recently published guidelines for the management of spontaneous preterm labor [1]. I was delighted to see that unlike the previous guidelines published in 2006 [2], these new ones also take into consideration the diagnostic marker insulin-like growth factor binding protein-1 (IGFBP-1) that I have worked with since the early 80s. However, I would like to bring the readers’ attention to some errors and points that may be misleading regarding evaluation of IGFBP-1 as a marker of ruptured fetal membranes (ROM) and in comparing it with placental α microglobulin-1 (PAMG-1). Firstly, human IGFBP-1 is a well characterized protein since more than 20 years [3,4]. Its synthesis by the liver and decidua, and levels in amniotic fluid and other body fluids have been thoroughly examined in all stages of pregnancy [5,6] and the data have been published in peer-reviewed journals. Meanwhile, the data available on PAMG-1 is more limited and partly confusing. In the most often cited papers regarding the PAMG-1 levels in amniotic fluid, blood and other body fluids [7–9], the values are quite different from those reported in the guidelines. This makes comparison between IGFBP-1 and PAMG-1 difficult. IGFBP-1 has been used as a marker of ROM since the mid 90s (Actim PROM test). Since then, several studies have consistently shown that this test identifies membrane rupture with high accuracy. Unfortunately, many of these studies were omitted in the analysis presented in Table I of the guidelines comparing the performance of the different tests [10–12]. As a consequence, the sensitivity and specificity of the IGFBP-1 test remain underestimated. For example, the lowest sensitivity (74%) is from a study by Lockwood 1994 using a quantitative radioimmunoassay with frozen samples in the laboratory with a different detection limit and assay conditions from the current IGFBP-1 based bed-side PROM test [13]. Secondly, the guidelines state that the detection limit of PAMG-1 with Amnisure ROM test (5 ng/ml) is lower than the detection limit of IGFBP-1 with Actim PROM test (25 ng/ml). This comparison is irrelevant, since the quoted levels of PAMG-1 protein in amniotic fluid (2000−25,000 ng/ml) are clearly lower than the known levels of IGFBP-1 (10,500−350,000 ng/ml [14]), which naturally calls for a need of a lower detection limit. In the guidelines the lowest level of IGFBP-1 is quoted to be 27 ng/ml in early pregnancy. Such low levels have not been reported at pregnancy weeks clinically relevant for diagnosis of ROM [15]. Thirdly, the sensitivity and specificity of any test has to be interpreted in the clinical context. The methods used for estimation of the accuracy and reliability of the PAMG-1 test compared to the IGFBP-1 test are questionable for several reasons. For example, samples of pure blood-free amniotic fluid obtained during intra-operative amniocentesis at cesarean section were diluted with 0.9% saline and serial dilutions were tested using both tests [16,17]. The study design does not correspond to the bed-side situation where amniotic fluid is contaminated by vaginal discharge or other possible fluids like urine, semen or blood that may affect the test result causing false positives, if the test is too sensitive. A high rate of positive PAMG-1 test results has been found among patients with intact membranes and labor at term [18] and in patients with a short cervix [19]. This data has not been considered when analyzing the specificity of PAMG-1 test. Also, the publication on the intra-amniotic dye test and its comparison with the PAMG-1 test is a congress abstract only, with no information on the numbers of patients or the study design [20]. Finally, IGFBP-1 test results have repeatedly been shown to be unaffected by the presence of blood [10,21,22]. Indeed, the monoclonal antibody used in the Actim PROM test does not recognize the highly phosphorylated IGFBP-1 which is the predominant isoform in maternal and fetal blood and decidua [4]. Since blood may be present in approximately 25% of cases with suspected PROM, this information is critical in order to estimate the accuracy and clinical usefulness of the marker. Suspected rupture of membranes in the presence of bleeding is the most challenging situation in the clinic, since the therapeutic measures differ depending on whether the membranes in such a case are intact or not. Yet, no information is available on the accuracy of the PAMG-1 test in patients with suspected membrane rupture and bleeding since patients with bleeding have systematically been excluded in PAMG-1 clinical studies, suggesting that PAMG-1 test cannot be used in such challenging cases. The statement that presence of blood up to 50% does not interfere with the PAMG-1 test result is only based on a conference poster, reporting serial dilutions of peripheral blood in 0.9% saline in vitro [23]. Again, the study design is not equivalent to the clinical situation where amniotic fluid in cervicovaginal swab sample is mixed with vaginal secretion and other possible contaminants. Also, this high rate of positive Amnisure results in the presence of blood raises a question on the validity of the reported range in the maternal blood (0.5–2 ng/ml) that should not react in a test with a detection limit of 5 ng/ml. Considering all the points above, the currently available data does not unequivocally support the superiority of the PAMG-1 test as compared with the IGFBP-1 test.

Objective: The aim of the study was to assess the short-term effects of direct intramuscular (i.m.) corticosteroid therapy on fetal biophysical profile, baseline fetal heart rate and the nonstress test, which indicate the degree of fetal hypoxia. Method: We evaluated the effect of direct i.m. fetal single-dose dexamethasone (4 mg/kg) on the fetal biophysical profile 2 h before and 2–4 h after corticosteroid therapy in 41 fetuses in the 32nd week of gestation at risk of preterm delivery. Risk factors for preterm delivery included pregnancy-induced hypertension and preeclampsia. Result: There was a statistically significant difference between fetal breathing movements before and after corticosteroid therapy (p = 0.019; 95% confidence interval for difference –11.75, –1.12). No significant changes were observed between baseline fetal heart rate before and after corticosteroid therapy (p = 0.99; 95% confidence interval for difference –4.81, +4.81), biophysical profile before and after fetal corticosteroid therapy, p = 0.235 as well as the nonstress test before and after therapy (p = 0.564). Conclusion: Direct corticosteroid i.m. fetal therapy results in increasing profound short-term fetal breathing movements. There are no changes in baseline fetal heart rate, biophysical profile score, and nonstress test.

