Maternal Plasma Osmolality Research Articles

Feto-maternal osmotic balance at term. A prospective observational study.

We performed the present study to investigate the feto-maternal osmotic relationship at term with the hypothesis that, in contrast to the literature, maternal plasma osmolality is lower than fetal levels. In a previous study, we found that maternal plasma sodium at delivery was consistently lower than the sodium in the umbilical artery. Our aim was to corroborate these results with analysis of osmolality. Blood was sampled from 30 women immediately before cesarean section and from the umbilical artery and vein before cord clamping and osmolality, sodium and albumin were analyzed. Maternal osmolality was (mean; 95% confidence interval) 287.0 (285.8-288.2) mOsmkg/kg, arterial cord osmolality was 289.4 (287.9-291.0) mOsm/kg and venous cord osmolality was 287.3 (286.0-288.5) mOsm/kg. The paired difference between maternal and umbilical arterial osmolality was mean (SD) -2.4 (3.3) mOsm/kg (P<0.001), between maternal and umbilical vein -0.3 (3.0) mOsm/kg (P=0.63) and between umbilical artery and vein -2.1 (2.8) mOsm/kg (P<0.001). Maternal osmolality was significantly lower than arterial cord osmolality confirming our previous results. The feto-maternal osmotic gradient favors water transport from the mother to the fetus and may increase the fetal risk of water intoxication when the mother ingests or is administered large volumes of electrolyte free solutions.

Early compensatory adaptations in maternal undernourished pregnancies in rats: role of the aquaporins

Objective. To investigate the effect of maternal undernutrition (MUN) during pregnancy on fetal and placental weight, amniotic fluid (AF) volume, AF osmolality and ion concentrations at gestational ages E16 and E20. We also quantified protein expression of water channels (aquaporins; AQPs).Methods. Pregnant rat dams were fed an ad libitum diet (AdLib; n = 6) or were 50% MUN (n = 6) beginning at E10 of gestation. At E16 and E20, we assessed the effect of MUN on fetal and placental weights, AF volume and osmolality, and placental expression of AQP1, 8 and 9. We focused on two uterine positions (proximal and mid-horns) with the extremes of nutrient/oxygen supply. We also separately studied the basal zone (hormone production) and the labyrinth zone (feto-maternal exchange).Results. We showed that at E16, MUN fetal, and placental weights were unchanged and that, similarly, MUN AF volume, osmolality were comparable to AdLib. At E20, however, MUN fetal and placental zonal weights were significantly decreased. Inversely, due to MUN, maternal and fetal plasma osmolality and Na+ concentrations were significantly increased. Further, MUN AF volume was significantly reduced, while AF osmolality and Na+ concentration were increased at E20.Conclusion. Placental basal zone showed variable changes in AQP expression unrelated to position in the uterus or the gestational age (and thus severity of the fetal/placental growth restriction). In the labyrinth zone, MUN placental AQP1 was significantly decreased, whereas AQP8 and 9 expressions were significantly increased at E16 and E20. Dysregulation of AQPs' expression prior to the occurrence of oligohydramnios may represent a compensatory mechanism under conditions of early MUN.

Fetal functional capabilities in response to maternal hypertonicity associated with altered central and peripheral angiotensinogen mRNA in rats

Although a number of studies have shown neural, hormonal, and behavioral capabilities in the control of body fluid regulation under conditions of dehydration in adults, limited information is available on the development of fetal functional abilities in response to osmotic challenge in rats. This study was performed to investigate the influence of maternal hypertonicity on fetal osmoregulatory capabilities at late gestational time in rats. Maternal and fetal plasma osmolality and blood sodium levels were determined and compared at continuous time points from 0.5 to 9 h following maternal injection of hypertonic NaCl. Subcutaneous administration of hypertonic saline evoked a rise in plasma osmolality and sodium concentrations in maternal rats and fetuses associated with an up-regulation in angiotensinogen gene mRNA in the fetal liver and down-regulation of the same gene in the fetal brain. The increased levels of fetal blood osmolality and sodium were less than that in their mothers, and the fetus took less time to balance the enhanced osmolality and sodium concentrations. The results suggest that there may exist additional mechanisms in utero at near-term in protecting fetuses from hypertonic challenge. In addition, molecular results in the present study provide new data on fetal angiotensinogen gene expressed differently in the liver and brain under the same condition of prenatal salt loading, indicating osmotic signals of intracellular dehydration related to an acute increase in angiotensinogen mRNA in the fetal liver, and subsequent decrease in angiotensinogen mRNA levels in the fetal brain.

