Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion

Objective: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus.

Methods: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132?±?1 days' gestation (term 145–150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25?ml/min) for the duration of the study. At time 4?h, leptin (0.075?mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6?h.

Results: During the basal period, fetal swallowing averaged 0.7?±?0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2?±?0.1 swallows/min; p?<?0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6?h (1.3?±?0.4, 1.4?±?0.3 and 1.5 ±?0.2 swallows/min, respectively; p?<?0.05 vs. control).

Conclusions: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.     

Effect of oral sucrose on ingestive behavior in the near-term ovine fetus

BACKGROUND: Dipsogen-mediated ingestion matures acutely in late gestation because the preterm fetus may demonstrate absent responses to putative dipsogens. Although central appetite-mediated ingestive behavior is functional near term, it is unknown whether peripheral mechanisms for stimulation of appetite also are functional. In the adult, sweet taste stimulates and potentiates ingestive behavior. We sought to determine whether oropharyngeal sucrose exposure stimulates ingestive behavior in the near-term ovine fetus. STUDY DESIGN: Time-dated pregnant ewes with near-term singleton fetuses (n = 6) were chronically prepared with fetal vascular and sublingual catheters and esophageal electromyogram electrodes and studied at 129 +/- 1 days of gestation. After an initial 2-hour baseline period, successive solutions of distilled water and 2.5%, 10%, and 40% sucrose were infused sublingually (0.25 mL/min), each for 2 hours. Maternal and fetal arterial blood samples were drawn at timed intervals. RESULTS: During the basal period, fetal swallowing averaged 0.9 +/- 0.1 swallows per minute. Swallowing did not change in response to distilled water (0.9 +/- 0.2 swallows per minute) but significantly increased after sublingual infusion of 2.5% sucrose (1.3 +/- 0.1 swallows per minute), 10% sucrose (1.8 +/- 0.1 swallows per minute), and 40% sucrose (1.3 +/- 0.1 swallows per minute, P =.001). There were no significant changes in other fetal or maternal parameters. CONCLUSIONS: The stimulation of fetal swallowing in response to sublingual sucrose infusion suggests that taste-mediated ingestive behavior is functional in the near-term fetus and that both central and systemic appetite mechanisms are intact near term. Fetal swallowing increased in response to an increase in sucrose concentration to peak at 10% and then decreased with further rises in concentration, possibly mediated by aversive fetal reaction to a high-intensity sucrose concentration.     

Persistent sucrose stimulation of ovine fetal ingestion: lack of adaptation responses.

OBJECTIVE: Sweet taste responsiveness is reduced in adult rats and humans following continued oral sucrose. We have previously demonstrated that sublingual sucrose stimulates near term ovine fetal swallowing, suggesting intact taste responsiveness. We sought to determine if prolonged oral sucrose infusion to the near term ovine fetus will evoke adaptation, as manifested by reduced swallowing stimulation. METHODS: Time-dated pregnant ewes and fetuses (n = 4) were chronically prepared with fetal vascular and sublingual catheters, and electrocorticogram and esophageal electromyogram electrodes and studied at 129 +/- 1 d gestation. Following an initial 2 h basal period, sucrose (2.5%) was infused sublingually (0.25 ml/min) to the fetus for 8 h. Fetal swallowing activity, blood pressure and heart rate were continuously recorded while maternal and fetal arterial blood samples were taken at timed intervals. RESULTS: During the basal period, fetal swallowing averaged 0.9 +/- 0.1 swallows/min. Fetal swallowing increased significantly following sublingual 2.5% sucrose infusion and remained significantly elevated at 2, 4, 6 and 8 h after initiation of sucrose infusion (1.3 +/- 0.1, 1.2 +/- 0.1, 1.3 +/- 0.1, 1.3 +/- 0.1 swallows/min; p < 0.001). There were no significant changes in fetal cardiovascular or arterial blood parameters. CONCLUSIONS: Although oral sucrose significantly stimulates near term ovine fetal ingestive behavior, sweet taste adaptation or habituation does not occur, in contrast to that observed in adult animals and human. The lack of taste adaptation in the fetus/newborn may facilitate increased neonatal food intake and accelerated growth.     

