Computer model of fetal-maternal heat exchange in sheep

We constructed and used a mathematical model of maternal-fetal heat exchange in the sheep to explore the effects of changes in certain parameters on steady-state fetal temperatures and to determine whether the fetus in the model has any potential to control its own temperature. The model took into account both fetal and placental heat production and exchange of heat in the placenta, across the fetal skin, via amniotic fluid, and through the uterine wall. The maternal ewe was assumed to be a constant temperature heat sink. Changes in placental or fetal heat production were calculated to change the ratio of heat exiting across the placenta or fetal skin significantly but to have little effect on fetal core temperature, e.g., a rise of only 0.8 degrees C was predicted after a twofold increase in fetal heat production. Fetal placental blood flow was calculated to affect fetal temperature the most of any flow, a reduction to zero causing fetal temperature to rise 5.0 degrees C. Changes in heat conductances between fetal skin and amniotic fluid, or between amniotic fluid and uterine wall, had minimal effect on fetal temperature. From the model calculations here and because heat exchange within the sheep placenta has previously been calculated to be extremely efficient, we conclude that the fetal sheep has little ability to control its temperature by changes in heat dissipated through extraplacental pathways. Thus the model predicts an effective heat clamp that closely links fetal to maternal temperature.     

Temperature responses following ventilation of the fetal sheep in utero

The mammalian fetus produces significant quantities of heat. This passes to the mother principally through the placenta and to a lesser extent via a pathway comprising the skin, amniotic fluid, and uterine wall. To assess the importance of the lesser pathway, temperature responses were recorded in 7 near-term fetal sheep after intrauterine ventilation with oxygen, after snaring the umbilical cord to block the placental route, and following fetal death. Four distinguishing characteristics of responses were observed: fetal temperature rose 0.10 +/- 0.03 (SEM) degrees C after oxygenation; it rose progressively an additional 0.9 +/- 0.1 degrees C during the 90-min interval after cord snaring; amniotic fluid temperature rose slowly until it was about midway between fetal and maternal temperature; and after fetal death, fetal amniotic fluid temperatures fell slowly. In a simple mathematical model with constant parameters these results could not be explained fully. It was necessary to assume that heat production rose with increased oxygenation and elevated body temperature and that ventilation increased heat transfer through the amniotic fluid, as would occur if chest wall movement were stirring the fluid. Using the model, the value for heat conductance from fetal skin to amniotic fluid was estimated to be 10.5 watts degrees C-1 under basal conditions.     

Fetal and uteroplacental heat production in sheep

To separate heat production of the fetus from that of the placenta, endometrium, and uterine muscle, we measured total uterine heat production first with the fetus intact and then after the umbilical cord was snared and the fetus killed. Heat production was measured with the Fick principle using thermistors chronically implanted in a maternal artery and major uterine vein and a flowmeter placed on the common internal iliac artery. In nine ewes, carrying lambs weighing 4.46 +/- 0.42 (SE) kg, total uterine heat production fell from 10.6 to 2.9 W after fetal death. Uterine blood flow fell progressively to 90% of control levels during the first hour after death. The caloric equivalent for O2 averaged 4.1 cal/ml O2 for the uterus, 2.2 for the uteroplacenta, and 4.6 for the fetus per se. It was not possible to explain these results using a simple model of maternal-fetal heat transfer. Rather, it was necessary to assume an additional pathway for heat transfer between small uterine veins on the surface of the uterus and cooler structures in the maternal abdomen, presumably the ventral abdominal wall.     

Measuring fetal and maternal temperature differentials: a probe for clinical use during labour

The healthy fetus maintains a higher temperature than that of its mother during gestation and labour. This results from the thermal balance between the heat generated by the fetus and the heat loss to its maternal surroundings. The heat loss can be by heat exchange via blood flowing in the umbilical cord and placenta, and via conduction through the fetal skin and amniotic fluid to the maternal wall. The temperature difference between the fetal and maternal tissue may reflect the metabolic state of the fetus and the magnitude and changing patterns of placental blood flow during labour. Physiological changes, such as those induced by epidural analgesia, and fetal infection have been shown to exhibit an increase in the absolute temperature. An intrauterine probe, previously used for non-invasive ECG detection, has been equipped with temperature sensors that measure fetal and maternal skin temperature in utero. Laboratory tests to characterize the performance of the probe reveal that absolute and differential temperatures can be resolved to around 0.01° C with a thermal time constant of approximately 9 s. Ideally the probe body should have infinite thermal insulation or thermal shunting across the probe will occur reducing the measured temperature difference. In this initial probe design, a high thermal isolation between sensors has been achieved but is not perfect, resulting in around 85% of the actual temperature difference across the probe being registered. Average feto-maternal differences of 0.2° C have been measured in a clinical investigation.     