Correlation of maternal plasma volume and composition with amniotic fluid index in normal human pregnancy

Objective: Early in human pregnancy, maternal plasma osmolality decreases and plasma volume begins to increase. Continued plasma volume expansion is linked to fetal fluid acquisition, and ultimately normal amniotic fluid volume. Although the mechanisms for these physiological responses are uncertain, we hypothesized that the time course of maternal plasma hypotonicity, plasma volume expansion and amniotic fluid index (AFI) were interrelated. We sought to examine these interrelationships during human pregnancy.Methods: Normal primiparous pregnant patients had monthly determinations of plasma volume using Evans blue from the second trimester to term, and 8 weeks after delivery. At each visit, fasting, morning blood samples were also drawn to measure hematocrit, osmolality, electrolytes, urea, glucose and creatinine. AFI was determined by ultrasound.Results: Plasma volume, blood volume and AFI demonstrated significant increases with advancing gestational age. There were no significant changes in plasma sodium or osmolality from the second trimester to term. AFI was not associated with either plasma volume or osmolality.Conclusion: Although similar factors may therefore be responsible for the initiation of plasma volume expansion and plasma hypotonicity, the magnitude and degree of change of these processes are probably under independent regulation. Individual patient variation in AFI is a result of factors other than maternal blood volume or composition.

Maternal plasma hypertonicity is accentuated in the postterm rat

Objective In humans and rats, pregnancy-associated maternal plasma volume expansion and plasma hypotonicity may facilitate maternal-to-fetal water transfer. Although reduced amniotic fluid volume occurs commonly in postterm pregnancy, the mechanisms are unknown. We previously demonstrated a reversal of pregnancy-induced maternal plasma hypotonicity that occurs in the near term (20 days) pregnant rats. We sought to determine whether the relative maternal plasma hypertonicity continues in the postterm period. Study design Rat gestation (normal, 21 days) was prolonged with subcutaneous progesterone injection. Pregnant rats at gestation, 18 days, 21 days, and 24 days and nonpregnant rats were studied. Maternal and fetal hematocrit levels, plasma osmolality, electrolyte levels, and amniotic fluid volume were determined. In addition, maternal and fetal tissues were analyzed for water and electrolyte content. Results Compared with term (21days), postterm pregnant rats (24 days) had a significant increase in maternal and fetal plasma osmolality (293.7±1.4 mOsm/kg vs 302.8±3.7 mOsm/kg and 301.0±2.0 mOsm/kg vs 310.3±3.2 mOsm/kg, respectively; P<.01) and sodium and chloride concentrations. Conversely, both maternal and fetal hematocrit levels decreased significantly in the postterm period. Postterm rats demonstrated an increased fetal mortality rate (24%) and a significantly reduced amniotic fluid volume (4.2±0.6 mL vs 6.6±0.6 mL, P<.01). Conclusion These results indicate that the near-term reversal of maternal plasma hypotonicity that has been observed previously is further accentuated in the postterm pregnancy. This continued hypertonicity may induce a fetal-to-maternal water flow and contribute to postterm oligohydramnios and increased fetal morbidity and mortality rates.