Resveratrol is a phytoalexin produced in a number of plant species including grapes. The benefit of resveratrol to health is widely reported. Resveratrol has been found to promote relaxation of non-pregnant and pregnant uterus, but its mechanism of action is unclear. The aims of our study were to investigate the involvement of inwardly rectifying potassium channels (Kir) in inhibitory effects of resveratrol on three models of contractions of non-pregnant rat uterus: the spontaneous rhythmic contractions (SRC), oxytocin-elicited phasic contractions and tonic oxytocin-elicited contractions.Uterine strips were obtained from virgin female Wistar rats in oestrus. Strips were mounted into organ bath for recording isometric tension in Krebs-Ringer solution. Experiments followed a multiple curve design. In order to test the involvement of Kirchannels in a mechanism of action of resveratrol(1-100 μM),BaCl2 (1 mM),a antagonist of inwardly rectifying pota­ssium channels was used. Resveratrol induced a concentration-dependent relaxation of all models of contractions. BaCl2 antagonized the response to resveratrolon SRC and oxytocin-elicited phasic contractions. Relaxation achieved by resveratrolon tonic oxytocin-elicited concentrations was insensitive to BaCl2.The antagonism of resveratrol effects by inwardly rectifying potassium channels antagonist suggests that Kir channels are involved in resveratrol action on phasic contractions of rat uterus. Inhibitory effect of resveratrol on tonic contractions did not include Kir channels. [Projekat Ministartsva nauke Republike Srbije, br. TR31020]

Background/Aim. Medicamentous abortion was first introduced in Serbia and Montenegro in September 2001. The aim of this study was to assess the efficiency, side effects, and acceptability of medicamentous abortion using mifeprostone orally (600 mg), and 48 hours later, misoprostol both orally and vaginally in different regiments in our population (400 mcg, 600 mcg, 800 mcg). Methods. A total of 235 consecutive women with pregnancies up to 49 days of gestational age were assigned to 4 groups according to the different misoprostol regiment (group I 400 mcg, group II 600 mcg, group III 800 mcg orally, and group IV 800 mcg both orally and vaginally). The principal outcome measure was a successful abortion defined as a complete expulsion of intrauterine contents without a need for surgical intervention 14 days after the procedure. Other outcome measures were the following: drug related effects, and adverse effects related to the abortion process. Results. In general, the success rate was 50%, 89.48%, 75% and 92.11% in the groups I, II, III, and IV, respectively, as judged by the complete expulsion of the intrauterine contents without surgical intervention (t1:4 = 7.005; t2:4 = 0.3872, t3:4 = 2.9784, p < 0.01). The incidence of adverse effects (vomiting, abdominal pain, bleeding, and fever) was low in general, but among our groups it occurred mostly with the higher doses of orally applied misoprostol (800 and 600 mcg). Only one case required urgent curettage for heavy vaginal bleeding, and two blood transfusions, as well. No cases of intact pregnancies were recorded in the study. Conclusion. Our study showed that a mifepristone dose of 600 mg orally, and misoprostol 400 mcg orally and 400 mcg vaginally were most effective. Thus, a combination of mifepristone and misoprostol for medicamentous abortion should take a higher proportion in the termination of early pregnancy in our population.

Introduction. Even though placentas from assisted reproduction programs often differ from placentas of women who conceived naturally, they are rarely examined. The aim of our investigation was to determine some gross characteristics of placentas of women who conceived with assisted reproduction. Material and methods. We examined 30 placentas from an assisted reproduction program (20 from in vitro fertilization and 10 from intrauterine insemination) and 30 placentas of women who conceived naturally. All women were age matched. All the women were at term. Results. The mean weight of placentas from assisted reproduction program was 573 g and of those after natural conception - 582.67g. The mean length of the umbilical cords was 64.3cm after assisted reproduction and 66.3cm after natural conception. The mean placenta thickness after assisted reproduction was 2,22 cm and after natural conception 2.28 cm. Eight pla?centas of the study group had a marginal insertion of the umbilical cord, which lead to a statistically significant difference when compared to placentas of women who conceived naturally: ?? =7.07; p>0.01. Discussion. Marginal cord insertion into the placenta after assisted reproduction is also often described in the literature (as a possible "consequence " of embryo-transfer). Conclusion. There were no statistically significant differences in the mean weight and dimensions of placentas, length of the umbilical cord, gross pathological features of placentas and cords, mean birth weight of babies and placental/fetal ratios between women from assisted reproduction program and those who conceived naturally. .

Women from in vitro fertilization program are at higher risk for developing pregnancy induced hypertension, so we analyzed the incidence of preeclampsia and eclampsia in women who conceived in an in vitro fertilization program. A seven-year study included 144 parturients from in vitro fertilization program. The control group consisted of 39,112 parturients from general population. We analyzed only women with singleton pregnancies. There were 2.08% parturients from the in vitro fertilization program, and 0.40% from the control group, with diagnosis of preeclampsia, with chi2=6.24; p0.05. Eclampsia occurred in 0.69% women who conceived using in vitro fertilization, and in 0.06% parturients from the control group (chi2=2.05; p0.10). Parturients from in vitro fertilization program are at statistically significantly higher risk for preeclampsia, but not for eclampsia, when compared with women from general population.

Placentas from assisted reproduction programs are a poorly investigated research material. The aim of this investigation was to perform microscopic examination of placentas from assisted reproduction programs and to compare them with placentas from spontaneous pregnancies. The investigation comprised 12 placentas from assisted reproduction programs and 12 placentas from spontaneous pregnancies. We found a statistically significant increa of villous edema in investigated placentas (p=0,001). We also found a statistically significantly increased incidence of microcalcifications in placentas from assisted reproduction programs (p=0,04). There was no statistically significant difference between the two groups in regard to syncytial knots (?2=0,67, p>0,25). Microscopic examination showed that placentas from assisted reproduction programs present with more frequent pathological findings. Further investigations of placentas from assisted reproduction programs could provide better understanding of different pathological conditions of pregnancies and labor in women with artificial insemination.

