Fetal transabdominal pulse oximeter studies using a hypoxic sheep model

Objective.?This study investigates the validity of transabdominal pulse oximetry using a sheep fetal hypoxia model with fetal arterial hemoglobin saturation.

Methods.?Four pregnant ewes were anaesthetized and cannulated through the brachial artery to measure direct arterial blood saturation, SaO₂. Next, the transabdominal pulse oximeter was used to measure indirect measurement of the arterial saturation of the fetus, SpO₂, from the maternal abdomen. Hypoxia was induced by a balloon placed in the maternal aorta.

Results.?There is a linear relationship between SaO₂, arterial blood saturation values of the fetus, and SpO₂, the values measured by the transabdominal pulse oximetry with a slope of 0.75 (r²?=?0.76).

Conclusion.?This information can be used to calibrate the transabdominal pulse oximeter as a measurement of fetal arterial saturation. With these results, we can advance the accurate, no-risk, noninvasive transabdominal fetal pulse oximeter for human use. This research may contribute to the more accurate diagnosis of the diseases of the fetus including Hypoxic Ischemic Encephalopathy.     

Cerebral Blood Flow and Metabolism in Ovine Fetuses During Asphyxia Resulting in Seizures

Severe fetal asphyxia can cause neurologic damage, but little is known about cerebral oxidative metabolism under these conditions. This study was designed to measure cerebral blood flow and oxygen consumption during severe global asphyxia in fetal sheep, asphyxiated to the point at which seizure activity subsequently occurred. Six sheep were chronically instrumented with fetal electrodes, fetal and maternal vascular catheters, and an adjustable occluder on the maternal common hypogastric artery. Measurements were made of fetal arterial blood gases, blood pressure, heart rate electrocorticogram (ECoG), nuchal muscle electromyogram (EMG), and regional blood flow (radioactive microspheres) during control, and at 30 and 60 min after complete occlusion of the maternal hypogastric artery. The ECoG became isoelectric, and the fetuses developed a marked respiratory and metabolic acidosis, the pH falling to 6.99 ± 0.03, the pCO₂ rising to 73 ± 11 mm Hg, and base excess falling to ?16 ± 1 mEq/L at 60 min of occlusion. Control fetal arterial blood pressure was 52 ± 9 mm Hg and did not change significantly with asphyxia at 60 min. Cerebral cortical blood flow was 127 ± 54 ml/100 g/min at control, and 204 ± 130 ml/100 g/min at 60 min of asphyxia. Cerebral oxygen consumption was 201 ± 50 μM/100 g/min at control, and 76 ± 57 μM/100 g/min at 60 min of asphyxia (P < 0.05), i.e., 45% of control. All 6 fetuses had episodic seizure activity based on ECoG and nuchal EMG activity, beginning 50 ± 47 min after release of the occluder. This seizure activity continued for 24-36 h. This study shows that 60 min of asphyxia associated with suppressed ECoG activity and severe acidosis induced neuronal damage, manifesting as seizure activity, and that this occurred when cerebral oxidative metabolism was reduced to ≤50% of control.     

Role of sex steroid hormones in relative refractoriness to angiotensin II during pregnancy

Normal human pregnancy is associated with significant vascular refractoriness to the pressor effects of infused angiotensin II, and in women destined to develop pregnancy-induced hypertension, this refractoriness is lost several weeks before the onset of hypertension. The plasma concentrations of sex steroid hormones gradually increase throughout pregnancy. In the present study, the effect of infusion of 17β-estradiol (E₂), progesterone, or 5α-dihydroprogesterone on the pressor response to infused angiotensin II (0.002 to 0.1 μg · min^?1 · kg^?1) was evaluated in eight unanesthetized and chronically instrumented nonpregnant ewes. Pressor response to infused angiotensin II (0.02 to 0.1 μg · min^?1 · kg^?1) was significantly suppressed by a 60-minute infusion of E₂ (0.8 μg · min^?1 · kg^?1), whereas infusion of progesterone (4 μg · min^?1 · kg^?1) or 5α-dihydroprogesterone (0.8 μg · min^?1 · kg^?1) did not affect the pressor response. Neither the acid-base status, plasma renin activity, nor serum electrolytes were altered by the administration of E₂ or progesterone. These results indicate that E₂ may play an important role in the refractoriness to infused angiotensin II during pregnancy, and that this refractoriness by E₂ is not mediated by changes in chemoreceptor reflex, renin-angiotensin system, or serum electrolytes, but more likely by the changes in the characteristics of the vascular wall.     

