PTH/PTHrP receptor and mid-molecule PTHrP regulation of intrauterine PTHrP: PTH/PTHrP receptor antagonism increases SHR fetal weight

Parathyroid hormone-related protein (PTHrP) has important roles in fetal growth and development through stimulation of placental calcium transport, vasodilatation of the uteroplacental vasculature and regulation of cellular growth and differentiation. The growth restricted spontaneously hypertensive rat (SHR) has reduced fetal plasma, placental and amniotic fluid PTHrP concentrations compared to its progenitor, the Wistar Kyoto (WKY) rat. The aim of this study was to determine whether intrauterine PTHrP infusions can restore PTHrP levels and promote SHR fetal growth. PTHrP(1-34), midmolecule PTHrP(67-94), the PTH/PTHrP receptor antagonist [Asn(10), Leu(11)]-PTHrP(7-34) or vehicle were infused via a mini-osmotic pump between 10 and 20 days of gestation into the uterine lumen of SHR and WKY rats. Uterine, placental, amniotic fluid and plasma (fetal and maternal) PTHrP were measured via N-terminal radioimmunoassay. PTH/PTHrP receptor antagonism and mid-molecule PTHrP(67-94) induced endogenous intrauterine PTHrP production with receptor antagonism eliciting a greater and more wide spread effect. The PTH/PTHrP receptor antagonist [Asn(10), Leu(11)]-PTHrP(7-34) acting through a receptor other than the PTH/PTHrP receptor increased SHR fetal and placental weights above vehicle (P<0.05) to that of the WKY and restored SHR amniotic fluid volume (P<0.05). This was associated with a highly significant up regulation of placental, uterine and plasma (fetal and maternal) PTHrP (P<0.05). Modest increases in placental and uterine PTHrP (P<0.05) following intrauterine infusions of PTHrP(1-34) and PTHrP(67-94) had no effect on WKY and SHR fetal weight. Effective growth promoting actions of increased endogenous PTHrP were observed following PTH/PTHrP receptor antagonism rather than exogenous PTHrP administration. A novel finding was that mid-molecule PTHrP also up regulates endogenous intrauterine N-terminal PTHrP production supporting the existence of a mid-molecule receptor. This study highlights that an increase in endogenous uterine, placental and fetal plasma PTHrP following PTH/PTHrP receptor antagonism was associated with increased SHR fetal growth presumably by improving placental growth and function.     

Disposition of acute, multiple-dose ethanol in the near-term pregnant ewe

The disposition of ethanol and its proximate metabolite, acetaldehyde, was determined in seven conscious instrumented pregnant ewes (127 to 132 days of gestation; term, 147 days) for intravenous infusion of four dosages of 0.5 gm ethanol/kg maternal body weight, administered over 5 hours to the mother. The maternal and fetal blood had ethanol concentrations that were maximal at 5 hours and were virtually identical during the 24-hour study. There was delayed transfer of ethanol into the amniotic and allantoic fluids during the dosing period, followed by higher ethanol concentrations in these fluids during the elimination phase compared with fetal blood. The ethanol elimination rate was similar for the four biologic fluids. Acetaldehyde concentrations in the four fluids were a thousandfold less than the respective ethanol concentrations. The maternal blood acetaldehyde concentration was greater than that in fetal blood. The data indicate that for a binge-type drinking episode during near-term pregnancy, there is unimpeded bidirectional placental transfer of ethanol between the mother and the fetus; the amniotic fluid surrounding the fetus is a reservoir for ethanol in utero; elimination of ethanol from the maternal-fetal unit is regulated by maternal hepatic biotransformation of ethanol; and there is appreciable acetaldehyde-oxidizing capacity in the maternal liver and at extrahepatic sites.     

Metabolism and disposition of ritodrine in a pregnant baboon

Relatively little is known about the detailed metabolism of ritodrine. The aim of this study was to examine ritodrine metabolism and pharmacokinetics in the maternal and fetal baboon. A fetal-maternal model was made with use of Papio anubis at 144 days of gestation. Tritiated ritodrine was injected as an intravenous bolus into the mother. Maternal and fetal blood samples, amniotic fluid, and maternal urine were collected at time intervals. Samples were analyzed by a combination of high-pressure liquid chromatography and radiochromatography. Conjugated metabolites were recovered and characterized by cleavage studies with use of beta-glucuronidase and sulfatase. The distribution half-life of ritodrine in the mother was 6 minutes and the elimination half-life was 61 minutes. Metabolites were found in both fetal serum and amniotic fluid. The concentrations of ritodrine and its metabolites in fetal serum were at or above the concentrations in maternal serum at 2 hours after maternal intravenous injection. The principal metabolite identified was the sulfate conjugate. The fetus appears to accumulate metabolites. These data indicate that ritodrine crosses the placenta and, in the baboon, achieves levels in the fetus equal to or higher than those in the mother.     

