Simultaneous measurements of lactate turnover rate and umbilical lactate uptake in the fetal lamb.

Lactic acid represents a major exogenous nutrient for the developing fetal lamb in utero. Our study was undertaken (a) to quantitate the net consumption of lactate by the fetus, (b) to quantitate the net lactate production and metabolism by the placenta, and (c) to compare the net fetal lactate consumption with fetal lactate use, measured simultaneously with radioactive tracers. 14 pregnant sheep were prepared with catheters in the maternal femoral artery and uterine vein and in the fetal aorta and umbilical vein. By simultaneous application of the Fick principle to the uterine and umbilical circulations, placental glucose consumption and placental lactate production were rapid, averaging 39.8 +/- 5.1 and 11.8 +/- 0.7 mg.min-1. Net lactate umbilical uptake averaged 1.95 +/- 0.16 mg-1.kg.min-1. During infusion of L-[14C(U)]lactate, fetal lactate turnover was much more rapid, averaging 6.5 +/- 0.8 mg.kg-1.min-1, and lactate utilization within the anatomic fetus was 5.9 +/- 0.7 mg.kg-1.min-1. During infusion of tracer glucose, endogenous fetal lactate production from glucose and nonglucose substrates averaged 3.0 and 1.5 mg.kg-1.min-1, respectively. The present studies have quantitated under well oxygenated, steady-state conditions, the rapid placental metabolism and production of lactate, the net fetal consumption of lactate, and the rapid endogenous fetal lactate production from glucose and nonglucose substrates.

The effect of maternal oxygen inhalation upon fetal oxygenation.

In eight sheep, uterine and umbilical blood flows and oxygen uptakes, the transplacental flow-limited clearance of an inert molecule, pH values, and oxygen pressures, saturations, and capacities in the main placental vessels have been measured during maternal air breathing and oxygen inhalation. The mean +/-SEM percentage changes during oxygen inhalation were +4.6 +/-8.4 for the umbilical flow, +2.8 +/-8.7 for the uterine flow, and +4.6 +/-6.2 for the clearance. None of these changes are statistically significant. Oxygen uptake rose slightly in two cases and remained unchanged in the others. In all cases the oxygen pressures, saturations, and contents rose significantly in the uterine and umbilical vessels with oxygen inhalation.

Umbilical uptake of amino acids in the unstressed fetal lamb.

The whole blood concentrations of 22 amino acids were measured in a chronic, unstressed fetal lamb preparations. Samples were taken daily from the umbilical artery, umbilical vein, and maternal artery over the latter quarter of gestation. 73 sets of samples (from the umbilical artery and vein and the maternal artery) from 13 animals were analyzed for amino acid levels. Oxygen contents were determined simultaneously in 48 sets (umbilical artery and vein) to relate fetal oxygen consumption to amino acid uptake via the umbilical circulation. The results indicate that there is no umbilical uptake of the acidic amino acids, glutamate and aspartate; there is, in fact, a net flux of glutamate out of the fetus into the placenta. As both of these amino acids are major constituents of body proteins, the data indicate that they are formed within the fetus. The umbilical uptake of some neutral and basic amino acids (e.g., valine, leucine, isoleucine, arginine, phenylalanine, and tyrosine) is in considerable excess of estimated growth requirements, suggesting that some amino acids undergo extensive transamination and oxidative degradation in the fetus. Finally, the net uptake of nitrogen, carbon, and calories by the growing ovine fetus in the form of amino acids, glucose, and lactate is compared to estimated requirements as determined in previous studies.

An evaluation of fetal renal function in a chronic sheep preparation.

Fetal renal function in the sheep was investigated in a chronic preparation which permitted repeated evaluations of urine flow and osmolality as well as renal clearances in animals which were unanesthetized and remote from acute surgical stress. Measurements of fetal blood pressure, pH, osmolality, fetal growth in utero, and final outcome did not indicate an adverse effect of the experimental procedure on the fetus. Fetal urine flow and osmolality were highly variable during the early postoperative period. They did not stabilize until 3-6 days after surgery, when urine osmolality became markedly hypotonic (range 65-160 mOsm/kg H(2)O) and urine flow rose to approximately 0.14 ml/min.kg. Fluctuations in urine flow and osmolality in the early postoperative period were the result of tubular reabsorption of water rather than a change in the glomerular filtration rate. The inulin-(14)C clearance, used as a measure of the glomerular filtration rate, was 1.05 +/-0.05 ml/min.kg (mean +/-sem) for all animals studied. Urea, fructose, sodium, and chloride were partially reabsorbed by the fetal kidney, while creatinine was secreted. Continuous drainage of fetal urine for 18 days in one animal demonstrated that the fetus was able to excrete large amounts of water, sodium, and fructose without apparent detrimental effects.