Neuropeptide Y administered into cerebral ventricles stimulates sucrose ingestion in the near-term ovine fetus

OBJECTIVE: In adults, nutrient intake is controlled by opposing actions of appetite stimulants (eg, neuropeptide Y [NPY]) and suppressors (eg, leptin). Because NPY may exert a preferential role in mediating adult carbohydrate intake, we sought to determine the effect of central NPY on near-term fetal carbohydrate ingestion. STUDY DESIGN: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual, and intracerebroventricular catheters, electrocorticogram, and esophageal electromyogram electrodes and studied at 131+/-2 days' gestation. After a 2-hour baseline period, 10% sucrose was infused sublingually for the duration of the study. At 4 hours' time, NPY was injected into the fetal cerebral ventricles and fetal swallowing monitored for an additional 6 hours. RESULTS: During the basal period, mean (+/-SEM) swallowing averaged 0.8+/-0.1 swallows per minute. Fetal swallowing increased significantly in response to sublingual sucrose (1.3+/-0.1 swallows/min, P=.001), and further significantly increased at 4 to 6 hours after NPY injection into the cerebral ventricles (1.8+/-0.3, P=.001). CONCLUSION: These results indicate central NPY stimulation of fetal ingestion beyond that resulting from sublingual 10% sucrose. The in utero development of NPY-induced ingestive behavior may be in preparation for high neonatal caloric intake.     

Nitric oxide modulates angiotensin II-induced drinking behavior in the near-term ovine fetus

OBJECTIVE: Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing. STUDY DESIGN: Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 microg; time, 2 hours) and N omega-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 microg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. RESULTS: Angiotensin II injection significantly increased mean +/- SEM fetal swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade). CONCLUSIONS: These results demonstrate that inhibition of central nitric oxide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallowing stimulation by maintenance of glutamate activation of hypothalamic N -methyl-D -aspartate receptors.     

Ovine fetal breathing and swallowing activity in response to plasma glucose changes.

Fetal swallowing activity generally occurs simultaneously with fetal breathing movements (FBM) in sheep. The present study investigated the FBM and swallowing responses to altered fetal plasma glucose. Fetal lambs were chronically prepared with laryngeal, esophageal and diaphragm electromyogram (EMG) wires, an esophageal flow probe and vascular catheters. Beginning at 138 +/- 1 day, FBM and swallowing were monitored during control periods and in response to intravenous glucose infusions (14 mg/kg/min for 120 min) to fetuses of fed and fasted ewes. Glucose infusions to fetuses of fed ewes resulted in significant increases in fetal plasma glucose (21.2 +/- 0.7 to 40.5 +/- 1.9 mg/dl) and time breathing (46.2 +/- 6.3 to 60.0 +/- 9.5 min/2 h). In response to maternal fasting, fetal glucose levels (13.4 +/- 1.0 mg/dl) and time breathing (23.0 +/- 7.2 min/2 h) decreased significantly. Glucose infusion to fetuses of fasted ewes resulted in significant increases in time breathing (50.3 +/- 13.4 min/2 h) and diaphragmatic EMG activity (1,295 +/- 654 to 3,012 +/- 1,182 spikes/2 h). There was no change from basal levels of fetal EMG swallows (83.2 +/- 4.3 swallows/2 h) or esophageal flow (40.8 +/- 7.9 ml/2 h) in response to maternal fasting or fetal glucose infusions.     

