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Circulatory and metabolic effects of anemia in hyperinsulinemic ovine fetuses.

Infants born to women with poorly controlled diabetes mellitus have an increased incidence of perinatal asphyxia, cardiovascular abnormalities, elevated catecholamines, and sudden fetal death. Although hyperinsulinemic fetuses of diabetic women often exhibit polycythemia, they may also develop anemia because of pregnancy- and/or delivery-related complications. Experimental fetal hyperinsulinemia results in cardiovascular changes and a surge in catecholamines. We hypothesized that reductions in fetal O2 availability via anemic hypoxia limits O2 transport and compromises the hemodynamically and metabolically stressed but compensated hyperinsulinemic fetus. Chronically catheterized fetuses receiving insulin (n = 9) or placebo (n = 5) for 48 h were rendered anemic by an isovolemic exchange transfusion. In the hyperinsulinemic state, anemic-hypoxia augmented the insulin-mediated surge in norepinephrine concentration and increases in blood flow to brain, heart, and adrenal glands. Insulin-related increase in the combined ventricular output was sustained during anemia. O2 delivery to the fetus decreased, extraction increased, and O2 uptake did not change. Regional O2 delivery to the brain, kidney, gastrointestinal tract, muscle, fat, pancreas, spleen, and carcass decreased. Hyperinsulinemic ovine fetus exposed to anemic hypoxia demonstrated an accentuated surge in norepinephrine, a sustained increase in the combined ventricular output, preservation of systemic O2 uptake, and compromised regional O2 delivery to certain vascular regions. We conclude that the hyperinsulinemic fetus was able to compensate for anemic hypoxia by increased or sustained regional vascular perfusion.

Anemia↗

Blood pressure and heart rate in the ovine fetus: ontogenic changes and effects of fetal adrenalectomy.

Ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (FABP) and heart rate (FHR) and their regulation by the fetal adrenal were studied in 18 fetal sheep chronically instrumented at 109-114 days gestation (GA). In the long-term study, FABP and FHR were continuously recorded from 120 days GA to spontaneous term labor (>145 days GA) in five animals. Peak times (PT) and amplitudes (Amp) of cosinor analysis were compared at 120-126, 127-133, and 134-140 days GA. Consistent, significant linear increases in FABP and linear decreases in FHR were observed in all fetuses. Significant 24-h rhythms in FABP and FHR were observed during all the time windows. In the adrenalectomy study, to test the hypothesis that fetal cortisol plays a key role in cardiovascular maturation, fetal adrenals were removed in eight animals (ADX); sham fetal adrenalectomy was performed on five animals (Con). Cortisol (4 microgram/min) was infused intravenously in four ADX fetuses from day 7 postsurgery for 7 days (ADX+F). No significant changes in PT and Amp in FABP and FHR were observed. Plasma cortisol levels remained low in Con and ADX fetuses (<4.9 ng/ml). Cortisol infusion increased fetal plasma cortisol to 22.3 +/- 3.2 ng/ml (mean +/- SE) on day 13 in ADX+F fetuses. FABP increased in control and ADX+F but not ADX fetuses; FHR decreased in control and ADX but rose in ADX+F fetuses. These results suggest that, in chronically instrumented fetal sheep at late gestation, 1) increases in FABP and decreases in FHR are maintained consistently from 120 to 140 days GA, with distinct 24-h rhythms, the PT and Amp of which remain unchanged, and 2) the physiological increase in FABP is dependent on the fetal adrenal; bilateral removal of the fetal adrenals does not prevent the ability of cortisol to produce a sustained increase in FABP.

Adrenal Glands↗

Congenital diaphragmatic hernia prevents absorption of distal air space fluid in late-gestation rat fetuses.