Reversal of pregnancy-mediated plasma hypotonicity in the near-term rat

Objective: Maternal plasma hypotonicity occurs early in rat and human pregnancy with resetting of the plasma osmolality threshold for vasopressin secretion and thirst. In humans, amniotic fluid volumereaches maximum levels in the mid-third trimester and decreases thereafter. We hypothesized that a reversal of maternal plasma hypotonicity occurs near term, contributing to reduced fetal and amniotic fluidwater content.Methods: Maternal plasma and amniotic fluid osmolality and sodium levels, including amniotic fluid volume, were measured at 16, 18 and 20 days of rat gestation. Additionally, maternaland fetal brains were analyzed for water and electrolyte content. Non-pregnant adult female rats represented controls.Results: Compared to non-pregnant adults, 16-day and 18-day pregnant ratshad significantly lower plasma osmolality (301.0 ± 2.3 vs. 295.4 ± 2.8 and 289.7 ± 3.3 mOsm/kg, respectively) and sodium levels (140.3 ± 1.0 vs. 135.7 ± 0.8 and 133.4± 1.4 mEq/l, respectively). Conversely, 20-day pregnant rats showed no significant difference in plasma osmolality (298.4 ± 3.1 mOsm/kg) or sodium levels (137.6 ± 1.0 mEq/l) from non-pregnantadults. With advancing gestation, the amniotic fluid volume decreased whereas the osmolality and sodium levels increased significantly. Maternal brain water content was significantly higher in 16-day and18-day pregnant rats compared to control rats (78.7 ± 0.1 and 78.1 ± 0.2 vs. 76.9 ± 0.2% wet weight) and returned to non-pregnant values in the 20-day pregnant rats (76.6 ± 0.2%).In association with the maternal changes, fetal brain water and electrolyte content significantly decreased from 16-day to 18-day to 20-day fetuses.Conclusion: These findings indicate a reversalof maternal plasma hypotonicity and reduced maternal brain water content in the near-term pregnant rat. We speculate that relative maternal plasma hypertonicity near term may contribute to reduced amnioticfluid volume.

Prolonged prenatal hypernatremia alters neuroendocrine and electrolyte homeostasis in neonatal sheep.

Arginine vasopressin (AVP) is a neuroendocrine hormone synthesized in the hypothalamus, and is stored and secreted by the posterior pituitary gland in response to stimuli such as plasma hypertonicity and hypotension. The primary physiologic roles of AVP include plasma osmolality and blood pressure regulation. We have previously demonstrated that chronic prenatal plasma hypertonicity alters the AVP regulatory pathway in newborn lambs. The objectives of the present study were to evaluate prolonged effects of antenatal plasma hypertonicity on neonatal plasma osmoregulation. Pregnant ewes at 119 +/- 3 days of gestation were water restricted to achieve and maintain hypertonicity until normal-term delivery. After delivery, ewes were provided food and water ad libitum and lambs were allowed maternal nursing. At the age of 28 days, blood samples were obtained for the analysis of plasma osmolality, electrolytes, and AVP levels from study (n= 5) and age-matched control (n= 6) lambs. Subsequently, lambs were euthanized, and the pituitary and hypothalamus were processed for the determination of pituitary AVP content by radioimmunoassay, and AVP gene expression by Northern analysis. In response to water restriction, maternal plasma osmolality significantly increased (306 +/- 1.1 to 326 +/- 1.2 mOsm/kg, P< 0.001). At the age of 28 days, plasma sodium level was higher in study (prenatally dehydrated) than control lambs (144.6 +/- 0.4 vs 142.6 +/- 0.3,P< 0.05). Study lambs had higher plasma AVP concentrations than the control lambs (4.1 +/- 0.4 vs 1.7 +/- 0.4 pg/ml,P< 0.05). Similarly, total pituitary AVP content was higher in thein utero hypertonic lambs than in the control lambs (6.5 +/- 1.0 vs 2.8 +/-1.2 microg, P< 0.05). However, there was no difference in hypothalamic AVP mRNA levels between the two groups. The present study demonstrates that chronic maternal and fetal plasma hypertonicity has prolonged effects on pituitary and plasma AVP, as well as plasma sodium in neonatal lambs, providing further evidence suggesting prenatal imprinting of osmoregulation through at least 1 month of age.