Development and mechanisms of fetal hypoxia in severe fetal growth restriction.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O(2) uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for 12h; approximately 35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All ewes were then placed in a control environment ( approximately 21 degrees C, 24h; approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p<0.0001), umbilical O(2) uptake/kg fetus was 76% of C (p<0.01) and umbilical venous PO(2) was reduced (20.2 vs. 29.7 Torr, p<0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs. 23 Torr, p<0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O(2) uptake.

Nutrition of the fetus and the premature infant.

Developments in fetal and placental nutrition have highlighted the interaction of the placenta and fetal liver for the exchange and metabolism of nutrients. Of particular importance is the exchange of serine and glycine and their interconversion within these two organs and the exchange of glutamine and glutamate. Placental metabolism of nutrients and the placenta's role in the production and utilization of certain amino acids alters significantly the delivery rate of nutrients into the fetal circulation. Postnatal nutrition has focused on the role of early nutritional intervention in the extremely low birth weight infants and the recognition of the category of semi-essential amino acids in these infants. The role of minimal enteral feedings in small babies and the changes in nutritional requirements induced by medical complications has also received increasing attention.

Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies.

L-[1-13C]Leucine, [1-13C]glycine, L-[1-13C]phenylalanine, and L-[1-13C]proline were infused as a bolus into the maternal circulation of seven appropriate for gestational age at 30.3 +/- 3.0 wk and 7 intrauterine growth-restricted pregnancies at 26.5 +/- 1.0 wk gestation to investigate placental transport in vivo. Umbilical venous samples were obtained at the time of in utero fetal blood sampling at 450 +/- 74 sec from the bolus injection. In normal pregnancies the fetal/maternal (F/M) enrichment ratios for leucine (0.76 +/- 0.06) and phenylalanine (0.77 +/- 0.06) were higher (P < 0.01) than the F/M ratios for glycine (0.18 +/- 0.04) and proline (0.22 +/- 0.02). This suggests that these two essential amino acids rapidly cross the placenta in vivo. Compared with the essentials, both glycine and proline had significantly lower F/M enrichment ratios, which were not different from each other. The results support the hypothesis that amino acids with high affinity for exchange transporters cross the placenta most rapidly. In intrauterine growth-restricted pregnancies, the F/M enrichment ratio was significantly lower (P < 0.01) for L-[1-13C]leucine (0.76 +/- 0.06 vs. 0.48 +/- 0.07) and for L-[1-13C]phenylalanine (0.77 +/- 0.06 vs. 0.46 +/- 0.07) compared with appropriate for gestational age pregnancies reflecting impaired transplacental flux. The F/M enrichment ratio did not differ for [1-13C]glycine (0.18 +/- 0.04 vs. 0.17 +/- 0.03), and L-[1-13C]proline (0.22 +/- 0.02 vs. 0.18 +/- 0.04).

An analysis of air transport results in the sick newborn infant: Part I. The transport team.

Regionalization of neonatal intensive care has necessitated air transport of the critically ill infant in sparsely populated areas. All newborn air transports to four Denver area newborn intensive-care units over a 14-month period were reviewed. An emergency-care nurse and a neonatal intensive-care nurse provided the basic transport team with physician assistance in selected cases. Infants were evaluated and stabilized at the referring hospital before moving the infant. The transports were analyzed for the type of air craft utilized, reason for referral, and mortality. The results indicate that prior planning will permit the use of the most appropriate aircraft and transport team. When using well-trained transport personnel, the presence of a physician may be limited to specific situations without adversely affecting overall neonatal mortality.

Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep.