Effect of respiratory acidosis on the rabbit fetus in utero

This report deals with acid-base relationships between maternal and fetal bloods. The new aspect is the presentation of nonsteady state measurements made simultaneously in both mother and fetus during the production of respiratory acidosis in the mother.Pure respiratory acidosis was induced in 12 pregnant rabbits near term by allowing them to breathe selected concentrations of carbon dioxide. The pH, Pco₂, and standard HCO₃^? determinations were made on maternal arterial and fetal umbilical vein blood. In all instances, both the mother and the fetus showed a decrease in pH and an elevation of arterial Pco₂ without a change in standard HCO₃^? concentrations. Severe respiratory acidosis over a 90 minute period did not produce metabolic acidosis in the mother or the fetus. In the presence of pure respiratory acidosis in the pregnant rabbit, measurements of pH, Pco₂, and standard HCO₃^? in the mother's blood provide reasonably accurate information of their concentrations in fetal blood. However, it cannot be concluded that other types of acid-base changes in the mother will be reflected by similar changes in the fetus.     

Effect of angiotensin infusion during pregnancy on fetal heart rate and on fetal activity

The angiotensin sensitivity test is of value in predicting patients at increased risk of pregnancy-induced hypertension and preeclampsia. Studies on the effects of angiotensin II on uterine blood flow in various species showed contradicting results. In the present study, 15 pregnant women were monitored by cardiotocography before, during and after an infusion of angiotensin II-amide (maximal infusion rates 6.3–23.2 ng · kg^?1 · min^?1). No remarkable changes in fetal heart rate, oscillatory frequency and amplitude, as well as in the number of accelerations and fetal movements could be observed. It may be concluded from these results that the fetal condition is not compromised by an angiotensin sensitivity test.     

Thromboxane synthetase inhibition produces maternal and fetal vasodilation during ovine pregnancy-induced hypertension: a Doppler flow velocimetric study.

Changes in maternal and fetal umbilical arterial vasoreactivity during ovine pregnancy-induced hypertension and following intravenous administration of CGS 12970 [3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid] were assessed. Continuous wave Doppler flow velocimetry was used to assess vascular reactivity during normotensive baseline, during ovine pregnancy-induced hypertension triggered by a 72-hour fast, and following thromboxane synthetase inhibition with CGS 12970. Uterine and umbilical arterial systolic/diastolic flow ratios increased significantly with the onset of sustained hypertension. After thromboxane synthetase inhibition, uterine and umbilical artery systolic/diastolic flow ratios were not different from baseline, and maternal blood pressure had returned to baseline values. These data indicate that thromboxane produces maternal and fetal vasoconstriction during ovine pregnancy-induced hypertension. Furthermore, these data provide strong evidence that thromboxane synthetase inhibition allows vasodilation, resulting in improved maternal and fetal condition.     

The Effect of Prostaglandin E1on the Pressor Response to Angiotensin II in Second Trimester Human Pregnancy and in the Non-Pregnant Subject

The effect of a simultaneous infusion of prostaglandin E₁ (PGE₁) on the pressor response to angiotensin II (AII) has been studied in 8 pregnant and six non-pregnant subjects to date. PGE₁ 15 ng kg^?1 min^?1 had no effect on basal blood pressures in the pregnant patients, but increased heart rate by 9.1 ± 1.6 bpm (P<0.001). Six of these eight wanen had scanewhat diminished pressor responses to AII (4, 8 and 16 ng kg^?1 min^?1) during PGE₁ infusion; this difference reached statistical significance at the lowest dose of AII (P<0.05). PGE₁ 10 ng kg^?1 min^?1 slightly increased basal diastolic pressure in the non-pregnant subjects (P<0.05) and increased heart rate by a similar amount (8.4 ± 1.8 bpm, P<0.01). Again, the overall pressor response to AII was sanewhat diminished in the majority of these subjects. The pregnant patients exhibiting the greatest initial pressor response to AII were those in whom the greatest decrease in response was seen; this correlation achieved statistical significance at 8 and 16 ng kg^?1 min^?1 AII (P<0.01, P(0.002 respectively). A similar trend was apparent in the non-pregnant subjects.     