Measurement of fetal heat production using differential calorimetry

These experiments were undertaken to measure heat production of fetal lambs in utero by using differential calorimetry. We used the principle that fetal heat production, H(fetus), can be calculated from measurements of base-line temperature difference between mother and fetus, delta T(fetus), heat introduced from an external source, H(heater), and the increase in body temperature, delta T(heater), that results, i.e., H(fetus) = H(heater) X delta T(fetus)/delta T(heater). We placed microheaters (1.8 mm diam) in the inferior vena cavae of eight near-term lambs and placed thermistors and catheters into maternal and fetal vessels and amniotic fluid. Five days later, fetal arterial temperature averaged 0.54 +/- 0.02 degrees C (SE) higher than maternal arterial temperature. When the heater was turned on to dissipate 29-103 cal/min, fetal temperature increased to approach 0.1-0.5 degrees C higher than control; the final temperature was estimated using the rate of increase during the first 20 min. Fetal heat production averaged 47.1 +/- 4.1 cal X min-1 X kg-1 during the warming phase in these lambs, which weighed 3.26 +/- 0.36 kg. This value would be 3-4% less if corrected for the increase in metabolic rate caused by heating, assuming a Q10 of 2.5. Fetal heating did not alter fetal heart rate, blood pressure, or blood gas values significantly, nor was hemolysis visible in plasma samples. When heat production was calculated from the decrease in fetal temperature after the heater was turned off, an average value of 41.2 +/- 2.5 cal X min-1 X kg-1 was found. Because this value is comparable to the heating phase, fetal metabolic rate and the insulating properties of the fetal shell are not likely to have been changed by the heating.     

Aquaporins in development – a review

Water homeostasis during fetal development is of crucial physiologic importance. It depends upon maternal fetal fluid exchange at the placenta and fetal membranes, and some exchange between fetus and amniotic fluid can occur across the skin before full keratinization. Lungs only grow and develop normally with fluid secretion, and there is evidence that cerebral spinal fluid formation is important in normal brain development. The aquaporins are a growing family of molecular water channels, the ontogeny of which is starting to be explored. One question that is of particular importance is how well does the rodent (mouse, rat) fetus serve as a model for long-gestation mammals such as sheep and human? This is particularly important for organs such as the lung and the kidney, whose development before birth is very much less in rodents than in the long-gestation species.     

Effect of cooling and heating on the regional distribution of blood flow in fetal sheep

This is a study on the effect of cooling and heating amniotic fluid on blood flow to fetal tissues and organs. In 8 unanaesthetized, chronically-catheterised fetal sheep (129-137 days gestation) cold or warm water was passed through tubing encircling the fetus in utero and blood flow was measured using the radionuclide-labelled 15 mu spheres. Following cooling for 30 min, amniotic fluid temperature fell 9.6 degrees C to 29.9 +/- 2.1 degrees C (SEM) fetal arterial temperature fell 2.37 degrees C to 37.30 +/- 0.36, and maternal arterial temperature fell 0.53 degrees C to 38.58 +/- 0.16. Blood flow through the fetal skin fell 60% (P less than 0.01) to 13.6 ml/min per 100 g tissue. Blood flow to the brown fat increased 186% (P less than 0.05) to 99.6 ml/min per 100 g. Following warming for 20 min, fetal temperature rose to 40.43 +/- 0.19 degrees C, and skin blood flow did not change significantly relative to initial control period but rose 200% above that during cooling (P less than 0.01). During both cooling and heating, blood flow to the adrenals rose significantly (P less than 0.05) whereas flow to the carcass, brain, kidneys, and placenta was not altered detectably. Continuous sampling of blood from the inferior vena cava during microsphere injection failed to detect any evidence of arterio-venous shunting through the skin at any temperature studied. Overall, the blood flow responses are consistent with a thermoregulatory role for the skin and brown fat in the near-term fetal sheep.     