Previous studies have demonstrated the presence of insulin receptors on the maternal surface of the placenta in several species and the specific binding of insulin to the placenta in sheep. However, both in-vitro and in-vivo studies have produced conflicting evidence concerning the effect of insulin on placental glucose uptake. To clarify this problem, we measured maternal hindlimb, uterine and fetal glucose and oxygen extractions and glucose/oxygen quotients in chronically catheterized, non-stressed, late-gestation pregnant sheep over 1 h at a constant concentration of arterial plasma glucose, and again during the next 2 h at the same glucose level but at a higher insulin concentration using glucose 'clamp' methodology. Insulin produced a 4.9-fold increase in glucose extraction and a 3.5-fold increase in glucose/oxygen quotient across the hindlimb; in contrast, insulin did not significantly affect uterine or fetal glucose extraction or glucose/oxygen quotient. We conclude that in contrast to other tissues of the pregnant ewe, placental glucose uptake and transfer are insensitive to variations in maternal insulin concentration.

Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency.

Pregnant ewes were exposed chronically to thermoneutral (TN; 20+/-2 degrees C, 30% relative humidity; n=8) or hyperthermic (HT; 40+/-2 degrees C 12 h/day, 35+/-2 degrees C 12 h/day, 30% relative humidity, n=6) environments between days 37 and 93 of pregnancy. Ewes were killed following 56 days of exposure to either environment (days in treatment (dit)), corresponding to 93+/-1 day post coitus (dpc). Maternal core body temperatures (CBT) in HT ewes were significantly elevated above the TN ewes (HT; 39.86+/-0.1 degrees C vs TN; 39.20+/-0.1 degrees C; P<0.001). Both groups of animals displayed circadian CBT, though HT ewes had elevated amplitudes (HT; 0.181+/-0.002 degrees C vs TN; 0.091+/-0.002 degrees C; P<0.001) and increased phase shift constants (HT; 2100 h vs TN; 1800 h; P<0.001). Ewes exposed to chronic heat stress had significantly reduced progesterone and ovine placental lactogen (oPL) concentrations from 72 and 62 dpc respectively (P<0.05), corresponding to approximately 30 dit. However, when compared with the TN ewes, HT cotyledonary tissue oPL mRNA and protein concentrations were not significantly different (P>0.1). Prolactin concentrations rose immediately upon entry into the HT environment, reaching concentrations approximately four times that of TN ewes, a level maintained throughout the study (HT; 216.31+/-32.82 vs TN; 54. 40+/-10.0; P<0.0001). Despite similar feed intakes and euglycemia in both groups of ewes, HT fetal body weights were significantly reduced when compared with TN fetuses (HT; 514.6+/-48.7 vs TN; 703. 4+/-44.8; P<0.05), while placental weights (HT; 363.6+/-63.3 vs TN; 571.2+/-95.9) were not significantly affected by 56 days of heat exposure. Furthermore, the relationship between body weight and fetal length, the ponderal index, was significantly reduced in HT fetuses (HT; 3.01+/-0.13 vs TN; 3.57+/-0.18; P<0.05). HT fetal liver weights were also significantly reduced (HT; 27.31+/-4.73 vs TN; 45.16+/-6.16; P<0.05) and as a result, the brain/liver weight ratio was increased. This study demonstrates that chronic heat exposure lowers circulating placental hormone concentrations. The observation that PL mRNA and protein contents are similar across the two treatments, suggests that reduced hormone concentrations are the result of impaired trophoblast cell development, specifically trophoblast migration. Furthermore, the impact of heat exposure during maximal placental growth is great enough to restrict early fetal development, even before the fetal maximal growth phase (100 dpc-term). These data highlight that intrauterine growth retardation (IUGR) may result primarily from placental trophoblast cell dysfunction, and secondarily from later reduced placental size.

In vivo characteristics of placental amino acid transport and metabolism in ovine pregnancy--a review.

The placental transport of amino acids which is nutritionally important is the net entry rate into the fetal circulation (the umbilical uptake). This entry rate is a function of transport across cell membranes, the effect of competition among amino acids for transport, particularly across the fetal surface of the trophoblast, and their metabolism and interconversion within the placenta. The result of these different interactive fluxes is that the relationship between maternal concentration and fetal supply of an amino acid differs for each amino acid. For some amino acids there are relatively large bidirectional fluxes at both the fetal and maternal surfaces of the placenta. These fluxes can be measured in vivo utilizing stable isotope methodology. There is an important interorgan exchange of amino acids between the placenta and fetal liver. This exchange is, at least in part, a function of the absence of gluconeogenesis in the fetal liver. Both glutamate and serine, which are released from the fetal liver, are taken up by the placenta from the fetal circulation and metabolized within the placenta.