Fetal-maternal nitrite exchange in sheep: Experimental data,a computational model and an estimate of placental nitrite permeability

IntroductionNitrite conveys NO-bioactivity that may contribute to the high-flow, low-resistance character of the fetal circulation. Fetal blood nitrite concentrations depend partly on placental permeability which has not been determined experimentally. We aimed to extract the placental permeability-surface (PS) product for nitrite in sheep from a computational model.MethodsAn eight-compartment computational model of the fetal–maternal unit was constructed (Matlab^® (R2013b (8.2.0.701), MathWorks Inc., Natick, MA). Taking into account fetal and maternal body weights, four variables (PS, the rate of nitrite metabolism within red cells, and two nitrite distribution volumes, one with and one without nitrite metabolism), were varied to obtain optimal fits to the experimental plasma nitrite profiles observed following the infusion of nitrite into either the fetus (n = 7) or the ewe (n = 8).ResultsThe model was able to replicate the average and individual nitrite–time profiles (r² > 0.93) following both fetal and maternal nitrite infusions with reasonable variation of the four fitting parameters. Simulated transplacental nitrite fluxes were able to predict umbilical arterial-venous nitrite concentration differences that agreed with experimental values. The predicted PS values for a 3 kg sheep fetus were 0.024 ± 0.005 l∙min⁻¹ in the fetal–maternal direction and 0.025 ± 0.003 l∙min⁻¹ in the maternal–fetal direction (mean ± SEM). These values are many-fold higher than the reported PS product for chloride anions across the sheep placenta.ConclusionThe result suggests a transfer of nitrite across the sheep placenta that is not exclusively by simple diffusion through water-filled channels.     

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.     

Cesarean delivery rate in the United States: a continuing challenge

Objective.?To evaluate the transplacental effect of allopurinol, which acts as a xanthine oxidase inhibitor and free radical scavenger, on inhibiting the production of superoxides during intermittent partial umbilical cord occlusion.

Methods.?Using four chronically instrumented fetal lambs, ewes received 400?mg allopurinol over a period of two hours. Concentrations of allopurinol and oxypurinol in blood samples from mothers and fetuses and fetal brain microdialysis perfusate were measured by HPLC. In another three cases the production of superoxide during intermittent umbilical cord occlusion was studied by measurement of chemiluminescence in perfusate before and after administration of Allopurinol.

Results.?(i) Allopurinol concentration in mothers had reached equilibrium by 30?min after starting administration and maintained a concentration about 6?μg/ml. Allopurinol concentration in fetuses increased gradually and reached 2.25?±?0.54?μg/ml at 120?min; (ii) Oxypurinol concentration in both mothers and fetuses increased during administration of allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates reached 0.32?±?0.12?μg/ml, 0.53?±?0.22?μg/ml at 120min respectively; and (iv) Administration of allopurinol significantly suppressed superoxide production during intermittent partial umbilical cord occlusion.

Conclusion.?These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.     

Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood

Objective: The study was aimed to compare trace elements concentrations in women with and without severe pre-eclampsia (PE). Methods: A prospective case-control study was conducted comparing 43 parturients with severe PE (who received magnesium sulfate [MgSO4]) and 80 healthy parturients and their newborns, matched for gestational age and mode of delivery. Inductively coupled plasma mass spectrometry (ICPMS) was used for the determination of zinc (Zn), copper (Cu), selenium (Se) and magnesium (Mg) levels in maternal as well as arterial and venous umbilical cord serum. Results: Zn levels (µg/L) were significantly higher in fetal arterial and venous blood of the PE group (947.3?±?42.5 vs. 543.1?±?226, 911.1?±?220.2 vs. 422.4?±?145, p?<?0.001; respectively). Se levels (µg/L) were significantly lower in maternal and fetal arterial and venous cord blood of the PE group (98.6?±?24.2, 110.7?±?19.4, 82?±?17.8 vs. 111.6?±?17.6, 82.1?±?17.4 vs. 107.1?±?25.7, p?<?0.001; respectively). Cu levels (µg/L) were significantly lower in fetal arterial and venous cord blood (581.6?±?367.4 vs. 949?±?788.8, p?=?0.022, 608.3?±?418.1 vs. 866.9?±?812.6, p?=?0.001 respectively) but higher in maternal blood (2264.6?±?751.7 vs. 1048?±?851.1, p?<?0.001). These differences remained significant while controlling for the mode of delivery. Mg levels were significantly higher in the PE group as compared with the control group. Conclusions: Severe PE is associated with abnormal concentrations of Zn, Cu and Se. Therefore, trace elements may have a crucial role in the pathogenesis of severe PE.     