Chronic in utero plasma hyperosmolality alters hypothalamic arginine vasopressin synthesis and pituitary arginine vasopressin content in newborn lambs

Objective: Arginine vasopressin is synthesized in the hypothalamus and secreted by the posterior pituitary gland in response to plasma hypertonicity. Previous studies suggest that in utero and neonatal exposure of rat pups to prolonged alterations of plasma osmolality may permanently alter (imprint) arginine vasopressin synthesis and secretion, thus adult responses to osmotic challenges. Little is known, however, of the potential for imprinting of neuroendocrinologic systems in precocial species. In view of the frequent occurrence of altered maternal and fetal plasma tonicity (eg, maternal dehydration, hyperemesis), we sought to determine the effect of prolonged maternal hypertonicity on arginine vasopressin gene expression and pituitary gland content in neonatal sheep. Study Design: Pregnant ewes at 119 ± 3 days of gestation were water restricted to achieve and maintain plasma hypertonicity (10-20 mOsm/kg above baseline level) until normal term delivery. Newborns were provided maternal nursing ad libitum. Within 24 hours after birth, study neonatal lambs (n = 6) and age-matched control neonatal lambs (n = 5) were killed, and the pituitary gland and hypothalamus were removed and frozen immediately. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamic arginine vasopressin gene expression was quantified with Northern blot. Differences in pituitary arginine vasopressin content and hypothalamic arginine vasopressin gene expression (arginine vasopressin/ β-actin ratio) between study and control newborn lambs were analyzed by unpaired t test. Results: In response to maternal water restriction, maternal plasma osmolality increased from 307 ± 0.9 mOsm/kg to 325 ± 1.3 mOsm/kg, and plasma sodium increased from 147 ± 1.3 mEq/L to 156 ± 1.2 mEq/L. The maternal plasma hyperosmolality and hypernatremia were maintained until normal term delivery. At the time of death, study (in utero dehydrated) lambs had higher plasma sodium (150 ± 0.4 mEq/L vs 146.5 ± 1.5 mEq/L; P <.05) and chloride (112.8 ± 1.0 mEq/L vs 108.5 ± 1.5 mEq/L; P <.05) levels, and lower potassium (4.5 ± 0.2 mEq/L vs 5.5 ± 0.3 mEq/L; P <.05) concentrations than control newborn lambs. Both newborn groups had similar plasma osmolality (320.0 ± 1.3 mOsm/kg vs 318.0 ± 3.4 mOsm/kg). Total pituitary arginine vasopressin content was significantly greater in the study than in the control newborn lambs (8.3 ± 2.8 μg vs 1.6 ± 1.3 μg; P <.05). Conversely, hypothalamic arginine vasopressin messenger RNA levels were lower in the study newborn lambs than in the control newborn lambs (arginine vasopressin/β-actin ratio: 0.29 ± 0.01 vs 0.68 ± 0.15; P <.05). Conclusion: Despite the presence of plasma hypernatremia, prolonged elevation of fetal plasma tonicity increases newborn pituitary arginine vasopressin content yet decreases hypothalamic arginine vasopressin gene expression. The present study suggests that prolonged prenatal exposure to plasma hypertonicity may imprint the hypothalamic-pituitary arginine vasopressin regulatory system. (Am J Obstet Gynecol 2002;187:191-6.)

Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus.

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.

Acute maternal rehydration increases the urine production rate in the near-term human fetus