Ovine fetal swallowing: expression of preterm neurobehavioral rhythms

OBJECTIVE: Fetal swallowing contributes importantly to amniotic fluid volume regulation and fetal gastrointestinal maturation. Near-term ovine fetal swallowing occurs in discrete bouts of activity (at approximately 30-min intervals) in association with fetal electrocortical voltage changes. Thus, swallowing rhythms have been hypothesized to be entrained to fetal neurobehavioral states. In the preterm ovine fetus, electrocortical activity does not demonstrate differentiation into high- and low-voltage periods until 120-130 days' gestation. We sought to quantify patterns of preterm (114 days, 0.75 gestation) ovine fetal swallowing activity and volume, and, in view of the lack of electrocortical pattern changes, to explore whether swallowing activity was regulated by an independent central pacemaker. METHODS: Six singleton ovine pregnancies were chronically prepared with fetal and maternal femoral artery and vein catheters. Biparietal electrocortical electrodes were placed on the fetal skull. Following a minimum 5-day recovery period, fetuses were studied at 114 +/- 1 days. Patterns of fetal swallowing behavior were quantified by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow during a 12-h period. RESULTS: Esophageal fluid flow was bidirectional, although antegrade flow predominated, leading to an average fluid acquisition rate of 13 +/- 3 ml/h (7.3 +/- 1.8 ml/h per kg) during the 12-h study (302 +/- 87 ml/day). Propagated esophageal EMG activity, representing coordinated 'swallows', averaged 56 +/- 6 swallows/h and correlated well with net esophageal fluid flow. 'Bouts' of swallowing activity (> or = 3 swallows/min) averaged 9 +/- 1 swallows/bout, lasted 1.8 +/- 1.4 min and accounted for 31 +/- 4% of the swallowed volume. Despite the absence of fetal electrocortical high-voltage/low-voltage transitions, there was a 26.1 +/- 3.9-min interval between periods of swallowing bout activity. CONCLUSIONS: Preterm (0.75 gestation) ovine fetal volume swallowed (302 ml/day) and volume swallowed for body weight (175 ml/day per kg) was significantly less than that previously noted at 0.85 gestation (831 ml/day, 274 ml/day per kg, respectively; p < 0.05) although the rates of swallowing activity were similar. The presence of swallowing bout activity at periodic intervals, in the absence of electrocortical differentiation, suggests an intrinsic central pacemaker regulating preterm fetal neurobehavior.     

Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity

OBJECTIVE: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. RESULTS: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). CONCLUSIONS: Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.     

Ovine hourly fetal urine production: relation to fetal electrocortical activity

OBJECTIVE: Ultrasound studies of hourly urine production rate in human fetuses have suggested that a fall in urine production occurs in state 2F (fetal quiet sleep) secondary to a state-dependent decrease in renal blood flow. We sought to ascertain the relationship between fetal hourly urine production rate and behavioral state in the near-term ovine fetus, a model in which urine production and fetal brain activity can be directly measured. METHODS: Six ewes with singleton pregnancies were prepared with vascular and amniotic fluid catheters. Fetuses were prepared with hindlimb vascular catheters, a bladder catheter, and biparietal ECoG electrodes. After at least 5 days of recovery (ga 130 +/- 2 days; term = 145-150 days), each animal was monitored for a 6-h period. Urine production was measured by draining the bladder catheter through a drop counter and fetal ECoG was continuously recorded (sampling rate of 50 Hz). ECoG activity was analyzed using power spectral analysis and periods of active and quiet sleep identified using both signal amplitude and corresponding 85% spectral edge frequency. RESULTS: Basal fetal arterial pH (7.36 +/- 0.01), pO2 (22.0 +/- 1.2 mmHg) and pCO2 (47.0 +/- 1.6 mmHg) and plasma (295 +/- 2 mOsm/kg) and urine (179 +/- 3 mOsm/kg) osmolalities were within normal ranges. Active and quiet sleep comprised 50 +/- 2 and 43 +/- 1% time, respectively. There was no difference in hourly urine production rate in active sleep (21.4 +/- 9.7 ml/h) and quiet sleep (18.8 +/- 7.7 ml/h). CONCLUSIONS: 1) Hourly fetal urine production rate is independent of ECoG activity state in the near-term ovine fetus. 2) Assuming only minor species differences, ultrasound measurement of human fetal hourly urine production rate can be performed without concern for fetal neurobehavioral state changes.     

Development of ovine fetal ileal motility: role of muscarinic receptor subtypes

OBJECTIVE: In the preterm human fetus, immaturity of gastrointestinal (GI) motility contributes to impairment of oral feeding and an increased risk of necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility development, and the primary role of the muscarinic system in adult GI motility, we examined the development of GI muscarinic receptor subtypes associated with ileal motility. STUDY DESIGN: Ovine term fetal, newborn, and pregnant adult ileal longitudinal muscle contractile responses to muscarinic agonists (bethanechol) and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4) were examined in organ baths. Immunohistochemical analysis of ileal muscle muscarinic receptor subtypes was correlated with contractile responses. RESULTS: Bethanechol induced a concentration-dependent ileal contraction at all 3 age groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and newborn, while 50% effective concentration (EC(50)) was similar at all ages. Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist exhibited robust inhibition at all age groups while the M2 antagonist demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis indicated coexpression of subtype receptors in fetal, newborn, and adult ileal smooth muscle with increasing expression with advancing age. CONCLUSION: These results demonstrate a specific developmental pattern of muscarinic receptor subtype expression. Knowledge and/or alterations of GI motility regulation may aid in the treatment of the preterm fetus or newborn.     