Introduction Many infertile couples try to become parents spontaneously, neglecting the possibility to conceive artificially, so they seek medical help in their late reproductive age. Maternal age Major aspects of maternal age in regard to assisted reproduction consider oocytes, ovaries and endometrium. Also, some habits and maternal diseases associated with aging may have an impact on fertility (smoking, atherosclerosis, previous gynecological operations etc.). Even though estimating the ovarian reserve is the most objective test in assessing female fertility, it has a limited predictive value in younger women. A short protocol of ovulation induction showed best results in women with poor ovarian reserve, but recent studies recommend low-dose gonadotropin-releasing hormone agonists in these cases. Paternal age With aging, sperm parameters become worse, which points to the neglected role of the father in assisted reproduction. Conclusion Thus, parental age plays an important role in assisted reproductive programs.

Apolipoprotein B is elevated in growth-retarded compared with normally grown fetuses, demonstrating a link between low birth weight and risk of subsequent atherosclerosis. Increased apolipoprotein B levels and an elevated apolipoprotein B to A-I ratio are predictors of atherogenesis. Elevated apolipoprotein B levels in young adults have been linked to atherosclerosis in later life, whereas impaired fetal growth has been linked to higher than normal apolipoprotein B levels in adulthood. We conducted this research to test the hypothesis that circulating apolipoprotein A-I and B concentrations differ in growth-retarded compared with normal fetuses. Fetal umbilical plasma samples were obtained at diagnostic cordocenteses in 18 growth-retarded and 23 normally grown fetuses. Levels of apolipoprotein A-I and B were measured by turbidimetric assay. There were no differences in median (range) plasma apolipoprotein A-I concentrations between growth-retarded and normal fetuses [0.61 (0.30-1.42) vs. 0.60 (0.30-1.63) g/L, respectively; P = 0.94]. In contrast, we found significantly higher plasma apolipoprotein B levels in growth-retarded vs. normal fetuses [0.62 (0.37-1.84) vs. 0.40 (0.16-1.47) g/L, respectively; P0.001]. Moreover, the ratio of apolipoprotein B to A-I was significantly higher in growth-retarded than in normal fetuses [1.00 (0.38-2.42) vs. 0.53 (0.31-1.80); P = 0.005]. Levels of apolipoprotein B are elevated in growth-retarded fetuses, suggesting a linkage between low birth weight and adult-onset atherosclerosis.

Background/Aim. Although lamellar bodies have been the center of interest over the last years, the published results of fetal pulmonary maturity determination according to their concentration in amniotic fluid are controversial. The aim of this study was to determine the significance of lamellar bodies, as well as the ratio lecithin/sphingomyelin (L/S) in amniotic fluid for the assessment of fetal pulmonary maturity. Methods. This prospective 2-year study included 102 female examinees, ranging from 17 to 44 years of age, in whom lamellar bodies concentrations in amniotic fluid were determined to check the efficacy of the applied therapy for obtaining arteficial fetal pulmonary maturity. The shake test was applied as a comparative test for determining a quantitative L/S ratio. To determine a fetus maturity and development stage we followed up biparietal diameter, abdominal circumference, femure length, ponderal index at birth and body mass. Results. Out of a total of 102 amniocenteses within a period from 26th to 40th gestation week only 70 results were considered due to 32 unknown neonatal outcomes. Biparietal diameter was 224-362 mm, femur length 56 - 78 mm, ponderal index 1.22-2.84, fetus body mass 1300- 4 350 g. There was found a significant relation between gestation age and lamellar bodies concentration (R = 0.396398, p < 0.01), as well as between gestation age and the ratio L/S (R = 0.691297, p < 0.01). Also, there was a significant correlation of lamellar bodies concentration to the ratio L/S determined (R = 0.493609, p < 0.01). Conclusion. Determination of lamellar bodies concentration values is a reliable method to confirm fetal pulmonary maturity.

Neopterin is generated by macrophages and monocytes in response to cytokine and endotoxin stimulation and is a sensitive marker of the severity of infectious-, autoimmune-, and alloimmune-mediated inflammatory disorders. This study was designed to evaluate fetal and maternal neopterin concentrations during the second half of pregnancy.We conducted a cross-sectional analysis of serum neopterin values with a sensitive radioimmunoassay in 35 paired fetal and maternal and 8 neonatal samples. The fetal and maternal samples were obtained between 20 and 38 weeks' gestation at the time of diagnostic cordocentesis. All maternal, fetal, and neonatal samples were derived from uncomplicated pregnancies resulting in term delivery of appropriately grown fetuses.Fetal neopterin concentrations increased across gestation (r = 0.64, P.001), and mean values were significantly higher than paired maternal values (6.28 [+/-2.44] ng/mL vs 2.05 [+/-0.87] ng/mL, P.001]. In contrast, maternal neopterin concentrations did not correlate with gestational age (r = 0.22, P =.24). No significant correlation was found between fetal and maternal values (r = 0.34, P =.07).Fetal neopterin values rise significantly across gestation. They are substantially greater than maternal levels and are not correlated significantly with paired maternal levels. These findings are the first report of a physiologically normal range for fetal neopterin concentrations in a sample of uncomplicated pregnancies. The values suggest progressive increases in fetal cell-mediated immunity and macrophage-monocyte activation as gestation progresses.