Objective: We sought to investigate the effect of a decrease of maternal plasma osmolality produced by hypotonic rehydration on the fetal urine production rate in normal near-term human fetuses. Study Design: Twenty-one healthy pregnant women attending the clinic for antenatal care were studied between 37 and 40 weeks’ gestation. The fetal urine production rate was assessed by serial measurements of 3 diameters of the fetal bladder. The hourly fetal urine production rate was determined by linear regression analysis of the calculated bladder volumes versus time and was initially determined after a period of 4 hours of fluid deprivation. Thereafter, the women were asked to drink 1 L of water, and the hourly fetal urine production rate was assessed again. The hourly fetal urine production rate was only studied during behavioral state 1F because it is dependent on the behavioral state. The fetal behavioral state was determined by assessment of fetal heart rate, fetal eye movements, and fetal body movements. Results: Successful recordings were obtained in 10 of the 21 women. The hourly fetal urine production rate increased significantly after hypotonic rehydration (P <.02). Compared with the initial hourly fetal urine production rate after 4 hours of fluid deprivation, the hourly fetal urine production rate showed an increase of 63.2% after hypotonic rehydration, from 38.2 ± 16.3 mL/h to 62.4 ± 34.6 mL/h (mean ± SD). After rehydration, the baseline fetal heart rate fell significantly, from 141 ± 6 to 132 ± 8 beats/min (mean ± SD; P =.005). Conclusion: The fetal urine production rate is augmented after acute maternal oral hypotonic rehydration after 4 hours of fluid deprivation. The current findings demonstrate that the near-term human fetus can handle such acute changes in fluid osmolality by increasing the urine production rate to maintain its fluid homeostasis. This mechanism implies that changes in maternal plasma osmolality and volume probably play an important role in determining amniotic fluid volume. Therefore the application of maternal hydration for the treatment of oligohydramnios should be further investigated. (Am J Obstet Gynecol 2000;183:226-9.)

Appearance of central dipsogenic mechanisms induced by dehydration in near-term rat fetus

Cellular dehydration of central osmoreceptors evokes an integration of behavioral (i.e. drinking) and endocrinologic (i.e. arginine vasopressin secretion) responses to maintain body fluid balance. These osmoregulatory mechanisms have been intensely investigated in adult models. However, there has been limited research of the fetal development of neural mechanisms regulating responses to dehydration. Although behavioral and neuroendocrine responses to dehydration have been demonstrated in utero in precocial species (e.g. ovine), there has been no study to date demonstrating that these responses develop before the neonatal period of altricial species (e.g. rat). This study is the first to use the near-term rat fetus to investigate the effects of maternal subcutaneous hypertonic (2 M NaCl) or isotonic (0.15 M NaCl) saline injection on fetal plasma osmolality and brain FOS-immunoreactivity (FOS-ir). Maternal subcutaneous hypertonic saline significantly increased maternal and fetal plasma osmolality to similar levels (328±6 and 326±6 mosM/kg, respectively). In response to plasma hypertonicity, maternal and fetal brain FOS-ir increased significantly in the regions including the lamina terminalis, and the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus. Together, these data indicate that central mechanisms for dipsogenic and arginine vasopressin secretory responses to hypertonicity are present and responsive in the fetal rat brain at near-term gestation. However, differences between fetal and maternal FOS-ir mapping suggest that fetal osmoreceptor development is not yet completed near term.

Effect of Maternal Hydration on Oligohydramnios

In Brief Objective To determine the effect of maternal hydration with intravenous (IV) isotonic fluid, IV hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios. Methods Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h IV isotonic fluid, 2 L/2 h IV hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration. Results Eighty-four patients (n = 21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the IV hypotonic and oral water groups (2.8 ± 1.9, P < .001; 3.8 ± 1.9, P < .001, respectively), but not in the IV isotonic group (0.5 ± 1.1), compared with the control group (0.5 ± 1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after IV isotonic hydration (32.0 ± 2.9 to 29.5 ± 2.3, P < .001; 11.0 ± 1.6 to 10.1 ± 1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the IV hypotonic group (r = .58, P < .001) and oral water group (r = .63, P < .001). Conclusion Maternal hydration with either IV hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration. Maternal plasma osmotic change has a more profound impact on acute increase of amniotic fluid volume when compared with maternal volume expansion.

Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods

Objective: To determine the effect of maternal hydration with intravenous (IV) isotonic fluid, IV hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios. Methods: Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h IV isotonic fluid, 2 L/2 h IV hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration. Results: Eighty-four patients ( n = 21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the IV hypotonic and oral water groups (2.8 ± 1.9, P < .001; 3.8 ± 1.9, P < .001, respectively), but not in the IV isotonic group (0.5 ± 1.1), compared with the control group (0.5 ± 1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after IV isotonic hydration (32.0 ± 2.9 to 29.5 ± 2.3, P < .001; 11.0 ± 1.6 to 10.1 ± 1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the IV hypotonic group ( r = .58, P < .001) and oral water group ( r = .63, P < .001). Conclusion: Maternal hydration with either IV hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration.

Maternal plasma hypo-osmolality: Effects on spontaneous and stimulated ovine fetal swallowing

Fetal swallowing is a major route of amniotic fluid resorption, and thus swallowing activity may alter amniotic fluid volume. Near-term ovine fetal swallowing increases in response to plasma and/or cerebrospinal fluid hypertonicity. As maternal hydration status alters amniotic fluid volume, we hypothesized that maternal plasma hypotonicity may alter fetal swallowing activity. Pregnant ewes (130 +/- 1 d; n = 6) were chronically prepared with maternal and fetal vascular catheters, a fetal esophageal flow probe, and fetal thyrohyoid and nuchal and thoracic esophagus electromyogram electrodes. Spontaneous fetal swallowing and hypertonic saline thresholds for stimulated swallowing were determined prior to and following maternal hypotonicity induced with water loading and intravenous DDAVP (arginine vasopressin V2 agonist). Fetal swallowing thresholds were determined with intracarotid injections (0.15 ml/kg) of increasing sodium chloride concentrations (0.15-1.2 M) at 2-min intervals. Maternal DDAVP infusion significantly decreased mean (+/-SEM) maternal and fetal plasma osmolalities (298 +/- 2-284 +/- 3; 295 +/- 2-278 +/- 3 mOsm/kg, respectively) and sodium concentrations (147.3 +/- 0.4-137.5 +/- 0.9; 142.7 +/- 0.8-133.5 +/- 1.0 mEq/l, respectively), suppressed spontaneous swallowing activity and volume (1.1 +/- 0.2-0.6 +/- 0.1 swallows/min; 0.7 +/- 0.2-0.5 +/- 0.1 ml/min, respectively) and significantly increased the osmotic threshold for swallowing stimulation (0.77 +/- 0.08-1.03 +/- 0.09 M NaCl). We conclude that: (1) maternal, and thus fetal, plasma hypotonicity results in suppression of spontaneous fetal swallowing activity and a decrease in volume swallowed, suggesting that spontaneous fetal ingestive behavior results, in part, from tonic dipsogenic stimulation, and (2) under hypotonic conditions, the intracarotid NaCl injection concentration for swallowing stimulation increases. These results suggest that the reset (lower) maternal plasma osmolality during human pregnancy may serve to minimize fetal ingestive and perhaps arginine vasopressin-mediated antidiuretic responses to acute maternal hypertonicity.

Treatment of oligohydramnios with maternal 1-deamino-[8-D-arginine] vasopressin–induced plasma hypoosmolality