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.     

Placental uptake and transfer of lipid in the postterm rabbit.

Gonadotropin-injected pregnant rabbits were delivered by cesarean section near term (30 days after conception (term, 31 days) and 3 1/2 and 4 days post term. Lipid metabolism of the postterm and near-term fetus was compared. Fetal and placental uptake of radioactivity and rate of lipid entry into the fetus, as well as fetal and maternal plasma free fatty acid (FFA) specific activities (at equilibrium) were determined following a single maternal injection of [1-14C]palmitate (50 muCi) administered at cesarean section. Evidence of placental malfunction in the postterm period includes decreased placental uptake and transport of labeled FFA occurring while maternal and fetal FFA dynamics (half times) remain unchanged and a loss in "organization": The strong positive correlation (p less than 0.001) between placental uptake and transfer to the fetus at 30 days' gestation is lost 5 days later. A comparison of maternal and fetal plasma FFA specific activities indicates a substantial (62%) near-term fetal contribution to its own circulating FFA pool. Total plasma FFA is elevated in the postterm fetus concomitant with a decreasing maternal supply. A postterm fetus must therefore contribute lipid from its own reserves (probably liver) in excess of amounts attributed to a near-term fetus, i.e., greater than 62%.     

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.     

In utero development of fetal thirst and appetite: potential for programming

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.     

Cardiovascular and metabolic responses to intermittent umbilical cord occlusion in the preterm ovine fetus

OBJECTIVE: To determine the cardiovascular and metabolic responses to umbilical cord occlusion in the preterm ovine fetus and the impact of repetitive intermittent insults over a 4-day period. METHODS: Repetitive umbilical cord occlusions (experimental group, n = 7; control group, n = 7) were performed daily (112-115 days' gestation, term = 147 days). Mean arterial pressure (MAP), fetal heart rate (FHR), and FHR variation were monitored, and arterial blood was sampled at predetermined intervals. RESULTS: During umbilical cord occlusions, arterial oxygen pressure (PaO2) (approximately 17 mmHg) and glucose (approximately 0.3) millimoles per liter (mmol/L) fell and arterial carbon dioxide pressure (approximately 8 mmHg) rose (P < .01) to a similar extent on days 1 and 4. Umbilical cord occlusion produced a rise in lactate over the course of successive umbilical cord occlusions each day, the magnitude of which tended to be reduced by day 4 (0.3 +/- 0.1 versus 0.6 +/- 0.1 mmol/L). Control hour FHR and MAP were unaltered over the 4 days, but the delta (delta) FHR to delta PaO2 ratio during umbilical cord occlusions was less on day 4 than on day 1 (6.0 +/- 0.4 versus 10.9 +/- 1.5 beats per minute/mmHg; P < .01). During occlusion hours, high FHR variation episodes, as a measure of fetal activity, were reduced (14.6 +/- 1.5 versus 4.2 +/- 1.3 min/h; P < .01), whereas the reduction in short-term (7.4 +/- 0.7 to 5.8 +/- 0.6 milliseconds; P < .05) and long-term (34.9 +/- 2.7 to 30.0 +/- 0.6 milliseconds; P < .05) FHR variation reached significance only on day 4. CONCLUSION: The increase in lactate and reduced high-FHR variation episodes over successive umbilical cord occlusions may affect fetal growth and development. Furthermore, repeated umbilical cord occlusions over several days alter the preterm FHR response to subsequent stresses, suggesting an altered chemoreflex response.     

Leptin secretion to both the maternal and fetal circulation in the ex vivo perfused human term placenta

The contribution of placental leptin, if any, to both the fetal and maternal circulation and its role in pregnancy remains to be determined. In an experiment to investigate this, 27 placentae from term pregnancies were perfused ex vivo (gestational age=39.5 s.d. 1.2; range=38-42 weeks: fetal weight=3285 s.d. 482; range=2480-4420; birthweight centile range=4th to the 98th) at both the maternal and fetal interface. Placental leptin was exported into both the maternal and fetal circulations. The log leptin production by the maternal side of the placenta was significantly greater (P=0.001) than that for the fetal side (5.193 s.d.1.049 versus 4.387 s.d. 0.768 ng/placenta/min). There was no significant relationship between maternal and fetal log leptin production and maternal body mass index, birthweight, birthweight centile, ponderal index or gestational age or with cord blood pO(2), pCO(2) and pH. There was however, a significant increase in the maternal log leptin production with increasing fetal to placental weight ratio (P=0.017; r(2)=20.7 per cent) but no corresponding relationship for fetal leptin production. It is proposed that such a mechanism would allow the placenta to modulate fat supply to the fetus in response to the fetal demand relative to placental supply.     