The role of fetal urinary excretion in the transfer of ethanol into amniotic fluid after maternal administration of ethanol to the near-term pregnant ewe

The objective of this study was to determine whether fetal urinary excretion is a major route of ethanol transfer into the amniotic fluid surrounding the fetus following maternal administration of ethanol. Conscious instrumented pregnant ewes between 130 and 137 days' gestation (term, 147 days) with (n = 3) or without (n = 3) a catheter in the fetal bladder were administered 1 g ethanol/kg maternal body weight as a 1-h maternal intravenous infusion. Maternal blood, fetal blood, and amniotic fluid samples were collected at selected times, and fetal urine was collected continuously from the bladder-cannulated fetus during the 14-h study for the determination of ethanol concentrations. Fetal urinary excretion of ethanol occurred, and the total amount of ethanol excreted represented 0.30 +/- 0.07 (SD)% of the maternal ethanol dose. The renal clearance of ethanol by the fetus was 0.43 +/- 0.06 mL/min. The pharmacokinetics of ethanol in the maternal-fetal unit and the amniotic fluid for the bladder-cannulated fetal preparation were similar to the data for the nonbladder-cannulated preparation. The data indicate that fetal urinary excretion of ethanol is a secondary route of ethanol transfer into the amniotic fluid. It would appear that diffusion of ethanol across membranes from the maternal and fetal circulations is a major route of ethanol transfer into this intrauterine compartment.     

Fetal CO2 kinetics

Knowledge of CO2 kinetics in the fetus is important for the design and interpretation of fetal metabolic studies that use carbon-labelled tracers. To study fetal CO2 kinetics, four fetal sheep were infused at constant rate with NaH14CO3 to simulate a constant rate of fetal 14CO2 production from the metabolism of a 14C-labelled substrate. Uterine and umbilical blood flows, and concentrations of 14CO2 and total CO2 in umbilical arterial and venous blood and in uterine arterial and venous blood were measured. During steady state, the excretion of 14CO2 via the umbilical circulation was 99.6 +/- 1.0 (SEM)% of the NaH14CO3 infusion rate. The irreversible disposal rate of CO2 molecules from the fetal CO2 pool was approximately 5 times greater than the metabolic production of CO2 by the fetus. This evidence demonstrates that measurements of fetal 14CO2 excretion via the umbilical circulation can provide an accurate measurement of fetal 14CO2 production and that the exchange rate of CO2 molecules between placenta and fetal blood is much greater than the net rate of excretion of CO2 molecules from fetus to placenta.     

Changes in permeability of fetal guinea pig skin during gestation

Permeability of fetal skin to tritiated water was measured in vitro using samples taken from the back and flanks of 21 guinea pig fetuses whose gestational age ranged from 30 to 67 days (term = 68 days). From 30 to 45 days, fetal skin was relatively permeable to water, with a permeability coefficient for unidirectional, diffusional transfer of labelled water that averaged 0.372 +/- 0.041 (SEM) X 10(-4) cm/s. Then during a 5-10 day interval, the measured permeability coefficient decreased abruptly to very low and barely detectable levels. These changes took place at the time during gestation when others have shown the skin becomes keratinized and growth of new hair follicles is completed. Thus these findings are consistent with a relatively free exchange of water between amniotic fluid and fetal interstitium across the skin during the first two-thirds of gestation and then with further maturation an abrupt functional separation between these fluid compartments during the last third of gestation.     

Effect of insulin on glucose uptake in near-term fetal lambs

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.     

Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.     

Amniotic fluid and plasma glycine/valine ratios in substrate deprived growth retarded fetal rats.

