Maternal estradiol response to alterations in uteroplacental blood flow

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.     

Maternal blood viscosity and uteroplacental blood flow velocity waveforms in normal and complicated pregnancies

According to the Poiseuille-Hagen law, viscosity influences flow resistance. A possible effect of blood viscosity upon the resistance index of the uteroplacental circulation as measured by continuous wave Doppler ultrasound was investigated in 50 pregnant women. It was found that blood viscosity variables explained only about 10% of the variation in the resistance index in all patients, which was not statistically significant. It is suggested, therefore, that the vascular contribution to flow resistance may be more important.     

Maternal blood viscosity and uteroplacental blood flow velocity waveforms in normal and complicated pregnancies

Summary. According to the Poiseuille-Hagen law, viscosity influences flow resistance. A possible effect of blood viscosity upon the resistance index of the uteroplacental circulation as measured by continuous wave Doppler ultrasound was investigated in 50 pregnant women. It was found that blood viscosity variables explained only about 10% of the variation in the resistance index in all patients, which was not statistically significant. It is suggested, therefore, that the vascular contribution to flow resistance may be more important.     

Maternal, uteroplacental, and fetoplacental hemodynamic and Doppler velocimetric changes during epidural anesthesia in normal labor

Pulsed Doppler and M-mode maternal echocardiography were combined with uterine and umbilical artery Doppler velocimetry to characterize the hemodynamic changes associated with fluid preload and epidural anesthesia in 12 normal laboring gravidas at term. Fluid preload alone was associated with significant (P less than .05) increases in heart rate (11%), stroke volume (10%), and cardiac output (20%), and a decrease in systemic vascular resistance (19%). There were no changes in mean arterial pressure (MAP) or ejection fraction during any stage of the study. Following placement of the epidural block, stroke volume and cardiac output returned to values not significantly different from baseline, whereas heart rate remained elevated and systemic vascular resistance remained decreased. There were no changes in uterine or umbilical artery systolic-diastolic (S-D) ratios during any stage of the study. We conclude that fluid preload and epidural anesthesia cause significant changes in maternal cardiac output, heart rate, stroke volume, and systemic vascular resistance without affecting MAP. These maternal changes do not correlate with any changes in uterine or umbilical artery S-D ratios following epidural anesthesia in the normal laboring gravida.     

Impaired development of uteroplacental circulation

OBJECTIVE: To sum up the knowledge of uteroplacental circulation, their dysfunction and etiology and pathogenesis of preeclampsia. TYPE OF STUDY: Review. SETTING: Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University, Prague, Institut of Pathological Physiology, 1st Faculty of Medicine, Charles University, Prague. SUBJECT OF STUDY: A summary of what is known about development of uteroplacental circulation predispose women to the development of preeclampsia and IUGR but the etiology of preeclampsia is still unknown.     

Dihydralazine and the uteroplacental blood flow

A tuberculous tuboappendiceal fistula was demonstrated on a hysterosalpingogram in an asymptomatic patient being evaluated for infertility. Antituberculous medical treatment resulted in closure of the fistula.     

Maternal indomethacin therapy in the treatment of polyhydramnios

Fifteen patients with polyhydramnios and clinical symptoms related to excess amniotic fluid volume were treated with indomethacin therapy that was started at a mean gestational age of 27.4 +/- 2.79 weeks and discontinued at a mean gestational age of 32.9 +/- 1.83 weeks. Patients were treated with 2.0 to 2.2 mg of indomethacin per kilogram of body weight per day, either orally or by rectal suppositories. No therapy was administered after 35 weeks, and the duration of therapy was no longer than 4 weeks. The majority of fluid reduction occurred within the first week of treatment. Subsequently, a smaller but steady reduction of fluid was observed. All patients were delivered after 38 weeks with a mean birth weight of 3543 +/- 586.3 gm. Examinations of newborns at birth and follow-up at 3 months, 6 months, and 1 year revealed no adverse effects of indomethacin administration.     

Modification of uteroplacental circulation by solcoseryl

Pulsed ultrasonic doppler flow measurements both on uterine arcadic arteries and umbilical arteries have been done in 10 pregnant women suspected for intrauterine fetal growth retardation before, during and after Solcoserylinfusions for ten days. Improvement of maternal uteroplacental blood flow may be caused by changed rheologic blood properties as well as by physical inactivity. Fetal umbilical cord blood flow could not be influenced by Solcoseryl.     