Rapid intramembranous absorption of water infused into the ovine allantoic cavity.

OBJECTIVE: Previously we found that water infused into the ovine amniotic cavity was rapidly absorbed into the fetal circulation through the vascularized fetal membranes and fetal surface of the placenta (i.e., the intramembranous pathway). The purposes of this study were to (1) estimate the conductance of the intramembranous pathway from the allantoic cavity and (2) determine if the conductance is adequate to offset the inflow of urine, which may be up to 500 ml/day in the near-term ovine fetus. STUDY DESIGN: Seven chronically catheterized fetal sheep averaging 132 +/- 2 (+/- SE) days' gestation underwent an infusion of warmed distilled water into the allantoic cavity at 6 ml/min. The infusions were continued until steady states were obtained in allantoic and amniotic fluid and in fetal and maternal blood osmolalities. During the steady state the conductance of the intramembranous pathway was estimated as the ratio of osmotic gradient to infusion rate. RESULTS: The allantoic and amniotic fluid and the fetal and maternal blood osmolalities decreased by 188 +/- 14, 36 +/- 8, 13 +/- 2, and 3 +/- 1 mOsm/kg, respectively, at steady state. From the fetal-allantoic osmolality gradients the conductance of the intramembranous pathway was 1.72 +/- 0.14 or 0.53 +/- 0.08 microliter/min/mm Hg/kg fetal weight. Assuming a similar conductance during the preinfusion period, the next volume movement would equal 0.67 ml/min (965 ml/day). CONCLUSIONS: The conductance of the intramembranous pathway in combination with the normal osmotic gradient is sufficient to remove the large volume of fetal urine that may enter the allantoic cavity each day.     

Mechanisms of meconium passage: cholinergic stimulation of electromechanical coordination in the fetal colon

OBJECTIVE: Fetal gastrointestinal function develops in utero, with evidence of enhanced motility near-term. Although colonic passage of meconium in utero may be associated with fetal maturation or stress, little is known of the mechanisms potentiating motility. We assessed the effect of bethanechol, a cholinergic prokinetic agent, on colonic muscle muscular contractile and electromyogram (EMG) activity in the near-term ovine fetus. METHODS: Near-term (130 days, n = 8) singleton ovine fetuses were chronically prepared with vascular catheters and three sets of miniature strain gauges and bipolar EMGs on the serosal surface of the transverse colon, left colic flexure, and distal colon. Following a 60-minute control period, fetuses received intravenous bethanechol (60 microg/kg, Low-Beth; 120 microg/kg, High-Beth) at 60 and 180 minutes. Colonic activity was recorded digitally and analyzed for short-duration (2相似文献   

Fetal oxygen saturation during normal delivery

The aim of the study is to monitor fetal oxygen saturation--SpO2 during uncomplicated labour; to assess normal values and compare them to the data from fetal blood analysis and from clinical finding in the newborn. The study includes 53 pregnant women in term during active labour without evidence of fetal distress. Study is carried out with Nellcor-N 400--a system for measuring fetal pulse oxymetry and fetal pulse rate; oxygen sensor FS-14 and printer P-400 /Nellcor Bennet Incorporation/. Fetal pulse rate is monitored by cardiotograph Hewlett Packard. Mean duration of monitoring during first stage of labour is 98 +/- 48 min, versus 37 +/- 11 min during second stage. Mean values of SpO2 are 48.8 +/- 10% during the first stage of labor v/s 46 +/- 9.6% during second stage. Baby is born in good health--Apgar score more than 7 and mean pH value from umbilical artery 7.25. The conclusion is made that pulse oxymetry is an easy non invasive method for fetal monitoring without side effects concerning woman on labour and fetus. A relatively large range of variations of normal values is observed.