To determine if intrauterine intravascular fetal transfusion affects fetal umbilical venous endothelin levels.Endothelin concentrations were measured by radioimmunoassay in fetal umbilical venous blood obtained immediately before and after 36 fetal transfusions performed for Rh alloimmune hemolytic anemia. Umbilical venous pressures also were recorded before and after transfusion.The mean (+/- standard deviation [SD]) gestational age at transfusion was 27.0 +/- 4.6 weeks, whereas the initial and post-transfusion hematocrits were 23.3 +/- 8.5% and 41.8 +/- 6.3%, respectively. Post-transfusion endothelin levels correlated significantly with the volume of transfused blood (r = .41; P = .03) and with post-transfusion increases in umbilical vein pressure (r = .86; P.001). Among fetuses undergoing initial transfusion, there were significant differences between mean (+/- SD) pre- and post-transfusion endothelin levels [3.6 (+/- 2.2) pg/mL versus 6.3 (+/- 4.0) pg/mL, respectively; P = .02]. In contrast, among fetuses undergoing a repeat fetal transfusion, no differences in mean (+/- SD) pre- versus post-transfusion endothelin levels were observed [3.8 (+/- 1.8) pg/mL versus 2.2 (+/- 1.77) pg/mL, respectively; P = .3)]. Step-wise multiple regression analysis identified order of transfusion as a significant predictor of change in endothelin levels from pre- to post-transfusion measurements (adjusted r2 = .26; P = .003).Rapid expansion of fetal intravascular volume by intravenous transfusion of packed red blood cells with a high hematocrit enhances fetal endothelin levels in those fetuses undergoing initial but not subsequent transfusions.

There is little information available concerning the ontologic development of the human hypothalamic-pituitary-adrenal (HPA) axis nor of the potential interactions among fetal, maternal and placental-derived HPA axis hormones. This study evaluated levels of these hormones in matched maternal and fetal pairs during the second half of uncomplicated pregnancies. Immunoassays were used to measure serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol in 104 matched fetal and maternal blood samples. Fetal specimens were obtained by percutaneous umbilical blood sampling (PUBS) between 18 and 40 weeks in patients whose pregnancies resulted in healthy, term infants. Correlations among these hormones, and the effect of gestational age were assessed. Maternal CRH concentrations [median (range)] [1.10 ng/ml (0.15 to 23.69)] were significantly greater than fetal values [0.35 ng/ml (0.07 to 1.0)]. Levels of maternal CRH (r = 0.73; p < 0.001) but not fetal CRH (r = 0.01; p = 0.98) correlated with gestational age. Maternal ACTH decreased (r = -0.21; p = 0.04) while fetal ACTH increased (r = 0.35; p < 0.003) with gestational age. Both maternal (r = 0.45; p < 0.001) and fetal (r = 0.57; p < 0.001) cortisol levels increased with gestational age. Maternal serum CRH values correlated best with fetal cortisol (r = 0.40; p = 0.0002) and correlated modestly with maternal cortisol (r = 0.28; p = 0.01), fetal ACTH (r = 0.24; p = 0.03) and fetal CRH (r = 0.23; p = 0.04); but not with maternal ACTH (r = -0.12; p = 0.3). Maternal CRH concentrations increase in the third trimester and correlate with rising fetal cortisol levels.

Our objective was to evaluate maternal and fetal endothelin concentrations in uncomplicated pregnancies across the second half of pregnancy.Paired (n = 64) maternal venous and fetal umbilical venous or arterial samples were obtained during cordocentesis. In addition, eight neonatal umbilical vein samples were obtained immediately after delivery. Samples were assessed for hematocrit and pH, and concentrations of endothelin were measured by sensitive enzyme immunoassay.No significant correlation was found between either fetal or maternal endothelin levels and gestational age (r = 0.01, p = 0.91 and r = 0.07, p = 0.5, respectively). Fetal plasma endothelin concentrations were significantly lower than neonatal umbilical vein endothelin levels [median 2.5 pg/ml (range 0.9 to 5.73) vs 15.77 pg/ml (8.12 to 19.58), respectively; p0.0001] but significantly higher than maternal levels [1.3 pg/ml (0.8 to 3.25); p0.0001]. In addition, endothelin values were higher in the umbilical artery than in the umbilical vein, but this difference failed to achieve statistical significance [2.89 pg/ml (1.61 to 5.73) vs 2.29 pg/ml (0.9 to 5.70), respectively; p = 0.06]. No correlation was noted between fetal and maternal endothelin levels (r = 0.12, p = 0.36).Fetal endothelin levels were significantly higher than maternal levels, but neither correlated with gestational age across the second half of pregnancy.

