Maternal hemodynamic influence on uteroplacental oxygen distribution during cesarean section.

This study investigated maternal hemodynamic influence on uteroplacental oxygen distribution and neonatal outcome during cesarean section (CS). CS was performed on 80 parturients using two anaesthetic techniques: spinal anaesthesia (SA) and general balanced anaesthesia (GBA). Indications for CS were exclusively obstetric related. Monitored maternal parameters were: ECG, heart rate (HR), non-invasive blood pressure (NIBP), saturation (SaO2). Gas parameters in umbilical artery, vein, and neonatal capillary blood were sampled. Vitality was assessed by the Apgar scoring, first breath-taking time and the first breastfeeding attempt. Hypotension was the most common finding after SA induction. GBA group presented changes such as QT inversion (12.5%), tachycardia (55%), and bradycardia (2.5%). SA group experienced higher rates of sinus tachycardia (45%) and ventricular dysrhythmias (2.5%). Neonatal oxygenation was significantly higher in SA group. Higher quality of early neonatal adaptation in the SA group confirms it as the technique with the least neonatal risk during CS.

Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium.

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.

Middle cerebral artery Doppler in prediction degree of fetal anemia and the best timing for the second intrauterine intravascular transfusion in red cell alloimmune disease.

AIM: To determine the role of fetal multiples of the median of middle cerebral artery peak systolic velocity (MoM MCA-PSV), predicts the rate of decline in fetal hematocrit (Hct) for determination of the best timing for the second intrauterine intravascular transfusion (IUIVT) in fetuses with Rh alloimmunisation. MATERIALS AND METHOD: Retrospective study of 59-monofetal alloimmunized pregnancies from 2005 to 2012 that underwent first and second IUIVT were assessed in Department of Gynecology and Obstetrics, Belgrade, Serbia. RESULT: There was an inverse statistically significant correlation between measurements MCA MoM-1 and fetal Hct-1 before the first IUIVT r = -0.622; p = 0.001 and MCA-MoM-3 and Hct-3 before the second IUIVT r = -0.381; p = 0.001, also as the significant correlation between the interval between both procedures (expressed in day) and measurement MCA-MoM-3, before the second IUIVT r = -0.284; p = 0.029. CONCLUSION: The measurements MoM-MCA before every IUIVT can be useful for prediction of the best timing for the next IUIVT.

Pregnancy and delivery after vesico ileocystoplasty--a case report.

Neobladder is continent urinary reservoir made from a detubularized segment of bowel, with implantation of ureters and urethra. The most common indication for this operation is bladder replacement after cystectomy following bladder cancer in elderly or cervical cancer Stage IV patients. Nowadays indications are expanded to many benign diseases (interstitial cystitis (IC), neurogenic bladder, chronic pelvic pain) in reproductive age. Pregnancy in women with neobladder is a rare condition, hence published experience is limited. Most of the published cases were delivered by cesarean, due to the concern for possible complications. The authors report a case of a 36-year-old woman who underwent a vesico ileocystoplasty for IC, became pregnant six years after the operation, and delivered a healthy baby vaginally. Her obstetric and urologic outcomes were assessed, during, and after pregnancy. Careful antenatal monitoring by both an obstetrician and a urologist, awareness of potential complications, and their prompt treatment, can result in a successful pregnancy and vaginal delivery where neither fetus or mother nor neobladder are endangered.

Perinatal outcome of singleton pregnancies following in vitro fertilization.

PURPOSE OF INVESTIGATION: To determine whether in vitro fertilization/intracytoplasmatic sperm injection (IVF/ICSI) singleton pregnancies are at increased risk for maternal and fetal complications than spontaneous singleton conceptions. MATERIALS AND METHODS: The pregnancy outcome of 634 singleton pregnancies after IVF/ICSI delivered at the Clinic for Gynecology and Obstetrics during the period January 2006 to January 2010 were compared to 634 matched singleton controls, matched one by one by age, parity, education, and body mass index (BMI). Differences in pregnancy outcomes between the groups were assessed using Student's t-test with Yates correction for continuous variables and Chi-squared test for categorical variables. RESULTS: The mean gestational age at delivery of the IVF group was 38.13 +/- 1.72 weeks, slightly shorter than spontaneously conceived singletons at 38.65 +/- 1.79 weeks. The diagnosis of gestational diabetes mellitus (GDM) was frequently made in the IVF group (11.82% vs 8.35%, t = 2.052, p < 0.05). Total preterm delivery rate of IVF pregnancies was 9.30%, significantly higher than the controls 5.85% (t = 2.33, p < 0.05), especially at the 30-32 weeks gestation period. The predominant mode of delivery after IVF pregnancy was cesarean section (80.75% vs 31.38% at spontaneously conceived, t = 17.71, p < 0.001), while vaginal route was the choice for naturally originated pregnancies 68.6% vs 19.24% (p < 0.01). No differences were found in the average birth weights, LBW, VLBW, SGA, and LGA regarding the pregnancy origin. Perinatal mortality rates were comparable among singletons with different pregnancy origin. CONCLUSIONS: Singletons from IVF/ICSI pregnancies have poorer perinatal outcome associated with higher rates of cesarean sections, preterm birth and prematurity, fetal malpresentation (breech presentation), and the occurrence of maternal GDM in pregnancy.