Placental transport and metabolism of amino acids.

This review examines the placental transport and metabolism of amino acids, with a special emphasis on unifying and interpreting in-vivo and in-vitro data. For a variety of technical reasons, in-vivo studies, which quantify placental amino-acid fluxes and metabolism, have been relatively limited, in comparison to in-vitro studies using various placental preparations. Following an introduction to placental amino-acid uptake and transfer to the fetus, the review attempts to reconcile in-vitro placental transport data with in-vivo placental data. Data are discussed with reference to the measured delivery rates of amino acids into the fetal circulation and the contribution of placental metabolism to this rate for many amino acids. The importance of exchange transporters in determining efflux from the placenta into the fetal circulation is presented with special reference to in-vivo studies of non-metabolizable and essential amino acids. The data which illustrate the interconversion and nitrogen exchange of three groups of amino acids, glutamine-glutamate, BCAAs and serine-glycine, within the placenta are discussed in terms of the potential role such pathways may serve for other placenta functions. The review also presents comparisons of the sheep and human placentae in terms of their in-vivo amino-acid transport rates.

Umbilical threonine uptake during maternal threonine infusion in sheep.

OBJECTIVE: The infusion into the maternal circulation of amino acid solutions failed to increase umbilical threonine (THR) uptake above normal even when THR was present in the infusate at a relatively high concentration. The purpose of the present study was to determine whether umbilical THR uptake can be increased by infusing a THR solution that does not contain any other amino acids. STUDY DESIGN: Five pregnant sheep (130+/-1.0 days after conception) were infused for 2h with a threonine solution (4.4+/-0.2 micromol.kg(-1).min(-1)). Plasma amino acids, glucose and lactate, hematocrit, blood O(2) content in maternal arterial, uterine venous, umbilical arterial and venous blood were measured. Uterine and umbilical blood flows were measured before and during the infusion and were used to calculate uterine and umbilical uptakes. Maternal and foetal plasma insulin and glucagon concentrations were also measured. RESULTS: The THR infusion increased maternal plasma THR (904 vs 236 microM, P< 0.001), foetal plasma THR (539 vs 334 microM, P< 0.01), and both uterine (20.4 vs 4.7 micromol.min(-1).kg(-1)(fetalweight), P< 0.05) and umbilical (8.6 vs 3.8 micromol.min(-1).kg(-1)(fetalweight), P< 0.001) THR uptakes. The uterine-umbilical THR uptake difference increased significantly (11.8 vs 0.9 micromol.min(-1).kg(-1)(fetalweight), P< 0.05). There were significant (P< 0.001) decreases in the foetal arterial plasma concentrations of tyrosine and the branched chain amino acids, as well as in isoleucine umbilical uptake (P< 0.05). There was a significant increase in maternal plasma glucagon (P< 0.01). CONCLUSION: A maternal THR infusion that causes a 3.8-fold increase in maternal plasma THR concentration above normal, with no significant increase in the concentration of other amino acids, leads to a 2.3-fold increase in umbilical THR uptake. This contrasts with the absence of a significant increase in umbilical THR uptake when THR was infused as part of an amino acid mixture in previous studies. The evidence supports the hypothesis that, in vivo, THR flux from placenta to foetus is mediated by a saturable, rate limiting transport system which is subject to inhibition by other neutral amino acids.

Comparison of leucine, serine and glycine transport across the ovine placenta.