Saline Amnioinfusion in the Pregnant Ewe: Fetal Responses,Uterine Compliance,and Amniotic Fluid Index

The purpose of this study was to measure the effects of saline amnioinfusion on the fetus, amniotic pressure, and amniotic fluid index (AFI). Eleven chronically catheterized fetal sheep at 137 ± 1 (SE) days gestation received intraamniotically 6 liters of warmed NaCl solution adjusted to be iso-osmotic to amniotic fluid in 1-liter increments at 30-min intervals. Decreases occurred in fetal arterial pressure (4.1 ± 1.0 mmHg, P < 0.01), arterial pH (0.06 ± 0.02, P < 0.001) and p0₂ (2.7 ± 0.8 mmHg, P < 0.01), whereas pC0₂ increased (1.9 ± 0.7 mmHg, P < 0.01). Increases occurred in plasma sodium (2.1 ± 0.5 mEq/L, P < 0.001) and chloride (3.1 ± 0.8 mEq/L, P < 0.001), while potassium decreased (0.3 ± 0.1 mEq/L, P < 0.001). Uterine compliance was 946 ±181 ml/mmHg. The AFI correlated with volume infused (R = 0.85, P < 0.00001). These findings suggest that saline amnioinfusion, although producing minor if any cardiovascular effects in the ovine fetus, significantly alters fetal plasma composition, possibly due to rapid absorption via the intramembranous pathway. In addition, this study demonstrates that the amniotic fluid index increases linearly with the amniotic fluid volume and demonstrates a relatively volume insensitive compliance of the ovine uterus.     

Insulin resistance and β-cell function influence postprandial blood glucose levels in Japanese patients with gestational diabetes mellitus

Abstract

Aims/introduction: The aim of this study in patients with gestational diabetes mellitus (GDM) was to evaluate the relationship of insulin resistance and secretion to area-under-the-sensor glucose concentration–time curve from before to 120?min postmeal (CGM-AUC_0–120?min) as determined with continuous glucose monitoring (CGM).

Materials and methods: Immunoreactive insulin and HbA1c were determined in 22 Japanese patients with GDM undergoing a 75?g oral glucose tolerance test. Patients underwent CGM within 3 weeks of receiving a diagnosis of GDM.

Results: HbA1c (NGSP) was 5.5?±?0.4%, BMI was 24.8?±?5.3?kg/m², mean sensor glucose by CGM was 94.2?±?10.3?mg/dL, standard deviation was 17.5?±?4.4?mg/dL, and CGM-AUC_0–120?min was 204.2?±?23.8?h?mg/dL. The insulin resistance indices the homeostasis model assessment ratio (HOMA-R), quantitative insulin sensitivity check index (QUICKI), and the Matsuda Index were correlated with CGM-AUC_0–120?min. The disposition index (DI), which was used to evaluate insulin secretion, was negatively correlated with CGM-AUC_0–120?min.

Conclusions: Not only insulin resistance but also beta cell dysfunction contributes to postprandial hyperglycemia in Japanese patients with GDM.     

The effect of loading dose of magnesium sulfate on uterine,umbilical, and fetal middle cerebral arteries Doppler in women with severe preeclampsia: A case control study

IV MgSO₄ administration in women with severe preeclampsia resulted in a decrease in umbilical artery, uterine artery, and fetal middle cerebral artery Doppler indices.

Objective: To evaluate Doppler parameters of the umbilical artery (UmA), uterine artery (UA), and fetal middle cerebral artery (MCA) before and after MgSO₄ administration in women with severe preeclampsia. Methods: A case control study included 100 pregnant women with severe preeclampsia. Umbilical artery, uterine artery, and fetal middle cerebral artery Doppler were measured before and 20 minutes after intravenous administration of 6 g of magnesium sulfate. Results: There was a significant difference between maternal systolic blood pressure (173.20 ± 22.72 vs. 156.60 ± 19.18), diastolic blood pressure (109.60 ± 9.14 vs. 101.90 ± 10.05), and heart rate (80.52 ± 11.52 vs. 88.48 ± 12.08) before and after administration of MgSO₄ in the studied patients (p value < 0.001). There was a significant difference between umbilical artery, middle cerebral artery, and uterine artery Doppler parameters before and after administration of MgSO₄ in the studied patients (p value < 0.001). There was no significant difference between umbilical artery/middle cerebral artery with regard to RI and PI. However, there was significant difference with regard to the S/D ratio (p value < 0.001). The decrease in the values of Doppler parameters before and after administration of MgSO₄ was more in the middle cerebral artery than in the umbilical artery. Conclusion: Intravenous administration of magnesium sulfate in pregnant women with severe preeclampsia resulted in a decrease in umbilical artery, uterine artery, and fetal middle cerebral artery Doppler indices with reduced resistance to blood flow in these vessels.     