We hypothesized that congenital diaphragmatic hernia (CDH) may decrease distal air space fluid absorption due to immaturity of alveolar epithelial cells from a loss of the normal epithelial Na+ transport, as assessed by amiloride and epithelial Na+ channel (ENaC) and Na-K-ATPase expression, as well as failure to respond to endogenous epinephrine as assessed by propranolol. Timed-pregnant dams were gavage fed 100 mg of nitrofen at 9.5-day gestation to induce CDH in the fetuses, and distal air space fluid absorption experiments were carried out on 22-day gestation (term) fetuses. Controls were nitrofen-exposed fetuses without CDH. Absorption of distal air space fluid was measured from the increase in 131I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. In controls, distal air space fluid absorption was rapid and mediated by beta-adrenoceptors as demonstrated by reversal to fluid secretion after propranolol. Normal lung fluid absorption was also partially inhibited by amiloride. In contrast, CDH fetuses continued to show lung fluid secretion, and this secretion was not affected by either propranolol or amiloride. CDH lungs showed a 67% reduction in alpha-ENaC and beta-ENaC expression, but no change in alpha1-Na-K-ATPase expression. These studies demonstrate: 1) CDH delays lung maturation with impaired distal air space fluid absorption secondary to inadequate Na+ uptake by the distal lung epithelium that results in fluid-filled lungs at birth with reduced capacity to establish postnatal breathing, and 2) the main stimulus to lung fluid absorption in near-term control fetuses, elevated endogenous epinephrine levels, is not functional in CDH fetuses.

Absorption↗

Differential maturation of beta-adrenoceptor-mediated responses in the lamb fetus.

To study the functional maturity of beta-receptor-mediated responses, seven chronically catheterized lamb fetuses, 93-107 days of gestation, and seven fetuses, 116-134 days of gestation, received intravenous randomly sequenced infusions of isoproterenol (ISO) 0.03, 0.06, and 0.125 micrograms.kg-1.min-1 for 10 min separated by 45-min intervals or two saline infusions followed by 0.125 micrograms.kg-1.min-1 ISO after treatment with 0.5 mg/kg propranolol (PRO). Each fetus received the two treatments 24-48 h apart. In immature fetuses, plasma renin activity (PRA) of 2.0 +/- 0.7 ng.ml-1.h-1 did not change with either protocol. In mature fetuses, PRA of 7.5 +/- 2.5 ng.ml-1.h-1 increased two- to three-fold after the infusion of the highest two doses of ISO (P less than 0.003). Propranolol blocked this response. No significant changes were observed after the infusions of the lowest dose of ISO or saline. Both groups showed significant heart rate increases with all doses of ISO. Propranolol injection decreased heart rate significantly and blocked responses to ISO. We conclude that although a cardiac beta-receptor-mediated response is present by 93 days of gestation in the lamb fetus, a renal beta-receptor-mediated response, renin secretion, is absent.

Animals↗

Intraruminal rehydration of ovine fetuses.

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

Animals↗

Renal function during chronic anemia in the ovine fetus.

Our purpose was to determine how prolonged anemia alters fetal renal function and acid-base balance. In seven ovine fetuses made progressively anemic over 1 wk by serial isovolemic hemorrhage, hematocrit was reduced from 33.3 +/- 4.5 to 14.0 +/- 1.0%. Femoral arterial oxygen content was less and renal plasma flow was greater in anemic fetuses (1.5 +/- 0.1 ml/dl and 339 +/- 58 ml.min-1.100 g kidney-1) than in 6 control fetuses (7.0 +/- 1.3 ml/dl and 160 +/- 34 ml.min-1.100 g kidney-1). Urine flow and sodium excretion were also greater in anemic fetuses (1.2 +/- 0.6 ml/min and 79 +/- 49.5 mumol/min) than in controls (0.5 +/- 0.2 ml/min and 16 +/- 9.8 mumol/min). This higher sodium excretion was apparently due to a lower fractional sodium reabsorption in anemic fetuses compared with controls (84.1 +/- 5.8 vs. 96.5 +/- 1.7%), rather than to differences in either glomerular filtration rate or amount of filtered sodium. In addition, the higher sodium excretion in anemic fetuses was associated with greater urinary lactate and inorganic phosphate excretions and larger amniotic fluid volumes than in controls. From these data we conclude that when fetal renal oxygen delivery is limited by a prolonged reduction in hematocrit, excretions of sodium and water, as well as other osmotically active solutes, increase, and this results in an increase in amniotic fluid volume.

Amniotic Fluid↗

Effects of infusions of ACTH in the chronically catheterized pregnant ewe and her fetus.