OBJECTIVE: Maternal 1-deamino-[8-D-arginine] vasopressin (a selective antidiuretic agonist) and oral water loading decrease maternal and fetal plasma osmolality and markedly increase fetal urine flow in sheep. We hypothesized that a titrated reduction in maternal plasma osmolality would increase human amniotic fluid volume. STUDY DESIGN: Pregnant women ( n = 5) with oligohydramnios at term were administered oral water loading (20 ml/kg) and intravenous 1-deamino-[8-D-arginine] vasopressin (2 μg) to induce antidiuresis. Maternal plasma and urine osmolality and urine production were measured hourly, and water replacement was titrated for 8 hours to reduce plasma osmolality by 15 to 20 mOsm/kg. The amniotic fluid index determined by ultrasonography was measured at baseline, 8 hours, and 24 hours. A control group of pregnant women ( n = 5) with oligohydramnios at term was observed for 8 hours with maintenance intravenous hydration. RESULTS: In 1-deamino-[8-D-arginine] vasopressin - treated women, maternal urine flow increased with oral water loading, decreased with 1-deamino-[8-D-arginine] vasopressin administration, and remained reduced for 8 hours. Maternal plasma osmolality significantly decreased (285 ± 4 to 265 ± 4 mOsm/kg) and the amniotic fluid index significantly increased (4.1 ± 0.6 to 8.2 ± 1.5 cm) at 8 hours. Although maternal urine osmolality returned to basal values at 24 hours, plasma osmolality was reduced and the amniotic fluid index remained significantly increased (8.2 ± 1.3 cm). There was no change in the amniotic fluid index (4.3 ± 0.4 to 4.7 ± 0.7 cm) in control patients observed with maintenance intravenous hydration. CONCLUSIONS: Maternal 1-deamino-[8-D-arginine] vasopressin and oral water administration can reduce and stabilize plasma osmolality and increase amniotic fluid volume. 1-Deamino-[8-D-arginine] vasopressin therapy has potential for the prevention and treatment of oligohydramnios. (AM J OBSTET GYNECOL 1996;174:1608-13.)

1-Deamino-[8-d-arginine] vasopressin - induced maternal plasma hypoosmolality increases ovine amniotic fluid volume

OBJECTIVE: Maternal 1-deamino-[8-d-arginine] vasopressin (a selective antidiuretic agonist) and oral water loading decrease maternal and fetal plasma osmolality and markedly increase fetal urine flow in sheep over 24 hours. We hypothesized that a sustained reduction in plasma osmolality would increase the amniotic fluid volume. STUDY DESIGN: Pregnant sheep (130 ± 1 days, n = 6) were given oral water loading (2000 ml) and intravenous 1-deamino-[8-d-arginine] vasopressin (20 μg injection followed by 4 μg/hr) to induce maternal urinary antidiuresis and to maintain a maternal plasma osmolality decrease of approximately 20 mOsm/kg for 48 hours. Fetal plasma osmolality, electrolytes, atrial natriuretic factor, and arginine vasopressin levels, fetal swallowing activity, and fetal urine flow and composition were measured each study day, and amniotic fluid volume was measured by tracer dilution before and at 48 hours of plasma hypoosmolality. RESULTS: In response to 1-deamino-[8-d-arginine] vasopressin and water loading, maternal plasma osmolality decreased (298 ± 1 to 275 ± 3 mOsm/kg), mirrored by fetal plasma hypoosmolality (293 ± 1 to 271 ± 3 mOsm/kg). Fetal urine osmolality (155 ± 16 to 117 ± 10 mOsm/kg) and amniotic fluid osmolality significantly decreased (281 ± 3 to 269 ± 5 mOsm/kg). Fetal urine flow rate significantly increased (0.33 ± 0.06 to 0.51 ± 0.04 ml/min), whereas fetal swallowing activity decreased (56 ± 7 to 33 ± 5 swallows per hour). In response to alterations in fetal fluid dynamics, amniotic fluid volume significantly increased from 493 ± 80 to 839 ± 160 ml. CONCLUSION: Chronic maternal 1-deamino-[8-d-arginine] vasopressin - induced plasma hypoosmolality induces a sustained reduction in fetal swallowing activity and an increase in fetal urine production, which results in a marked increase in amniotic fluid volume. Use of maternal 1-deamino-[8-d-arginine] vasopressin and oral fluid loading has the potential for manipulation of amniotic fluid volume homeostasis and may prove useful in the treatment of oligohydramnios. (A M J O BSTET G YNECOL 1996;174:1118-27.)