Characteristic profiles of the free amino acid concentration in umbilical cord blood of growth retarded newborns have been observed. We hypothesized that the amniotic fluid of growth retarded fetal rats would show an increase in the ratio between glycine and valine which would parallel the pattern observed in the cord blood of growth retarded neonates, thus providing an index for the antepartum identification of the substrate deprived growth retarded fetus. Six test and 6 control dams were tested. Four fetuses per dam, matched for uterine location were examined. Test animals were fasted for 72 hours. Sampling was performed on day 21 under anaesthesia. Fetal size was significantly reduced (P < 0.0001) in the test group. [T = 2.68 gs. +/- 0.28 vs. C = 3.67 gs. +/- 0.25]. Fetal plasma concentrations of glycine showed an increase in test animals (P < 0.01) while valine showed a significant reduction (P < 0.0001). Glycine (pm/microliters) T = 308 +/- 64 vs. C = 269 +/- 47, valine (pm/microliters) T = 424 +/- 79 vs. C = 671 +/- 218]. Amniotic fluid concentrations for both glycine and valine were significantly decreased (P < 0.0001) in test animals. [Glycine (pm/microliters) T = 710 +/- 124 vs. C = 931 +/- 178; valine (pm/microliters) T = 845 +/- 169 vs. C = 1,339 +/- 234]. The glycine/valine ratio was significantly increased (P < 0.01) in both fetal plasma and amniotic fluid in test animals [Plasma T = 0.74 +/- 0.18 vs. C = 0.43 +/- 0.13. Amniotic fluid T = 0.85 +/- 0.08 vs. C = 0.69 +/- 0.09]. Consistent with our hypothesis, the amniotic fluid concentrations generally parallel the observations made in the plasma. This finding could enhance the antepartum identification of the substrate deprived growth retarded fetus.     

Placental and fetal candidiasis

The authors present a case of intrauterine fetal infection by Candida, in an abortion of four months, associated with an I.U.D. In the placenta and adnexa we observed an acute inflammation consisting of extraplacental membranitis, omphalitis, chorio-amnionitis and choriovasculitis with a marked villitis and intervillitis. In the fetus, involvement of the skin, lungs and pharynx was observed.This case represents, probably the 15th reported instance of congenital fetal candidiasis, and the first case of a Candida hematogenic placental infection acquired from the fetal blood. The fetus undoubtedly acquired its infection by an ascending route, through the contamined amniotic fluid.     

Bile acid metabolism in early life: studies of amniotic fluid

Bile acid metabolism of the human fetus was examined in early gestation (weeks 13-19) and compared with the full-term fetus from the analysis of amniotic fluid collected from healthy pregnant women. Total individual bile acids were determined by gas-liquid chromatography-mass spectrometry after solvolysis and hydrolysis of bile acid conjugates. Additionally, bile acids were separated according to their mode of conjugation by lipophilic anion exchange chromatography. Qualitatively the bile acid profiles of amniotic fluid in early gestation were similar and markedly different from those of full-term fetuses. Chenodeoxycholic acid was the major bile acid identified in early gestation and concentrations exceeded those of cholic acid, but by full term this relationship was reversed. Over 50 bile acids were identified in the amniotic fluids, these included C-1, C-4, and C-6 hydroxylated species and reflected primary hepatic synthesis by the fetus. At full term, 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid was one of the major bile acids identified in amniotic fluid. The monohydroxy bile acids lithocholic and 3 beta-hydroxy-5-cholenoic acids were present in significant proportions during early gestation, but by full term these accounted for only a few percent of the total bile acids. Quantitatively the total bile acid concentration of amniotic fluid was less than 4 mumol/l. The majority of bile acids were found to be glyco-, tauro-, and sulfate-conjugates. The more hydrophobic bile acids tended to be preferentially sulfated. These data indicate that significant and major changes in bile acid metabolism take place between early and late gestation in the human fetus.     

Insights into viral transmission at the uterine-placental interface

During human gestation, viruses can cause intrauterine infections associated with pregnancy complications and fetal abnormalities. The ability of viruses to spread from the infected mother to the fetus arises from the architecture of the placenta, which anchors the fetus to the uterus. Placental cytotrophoblasts differentiate, assume an endothelial phenotype, breach uterine blood vessels and form a hybrid vasculature that amplifies the maternal blood supply for fetal development. Human cytomegalovirus - the major cause of congenital disease - infects the uterine wall and the adjacent placenta, suggesting adaptation for pathogen survival in this microenvironment. Infection of villus explants and differentiating and/or invading cytotrophoblasts offers an in vitro model for studying viruses associated with prenatal infections.     