To estimate the transport rate of maternal glycine across the placenta [1-13C]glycine and L-[1-13]serine were infused intravenously in pregnant sheep using both continuous and bolus infusions. Each tracer was infused together with L-[1-13C]leucine, to enable a comparison with the placental transport of an essential amino acid. At steady state, fetal plasma leucine enrichment was 40 per cent of maternal enrichment, indicating that approximately 60 per cent of the entry rate of leucine into fetal plasma is derived from protein breakdown in the placenta and fetus. Fetal plasma glycine enrichment was 11 per cent of maternal and there was no detectable fetal serine enrichment. The direct flux of maternal leucine into the fetal circulation was approximately 3.0 (bolus experiments) to 3.6 (continuous infusion experiments) mumol/min (kg fetus) and greater than the estimated 1.4 mumol/min (kg fetus) direct flux of maternal glycine, despite the fact that the net umbilical uptake of glycine exceeds that of leucine. This supports the conclusion that placental glycine production is a quantitatively important contribution to fetal glycine uptake via the umbilical circulation. The fetal glycine supply from the placenta is provided by a relatively small direct maternal glycine transplacental flux and a larger contribution derived from serine utilization within the placenta for glycine production.

Uptake and transport by the ovine placenta of neutral nonmetabolizable amino acids with different transport system affinities.

Placental uptake and transport of three nonmetabolizable amino acids with different reactivities for transport systems were studied in sheep under normal physiologic conditions. Methylaminoisobutyric acid (MeAIB), which has specific affinity for the sodium-dependent A system transporters, demonstrated placental concentrative uptake from the uterine and the umbilical circulations, but virtually no transport from mother to fetus. By contrast, aminoisobutyric acid (AIB) and aminocyclopentane-1-carboxylic acid (ACP), which have affinity for both sodium-dependent and sodium-independent transporters, demonstrated both concentrative uptake and transport from mother to fetus. ACP transport rate to the fetus was approximately twice the AIB transport rate. It is concluded that a neutral amino acid which interacts almost exclusively with the weakly reversible system A transporters may be transported rapidly into the placenta and may attain high concentrations within this organ but cannot escape from placenta to fetus down its own concentration gradient because the exit route is controlled by reversible amino acid transporters at the fetal surface of the placenta. Conversely, high affinity for reversible Na-independent transporters may be a necessary condition for the rapid transport of an amino acid from placenta to fetus.

A multiple infusion start time (MIST) protocol for stable isotope studies of fetal blood.

A new approach utilizing multiple infusion start times for two stable isotopes of leucine was applied to seven pregnancies in order to assess equilibration times for isotopic studies when a single fetal blood sample is available. Two infusates, one containing l -[1-(13)C]-leucine and the other l -[5,5,5-D3]-leucine, were given as a primed constant infusion in the maternal circulation at fetal blood sampling (FBS). In five patients l -[1-(13)C]-leucine infusion was started at time zero (T(0)) whereas l -[5,5,5-D3]-leucine infusion began 30 min later, and both were continued until the umbilical sample was obtained at 149.7+/-8.8 min. In order to assure non-steady state conditions, in two patients the first infusion started at T(0)and the second 17 and 6 min before FBS was performed at 115 and 154 min, respectively. The fetal/maternal ratio for l -[5,5,5-D3]-leucine over the fetal/maternal ratio for l -[1-(13)C]-leucine was 0.98+/-0.03, indicating steady state conditions for both infusions for the first six patients. In the last patient the ratio was 0.51, indicative of non-steady state conditions for the shortest infusion time. Our results show that a single fetal sample can provide data for fetal amino acid enrichments reflecting multiple time points. Leucine steady state is achieved 20 min after a primed continuous infusion both in the maternal and fetal circulations.

Doppler investigation in intrauterine growth restriction--from qualitative indices to flow measurements: a review of the experience of a collaborative group.

In 1997 we started a collaboration among three groups, combining our experience with Doppler examination of the human fetus, blood flow studies on fetal lamb, and mathematical modeling of human circulation. In preliminary investigations on fetal lambs, the same Doppler method designed for the human fetus was used to measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler measurements and diffusion technique groups for umbilical venous flow were 210.8+/-18.8 and 205.7+/-38.5 ml/min/kg, respectively (p = 0.881). In human pregnancy the interobserver variabilities for the vein diameter, mean velocity, and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A cross-sectional study allowed us to establish normal reference values. Venous blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38 weeks. In a series of 37 growth-restricted fetuses, the UV flow per kilogram was significantly lower in the more severe growth-restricted fetuses (abdominal circumference below the second percentile and abnormal umbilical arterial p.i.) than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses, we calculated that the absolute blood flow rate in the ductus venosus (DV) increases significantly with advancing gestational age from 20 to 38 weeks of gestation (from 23.2+/-9.6 ml/min to 43.5+/-21.5 ml/min). This means that the percentage of umbilical blood flow shunted through the DV decreases significantly during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45 growthrestricted fetuses, delivered because of nonreactive fetal heart rate (group 2) and for other reasons but still with a normal heart rate pattern (group 1), we measured the ductal inlet diameter. In these fetuses, the diameters at the ductal isthmus, normalized for the dimension of the abdominal circumference (inlet diameter/abdominal circumference), were significantly larger (group 1 = 6.8+/-2.3; group 29.4+/-2.8 ) than in the control group (6.1+/-0.3). This means that in this subset of fetuses the amount of blood shunted can be increased as a compensatory mechanism.