Dynamics of adenosine-3', 5'- monophosphate transfer among mother, fetus, and amniotic fluid in the rhesus monkey.

Cyclic AMP exchange among the mother, amniotic fluid, and fetus was studied in normal rhesus monkeys at term pregnancy. Following a pulse intravenous administration of 3H-cyclic AMP into the mother, a small fraction of the dose appeared in less than 1 minute in fetal blood. It appeared in the amniotic fluid after 5 minutes and reached maximum level in 20 minutes. The accumulation of 3H-cyclic AMP in the amniotic fluid in 1 hour was 0.03 per cent of the injected dose. The amount and time course of 3H-cyclic AMP accumulation in the fluid were not altered by tying the umbilical vessels. The transfer of 3H-cyclic AMP injected in utero into the fetal femoral artery resembled that in the mother; in 1 hour the amniotic fluid contained 0.22 per cent of the injected dose. When injected directly into the amniotic sac, more than 65 per cent of the injected dose remained unchanged after 1 hour, with minimal transfer into the maternal and fetal compartments. This study showed rapid bidirectional exchange of cyclic AMP between the mother and the fetus. Both of these compartments can contribute cyclic AMP to the amniotic fluid, independently or in concert. It remained fairly stable in the fluid and was not readily metabolized or transported out.     

Role of fetal catecholamines before and during birth

It is true that developing fetus in uterus may be mostly influenced by maternal conditions. However, there is little evidence to prove the existence of nervous connection between fetus and mother. The biochemical and physiological phenomena of fetus in utero may be controlled mainly by fetal autonomy with nutritional supply from mother. The sympathoadrenal system of fetus has received much attention with the technical progress of catecholamine assays. Fetal plasma catecholamine concentrations during birth are remarkably higher than those in adult life. The function of those high catecholamine concentrations has been shown to control fetal circulation during hypoxia, to maintain glucose supply to the heart and brain, and to prepare the lung for ventilation. So it may be said that fetal plasma catecholamine surge at birth is essential to neonatal adaptation. Amniotic fluid catecholamines and their metabolites were higher in intrauterine growth retarded fetus, which consumed own catecholamine reserve in adrenal medulla before parturition. It is possible to estimate the fetal condition by measuring the concentration of catecholamines and their metabolites in amniotic fluid. The amniotic norepinephrine, epinephrine and particularly dopamine concentration has been found to increase toward term. The rise in dopamine has been assumed to stimulate intrauterine synthesis of prostaglandins. We demonstrated that L-dopa was metabolized to dopamine in fetal kidney and that dopamine in amniotic fluid was originated from fetal urine.     

Transplacental transfer of zidovudine in the near-term pregnant baboon

Approximately one third of infants born to human immunodeficiency virus type 1 seropositive mothers have evidence of infection or of acquired immunodeficiency syndrome by the age of 18 months. One fifth of infected infants also have died by age 18 months. This prevalence, combined with the demonstration that zidovudine (formerly azidothymidine) can decrease mortality and the frequency of opportunistic infections in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome--related complex, may lead to increasing use of azidothymidine in pregnancy despite a paucity of information regarding its pharmacokinetics. To further investigate the distribution of azidothymidine and its inactive metabolite 5'-glucuronide azidothymidine in the mother, fetus, and amniotic fluid, 12 near-term pregnant baboons were given oral azidothymidine (21 mg/kg/day in four divided doses every 6 hours, equivalent to the usual nonpregnant human dose of 1500 mg/day). Specimens of maternal blood, fetal arterial blood obtained by percutaneous umbilical cord blood sampling, and amniotic fluid were obtained after from one to 17 doses of azidothymidine. Azidothymidine levels were measured by radioimmunoassay with the INCSTAR commercial radioimmunoassay kit and using Escherichia coli beta-glucuronidase for determination of 5'-glucuronide azidothymidine levels. Paired analyses revealed significant concentration gradients between amniotic fluid, fetal serum, and maternal serum for both azidothymidine (p less than 0.019) and 5'-glucuronide azidothymidine (p less than 0.002). The amniotic fluid 5'-glucuronide azidothymidine level increased with increasing doses of azidothymidine despite the fact that the maternal azidothymidine and 5'-glucuronide azidothymidine concentrations were unchanged. This accumulation of amniotic fluid 5'-glucuronide azidothymidine may provide a functional drug reservoir and contribute to the higher fetal concentrations of the medication and its metabolite. Alternatively, the higher fetal levels may represent slower clearance in the fetus than in the mother. Further studies appear warranted with respect to possible adverse fetal effects, especially bone marrow suppression with prolonged and chronic exposure to azidothymidine.     