Diffusion permeability and ultrafiltration-reflection-coefficients of Narand Cl- in the near-term placenta of the sheep

Experiments were performed on unanaesthetized ewes in the last third of pregnancy. Fetuses and ewes had indwelling vascular catheters. In some of the experiments fetal urine was drained to the exterior by means of an indwelling vesicular catheter. Placental diffusion permeabilities were measured with 22Na+ and 36Cl- injected into eight fetuses. Volumes of distribution of Na+ and Cl- in the conceptus were Na+: 548 +/- 24, Cl-: 760 +/- 51 (ml/kg fetal wt +/- SEM). Diffusion permeabilities were Na+: 5.2 X 10(-3) +/- 0.3 X 10(-3), Cl-: 9.8 X 10(-3) +/- 0.9 X 10(-3) (ml.s-1.kg-1 +/- SEM). Ultrafiltration-reflection-coefficients of Na+ and Cl- in the placental exchange barrier were measured 17 times in seven fetuses with vesicular catheters. The transplacental e.m.f. was estimated from these results, on the assumption that the individual reflection-coefficients of Na+ should correlate with those of Cl-. The best estimate was -1.0 mV (fetus negative), and the best estimates of the placental reflection-coefficients were Na+: 0.83 and Cl-: 0.79. There was a reliable negative correlation (P < 0.01) between the calculated reflection-coefficients and the osmolality of the urine secreted by the fetus. This suggested that the concentration of vasopressin in fetal plasma affects the membrane characteristics of the placenta. The mean total osmotic force across the placental barrier of the sheep in these experiments was calculated to be 260 Pa (2 mmHg).     

Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.     

Fetal metabolism and placental transfer of vasoactive intestinal peptide in sheep

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid putative neurotransmitter that may have a role in the regulation of myometrial blood flow and uterine contractility. The chronically cannulated fetal sheep preparation was used to examine the fetal clearance and placental transfer of VIP. Metabolic Clearance Rate (MCR) and placental transfer of VIP were measured by alternate steady-state infusion of VIP into the mother and fetus. Plasma concentrations of VIP were measured by radioimmunoassay. MCR was similar in the pregnant (45 +/- 10 ml/kg/min) and nonpregnant ewes (35 +/- 5 ml/kg/min). However, compared to both pregnant and nonpregnant ewes, fetal MCR was significantly increased at 77 +/- 15 ml/kg/min, indicating highly developed clearance mechanisms in the fetus. VIP did not cross the placenta in either direction. Both the placenta and fetal liver metabolized VIP and contributed to the elevated fetal clearance of VIP. The results show that VIP in fetal tissue is unlikely to influence maternal uterine activity with any VIP-mediated effects emanating from maternal and/or placental sources.     

Plasma clearance of radiolabelled IGF-1 in the late gestation ovine fetus

We investigated the distribution of radiolabelled IGF-1 in the late gestation ovine fetus by exclusion gel chromatography following intravenous injection of 125I rh (recombinant human) met-IGF-1 into the chronically instrumented fetal lamb (120-130 days, n = 7). One minute after injection of 125I rh met-IGF-1 into the fetal femoral vein, 20.9 +/- 3.1% of the counts circulated in the 150K binding protein region, 55.0 +/- 3.7% in the 50K binding protein region and 18.7 +/- 0.6% in the free or 7K region. The chromatographic profiles obtained in the fetus were in general similar to those previously seen in the adult sheep. After an initial equilibration phase the half life of IGF-1 associated with the 150K binding fractions were 412.1 +/- 103.6 min. Two phases of clearance were observed for IGF-1 in association with the 50K binding fractions, an initial phase with a half life of 30.6 +/- 4.5 min followed by a second phase with a half life of 202.3 +/- 10.3 min. The 7K or 'free' form of IGF-1 had an initial half life of 12.6 +/- 5.1 min. Chromatography of samples of fetal tracheal fluid, fetal urine, amniotic fluid, maternal uterine venous plasma and maternal systemic plasma showed no movement of intact IGF-1 out of the fetal circulation into the fetal fluids or into the maternal circulation. However, when simultaneous samples were obtained from the fetal femoral artery and umbilical vein, higher radioactivity was consistently observed in the fetal femoral artery raising the possibility of placental uptake of IGF-1.(ABSTRACT TRUNCATED AT 250 WORDS)