INTRODUCTION The role of the adrenal gland in the metabolism of foetus and its role in maturation of foetal organs are the principal motives for paying more attention to this vital organ, which is still a great enigma for gynaecologists. The control of the gland is important in normal as well as in risk pregnancies. Of the entities that most often imperil the growth of foetus and adrenal glands are diabetes and hypertension in pregnancy. A consequence of the maternal diabetes may be macrosomy of foetus manifested by increase in foetal body mass and enlargement of organs sensitive to increased concentration of insulin in the foetal blood [6], i.e., the liver, fat tissue, lungs, adrenal glands, heart. Brown and Singer (1988) [2] established that adrenal glands of foetus are imperiled in pregnancies complicated by mother's hypertension. Their conclusion was derived from pathologic findings in foetuses from unsuccessful pregnancies of patients with hypertension. The glands were of reduced sizes. The way to perform precise measuring of glands, which are of dilapidated composition during post mortem examination, is not quite acceptable, since during the manipulation the size may, to some degree, be altered. By introduction of the ultrasound method in medical practice the problem of biometry has been overcome. Besides measuring, of great importance for the study of physiology of the gland is also the analysis of the foetal fluid and foetal blood. The first successful measuring of the adrenal gland of foetus by ultrasound was performed in mid 80s of the last century by Jeanty and Romero [3] via transabdominal path. The aim of our study is the comparison of foetal adrenal glands in normal and high-risk pregnancies. MATERIAL AND METHODS During a prospective follow-up carried out at the Institute of Gynaecology and Obstetrics, Clinical Centre of Serbia, 213 patients, aged from 19 to 44 years were examined. Gestation periods were from the 11th to the 40th week. We divided the patients in 3 groups. The first group consisted of 131 patients with no pathologic changes and whose children were born alive. The second group was formed of 75 pregnant women in whom the course of pregnancy was impaired and disorders in the foetal. From these pregnancies the children were born alive. The third group was composed of 7 patients in whom abortion was indicated. The measured values of foetal adrenal glands diameter in the first group (131 patients), were used for making a nomogram of the glands growth. The measuring was performed with ultrasound apparatus "Toshiba 100 SSA". Transabdominal examination with a probe of 3.75 MHz and transvaginal examination with probes of 5 and 7 MHz were performed. Since the picture of the adrenal gland resembled an ellipse, on the basis of measured diameters and using the formula for circumference of this geometric figure [O = (d1 + d2) x pi/2], we obtained the desired value, which increased with advancement of pregnancy. Patients included in the study were with one-foetus pregnancy, whose last menstruation was precisely dated. Data are presented in a chart. For analysis of the obtained data, in addition to parameter methods, we also used the linear correlation and regression and one-factor analysis of variance. Data base analysis was made in the SPSS for DOS package. RESULTS In making a nomogram of adrenal glands growth of a foetus old between 11 and 40 weeks, 131 of 213 patients were included, while the other foetuses were excluded as they belonged to high-risk pregnancies. Correlation of the growth of adrenal glands circumference and gestation period of pregnancy are also highly statistically important. The correlation coefficient of the straight line which represents this dependancy, is R = 0.8916, for the significance level of p 0.05 (p = 0.06 and it was close to the border value for the significance level of p < 0.05); however, for glands of pregnancies complicated with hypertension the value was F = 1.61; p = 0.063 and the border value near -2 SD. Data are presented in a chart, regarding nomograms and adrenal glands of risk pregnancies. DISCUSSION In 1993 Bronstein and colleagues [1] proved that the route of visualization of an adrenal gland was not only transabdominal. They succeeded in detecting the glands by transvaginal ultrasound examination in the 12th week. Jeanty and Romero [3] performed a successful transabdominal visualization in the 23rd week of gestation. By ultrasound prenatal examination we can determine the existence of hyperplasia of adrenal glands (Kelnar 1993) [5]. With ultrasound examination we can also diagnose tumours of the medulla, such as neuroblastoma (Jennings and colleagues 1993) [4]. In our study we reported on the visualization and growth of foetal adrenal glands in the period from the 11th to the 40th week of gestation. We presented the growth of foetal adrenal glands in normal gestations with the growth nomogram. The coefficient of correlation of adrenal glands circumference was R = 0.8916. The level of significance was p < 0.01. In conclusion, we can say that risk factors in pregnancy could impair the growth of adrenal glands. We have found that foetal adrenal glands in pregnancies impaired with maternal diabetes were hypertrophic, while those in pregnancies impaired with hypertension were almost at hypotrophic border. The nomograms of adrenal glands growth were of clinical importance, since they help us to control the state of a foetus in high-risk pregnancies. CONCLUSION Improvement of the methods used in prenatal diagnosis will contribute to a timely detection of a diseased foetus, and will be the first step in its recovery. Regulating the pathological condition of the mother will surely contribute to decrease the risk of delivering children with an increased risk of morbidity.

In utero evolution and postnatal outcome were studied for 18 cases of congenital adenomatoid malformation (CAM) diagnosed by prenatal ultrasound. Five were macrocystic CAM, 9 were microcystic, and 4 were homogeneously hyperechogenic. Three fetuses presented with hydrops. Pulmonary amniotic shunting was performed in 3 patients. Outcome was the following: 4 were aborted, 1 died neonatally, and 13 survived. Four of these infants required no surgery in the neonatal or postneonatal period. In three of these, the size of the mass had decreased spontaneously in utero. Outcome did not appear to be related to the anatomic type of CAM nor to the presence of moderate polyhydramnios, but was related to the degree of mediastinal compression and to the existence of hydrops. A clearer understanding of the natural evolution of CAM is useful to determine the indications for in utero therapy.

Endogenous opiates may play a role in both fetal physiologic functions and the adaptation to intrauterine stress. However, our understanding of this role is hampered by an absence of data on circulating levels of these substances during fetal life.We measured serum beta-endorphin values with a radioimmunoassay in 81 paired fetal and maternal blood samples and 24 neonatal cord specimens. The former samples were uneventfully obtained from uncomplicated pregnancies between 18 and 39 weeks of gestation at the time of cordocentesis for prenatal diagnosis.Mean fetal beta-endorphin concentrations were significantly lower than beta-endorphin values from neonates (90.5 pg/ml [+/- 59.4] vs 228.4 pg/ml [+/- 166.2]; p less than 0.001), but significantly higher than mean maternal values (70.5 pg/ml [+/- 48.8]; p less than 0.02). Although fetal beta-endorphin levels decreased between 18 and 28 weeks' gestation, the correlation between fetal beta-endorphin values and gestational age was not significant (r = -0.193; p = 0.07). However, fetal beta-endorphin concentrations were significantly correlated with maternal values (Spearman's rank r = 0.47; p less than 0.001).These findings suggest that delivery or fetal adaptation to an extrauterine environment is associated with significant increases in beta-endorphin release. Moreover, although the fetal pituitary may be the primary source of circulating fetal beta-endorphin, a maternal or placental contribution cannot be excluded. Our data identify a physiologic range for fetal beta-endorphin concentrations.

Hydrops caused by isoimmune hemolytic anemia is frequently associated with fetal death following intrauterine intravascular transfusion. To identify possible predictors of procedure-related fetal death, we examined changes in fetal blood volume and hematocrit resulting from the initial transfusion performed on 19 severely anemic, hydropic fetuses. Seven fetuses (36.8%) died at 24-72 hours after transfusion, but in no case was the procedure associated with fetal distress. There were no significant differences between fetuses who died and those who survived in terms of total volume of blood transfused, volume transfused as a percentage of total fetoplacental blood volume, hematocrit of transfused blood, post-transfusion hematocrit, umbilical vein pH, or gestational age at transfusion. Significant differences were noted between hydropic fetuses who died compared with those who survived in the mean pretransfusion hematocrit, 6.7% (+/- 2.0) versus 8.7% (+/- 1.6) (P = .03), and the relative increase in post- over pre-transfusion hematocrit, 5.5-fold (+/- 1.4) versus 3.5-fold (+/- 0.8) (P = .001). Stepwise logistic regression analysis confirmed that only the relative increase in hematocrit was predictive of fetal loss. Moreover, six of seven fetal deaths occurred when the relative increase in hematocrit was greater than fourfold, whereas ten of 12 surviving fetuses had relative increases of less than fourfold. We conclude that large, acute increases in fetal hematocrit following intrauterine transfusion are associated with substantial mortality in hydropic fetuses.