Fetal heart rate patterns associated with amniotic fluid embolism

Two cases with recorded fetal heart rate response during maternal amniotic fluid embolus are reported. Fetal heart rate abnormalities can be associated with the development of amniotic fluid embolus or occur during the acute events of amniotic fluid embolus. Attention to the management of amniotic fluid embolus in the mother must not neglect the fetus. Improvement of maternal oxygenation and perfusion can effect intrauterine resuscitation; however, when this is not successful early delivery of the fetus may be necessary for its survival.     

Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments

Objective.?An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid.

Study Design.?Maternal plasma was obtained from patients with fetal death (n?=?59) and normal pregnant women (n?=?134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n?=?160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied.

Results.?(1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p?<?0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p?=?0.006, p?<?0.001 and p?=?0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4–7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p?<?0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5–164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p?=?0.9).

Conclusion.?Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.     

Changes in amniotic fluid glucose, beta-hydroxy-butyrate, glycerol, and lactate concentration in diabetic pregnancy

Amniotic fluid glucose, beta OH butyrate, glycerol, and lactate concentrations were measured in 75 samples collected in the third trimester of pregnancy from 50 diabetic patients, all but four of whom required insulin. Increases in maternal fasting plasma sugar were accompanied by corresponding increases in amniotic fluid glucose and on occasion increases in amniotic fluid beta OH butyrate. These data correspond to previous reports of placental glucose transfer and in addition, provide statistically significant evidence of placental betaOH butyrate transfer since the hyperglycemic, hyperinsulinemic fetus of a diabetic mother would be a poor primary source for ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketoacidosis, and over-all reduced neonatal morbidity-mortality rates in this group of metabolically well-controlled, predominantly insulin-requiring diabetic patients managed in a regional high-risk perinatal center.     

Exclusion of the fetal brain as the main source of rat and human amniotic fluid oxytocin

Summary. At term relatively high oxytocin concentrations are found in maternal plasma and in rat and human amniotic fluid. To determine the contribution of the fetal brain to these oxytocin levels, the peptide was measured in maternal rat plasma and amniotic fluid 2 days after intrauterine removal of the fetal brains, and in the amniotic fluid of 16 human anencephalics. After removal of the fetal rat brains and in human anencephalic pregnancies normal maternal plasma concentrations and amniotic fluid oxytocin contents were found. Consequently, both maternal plasma oxytocin and amniotic fluid oxytocin are not determined to any substantial degree by the fetal brain.     

Disposition of ethanol in maternal blood,fetal blood,and amniotic fluid of third-trimester pregnant ewes

The disposition of ethanol in maternal arterial blood, fetal arterial blood, and amniotic fluid of nine conscious, cannulated pregnant ewes (128 to 137 days' gestation) was determined for 1-hour maternal intravenous infusion of ethanol, 1 gm/kg maternal body weight. The maternal arterial blood and fetal arterial blood ethanol concentration-time curves were virtually superimposable up to 14 hours. The apparent zero-order ethanol elimination rates for maternal arterial blood and fetal arterial blood were similar. There was a time lag in the transfer of ethanol into amniotic fluid relative to fetal arterial blood, and the peak ethanol concentration in amniotic fluid was significantly lower than the concentrations in maternal arterial blood and fetal arterial blood. The apparent zero-order ethanol elimination rate for amniotic fluid was slower, but not significantly so, compared with the ethanol elimination rates for maternal arterial blood and fetal arterial blood. Ethanol-derived acetaldehyde was found in maternal arterial blood, fetal arterial blood, and amniotic fluid at concentrations at least 1000-fold lower than the respective ethanol concentrations. The data indicate that, for administration of this ethanol dosage regimen to the third-trimester pregnant ewe, there is rapid, bidirectional placental transfer of ethanol; elimination of ethanol from the fetus is regulated primarily by maternal elimination of ethanol; the amniotic fluid may serve as a reservoir for ethanol in utero; and there is appreciable acetaldehyde-metabolizing capacity.     

