Tissue and plasma concentrations of pregnancy-associated plasma protein-A (PAPP-A): comparison with other fetoplacental products

Human placental lactogen (hPL), alpha fetoprotein (AFP), prolactin (PRL) and pregnancy-associated plasma protein-A (PAPP-A) were measured by radioimmunoassay in plasma, in homogenates of trophoblast, decidua, chorion, amnion and in amniotic fluid from 10 patients after non-complicated term delivery. Plasma samples and homogenates of trophoblast and decidua were also collected from 10 patients undergoing surgical termination of pregnancy between 7 and 12 weeks gestation. In addition, plasma and endometrial samples from 10 patients undergoing hysterectomy for other indications than malignancy were analysed for comparison. The highest tissue concentrations of hPL, AFP and PRL corresponded in each case to the known site of synthesis. For PAPP-A the highest concentration was found in maternal plasma at term [238.8 +/- 75.6 (SEM) micrograms/ml]. The highest tissue concentration was found at term in the decidua (57.0 +/- 2.0 micrograms/g), more than three times higher than that in the trophoblast (16.9 +/- 5.4 micrograms/g). The concentrations of PAPP-A in endometrial samples from non-pregnant women (1.9 +/- 0.6 micrograms/g) was 40 times higher than that in the corresponding plasma samples (0.05 +/- 0.02 microgram/ml). These observations point to the decidua as a possible source of PAPP-A.     

Placental transfer of metronidazole in the first trimester of pregnancy

Concentrations of metronidazole and its hydroxy metabolite (I) were determined by a specific chromatographic method in blood, placenta and fetus from 10 women receiving oral metronidazole prior to legal first trimester abortion. In one woman given 2 g of metronidazole 9 hours before abortion, placenta and plasma levels were 6.6 micrograms/g and 13.4 micrograms/ml, respectively. The corresponding values for the hydroxy metabolite (I) were 1.8 micrograms/g and 5.6 micrograms/ml. In nine women receiving 400 mg metronidazole 1 hour before abortion, concentrations of metronidazole in plasma ranged from less than 0.1 to 9.4 micrograms/ml, in placenta from less than 0.1 to 6.3 micrograms/g, and in a fetal tissue from 1.9 to 3.0 micrograms/g. The concentrations of hydroxy metabolite (I) in plasma and placenta and fetal tissue all ranged below those of metronidazole.     

Adrenal androgen production in hyperprolactinemic states

In order to better define the kinetics of the adrenal androgens in hyperprolactinemic states, we have studied 10 patients suspected of having a pituitary prolactinoma. Compared with the levels in 10 healthy control women (normal range: N), no significant differences in the mean (+/- standard error) plasma concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), androstenedione (A), and testosterone (T) were found: F, 22.7 +/- 2.6 micrograms/100 ml (N = 10 to 25); DHEA, 7.5 +/- 1.4 ng/ml (N = 3.0 to 12.5); DS, 1.7 +/- 0.3 micrograms/ml (N = 1.1 to 3.6); A, 2.2 +/- 0.3 ng/ml (N = 0.5 to 3.5); T, 30.5 +/- 6.4 micrograms/100 ml (N = 20 to 80). Using constant infusions of unlabeled steroid, the metabolic clearance rates (MCR) of the adrenal androgens DHEA and DS were found to be 1282.6 +/- 342.6 liters/day and 5.6 +/- 1.4 liters/day, respectively, which were no different from the MRC of 1689.4 +/- 364.2 liters/day and 6.8 +/- 1.9 liters/day, respectively, found in the normal control women. Medical therapy with a dopaminergic agent in three of these patients reduced mean circulating levels of prolactin from 81.1 +/- 4.7 ng/ml to less than 15 ng/ml but did not change any of our results. It is concluded that, in the study group, hyperprolactinemia exerted minimal trophic effects on the production rates of adrenal androgens.     

Acetyl-l-carnitine as possible drug in the treatment of hypothalamic amenorrhea.