To study the effects of elevated maternal levels of adrenocorticotropic hormone (ACTH) on the fetus, nine chronically catheterized pregnant ewes (132 +/- 0.9 days of gestation) were infused intravenously for 3 days with Synacthen (5 micrograms.kg-1.day-1). Four ewes were given 0.15 M saline intravenously over the same period. ACTH induced hypertension in the ewe. Mean arterial pressure (MAP) increased from 101 +/- 4.4 to 114 +/- 3.9 mmHg at 48 h (P < 0.05); cardiac output increased from 8.6 +/- 0.5 to 10.4 +/- 1.0 l/min after 24 h (P < 0.05). Within 2-4 h, maternal cortisol levels increased from 24.6 +/- 6.3 to 287 +/- 30 nM (P < 0.05) and remained high. Fetal plasma cortisol levels increased from 20 +/- 4.5 to 60 +/- 4.5 nM (P < 0.05) within 2-4 h and then increased further. Fetal MAP was increased at 24 h. There was no effect on fetal blood gases or pH. Ewes became hyperglycemic and lactacidemic by 24 h (P < 0.05), and the fetuses were also hyperglycemic and lactacidemic (P < 0.05) at this time. There were no changes in fetuses carried by saline-infused ewes. Both ewes and fetuses had raised plasma osmolalities and, since hematocrit fell, retained fluid. Ewes became hypokalemic; the fetuses did not, but there was an increase in fetal K excretion. Thus ACTH-induced hypertension in the ewe had minimal effects on fetal MAP, fetal blood gas status, and pH. The fetus, however, did show many of the other effects of maternal glucocorticoid and mineralocorticoid excess, partly because its cortisol levels were increased but also as a consequence of metabolic and endocrine changes in the ewe.

Adrenocorticotropic Hormone↗

Activity of the pituitary-adrenal system in rat fetuses subjected to encephalectomy in early or late stages of pregnancy.

The corticostimulating activity of the fetal rat hypophysis was studied on day 21, in fetuses deprived of their hypothalami by total removal of the brain (encephalectomy) in early (day 16) or late (day 19) stages of gestation. On day 19, the fetal manipulation was performed either on intact or adrenalectomized dams. The data show that: (1) Compared to controls, encephalectomy does not alter pituitary ACTH content in fetuses of intact mothers but that pituitary ACTH content does not significantly increase in encephalectomized fetuses of adrenalectomized mothers whereas it does in the littermate control fetuses. (2) Compared to controls, circulating ACTH levels are reduced by encephalectomy on both day 16 and day 19; an increase in ACTH levels occurs in both fetal groups in response to maternal adrenalectomy. Decapitation removes this fetal source of ACTH. (3) Adrenal glands are not as much atrophied by encephalectomy as by decapitation on day 16, whereas adrenal weight is decreased to the same extent by encephalectomy and by decapitation on day 19. However, the marked increase in circulating ACTH in both control and encephalectomized fetuses caused by maternal adrenalectomy is probably the cause of the significant increase in adrenal weight in these groups. (4) Adrenal corticosterone content in all the groups but not always adrenal weight, is a fairly accurate reflection of the ACTH levels measured. The results suggest that: (1) Pituitary ACTH content is not a sensitive measure of dynamic changes in synthesis and secretion in rat fetuses. (2) Changes in basal plasma ACTH in response to fetal encephalectomy show the presence of both an autonomous corticotropic function and a cephalic regulation of the corticotropic function from day 16 of fetal life and beyond. Pituitary autonomy seems higher in earlier than in later stages of gestation. (3) There is feedback of corticosterone into the pituitary of fetal rats; a marked increase in ACTH release is caused by the removal of the maternal corticosteroids.

Adrenal Glands↗

Relationship between brain volume and size of dural venous sinuses in human fetuses and adults.

A quantitative study of 50 human fetuses, ranging in size from 64 to 259 mm crown-rump length (CRL), and 12 adult cadavers was carried out. After removal of each brain from the cranial cavity and measurement of its volume (BV), the cross-sectional area (CSA) of the transverse (TS) and sigmoid (SS) dural venous sinuses were measured; the measurements were taken at the same anatomical point in all fetuses and adults. For each fetus and adult, indices CSA . TS/BV and CSA . SS/BV were calculated. The results of the statistical analysis showed that the mean CSA TS/BV . and CSA . SS/BV indices in fetuses were significantly greater than those of the adults, i.e., relative to the size of the brain, the dural venous sinuses in fetuses were greater than in adults. Furthermore, a significant negative correlation was found between the CSA . SS/BV index and the CRL of the fetuses; this means that as the brain and sinuses grow during fetal development, the growth rate of the sinuses decreases. By implication, the rate of growth of the arterial blood supply decreases proportionately. A similar, progressive decrease in the growth rate of the brain takes place during fetal life.

Adult↗

Umbilical blood flow and glucose uptake in lamb fetus following single umbilical artery ligation.