Thyroid hormones, thyroxine-binding globulin (TBG) and thryrotropin (TSH) concentrations were measured in 46 paired fetal and maternal blood samples collected between 17 and 36 weeks of gestation. The samples were selected retrospectively from fetuses that had undergone cordocentesis for prenatal diagnosis, had been found to be unaffected and confirmed healthy at birth. In maternal serum, total thyroxine (TT4) and triiodothyronine (TT3) concentrations were high, but free thyroxine (FT4) and free triiodothyronine (FT3) were within normal adult ranges; reverse T3 (RT3) increased and TSH levels decreased towards term. Fetal TT4, FT4, TT3, FT3, TBG and TSH levels significantly increased whereas RT3 sharply decreased with gestational age. The ratio of fetal TSH/FT4 significantly decreased, suggesting that the set point for negative feedback of pituitary TSH secretion is changing while the sensitivity of the thyroid gland to TSH increases throughout gestation. There was no significant correlation between the maternal and fetal TBG, TSH, TT4 and FT4, whereas maternal TT3 was positively correlated with fetal TT4, FT4, TT3 and FT3. Normal reference values for maternal and fetal iodothyronines, TBG and TSH throughout the second half of gestation provide insight into fetal thyroid development and may be useful for prenatal diagnosis.

Bradykinin (BK) and serotonin (5-HT) are vasoactive agents that significantly contribute to the normal functioning of fetoplacental blood flow, including modulation of smooth muscle tone in umbilical vein and arteries. Accordingly, umbilical artery is a crucial component of fetoplacental circulation with the vital function of providing suitable perfusion and nutrition for placenta. The aim of this study was to investigate the effect of potassium channel blockers, namely glibenclamide (an ATP-sensitive K+ channel blocker), tetraethylammonium (a non-selective K+ channel blocker), Ba2+ (an inwardly rectifying K+ channel blocker) and apamin (a small conductance Ca2+-activated K+ channel blocker) in BK- and 5-HT-induced actions on isolated human umbilical artery (HUA) in normal pregnancy. The experiments were performed on vascular rings of HUA isolated from umbilical cords that were obtained immediately after vaginal delivery in women with uncomplicated pregnancy. Only the remnant tissue, which would have been otherwise disposed of, has been utilized. Isometric tension of suspended artery rings was continuously recorded. BK (1 nM – 1 μM) and 5-HT (1 nM – 30 μM) produced concentration-dependent contractions of HUA. Control contractions produced by BK were notably (p < 0.05) enhanced only in the presence of apamin (20 μM), while unaltered by other inhibitors. 5-HT-induced effect was not influenced by any of applied blockers. Our results suggest that small conductance Ca2+-activated potassium channels contribute to the fine regulation of maximal BK-induced contraction of HUA in normal pregnancy. On the other hand, potassium channels do not seem to be involved in 5-HT-evoked contractile response of umbilical artery.

The aim of this investigation was to evaluate serotonin (5-HT) action on isolated human umbilical arteries (HUA) from normal and gestational diabetes mellitus (GDM) pregnancies. 5-HT caused HUA contraction in a concentration-dependent manner in both investigated groups but with lower efficacy in GDM. After endothelial denudation or in the presence of indomethacin (cyclooxygenase inhibitor), the 5-HT-evoked response was comparably augmented, but only in arteries from uncomplicated pregnancies. 5-HT contractions were unchanged by L-NOARG (NO-synthase inhibitor) or glibenclamide (K(ATP) channel blocker) in both investigated groups. Whereas nifedipine (Ca(2+) channel blocker) reduced the contractile effect of 5-HT and was more potent in GDM, ouabain (Na(+)/K(+)-ATPase inhibitor) caused the contraction of HUA prior to 5-HT addition in both groups, but with a significantly reduced effect in GDM. In vascular rings from GDM, methiothepin (a 5-HT(1)/5-HT(2) receptor antagonist) significantly reduced 5-HT-induced contraction to a similar extent as compared to uncomplicated pregnancies. Ketanserin (a 5-HT(2A) receptor antagonist) produced a concentration-dependent inhibition of the 5-HT effect in GDM. In conclusion, in normal pregnancies, 5-HT produced a concentration- and endothelium-dependent contraction of HUA, most probably via endothelial prostacyclin. In contrast, the contractile effect of 5-HT in GDM was reduced with apparent endothelial dysfunction. In both normal and diabetic pregnancies, voltage-gated Ca(2+) channels and Na(+)/K(+)-ATPase contribute to the 5-HT-evoked contraction, as well to the regulation of basal vascular tone, but those actions were notably impaired in GDM. In uncomplicated and diabetic pregnancies, the transduction mechanism of 5-HT involves activation of mixed population of 5-HT(1) and 5-HT(2A) receptors in the HUA.