Several neuroendocrine disregulations have been demonstrated in patients with hypothalamic amenorrhea, but a definite therapeutic strategy has not yet been found. Since acetyl-l-carnitine (ALC) has been reported to have a specific effect on central cholinergic, serotoninergic, dopaminergic and opioidergic systems, 20 patients with hypothalamic amenorrhea were treated with ALC (2 g/day, per os). Both the clinical efficacy and the endocrine parameters were evaluated after 6 months. The patients were subdivided in two groups according to their LH plasma levels: A) hypogonadotropic: 10 subjects with plasma LH less than 3 mIU/ml, and B) normogonadotropic: 10 subjects with plasma LH greater than 3 mIU/ml. All subjects underwent: 1) a pulsatility study (4 h sampling every 10 min), 2) GnRH test (two bolus injections of 10 micrograms at time 0 and +120), 3) TRH test (200 micrograms). These parameters were evaluated before and after 6 months of ALC administration. The occurrence of a spontaneous menstruation was observed in 6 out of 10 hypogonadotropinemic and in 4 out of 10 normogonadotropinemic patients. Menstrual bleeding occurred between the 3rd and the 6th month of therapy. Major hormonal changes after ALC administration were observed in the hypogonadotropic subjects. They showed a significant increase in baseline plasma LH levels (from 0.9 +/- 0.1 to 3.5 +/- 0.7 mIU/ml, p less than 0.05) (mean +/- SEM), a significant increase in LH pulse amplitude (p less than 0.01) with no changes in LH pulse frequency, and a significantly increased response of LH to the latter GnRH bolus during the GnRH test. Hypogonadotropic patients also showed a significant increase in both estradiol (from 18.8 +/- 2.5 to 48 +/- 3.3 pg/ml, p less than 0.05) and PRL (from 6 +/- 1 to 11.4 +/- 1.7 ng/ml, p less than 0.05). No significant differences were observed in the hormonal parameters of normogonadotropic patients after 6 months of ALC therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired gonadotropin responses to gonadotropin-releasing hormone stimulation in endurance-trained women

The effects of endurance running on body composition, menstrual cycles, and gonadotropins were studied in 19 healthy, young, regularly menstruating women. Midfollicular plasma concentrations of unstimulated and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone and follicle-stimulating hormone were examined at baseline and after each subject's weekly mileage had increased 30 miles (delta 30) and 50 miles (delta 50) above baseline. Mean +/- standard error of the mean unstimulated luteinizing hormone and follicle-stimulating hormone did not change significantly. GnRH-stimulated luteinizing hormone was 76.3 +/- 22.0 micrograms/min/ml at baseline and declined to 20.2 +/- 4.5 micrograms/min/ml at delta 50 (P less than 0.02). GnRH-stimulated follicle-stimulating hormone was 28.4 +/- 7.0 micrograms/min/ml at baseline and declined to 9.6 +/- 2.1 micrograms/min/ml at delta 50 (P less than 0.02). There were no significant correlations between changes in body composition and changes in gonadotropin responses. Eighteen subjects developed oligomenorrhea.     

Cytosol progesterone and 17 alpha-hydroxyprogesterone levels and luteinizing hormone and chorionic gonadotropin receptors in human corpora lutea

Cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) levels and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors were measured in 27 corpora lutea and four corpora albicantia. Cytosol P concentrations were highest in corpora lutea (mean +/- SEM, 3.1 +/- 0.8 micrograms/g) during the midluteal phase (days 15 to 19) rather than the early (2.2 +/- 0.8 micrograms/g, days 20 to 25) and late luteal phases (1.8 +/- 0.8 micrograms/g, days 26 to 30). Cytosol 17-OHP concentrations also were 3.3 +/- 0.5, 4.3 +/- 0.6, and 3.3 +/- 1.0 micrograms/g in early, midluteal, and late luteal phases, respectively, and was significantly inversely correlated with occupied LH/hCG receptors in midluteal phase. Corpora albicantia had the lowest P (0.3 +/- 0.05 microgram/g) and 17-OHP (0.9 +/- 0.6 micrograms/g) concentrations. Cytosol P and 17-OHP may therefore reflect the balance between the luteal cell production and secretion, whereas the amount of occupied and unoccupied LH/hCG receptors may partially explain the relationship between LH and P secretion.     