Galactose clearance and carbohydrate metabolism across the gastrointestinal tract in the newborn lamb.

We prepared 16 newborn lambs with chronically indwelling catheters in the portal vein, mesenteric vein, femoral vein, and femoral artery to study galactose clearance, portal venous blood flow, and carbohydrate metabolism across the gastrointestinal (GI) tract. Galactose clearance was measured by infusing galactose into the femoral vein to achieve a steady-state galactose concentration in the femoral artery. We observed a curvilinear relationship between galactose clearance and the steady-state galactose concentration. The relationship could be modeled as an apparent Michaelis-Menten system: Clearance = Vmax/(Km + [Gal]ssa), where Vmax = 17.0 +/- 2.5 mg/min/kg body weight and Km = 11.0 +/- 0.4 mg/dL. Substrate/oxygen quotients across the viscera drained by the portal vein were measured in the fasted state and during systemic galactose infusion. A net uptake of glucose and galactose by the GI tract was found with quotients of 0.19 +/- 0.07 and 0.05 +/- 0.02, respectively. There was a relatively large net efflux of lactate across the portal circulation, with a quotient of -0.13 +/- 0.03. The indicator-dilution technique was used to estimate portal venous blood flow (PVBF) in the neonatal period with a resting, fasted state value of 92.8 +/- 4.4 mL/min/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Leucine disposal and oxidation rates in the fetal lamb.

To verify previous indirect evidence suggesting an important role of amino acids as substrates of fetal oxidative metabolism, leucine disposal and oxidation rates were measured in chronically catheterized fetal lambs during the last month of gestation. Under normal physiologic conditions the leucine oxidation rates were 6.43 +/- 1.02 mumol min-1 for fetuses with an average weight of 3.22 +/- 0.07 kg and comparable in magnitude to the fetal rate of leucine accretion. In seven animals studied before and during fasting, the fetal leucine oxidation rate increased with fasting from 5.8 +/- 1.0 to 10.8 +/- 1.3 mumol min-1. These data demonstrate that there is rapid oxidative degradation of leucine by the fetus and that the rate of this process increases in response to maternal fasting.

The relationship of maternal and fetal glucose concentrations in the human from midgestation until term.

The relationship between maternal and fetal glucose concentrations was investigated in pregnant women at different gestational ages. Maternal and fetal blood samples were obtained during 14 fetoscopies (17 to 21 weeks), four umbilical cord samples (32 to 36 weeks), nine elective cesarean sections with appropriate for gestational age (AGA) fetuses (35 to 39 weeks) and nine elective cesarean sections with small for gestational age (SGA) fetuses (34 to 37 weeks). A significant linear relationship between maternal and fetal glucose concentrations was demonstrated at midgestation (P less than .001) and at late gestation (P less than .001). At equal maternal concentrations there were no significant differences in fetal glucose concentration between the cord samples obtained in late gestation and those obtained at cesarean section. At midgestation fetal glucose concentration is independent of and may exceed maternal concentration at maternal glucose levels less than 4.44 mmol/L. Furthermore, the relationship between maternal and fetal concentrations at maternal glucose concentrations greater than 4.44 mmol/L is significantly different at midgestation from that at late gestation (P less than .01); at equal maternal concentrations there were higher glucose concentrations in the mid trimester fetus. In late gestation as the maternal glucose concentration increases there is an increase in the maternal arterial-umbilical arterial glucose concentration difference and the umbilical glucose/oxygen quotient (P less than .003) reflecting increased glucose utilization by the fetus. There were no significant differences between AGA and SGA babies with respect to these relationships.