Preeclampsia (PE) is an important and a leading cause of both maternal morbidity and adverse perinatal outcomes. Despite progress in perinatal medicine for patients with an established diagnosis of PE, a therapeutic approach other than termination of pregnancy was unsuccessful. Women predisposed to PE begin pregnancy with a certain degree of endothelial dysfunction, a lesion that precedes shallow placentation. The proposed sequence of events comprises endothelial dysfunction, defective trophoblast invasion, and consequential impaired placental perfusion, immune maladaptation and inflammation. The possible link between these could be oxidative stress by excessive production of reactive oxygen species coupled with inadequate or overwhelmed antioxidant defense mechanisms. These defense mechanisms, involving antioxidant vitamins and enzyme systems, may restrain the extent of damage caused by oxidative stress. Markers of oxidative stress in women with established PE were confirmed. Accordingly, these findings support an expected beneficial effect of antioxidant therapy in the prevention of PE and other pregnancy-related disorders. Numerous studies have been carried out in order to investigate this possible and simple prophylactic and/or therapeutic approach in prevention of oxidative stress and eventual reduction of PE and its perinatal complications. In this review the role of vitamin antioxidants in prevention and treatment of PE is discussed. Despite the logic behind using antioxidant vitamins, the data, thus far, are at best conflicting.

To assess the effects of chorionic villus sampling (CVS) on fetal heart rate (FHR).A prospective longitudinal study was conducted among 300 patients undergoing transabdominal CVS between 8 and 13 weeks of gestation. Duration of the procedure, number of needle passes, sample weight, maternal age, fetal gender, and FHR response to CVS were recorded.The FHR before but not after CVS was inversely correlated with gestational age (r = -0.406, p0.001). Conversely, following CVS, no correlation was observed between FHR and gestational age (r = -0.06, p = 0.27). The difference between FHR after CVS and that obtained before CVS (delta FHR) increased with increasing gestational age at sampling (r = 0.372, p0.0001), decreased with increasing specimen weight (r = -0.16, p = 0.01) and increased with increasing maternal age (r = 0.22, p0.0001). Duration of the procedure, fetal gender and number of needle passes did not affect delta FHR. Multiple logistic regression indicated that gestational age at CVS and maternal age but not the other variables significantly affected delta FHR and together they accounted for over 22% of the variance (R(2) = 0.224, p0.0001).In summary, our results suggest that acute fetal hemodynamic changes accompany CVS and that these changes vary with gestational age.

Proper nutritional status of women before, during, and after pregnancy is an important element of reproductive health. It maintains maternal health and reduces the risk of adverse pregnancy outcome, birth defects and chronic disease in children later in postnatal life. Pregnancy creates a special metabolic demand for high-quality nutrients. With careful food selection, it is possible to obtain most of the recommended levels of nutrients. Apart from the dietary intake, nutrition is highly dependant on economic status, social and cultural environment, and personal habits of the mother. Nutritional imbalance could cause detrimental effects to the pregnant woman, influence pregnancy outcome, and impair breast milk composition. Despite the extensive research, we still do not have a complete understanding how nutritional status of the mother influences her health as well as fetal growth and development. It is well known that fetal growth and development is strongly linked with maternal supply of essential nutrients, e.g. vitamins. The exact role of the variety of micronutrients in fetal growth and development has yet to be explored in detail. It is estimated that up to 30% of pregnant women suffer from a vitamin deficiency. Without supplementation, about 75% would show a deficit of at least one vitamin. Moreover, multivitamin deficit combinations often co-exist, and subclinical depletations are probably common; consequences could be severe. Studies carried on in developing countries have shown that improving micronutrient intake in deficient women can reduce maternal morbidity and mortality. Also, proper maternal intake of important micronutrients directly enhances the quality of breast milk. To meet the increasing demands during pregnancy and the breastfeeding period women should not be dependent only upon the dietary intake: adequate reserve is essential for the successful pregnancy outcome.

It is widely accepted that micronutrients have a major function in many periods of women's life, particularly during pregnancy and lactation. Inadequate stores or intake of micronutrients might have adverse effects both to the mother (hypertension, anemia, complications of labor) and the fetus (congenital malformations, pre-term delivery, intrauterine growth retardation). The effect of improper nutrition is influenced by gestational age, severity of deficiency, or both. Generally, the daily requirements in minerals and trace elements are easily met in women having a balanced diet. Such diet during pregnancy should provide the recommended daily allowance of all nutrients except elemental iron. Consequently, deficiency states are supposed to be rare in developed countries, and supplementation should be made on an individual basis. On the other hand, nutritional deficiencies during pregnancy might be difficult to detect. Studies from developing countries where micronutrient malnutrition is common during pregnancy gave us strong evidence that supplementation of certain trace elements and minerals could prevent some of the most severe adverse pregnancy outcomes. While some micronutrients have been studied extensively (e.g. calcium, iron, zinc, iodine), much less is known about others. It has been shown that multiple micronutrient deficiencies, rather than single deficiencies, are common. Our knowledge about the significance of interactions between micronutrients in relation to pregnancy outcome is limited. The role of these interactions in improving pregnancy outcome need to be investigated more precisely. According to the summarized data, the potential benefits of routine supplementation seem to outweigh any potential adverse reaction that can be attributed to their consumption.

Women conceiving by assisted reproduction are at higher risk for preterm and premature rupture of membranes. The aim of our study was to estimate and compare incidence of preterm premature rupture of membranes in singleton pregnancies of women who conceived by intrauterine insemination and in vitro fertilization, from 1999 to 2003. We investigated 87 women from the intrauterine insemination, and 102 from the in vitro fertilization program. There were no statistically significant differences in regard to preterm and premature rupture of membranes: p>0.75 in two groups. The incidence of premature rupture of membranes was 2.30% (after intrauterine insemination) and 2.94% (after in vitro fertilization). There was no statistically significant differences in regard to preterm and premature rupture of membranes in women who conceived by insemination and in vitro fertilization. Estimated incidence of preterm and premature rupture of membranes was similar to the literature data and also similar to incidence after natural conception.