Umbilical blood flow (UBF) and fetal glucose uptake were measured in 5 lamb fetuses 4-20 days following single umbilical artery ligation (SUAL). The ligation was performed at 108-119 days gestation (sheep pregnancy = 145-150 days), and the blood flow and glucose uptake studies were performed as chronic preparation at 120-137 days of gestation. In comparison with 9 control subjects at matched gestation, the SUAL fetuses had significantly lower UBF (mean plus or minus SEM, 735 plus or minus 70 vs. 475 plus or minus 24 ml/min, p less than 0.01) and fetal glucose uptake (2190 plus or minus 1.6 vs. 14.8 plus or minus 1.9 mg/min, p less than 0.05). When the values were expressed per kilogram fetal weight, the UBF decreased with increasing gestational age in SUAL fetuses. In the control fetuses, the UBF increased with increasing gestational age. The fetal glucose uptake (FGU), when expressed per kilogram fetal weight, was essentially similar to that of the control subjects. The glucose gradients across the placenta were similar in both groups of fetuses. These data suggest that in lamb fetuses with placental vascular insufficiency induced by SUAL, the reduction of UBF and FGU may account for growth retardation in utero. It was also suggested that placental transfer of substrate other than glucose may also be impaired as a result o

Animals↗

Plasma calcium control in the rat fetus. II. Influence of fetal hormones.

Total and ionized plasma calcium concentrations are higher in the fetus than in the mother at the end of gestation. Using thyroparathyroidectomized (TPTX), nephrectomized (NX), or decapitated fetuses from normal or TPTX pregnant rats, we have investigated the influence of some fetal hormones on fetal plasma calcium level. Surgical ablations were performed at 19.5 days of gestation, and the animals were sacrificed 2 days later. TPTX fetuses from normal mothers showed a decrease in fetal plasma calcium (approximately 1 mg/dl), but decapitation, which removes brain, hypophysis, and the thyroparathyroid complex, had no effect. By contrast, in TPTX mothers, decapitated fetuses exhibited a sharp decrease in plasma calcium (2.37 mg/dl), and a rise in plasma phosphate (1.39 mg/dl), but surprisingly, plasma calcium was unchanged in TPTX fetuses. NX fetuses both in normal and TPTX mothers showed unaltered plasma calcium and phosphate levels. Some of these findings are as yet unexplained and suggest the contribution of other unknown fetal hormones in the control of fetal plasma calcium.

Animals↗

Arginine vasopressin and acute, intravascular volume expansion in the human fetus.

There is presently no information concerning the ontogeny and control of arginine vasopressin (AVP) in the human fetus. AVP was measured in 22 nonanemic control fetuses and 7 fetuses with hemolytic anemia undergoing 13 intravascular transfusions. Each transfused fetus received pancuronium (0.3 mg/kg) and furosemide (2 mg/kg). Compared to the control group of nonanemic fetuses with hemolytic disease, AVP was significantly lower in the anemic fetus prior to transfusion (2.6 +/- 0.4 microU/ml versus 10.4 +/- 4.1 microU/ml, p less than 0.05). This suggests that hemolytic anemia is associated with a relative increase in fetal intravascular volume. Intravascular transfusion was associated with a significant increase in AVP (p less than 0.05). These findings could not be explained by changes in either blood pressure, plasma osmolality, or fetal oxygenation.

Anemia, Hemolytic↗

Pathology of maternal genital tract, placenta, and fetus in equine viral arteritis.

Six pregnant mares were given equine viral arteritis virus intravenously. Tissues from genital tracts, placentae, and fetuses were examined by light and electron microscopy to study the mechanism of abortion. Four mares which died with acute disease had diffuse vacuolation of endometrial epithelium and systemic necrotizing vasculitis. Two of these mares had dead fetuses and two had live fetuses; virus was isolated from tissues of one live fetus. Placentae of mares dying from acute disease did not have lesions attributable to infection; virus was isolated from two of these placentae. One of the two mares which recovered from clinical disease aborted a dead fetus eight days after inoculation. The mare had severe necrotizing myometritis and virus was isolated from maternal ovaries and from fetal tissues. The fetus did not have lesions attributable to arteritis virus. These results suggest that although fetal death may occur in utero during acute equine viral arteritis, abortion probably is due to lesions in the uterus of the mare.

Abortion, Spontaneous↗

Origin and metabolic fate of plasma glycerol in the rat and rabbit fetus.