Amniotic fluid norepinephrine concentration as an indicator of fetal sympathetic nervous activity. Effect of pregnancy complications

The concentrations of norepinephrine in amniotic fluid and maternal plasma were measured in 71 third trimester pregnancies, 31 of which were uncomplicated and 40 complicated. The amniotic fluid norepinephrine concentration (mean +/- SD) in cases of hypertension treated with clonidine (0.4 +/- 0.1 ng/ml, n = 12) and in insulin-dependent diabetes (0.5 +/- 0.2 ng/ml, n = 7) was lower, and in renal insufficiency (1.7 +/- 0.8 ng/ml, n = 8) higher than in control subjects (0.7 +/- 0.4 ng/ml, n = 31). In fetal-growth retardation (0.6 +/- 0.2 ng/ml, n = 8) and in latent diabetes (0.7 +/- 0.2 ng/ml, n = 5) the values were similar to those in the control subjects. There was a significant positive correlation between mature lecithin-sphingomyelin (L/S) ratio and norepinephrine concentration. Clonidine-treated hypertension was associated with decreased (0.2 +/- 0.1 ng/ml) and renal insufficiency with increased (0.9 +/- 0.7 ng/ml) maternal plasma norepinephrine concentrations (control group, 0.3 +/- 0.1 ng/ml). The present results indicate that measurement of catecholamines in amniotic fluid can be useful in the evaluation of fetal sympathoadrenal function.     

Follicular fluid concentrations of thiopental and thiamylal during laparoscopy for oocyte retrieval

Because access into ovarian tissue of drugs used during anesthesia may be potentially harmful to the oocyte and/or follicular structure, we measured concentrations of thiopental (n = 15) and thiamylal (n = 9) in follicular fluid (FF) aspirates of 24 patients who underwent laparoscopic oocyte retrieval. In both groups, measurable amounts of the respective drug were found in all FF aspirates. Within individual patients, plasma concentrations of both drugs declined during the period of sampling between initial and final follicular aspiration. The mean plasma drug concentration was 7.99 +/- 3.97 micrograms/ml in the thiamylal group and 4.13 +/- 0.90 micrograms/ml in the thiopental group. Mean drug concentrations in FF were similar in both groups (thiopental 1.62 +/- 0.61 micrograms/ml; thiamylal 1.67 +/- 0.83 micrograms/ml). The mean FF/plasma concentration ratio during the sampling period was greater in the thiopental group (0.41 +/- 0.19) as compared with the thiamylal group (0.22 +/- 0.14). Several steps in the clinical management of these patients can be taken to reduce exposure of oocytes to drugs used during anesthesia.     

Pharmacokinetics of ritodrine administered intravenously: recommendations for changes in the current regimen

We define the pharmacokinetics of ritodrine in 13 pregnant women who received the drug intravenously. With constant infusion of 50 micrograms/minute, steady state ritodrine concentrations reached 28 +/- 11 ng/ml (SD) with a range of 15 to 45 ng/ml. This wide variation is a result of differences in plasma clearance, which ranged from 1.0 to 3.3 L/min, mean 1.94 +/- 0.71 L/min. The apparent volume of distribution was 6.95 +/- 3.54 L/kg, indicating that ritodrine is extensively bound to extravascular tissue. When an infusion of ritodrine is stopped, plasma concentrations fall rapidly initially with a distribution half-life of 5.9 +/- 6.0 minutes. After the initial rapid fall, plasma concentrations decrease more slowly with a mean disposition half-life of 156 +/- 51 minutes. On the basis of the pharmacokinetic parameters defined, we recommend that the current infusion regimen for ritodrine be changed. The infusion rate of ritodrine should start at 50 micrograms/minute rather than 100 micrograms/minute. The maximal infusion rate of 350 micrograms/minute should be increased and once labor is inhibited, the infusion rate should be reduced.     

Plasma fibronectin levels in normal pregnancy and pre-eclampsia: a preliminary report

Fibronectin, a major component of the extracellular matrix and basement membranes throughout the body, is thought to maintain the integrity of both the reticulo-endothelial system and microvasculature. In this study, plasma fibronectin levels were assayed by nephelometry in nine pre-eclamptic gravid women, nine normotensive gravid women and ten non-gravid women. The mean plasma fibronectin level (+/-S.E.M.) in pre-eclamptic gravidas (1687 +/- 101 micrograms/ml) is significantly higher than that of either normotensive gravidae (1129 +/- 99 micrograms/ml) or non-gravid women (897 +/- 60 micrograms/ml). Although the mechanism for elevated levels of plasma fibronectin in patients with pre-eclampsia is not clear, it may serve as an early biochemical marker for this disorder.     

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.     