Assessment of uteroplacental circulation with radioisotopes

The authors have evaluated placental blood flow using a non-invasive radioisotopic approach, with the intravenous administration of 1 mCi 113mIn. The method is evaluated in 20 normal pregnancies, in 24 patients with intrauterine growth retardation, in 8 patients with iso-Rh-immunization and in 9 patients with gestational diabetes. In the group with intrauterine growth retardation 2 pregnancies with extensive fetal malformations were included. In one case without evident histological placental alteration the index was 3.94 at 34 weeks of gestation and 5.62 at 36 weeks of gestation. In the second one with placental infarcts the index was 3.46 at 38 weeks of gestation. Normal pregnancies showed a flow index of 5.50 +/- 1.57 (1 s.d.) units compared to the pathological pregnancies value of 2.74 +/- 0.90 (1 s.d.) units. (p less than 0.001). The conclusions drawn are: The method is very well suited to clinical evaluation of placental blood flow. The evaluation of placental blood flow cannot be directly equated with fetal development as it is not its only determinant. This method is a indirect index of placental function in small for gestational age fetuses with malformations.     

Maternal pulmonary edema resulting from betamimetic and glucocorticoid therapy

Four cases are presented of maternal pulmonary edema occurring in patients who had no primary cardiac disease but who were receiving terbutaline and glucocorticoids or terbutaline alone for treatment of premature labor. Fluid overload was the event that triggered this decompensation. The physiologic high-output cardiac state of pregnancy is described and the manner in which betamimetic drugs and corticosteroids exacerbate this situation and cause congestive heart failure is shown. Methods of management to avoid this complication of premature labor therapy are suggested.     

Current topic: the uteroplacental renin-angiotensin system

The components of the renin-angiotensin system (RAS) are expressed in the uteroplacental unit. The expression varies between species, probably due to the marked species differences in placental architecture. The conditions for angiotensin (Ang) II formation exist and Ang II receptors are present throughout the human uteroplacental unit, indicating the presence of a functional local RAS. The uteroplacental RAS interacts with other regulatory systems and in this way modulates various aspects of tissue function. It is suggested that the uteroplacental RAS is important for the regeneration of the endometrium after shedding, and for decidualization, implantation and placentation. The RAS participates in the regulation of the uteroplacental blood flow, prostaglandin synthesis and oestradiol secretion. Disturbances of the uteroplacental RAS may lead to dysfunctional bleeding and to reduced uteroplacental blood flow in pregnancies complicated by pre-eclampsia and intrauterine growth retardation.     

Effects of smoking on uteroplacental blood flow

The effects of nicotine consumption on uteroplacental blood flow were studied in 20 pregnant women by means of placental blood flow measurements using indium-113m-transferrin. Smokers were found to have a higher rate of poor perfusion patterns than subjects of a control group. In addition, the number of cigarettes smoked daily was significantly correlated with the placental perfusion type. The mean birth weight of infants born by smokers was 250 g lower than in the control group. The results suggest that smoking during pregnancy may compromise uteroplacental blood flow and thus result in poor fetal development.     

Fetal gene therapy

Fetal gene therapy has the potential to treat inherited genetic diseases in utero before significant organ damage has occurred. Rapidly expanding stem cell populations may be targeted and the introduction of transgenes to the fetus during development of the immune system could result in immune tolerance and facilitate repeat treatment postnatally. Genetic diseases such as cystic fibrosis, which are life-threatening and for which there are no currently acceptable treatments available, are suggested targets for this therapy.

Ultrasound may be a safe method of delivering a therapeutic gene into the fetus, although most studies have used more invasive techniques, even in large animal models. Viral vectors currently offer the most potential. Adenovirus-based vectors are stable, independent of host cell replication, efficient at tissue infection and have been used as a 'pathfinder' to test routes of administration. Unfortunately, they are also highly immunogenic and other systems based on retrovirus or adeno-associated virus may offer advantages because of their lower immunogenicity and potential for permanent transgene expression.

Our group is developing the fetal sheep model for the investigation of ultrasound-guided gene therapy in utero. This model is suitable since the sheep fetus is tolerant to manipulations, has a consistent gestation period and shows many similarities with human pregnancy. We have demonstrated significant transfection of the fetal liver and adrenal cortex after ultrasound-guided percutaneous injection of the umbilical vein with adenoviral vectors in the late gestation sheep. We are investigating and here discuss alternative routes of administration to target the fetus in early gestation via ultrasound-guided minimally invasive techniques.