Perinatal outcomes of pregnancies wıth borderline amniotic fluid index

Objective Our aim was to determine whether a borderline amniotic fluid index observed during antepartum testing confers a significant risk of adverse perinatal outcome Methods Between April 2001 and May 2005, uncomplicated gestations with a singleton non-anomalous fetus, who underwent weekly monitoring of amniotic fluid index (AFI) until delivery during the last trimester and who gave birth at our hospital, were identified for our study. Normal amniotic fluid volume and borderline amniotic fluid were defined as AFI of >10 and <24 cm and >5 and <10 cm, respectively. The groups were compared on maternal data, mode of delivery and perinatal outcomes such as fetal distress, intrauterine growth restriction and meconium fluid Results A total of 90 cases were identified as borderline amniotic fluid and 277 cases as normal AFI. We observed significant increased incidences of admission to neonatal intensive care unit, intrauterine growth restriction, meconium-stained amniotic fluid, intrapartum fetal distress in the group with borderline amniotic index (P < 0.05). Conclusions A borderline amniotic fluid index observed in antepartum testing during the last trimester carries an increased risk of adverse perinatal outcomes. These patients should be followed up carefully during the antepartum and intrapartum period. Poster presentation at XXth European Congress of Perinatal Medicine, 24–27 May 2006, Prague, Czech Republic     

Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats.

In order to find out if inefficient transport of amino acids contributes to a decrease in fetal weight during maternal malnutrition, we injected [14C]- and [3H]-labelled aminoisobutyric acid (AIB), respectively, in the mother and its fetuses and determined its transplacental kinetics on day 20 of gestation in rats fed a 21 per cent (control) or a low (5 per cent) protein diet. Rats fed a low protein diet consumed significantly less food than did the rats fed a control diet and thus suffered from protein-calorie malnutrition. A low protein diet led to a significant (P less than 0.05) decrease in maternal and fetal volume of distribution of AIB, a decrease in the clearance of AIB from the mother to the fetus and an increase in the time required for the fetal plasma AIB concentration following maternal injection to exceed the maternal plasma AIB concentration. The clearance of AIB from the fetus into the mother or to outside (e.g. amniotic fluid) was not altered by protein deficiency. It is concluded that a decrease in the efficiency of the placenta to deliver amino acids to the fetus may be a contributing factor in fetal growth retardation during maternal protein malnutrition.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

The influence of leptin on placental and fetal volume measured by three-dimensional ultrasound in the second trimester

For a couple of years mechanisms influencing placental and fetal growth and the functioning of leptin, the protein product of the ob/ob gene, have been subjects of intensive research. This study's aim was to investigate whether maternal serum leptin and amniotic fluid leptin have an influence on placental and fetal size measured by three-dimensional ultrasound in the second trimester. To determine this, 40 women with a singleton intrauterine pregnancy at the time of the amniocentesis were included in the study. Placental and fetal volume measurements were obtained and correlated to maternal serum leptin, amniotic fluid leptin, body mass index and gestational age. Multiple regression analysis identified amniotic fluid leptin as an independent negative predictor of placental and fetal volume (r = -2.29, p = 0.032 and r = -0.95, p = 0.011, respectively). In contrast, there was no correlation between maternal serum leptin and placental or fetal volume. The median leptin level in amniotic fluid (9.5 ng/ml) was significantly lower than in maternal blood (18.6 ng/ml). However, there was no significant correlation between maternal serum leptin and amniotic fluid leptin (r = 0.208, n.s.). Body mass index did not reveal any significant influences on placental or fetal volume. The relatively high level of amniotic fluid leptin and its inverse correlation on placental and fetal volume in the second trimester suggest that it possibly plays a role as an anti-placental growth hormone or feedback modulator of substrate supply to the fetus and placenta.     

Feto-maternal concentrations of diazepam and W-demethyldiazepam after intra-amniotic diazepam injection.

Ten milligrams of diazepam were injected intraamniotically in 8 mothers prior to therapeutic abortion between 12 and 19 weeks. The diazepam concentrations in the maternal plasma were comparable to those found after the same intramuscular diazepam dose to the mother. The concentration of diazepam in the amniotic fluid 12 to 18 hours after the injection was no longer significantly higher than in the maternal plasma. The concentrations of diazepam in the fetal plasma, liver and brain were comparable to the concentrations resulting from a 10 mg intramuscular diazepam dose to the mother about 2 hours before legal abortion. The feto-maternal ratio of diazepam was of same magnitude as after the intramuscular application to the mother. The results indicate that the disappearance of diazepam from the amniotic fluid in this stage of pregnancy occurs extraplacentally, through the mambranes into the uterine circulation. In the treatment of a fetus with drugs having properties similar to diazepam, intra-amniotic administration is no better than intramuscular administration to the mother.     

Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands.