The role of vitamin E during pregnancy--anti-platelet aggregation activity of alpha-tocopherol

To clarify the role of vitamin E (alpha-tocopherol) during pregnancy, we mainly investigated the relation between platelet function and vitamin E and obtained the following results. 1. The concentration of vitamin E (alpha-tocopherol) in plasma and platelet increased gradually during pregnancy. The concentration of vitamin E in plasma was 6.65 micrograms/ml in non pregnant women and 15.5 micrograms/ml in full term pregnant women. And the concentration of vitamin E in platelet was 99 micrograms/g protein in non pregnant women and 244 micrograms/g protein in full term pregnant women. 2. Vitamin E (alpha-tocopherol) inhibited platelet aggregation induced by ADP (adenosine diphosphate) and PAF(platelet activating factor). At a concentration of 500 micrograms/ml vitamin E almost completely inhibited platelet aggregation induced by ADP and PAF. 3. There exists a strong platelet aggregation inhibiting activity in human placental brush border membrane vesicles. At a protein concentration of 20 micrograms/ml the brush border membrane vesicles almost completely inhibited platelet aggregation induced by ADP and PAF. 4. With the co-existence of the brush border membrane vesicles, the platelet aggregation inhibiting activity of vitamin E (alpha-tocopherol) increased prominently. These results indicate that vitamin E plays an important role in the regulation of platelet function and might contribute to the maintenance of placental microcirculation by inhibiting platelet aggregation.     

Bioavailability of nafarelin in healthy volunteers.

The bioavailability of a single dose of intranasal nafarelin was evaluated in 15 healthy female volunteers. Each subject received a 400 micrograms intranasal and a 25 micrograms intravenous dose of nafarelin separated by at least 7 days. Blood samples were obtained frequently after each dose for determination of nafarelin plasma levels. After intravenous administration, time to maximum concentration (Tmax) was 2 minutes, and maximum serum concentration (Cmax) was 8.2 +/- 2.09 (SD) ng/ml. For intranasal nafarelin, mean Tmax was 18.4 +/- 7.9 minutes (range, 5 to 40 minutes), and Cmax was 2.04 +/- 1.29 ng/ml (range, 0.49 to 5.7 ng/ml). Systemic bioavailability of nafarelin ranged from 1.15% to 5.62% and averaged 2.82% +/- 1.23%. Nafarelin's bioavailability is adequate to achieve the desired therapeutic effect because of its inherent high biologic potency and its pharmacokinetic properties. Nafarelin is readily absorbed by the nasal mucosa, and therapeutic blood levels are rapidly achieved and maintained for a prolonged period of time.     

Utility of a Single Plasma Fibronectin Level for the Prediction of Preeclampsia

Previous studies have indicated that repeated maternal plasma fibronectin (FN) levels may aid in the prediction of preeclampsia. To investigate the development of a preeclampsia screening test, avoiding the requirement for repeated maternal blood samples throughout pregnancy, we examined the efficacy of a single screening plasma FN level for the prediction of preeclampsia. Total plasma FN levels were determined between 24 and 32 weeks' gestation in 115 normotensive patients, and cellular FN was determined in a subgroup of 81 of these patients. Among nulliparas (n = 76) total plasma FN values were significantly (P = 0.007) greater in patients (n = 13) who subsequently developed preeclampsia (median = 370, range 130-1104 μg/ml) than among those who remained nonpreeclamptic (median = 283, range 80-490 μg/ml). Based on maximization of the receiver/operator curve, a cut-off plasma FN value of 300 μg/ml was selected as a positive screen in the nulliparous group, resulting in a sensitivity of 85%, specificity of 60%, positive predictive value of 31% and a negative predictive value of 95%. Eleven of the thirteen nulliparous preeclamptics had positive plasma FN screens prior to onset of disease, with increased plasma FN occurring 8-14 weeks prior to the clinical onset of preeclampsia. There were no significant differences in cellular FN values between the nulliparous preeclamptics (median = 3.40, range 2.80–4-20 μg/ml) and nonpreeclamptics (median = 3.30, range 2.40-5.20 μg/ml; P = 0.41). Due to the low incidence of preeclampsia in the multiparous patients in our study (2.6%), measurements of neither total plasma nor cellular FN were found to be of value as a screening test in this group. These results indicate the potential value of a single maternal plasma FN screen at 24-32 weeks' gestation for predicting preeclampsia in nulliparous women.     