The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K(+) channels.

This study was aimed to evaluate resveratrol (1-100 µM) effect on the spontaneous rhythmic contractions (SRC), oxytocin-induced (0.2 nM, POxC) phasic and tonic (20 nM, TOxC) contractions of isolated rat uterus. The SRC and POxC were more sensitive to resveratrol than TOxC (pD2 values: 4.53 and 4.66 versus 4.06). Different blockers of K(+) channels (glibenclamide, tetraethylamonium, iberiotoxin, 4-aminopyridine) antagonized the response to resveratrol on the SRC and phasic contractions, but did not antagonize the effect of resveratrol on the TOxC. In order to compare the relaxant activities of resveratrol on the TOxC with that of potassium channel openers, a separate experiments with NS 1619, a highly specific big Ca(2+)-sensitive K(+) (BKCa) channels opener and pinacidil, a predominant opener of ATP-sensitive K(+) (KATP) channels were done. NS 1619 (10-100 µM) and pinacidil (10-100 µM) produced more potent inhibition of TOxC than resveratrol (pD2 values were 6.00 and 5.29). Iberiotoxin, a highly selective BKCa channels blocker, antagonized the response to NS 1619 and glibenclamide, a highly selective KATP channels blocker, antagonized the response to pinacidil on the TOxC. To test K(+)- and extracellular Ca(2+)- independent mechanism(s) of resveratrol on TOxC, a K(+)-rich, Ca(2+)-free solution was used. Under this condition, only high concentrations (≥30 µM) of resveratrol inhibited TOxC. Western blots analysis confirmed expression of Kir6.1, Kir6.2, KCa1.1, Kv2.1 and Kv4.2. channel proteins in myometrium. Thus, the effect of resveratrol is dependent on the types of contractions. The inhibitory response of resveratrol on the SRC and phasic contractions involves different myometrial K(+)- channels. When applied in high concentrations, resveratrol has an additional K(+)- channels independent mechanism(s) of action. As the effects of NS 1619, pinacidil and resveratrol on the TOxC are different, we can conclud that resveratrol does not behave as a classical potassium channel opener.

Intramuscular fetal corticosteroid therapy: short-term effects on the fetus.

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.

Intramuscular fetal corticosteroid therapy short-term effect on maternal-fetal Doppler velocimetry.

AIM: The aim of the study was to assess the short-term effects of intramuscular (IM) corticosteroid therapy (CST) on fetoplacental and fetal circulation in high-risk pregnancies of preterm labor. METHOD: We evaluated the effect of IM fetal single-dose dexamethasone (4 mg/kg) on fetoplacental and fetal circulation two hours before and 0-4 hours after CST in 38 fetuses after the 32nd week of gestation. RESULT: Changes in the umbilical artery (UA) resistance index (RI) after fetal CST (AU RI1) were significantly correlated with gestational age after the 32nd week at recording r = 0.354; p < 0.05. There was a statistically significant difference of RI in the descending aorta (DAo) before and after therapy; p < 0.001 (-0.04-0.01), 95% confidence interval (CI) for differences. CONCLUSION: Short-time effects after fetal IM CST include an increased index resistance in DAO as well as decreased RI in UA after the 32nd week.

Two cases of immature teratoma with positive reproductive outcomes.

The peak incidence of immature teratoma is in the early reproductive period of a woman's life and fertility preservation is an inevitable topic when discussing treatment options. We present two cases of immature teratoma with positive reproductive outcome. Our experience supports the standpoint that surgery alone is curative in most cases, irrespective of tumor grade. Bearing this in mind, the long-term effect of chemotherapy on ovarian function can be avoided and fertility, an important factor in the overall quality of life, can be preserved.