Fetoplacental vascular responses to prostacyclin after thromboxane-induced vasoconstriction

The vasodilator prostacyclin is produced by fetal tissues and may serve to protect umbilical blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by a thromboxane mimic (U-46619). Fetal regional blood flow was measured by the radioactive microsphere technique in six unanesthetized, near-term ovine fetuses. Measurements were made in the control period, again 20 minutes after a fetal infusion of U-46619 was begun, and finally 20 minutes after prostacyclin was added to the U-46619 infusion. Mean arterial pressure rose significantly in response to U-46619 (38 +/- 1 to 51 +/- 2 mm Hg, p less than 0.01) and returned to baseline after prostacyclin (42 +/- 2 mm Hg). Renal resistance was increased from 0.16 +/- 0.01 to 0.22 +/- 0.01 mm Hg.ml-1.min.100 gm-1 (p less than 0.05) by U-46619 and decreased significantly (p less than 0.05) below baseline by addition of prostacyclin (0.10 +/- 0.02 mm Hg.ml-1.min.100 gm-1). Placental resistance also increased significantly (p less than 0.03) in response to U-46619 (from 0.15 +/- 0.01 to 0.21 +/- 0.01 mm Hg.ml-1.min.kg-1 fetal weight) but was further increased to 0.29 +/- 0.03 mm Hg.ml-1.min.kg-1 fetal weight by the addition of prostacyclin. Umbilical placental blood flow decreased significantly (p less than 0.03) when prostacyclin was added to U-46619 (315 +/- 40 to 195 +/- 30 ml.min-1.kg-1 fetal weight). Whereas U-46619 had no effect on fetal arterial blood gases, the addition of prostacyclin resulted in significant fetal acidosis (p less than 0.03). We conclude that thromboxane mimic causes fetal hypertension and renal and placental vasoconstriction. Prostacyclin reverses hypertension and renal vasoconstriction but, unexpectedly, worsens fetal placental vasoconstriction produced by thromboxane. It is likely that the observed fetal acidosis is a result of compromised placental function.     

Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep.

Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.     

Relationship of fetal oxygen consumption and acid-base balance to fetal hematocrit

We evaluated the effects of alterations in fetal hematocrit on fetal oxygenation in 10 chronically catheterized fetal lambs. Hematocrit was varied from 10% to 55% by slow isovolemic exchange transfusions with plasma or packed red blood cells obtained freshly from donor fetuses. At each hematocrit studied, we measured umbilical blood flow (Q̇_umb) and the oxygen concentrations in umbilical venous blood (Cuv_O2) and arterial blood (Ca_O2) and calculated fetal oxygen delivery (Q̇_umb · Cuv_O2), oxygen extraction [(Cuv_O2 − Ca_O2], and oxygen consumption [Q̇_umb (Cuv_O2 − Ca_O2)]. Fetal oxygen delivery was maximal at a fetal hematocrit of 33% (mean oxygen delivery = 23 ml of oxygen per minute per kilogram of fetus) and decreased as hematocrit was raised or lowered from that value. Despite these reductions in oxygen delivery, fetal oxygen consumption was relatively stable (at about 7 ml of oxygen per minute per kilogram) at hematocrits ranging from about 16% to 48% because of compensatory increases in fetal oxygen extraction. Regardless of whether oxygen delivery decreased because of anemia or polycythemia, fetal oxygen consumption was maintained as long as oxygen delivery was greater than about 14 ml of oxygen per minute per kilogram of fetus. When oxygen delivery was <14 ml of oxygen per minute per kilogram, fetal oxygen consumption fell while arterial blood base deficit increased, indicating that oxygen supply was inadequate for fetal oxygen demands. These results indicate that fetal aerobic metabolism can be sustained over a wide range of fetal hematocrits. Furthermore, our data support the concept that the level of fetal oxygen delivery is an important determinant of the adequacy of fetal oxygenation.     

The effect of insulin on ovine fetal oxygen extraction

Infusion of exogenous insulin (54 +/- 19 mU/kg/hr) to seven fetal lambs caused hyperinsulinism and arterial hypoxemia but not hypoglycemia. We measured the relationship between fetal oxygen delivery and oxygen use for a better understanding of the cause of the observed hypoxemia. Oxygen delivered to the fetus is the product of fetal umbilical venous oxygen content and umbilical blood flow. Both of these quantities decreased as fetal insulin concentration rose. The fall in umbilical blood flow was due to a change in the distribution of cardiac output. Cardiac output rose, but placental perfusion decreased while blood flow to the fetal carcass increased. Oxygen consumption by the ovine fetus increased as insulin concentration rose. Since the delivery of oxygen to the fetus did not increase when its use was rising, fetal extraction of available oxygen increased. Fetal arterial hypoxemia is the result of this increased extraction of available oxygen.     

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.     

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.