Concentration of thrombin activatable fibrinolysis inhibitor (TAFI) in cord blood and maternal blood during labor

The concentration of TAFI in cord blood plasma has not been studied yet. We have measured its activity in plasma both in cord blood and mother's blood during labour. The study group consisted of 26 parturient women, 18 primiparas and 9 multiparas with normal course of pregnancy and delivery. Activity of TAFI was evaluated by chromogenic method (Actichrome Plasma TAFI Activity Kit). The level of TAFI in cord blood plasma was 4.20, range 3.80-6.40 micrograms/ml and in mother's blood 10.50, range 7.60-13.50 micrograms/ml, thus it was significantly lower (p < 0.0001). CONCLUSION: TAFI is present in the cord blood plasma but its concentration is about 50% of that in the mother's blood.     

Long-term treatment of hirsutism: desogestrel compared with cyproterone acetate in oral contraceptives.

OBJECTIVE: Effectiveness of 2-year treatment of hirsutism with low estrogen oral contraceptives (OCs) containing nonandrogenic or antiandrogenic progestogen. Evaluation of changes in plasma lipids. DESIGN: Ten patients treated with desogestrel 150 micrograms + 30 micrograms ethinyl estradiol, 6 with desogestrel 150 micrograms + 50 micrograms ethinyl estradiol, 10 with cyproterone acetate 2 mg + 35 micrograms ethinyl estradiol. Random allocation. Paired comparisons. Control group: 19 normal women, not treated. SETTING: Academic tertiary care. PATIENTS: Women with hirsutism (idiopathic and/or polycystic ovary), 24 of 26 completed treatment. INTERVENTION: Two-year treatment. MAIN OUTCOME MEASURES: Hirsutism score, plasma testosterone, and lipids. RESULTS: Initial hirsutism scores (11.8 +/- 0.6 SE) declined with treatment (-7.2 +/- 0.4, P less than 0.01) to 4.7 +/- 0.6, almost reaching control (3.6 +/- 0.3). Initial plasma cholesterol (4.33 mmol/L +/- 0.30 SE), similar to control (4.78 +/- 0.24), increased slowly over 2 years (+2.04 +/- 0.34, P less than 0.01). High-density lipoproteins cholesterol (1.05 mmol/L +/- 0.04 SE), similar to control (1.12 +/- 0.07), did not change the 1st year and increased at 2 years (+0.57 +/- 0.11, P less than 0.01). No differences appeared among treatment groups. CONCLUSIONS: Treatment is very effective, 2 years for best results. The OCs tested are equally efficacious. Changes in plasma lipids are of some concern but of difficult interpretation.     

Plasma fibronectin receptor levels during pregnancy complicated by preeclampsia and abruptio placentae.

The level of human fibronectin receptor (FNR) in plasma was measured by enzyme-linked immunosorbent assay in samples from normal pregnant women in the 1st trimester (n = 5), 2nd trimester (n = 7), 3rd trimester (n = 23), normal postpartum women day 1 (n = 4), day 2 (n = 5), day 3 (n = 8), nonpregnant women (n = 18), 20 preeclamptic patients in the 3rd trimester, and 8 patients with abruptio placentae in the 3rd trimester. In normal pregnancy, the mean value of FNR was 1.4 +/- 0.4 micrograms/ml in the 1st, 1.4 +/- 0.2 micrograms/ml in the 2nd, and 1.9 +/- 0.3 micrograms/ml (p less than 0.05) in the 3rd trimester. FNR values increased with pregnancy. During the puerperium, its level decreased with time, being 1.4 +/- 0.5 micrograms/ml (p less than 0.01) on day 1, 1.0 +/- 0.3 micrograms/ml on day 2, and 0.8 +/- 0.2 micrograms/ml on day 3. The level in preeclamptic patients was 2.0 +/- 0.4 micrograms/ml, and that in abruptio placentae was 2.7 +/- 0.4 micrograms/ml. There were significant differences between the levels in abruptio placentae versus preeclampsia (p less than 0.05) and 3rd-trimester normal pregnant women (p less than 0.01). In the immunohistochemical study, the surface of normal decidual cells stained weakly for FNR, and the decidual cell membranes of the cases of preeclampsia stained moderately or strongly. Decidual cells and their extracellular matrix close to hematomas of abruptio placentae stained very strongly for FNR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal-fetal transfer of aminophylline