Fetal and maternal plasma leptin levels during the second half of normal pregnancies and those with Down syndrome.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p < 0.001, 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; p < 0.001). 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; p < 0.002). However, there was no difference in maternal leptin concentrations between euploid and Down syndrome pregnancies. CONCLUSION: 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 transfusion for rhesus alloimmunization elevates fetal beta2-microglobulin levels.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p < 0.05; and r = -0.58, p = 0.04, respectively). CONCLUSIONS: 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.

Plasma apolipoprotein A-I and B concentrations in growth-retarded fetuses: a link between low birth weight and adult atherosclerosis.

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; P<0.001]. 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.

Neopterin concentrations in fetal and maternal blood: a marker of cell-mediated immune activation.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

New technique for artificial lung maturation. Direct intramuscular fetal corticosteroid therapy.

The aim of this study was to present a new technique of administration of antenatal corticosteroid therapy in order to cause fetal lung maturation. A single dexamethasone dose of 4 mg was applied directly to the fetal gluteal musculature by ultrasound-guided intramuscular injection 48 h before delivery. This technique of fetal corticosteroid therapy was applied in six cases. Our patients had high risk pregnancies (preeclampsia diabetes mellitus, intracranial hemorrhage, epilepsy, hyperthyreosis). The pregnancies were terminated in the mother's vital interest. The lecithin/sphyngomyelin (US) ratio was < 1.5:1. There were no procedure-related complications. The fetuses were delivered by cesarean, 48 hours later except for the vaginal delivery in the patient in which fetal death occurred in utero. In five cases an uneventful outcome of fetuses indicated that direct fetal corticosteroid treatment improved postnatal lung function in preterm fetuses. A new technique of corticosteroid application successfully prevents respiratory distress in preterm infants decreasing the risk of maternal complications. To our knowledge, this is the first report of fetal intramuscular corticosteroid therapy in the human population.

The effect of fetal intravascular blood transfusion on plasma endothelin levels in fetuses with rhesus alloimmunization.

OBJECTIVE: To determine if intrauterine intravascular fetal transfusion affects fetal umbilical venous endothelin levels. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Corticotropin-releasing hormone and related pituitary-adrenal axis hormones in fetal and maternal blood during the second half of pregnancy.

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.

Intra-amniotic Chlamydia trachomatis infection.

Chlamydia trachomatis is one of the most prevalent genital pathogens in pregnant women. Ascending, transcervical infection may reach fetal membranes creating chorioamnionitis or amniotic fluid infection. The aim of this study was to examine amniotic fluids obtained during cesarean section for the presence of chlamydial IgM- and IgG-specific antibodies, and for the presence of C. trachomatis antigen. Five of 52 (9.6%) amniotic fluid samples were seropositive. Two of 52 (3.8%) amniotic fluid samples had C. trachomatis antigen in the epithelial cells of the amnion. In conclusion, our data indicate that there is a high rate of transmission of C. trachomatis from mother to infant and that the pathogen can be identified in the amniotic fluid.

[Chlamydia trachomatis infection in newborn infants]. / Infekcija novoredjenceta uzrocnikom Chlamydia trachomatis.

The aim of our study was to examine the frequency of Chlamydia trachomatis infection in newborns by detecting specific antibodies, and to examine the Apgar score and the birth weight of Chlamydia trachomatis-antibody positive children. Fifty-two newborn infants were tested. High serum IgG chlamydial specific antibody titers had 11 (21%) newborns, while high serum IgM titers had 9 (17%) newborns. Our results showed that serum Chlamydia trachomatis-specific IgM antibodies were detected statistically more often in low birth weight newborns (<2500 g) (p < 0.05).

Fetal and maternal plasma endothelin levels during the second half of pregnancy.

OBJECTIVE: Our objective was to evaluate maternal and fetal endothelin concentrations in uncomplicated pregnancies across the second half of pregnancy. STUDY DESIGN: 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. RESULTS: 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; p < 0.0001] but significantly higher than maternal levels [1.3 pg/ml (0.8 to 3.25); p < 0.0001]. 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). CONCLUSION: Fetal endothelin levels were significantly higher than maternal levels, but neither correlated with gestational age across the second half of pregnancy.