On day 21.5 a pregnant rat received a single injection of [1-14C]glycerol. The purpose was to study the transfer of glycerol through the placenta from the maternal to fetal plasma. From 3-20 min after injection the specific activity of glycerol in maternal and fetal plasma was measured. The results indicate that the mother can provide this molecule to the fetus. Similar results were obtained with the rabbit on day 28 of pregnancy. The possibility of the conversion of plasma glycerol to glucose has been investigated in the rat and rabbit fetus. This molecule was chosen chiefly to see whether the gluconeogenic pathway was functioning in the fetus above the triose phosphate step. At two stages of fetal development the capacity of the fetus to incorporate [1-14C]glycerol into glucose plus glycogen has been shown in the two species. In the rat fetus the conversion of [1-14C]glycerol to [14C]glucose increases from 19.5 to 21.5 days of gestation. For the rabbit this parameter increases from 25 to 28 days of gestation. On day 25 in the rabbit and day 19.5 in the rat the liver glycogen was labeled, but it did not accumulate the [14C]glucose from [1-14C]glycerol during the time that we have studied. In contrast, on day 28 in the rabbit and day 21.5 in the rat the incorporation of radioactivity increased as function of the time. However, the relative importance of glycerol as precursor of the glucose plus glycogen in the fetus remains to be elucidated.

Animals↗

Pulmonary superoxide dismutase activity in the euthyroid and hypothyroid ovine fetus.

Pulmonary superoxide dismutase (SOD) activity was measured in 11 euthyroid and 15 hypothyroid ovine fetuses at 130 days gestation. In the euthyroid fetus, the mean pulmonary SOD activity was similar in saline- and thyroxine-infused groups. Compared to the euthyroid fetus, the mean pulmonary SOD activity was significantly lower in the noninfused or saline-infused athyrotic fetus. Administration of thyroxine to the hypothyroid fetus results in a normalization of pulmonary SOD activity to control values. Thus, thyroxine appears to influence the maturation of pulmonary SOD activity in the ovine fetus during the third trimester.

Animals↗

Myocardial excitation-contraction coupling in the fetus of alloxan-diabetic rabbit.

This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o (control), the force of myocardial contraction in FDM was not significantly different from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]o caused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+ and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+ from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+ uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+ is greater and the toxic effect of Ca2+ is less than in the control fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Lung maturation in the hyperinsulinemic rat fetus.

Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin-injected fetuses (n = 15), surfactant (S) fraction phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) were significantly decreased (3.6 +/- 0.1 nmol Pi/mg tissue; p less than 0.001 and 2.8 +/- 0.1 nmol/mg; p less than 0.025, respectively) as compared with their saline-injected controls (4.8 +/- 0.2 and 3.3 +/- 0.1 nmol/mg, respectively, n = 19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 +/- 0.13 micron 2 (n = 72) versus 1.99 +/- 0.14 micron 2 (n = 129) p less than 0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 +/- 1.0 micrograms/mg, n = 17) than in their controls (15.1 +/- 0.8 micrograms/mg, n = 18; p less than 0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin-injections: 4.3 +/- 0.25 and 3.4 +/- 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n = 10) versus 5.7 +/- 0.45 and 4.3 +/- 0.3 nmol Pi/mg, respectively, in controls (n = 10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum growth-promoting activity in normal and hypotrophic fetuses at midpregnancy.

Blood from 24 human fetuses aged 19-24 wk was collected by ultrasound-guided puncture of the umbilical cord in utero, performed for prenatal diagnosis of mother to fetus transmissible infections. Fetal serum growth-promoting activity (thymidine activity) was measured by its effect on 3H-thymidine incorporation into human lectin-activated lymphocytes. Ten blood samples were obtained at 19-22 wk of pregnancy and 14 at 23-24 wk. The pregnancies were maintained and the fetuses delivered, free of infection, at 38-40 wk, nine of them being small for date and 15 having a normal weight for gestation age. The bioassayable thymidine activity was significantly lower in the hypotrophic (0.84 +/- 0.04 U/ml) than in the normal fetuses (1.28 +/- 0.09 U/ml) whatever the time of sampling. Thymidine activity was significantly negatively correlated with gestational age in the normal for date fetuses, not in the small for date. It is suggested that early measurement of thymidine activity in fetal blood might be of value in the assessment of fetal growth despite the fact that the tissue growth factors may be more important in fetus than are the serum factors.

Adult↗