Ten women with normal pregnancies who underwent an elective cesarean section received orally 200 mg of aminophylline every 6 hours for 24 - 36 hours prior to surgery. The levels of aminophylline and caffeine were measured in maternal and cord sera and in amniotic fluids. The mean level of aminophylline (+/- SD) in maternal serum was 10.4 +/- 1.74 micrograms/ml, and in cord serum 11.2 +/- 1.25 micrograms/ml. The mean aminophylline level in amniotic fluids was 8.2 +/- 1.42 micrograms/ml. The serum aminophylline levels were within the therapeutic level range. Caffeine levels in those specimens ranged between traces to 6 micrograms/ml which correspond to the normal dietary range.     

Dehydration increases the renal response to atrial natriuretic peptide in fetal sheep.

OBJECTIVE: In sheep, maternal water deprivation results in urinary natriuresis in spite of suppression of plasma atrial natriuretic factor levels. Near-term fetal sheep also have a urinary natriuresis without change in plasma atrial natriuretic factor during maternal dehydration. This study was designed to explore the role of plasma atrial natriuretic factor levels in fetal dehydration-natriuresis. STUDY DESIGN: Eight chronically instrumented preterm (113 +/- 1 days) ovine fetuses received two atrial natriuretic factor infusions (3 and 15 ng/kg/min) in a euhydrated state and after 48 +/- 1 hours of maternal water deprivation. RESULTS: Dehydration significantly increased maternal plasma osmolality (302 +/- 2 to 313 +/- 2 mOsm/kg water), sodium (148.1 +/- 0.8 to 154.3 +/- 0.4 mEq/L), chloride (112.4 +/- 0.6 to 116.8 +/- 0.9 mEq/L), and arginine vasopressin (4.2 +/- 1.2 to 23.0 +/- 4.0 pg/ml) and significantly decreased plasma atrial natriuretic factor (36 +/- 6 to 19 +/- 4 pg/ml) concentrations. Fetal plasma osmolality (296 +/- 1 to 308 +/- 2 mOsm/kg), atrial natriuretic factor (128 +/- 16 to 241 +/- 36 pg/ml), and arginine vasopressin (3.5 +/- 0.8 to 12.3 +/- 4.8 pg/ml) concentrations and urine osmolality (170 +/- 10 to 253 +/- 10 mOsm/kg), osmolar clearance (0.80 +/- 0.02 to 0.14 +/- 0.02 ml/kg/min), and fractional sodium excretion (3.3% +/- 1.7% to 8.5% +/- 2.1%) increased significantly with dehydration, whereas the plasma atrial natriuretic factor clearance decreased from 127 +/- 27 to 63 +/- 10 ml/kg/min. Dehydration had no effect on fetal hematocrit, vascular pressures, glomerular filtration rate, urine flow, or free water clearance. In euhydrated fetuses plasma atrial natriuretic factor increased from 128 +/- 16 to 287 +/- 46 pg/ml with sequential atrial natriuretic factor infusion, and no significant increases were observed in urine flow, fractional sodium excretion, and glomerular filtration rate. In contrast, atrial natriuretic factor infusion to dehydrated fetuses significantly increased urine flow (0.17 +/- 0.03 to 0.32 +/- 0.07 ml/kg/min), osmolar clearance (0.14 +/- 0.02 to 0.28 +/- 0.06 ml/kg/min), and fractional sodium excretion (8.5% +/- 2.1% to 14.8% +/- 4.0%). CONCLUSION: These results demonstrate that in the fetus at 113 days' gestation plasma atrial natriuretic factor levels increase with dehydration, probably a result of decreased plasma atrial natriuretic factor clearance, and the fetal renal responsiveness to atrial natriuretic factor infusion increases during maternal dehydration.     

Circulating concentrations of fetal fibronectin do not reflect reduced trophoblastic invasion in preeclamptic pregnancies.

This prospective, nested, case-control study investigated whether maternal plasma fetal fibronectin reflects reduced trophoblastic invasion at 16 to 20 weeks in women who later have preeclampsia. Concentrations of fetal fibronectin were 8.7 +/- 2.6 micrograms/ml in women with preeclampsia and 8.1 +/- 2.5 micrograms/ml in matched controls (p greater than 0.5). These results are discussed.