Acute maternal hydration in third-trimester oligohydramnios: Effects on amniotic fluid volume, uteroplacental perfusion, and fetal blood flow and urine output

OBJECTIVE: Our purpose was to determine whether acute maternal hydration in pregnancies with third-trimester oligohydramnios (1) increases amniotic fluid index and hourly fetal urine production rate and (2) alters uteroplacental perfusion and fetal blood flow. STUDY DESIGN: Ten women with third-trimester oligohydramnios (amniotic fluid index ≤5 cm) and 10 controls with normal amniotic fluid volume (amniotic fluid index >7 cm) were prospectively recruited for this study. Maternal plasma and urine osmolality, amniotic fluid index, hourly fetal urine production rate, and Doppler flow velocimetry of maternal uterine artery and fetal umbilical, descending aorta, middle cerebral, and renal arteries were determined before and after oral hydration by having the patient drink 2 L of water over 2 hours. RESULTS: There was a significant reduction in maternal plasma ( p < 0.05) and urine osmolality ( p < 0.0001) in both groups after short-term oral hydration. Hydration increased amniotic fluid volume in women with oligohydramnios (mean change in amniotic fluid index 3.2 cm, 95% confidence intervals 1.1 to 5.3; p < 0.02) but not in those with normal amniotic fluid volume (mean change in amniotic fluid index −2.0, 95% confidence intervals −4.1 to +0.2). The hourly fetal urine production rate, however, did not increase in either group (mean change in hourly fetal urine production rate 3.5 ml/hr, 95% confidence intervals −11.7 to +18.7 and −6.8 ml/hr, 95% confidence intervals −2.9 to −10.7, respectively). Hydration was associated with an increased in uterine artery mean velocity in the oligohydramnios group (mean change in mean velocity 16.7 cm/sec, 95% confidence intervals 8.0 to 25.3; p < 0.006) but not in controls (mean change in mean velocity 1.2 cm/sec, 95% confidence intervals −19.7 to +22.1). There was no change in pulsatility index or in velocity in any of the fetal vessels studied in either group. CONCLUSIONS: Short-term maternal oral hydration increases the amniotic fluid index in women with third-trimester oligohydramnios. Although the mechanism for this effect remains unclear, it could not be accounted for by fetal urination in this study but instead was associated with improved uteroplacental perfusion.

DDAVP-induced maternal hyposmolality increases ovine fetal urine flow.

Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal-to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1-desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume.

Maternal/fetal dehydration: prolonged effects and responses to oral rehydration

Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration.

A unique hypertonic response to hypotonic infusion in the pregnant ewe

OBJECTIVE: The purpose of this study was to compare the responses of the maternal ewe to intravenous volume expansion with either sufficient lactated Ringer's solution to elevate maternal venous pressure or sufficient hypotonic fluid to reduce blood osmolality.STUDY DESIGN: Chronically catheterized pregnant sheep were intravenously infused over 4 hours with either commercial lactated Ringer's solution (5.55 ± 0.50 Uhr, 255 mOsm/kg, mildly hypotonic) or diluted Ringer's solution (2.04 ± 0.27 Uhr, 150 mOsm/kg, markedly hypotonic). Data were statistically analyzed with two- and three-factor analyses of variance and bivariate regression analysis.RESULTS: During the mildly hypotonic infusion (n = 8) the maternal blood osmolality changes were -5.1 ± 1.2, + 2. 7 ± 1.0 and + 6.8 ± 1.1 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. In four of the eight animals in this group profuse diarrhea developed. During the markedly hypotonic infusion (n = 11) the maternal blood osmolality changes were -9.9 ± 1.1, -15.9 ± 2.5, and -10.4 ± 2.2 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. Although urine osmolalities were significantly less than the osmolality of the infusate in both groups, only during the mildly hypotonic infusion was there a net loss of free water by the kidneys. The renal free water loss, the venous pressure increase, and the blood osmolality decrease were not significantly different whether diarrhea did or did not develop.CONCLUSION: The infusion of large volumes of mildly hypotonic Ringer's solution to the pregnant ewe produces a paradoxic increase in maternal plasma osmolality as a result of the excretion of large volumes of free water by the kidneys, and if the venous pressure is increased more than about 6 mm Hg with this infusion, diarrhea develops in the animals. (AM J OBSTET GYNECOL 1992;167:1698-709.)