To assess the correlation of fetal and maternal plasma leptin concentrations during the second half of uncomplicated, euploid pregnancies and to compare these values with those obtained from pregnancies with Down syndrome.Paired maternal venous and fetal umbilical blood samples were obtained during cordocentesis in 36 uncomplicated, euploid pregnancies and nine pregnancies with Down syndrome fetuses. Concentrations of leptin were measured by sensitive radioimmunoassay.Among pregnancies with euploid fetuses, there was significant correlation between both fetal and maternal leptin levels and gestational age (r = 0.464, p = 0.005 and r = 0.629, p0.001, respectively). Fetal plasma leptin concentrations also correlated with maternal levels (r = 0.485, p = 0.003), but fetal levels were significantly lower than maternal values (mean 2.12 +/- 0.44 ng/ml vs. 17.79 +/- 5.48 ng/ml, respectively; p0.001). Down syndrome fetuses had significantly lower fetal plasma leptin levels than gestational age-matched control euploid fetuses (0.72 + 0.54 ng/ml vs. 2.12 + 0.44 ng/ml; p0.002). However, there was no difference in maternal leptin concentrations between euploid and Down syndrome pregnancies.In euploid pregnancies, fetal leptin levels were significantly lower than the corresponding maternal values but increased across gestation. Down syndrome was associated with significantly lower fetal leptin levels.

Intrauterine transfusions for rhesus alloimmunization leads to alterations in circulating T-cell populations. Given that elevations in circulating beta2-microglobulin are a marker of T-cell-mediated organ transplant rejection, we evaluated the effect of intrauterine transfusion on fetal beta2-microglobulin levels.Umbilical venous samples were obtained immediately prior to initial transfusion in ten anemic fetuses and in 12 fetuses with prior transfusions. Samples were also obtained from 18 gestational age-matched non-anemic fetuses and eight healthy neonates.The median concentration of beta2-microglobulin was significantly higher in fetuses with prior transfusions compared with non-anemic controls. In non-anemic controls, and in transfused fetuses, beta2-microglobulin levels decreased throughout gestation (r = -0.69, p = 0.01; and r = -0.80, p = 0.01, respectively). Among anemic and transfused fetuses, beta2-microglobulin levels displayed a negative correlation with fetal hematocrit (r = -0.62, p0.05; and r = -0.58, p = 0.04, respectively).We conclude that intrauterine transfusion for fetal anemia is associated with increased beta2-microglobulin levels, suggesting immunomodulatory effects of intrauterine transfusion on host immune responses to donor leukocyte antigens.

Background Resveratrol (RSV) is polyphenol present in various kinds of food which we consume on daily basis. In the last ten years there has been growing importance of RSV in the literature. It is well known that RSV has many different beneficial effects on human health. RSV is partly responsible for the cardiovascular benefits of red wine. However, the mechanism of vasodilatation induced by RSV is unclear. There are many target molecules of RSV which could play an important role in the mechanism of action of RSV. The aim of our study was to define the role of K channels in the RSV-induced vasodilatation of human umbilical vein (HUV) denuded of endothelium.

This study was conducted to determine whether fetal blood sampling during the second trimester is associated with changes in circulating fetal beta-endorphin (BE) concentrations. We measured BE concentrations in 68 paired fetal and maternal blood samples obtained between 18 and 28 weeks' gestation. Patients were divided into a control group (n = 50), if the fetal blood samples were obtained by a single umbilical cord puncture, or multiple insertion group (n = 18), if multiple cord punctures were required to obtain a sample. The mean (+/- SE) fetal BE value for the multiple insertion group was significantly higher than BE levels from the control group (771.2 +/- 79.2 pg/ml versus 107.1 +/- 11.7 pg/ml; p0.001]. This elevation did not appear to be related to acidosis, since no differences in fetal umbilical pH were observed between the two groups. Fetal BE levels from the control but not from the multiple insertion group significantly correlated with maternal values (Spearman rank r = 0.59; p0.001 vs r = -0.08; p0.5). In neither group did fetal BE levels correlate with gestational age. These findings indicate that multiple cord punctures at the time of fetal blood sampling are associated with significant increases in BE release. Furthermore, although a maternal or placental contribution to steady state circulating fetal BE cannot be excluded, it would seem that the fetus itself is the primary source of elevated circulating BE levels following multiple cord punctures.

Background Serotonin (5-HT), is a vasoactive substance involved in physiological functioning of fetoplacental blood flow and continuous modulation of smooth muscle tone in umbilical vein and arteries. Since umbilical blood vessels have been shown to be deficient in autonomic innervation, the action of local autocrine vasoactive substances (including serotonin) is of considerable importance. Although seven main groups of 5-HT receptors (5-HT1-7) have been characterized, it has been established that only several 5-HT receptor subtypes may be involved in vascular effects of this biogenic amine. Therefore, the aim of this study was to characterize receptors involved in serotonin-induced effect on isolated human umbilical artery (HUA) in uncomplicated pregnancy.

OBJECTIVE: Endogenous opiates may playa role in both fetal physiologic functions and the adaptation to intrauterine stress. However, our understanding of this role is hampered by an absence of data on circulating levels of these substances during fetal life. STUDY DESIGN: We measured serum J3-endorphin values with a radioimmunoassay in 81 paired fetal and maternal blood samples and 24 neonatal cord specimens. The former samples were uneventfully obtained from uncomplicated pregnancies between 18 and 39 weeks of gestation at the time of cordocentesis for prenatal diagnosis. RESULTS: Mean fetal J3-endorphin concentrations were significantly lower than J3-endorphin values from neonates (90.5 pg/ml [± 59.4] vs 228.4 pg/ml [± 166.2]; p < 0.001), but significantly higher than mean maternal values (70.5 pg/ml (±48.8]; p < 0.02). Although fetal J3-endorphin levels decreased between 18 and 28 weeks' gestation, the correlation between fetal J3-endorphin values and gestational age was not significant (r = 0.193; P = 0.07). However, fetal J3-endorphin concentrations were significantly correlated with maternal values (Spearman's rank r = 0.47; P < 0.001). CONCLUSION: These findings suggest that delivery or fetal adaptation to an extrauterine environment is associated with significant increases in J3-endorphin release. Moreover, although the fetal pituitary may be the primary source of circulating fetal J3-endorphin, a maternal or placental contribution cannot be excluded. Our data identify a physiologic range for fetal J3-endorphin concentrations. (AM J OSSTET GVNECOL 1992;167:740-4.)