Amniotic fluid alpha-fetoprotein (AFP) concentrations were measured in 2180 patients at risk of fetal abnormality because of previous history, family history, advanced maternal age, suspected fetal growth retardation and hydramnios. In 12 patients investigated before 20 weeks gestation, pregnancy was terminated because of a raised amniotic fluid AFP-level: 11 fetuses had neural tube defects (NTDs) and one had a congenital nephrosis. There were no false negative results in the 1927 patients tested before 20 weeks and with a pregnancy of known outcome. In patients tested after 20 weeks, the amniotic fluid AFP concentration was raised in 20 cases of anencephaly, in 9 fetuses with severe congenital malformations without NTD and in one apparently normal fetus. Of 428 patients with a previous offspring who had a NTD, only 8(1.9 per cent) again had a fetus with a NTD.     

Lead and cadmium concentrations in maternal and umbilical cord blood, amniotic fluid, placenta, and amniotic membranes

The lead and cadmium concentrations in maternal and umbilical cord blood and amniotic fluid were determined in 19 parturient women at delivery. Six placental and amniotic membrane tissue specimens were also investigated. The mean lead concentrations (mean +/- SD) in maternal (40.4 +/- 18.2 ng/ml) and umbilical cord (37.1 +/- 13.5 ng/ml) blood were similar and correlated significantly with each other (r = 0.77, p less than 0.001). The lead concentration in amniotic fluid (59.6 +/- 8.3 ng/ml) was significantly higher than in maternal or umbilical cord blood. Cadmium concentrations in maternal blood (1.1 +/- 0.9 ng/ml) and amniotic fluid (1.0 +/- 0.2 ng/ml) were significantly higher (p less than 0.001) than in umbilical cord blood (0.4 +/- 0.2 ng/ml) and there was no significant correlation among these values. The highest concentrations of cadmium (35.1 +/- 24.2 ng/gm of wet weight) and lead (87.3 +/- 154.2 ng/gm of wet weight) were found in the amniotic membranes. Our results show that lead and cadmium accumulate in amniotic fluid and amniotic membranes and that the distribution of lead and cadmium is different in the human maternal-fetoplacental unit. The fetal exposure to lead is similar and that to cadmium, lower, compared with maternal exposure. The inability of the placenta to totally prevent the fetus from exposure to lead and cadmium suggests that pregnant women should avoid occupations where exposure to these toxic elements is possible.     

Effect of prenatal betamethasone administration on maternal and fetal corticosteroid-binding globulin concentrations

OBJECTIVE: This study was undertaken to examine the effects of prenatal betamethasone administration on corticosteroid-binding globulin concentrations in maternal and fetal plasma and amniotic fluid. STUDY DESIGN: Two groups of patients with preterm labor at 24 to 35 weeks' gestation who were receiving prenatal betamethasone (2 intramuscular doses of 12 mg) were studied. Maternal plasma was obtained before and at variable intervals until 1 week after betamethasone administration. Umbilical cord blood and amniotic fluid samples were collected at the time of delivery. Samples were also collected from patients at risk for preterm delivery who did not receive glucocorticoids. RESULTS: Betamethasone suppressed maternal cortisol concentration by >70% within 24 hours of injection but did not significantly alter corticosteroid-binding capacity or relative concentrations of corticosteroid-binding globulin isoforms in either maternal or umbilical cord plasma. Betamethasone reduced corticosteroid-binding capacity in amniotic fluid within 24 hours of injection, and values remained suppressed 1 week after treatment. CONCLUSION: Maternal and fetal plasma corticosteroid-binding globulin concentrations were unchanged after maternal betamethasone administration at 24 to 32 weeks' gestation but amniotic fluid corticosteroid-binding globulin concentrations decreased significantly, suggesting different sites of either corticosteroid-binding globulin production or regulation or both.     

Arginine vasopressin in amniotic fluid, arterial and venous cord plasma and maternal venous plasma

High concentrations of arginine vasopressin (AVP) in arterial umbilical cord blood at the time of delivery have been attributed to either a generalized increase in the activity of the fetal endocrine system at the onset of labor or to fetal asphyxia. We measured AVP in amniotic fluid, arterial and venous cord blood and in maternal venous blood from 13 patients at 38-40 weeks of gestation at the time of elective cesarean section with a nonasphyxic fetus (group I), in amniotic fluid from 19 patients at 15-17 weeks of gestation (group II) and in venous blood from 13 nonpregnant control subjects (group III). Our results showed a high concentration of AVP in the amniotic fluid both in the middle and at the end of normal pregnancy and at the same level as in arterial cord blood, whereas AVP in the venous cord blood was significantly lower and at the same level as in the maternal venous blood and in the control group. It is concluded that the fetus produces AVP and this is at least not solely caused by fetal asphyxia or related to parturition.