Effect of maternal cocaine administration on maternal and fetal glucose, lactate, and insulin in sheep

Although cocaine use during pregnancy is an important cause of perinatal morbidity and mortality, there are no reports of its effect on maternal and fetal carbohydrate metabolism. Six pregnant ewes and their fetuses were instrumented under halothane general anesthesia at 113-119 days' gestation. Between 124-135 days' gestation, the ewes received a single infusion of vehicle or cocaine (1.0 or 2.0 mg/kg) into the jugular vein. At least 24 hours was allowed between successive injections. Maternal and fetal blood samples were drawn at 30 and 20 minutes before and at 5, 15, 30, and 60 minutes after the injection. Both maternal and fetal glucose and lactate concentrations increased (P less than .05) after injection of cocaine at 2.0 mg/kg. There were no significant changes in maternal or fetal plasma insulin concentrations after vehicle or cocaine administration. Induction of hyperglycemia and lactacidemia could be mechanisms whereby cocaine exerts its adverse effects during pregnancy.     

Fetal and maternal blood glucose, insulin and acid base observations following maternal glucose infusion.

The aim of the present investigation was to examine the fetal and maternal blood glucose and insulin response following glucose infusion to the mother. The studies were performed on 11 primigravid patients with a gestational age of 38-40 weeks during the first stage of labor. Glucose was given intravenously by a bolus injection of 330 mg/kg body weight, followed by a glucose infusion of 27.5 mg/kg/min for 60 min. Glucose concentration, immuno-reactive insulin (IRI), pH and base excess of the maternal and fetal blood were measured before and during maternal glucose load. Maternal blood glucose rose within 10 min. up to 280.0 mg% (SD 25.9). This level could be fairly maintained throughout the experiment. The maternal glucose was after 60 min. infusion 326.5 mg% (SD 46.9). Fetal glucose concentration rose continuously from 65.8 mg% (SD 5.8) at control to 249.2 mg% (SD 23.3) after 60 min. The increase of maternal and fetal glucose was associated with an elevation of immuno-reactive insulin (IRI). The maternal insulin was 24.0 micronU/ml (SD 8.0). It was scattered over a wide range (55.4 micronU/ml-217.1 micronU/ml) after 60 min. glucose infusion. The fetal insulin was 17.0 micronU/ml (SD 5.2) at control and rose by 86.5% (SD 80.5) after 60 min. glucose load. One case of a mother with a subclinical diabetes mellitus deviated where the fetal insulin rose from 26.0 micronU/ml at control to 215.6 micronU/ml after 60 min. infusion. The increase of insulin per glucose rise was correlated to fetal body weight. During glucose infusion to the mother of both, fetal and maternal, acid base parameters remained unchanged. From these observations it may be concluded that in the human fetus insulin secretion following a single glucose load is generally low, however, it increases in cases where the maternal insulin response to glucose load is abnormal. This might be related to a chronic stimulation by glucose of the fetal pancreatic islet cells in poorly controlled diabetic and possibly prediabetic patients.     

Use of intravenous fluids before cesarean section: effects on perinatal glucose, insulin, and sodium homeostasis

Perinatal glucose, insulin, and sodium homeostases were assessed in relation to antepartum intravenous infusions administered to 59 normal mothers undergoing cesarean section at term without labor under epidural anesthesia. Group A (N = 20) received 1 L of Ringer's lactate without dextrose during one hour; group B (N = 20), 1 L of 5% dextrose in water during one hour; and group C (N = 19), 1 L of 5% dextrose in water during two and one half hours. Mean maternal and fetal serum glucose and insulin and sodium concentrations at delivery differed among all groups in direct relationship to the rate of glucose infusion. Neonatal hypoglycemia (30 mg/dL or less) correlated with the presence of a glucose infusion, a maternal glucose concentration of 117 mg/dL or greater, and an umbilical venous insulin concentration of 26 microU/mL or greater. Among group A patients who received sodium, and group B and C patients who did not, fetal hyponatremia (umbilical venous sodium 130 mEq/L or less) correlated with the absence of sodium in the prepartum infusion. The results suggest that the antepartum administration of a balanced electrolyte solution without excess glucose infusion can minimize the incidence of fetal hyperglycemia and hyponatremia and neonatal hypoglycemia.     

Glucocorticoid-associated maternal hyperglycemia: a randomized trial of insulin prophylaxis

OBJECTIVES: To study the degree and timing of maternal hyperglycemia following betamethasone therapy in nondiabetic patients and establish a prophylactic dose of insulin. METHODS: Forty-five patients receiving betamethasone 12 mg i.m. at 7 AM on two consecutive days were randomized to no insulin (n = 20), low-dose insulin (n = 18), and high-dose insulin (n = 7) protocols. Each treatment group received s.c. insulin at 7 AM on the 2 days of betamethasone therapy (20 units NPH/10 units regular, and 40 units NPH/20 units regular, respectively). Capillary plasma glucose measurements were obtained at fasting and 2 h after meals for 3 days. A multivariate normal regression model was used to estimate and compare mean glucose levels. RESULTS: Eighty-five percent of patients who did not receive insulin exhibited hyperglycemia at levels previously associated with fetal acidosis. Significant differences in mean postprandial plasma glucose levels were found between the no-treatment and insulin groups on days 1 and 2. No significant differences were noted between groups on day 3. CONCLUSIONS: Transient maternal hyperglycemia occurs in a consistent pattern in nondiabetic patients receiving betamethasone, which can be limited by the concurrent use of insulin. Further studies to assess fetal acidosis in this setting are warranted.     

Effects of maternal hyperglycemia on fetal growing mechanism

The aim of this study was to clarify the effects of maternal hyperglycemia on fetal growth in rats. In streptozotocin (STZ)-induced diabetic rats, maternal serum glucose levels during pregnancy were controlled by daily injection of NPH insulin or saline from day 3 to 21 of pregnancy. The body weight, hepatic glycogen content and serum concentrations of insulin and Insulin-like Growth Factor-I (IGF-I) in fetuses from these rats were measured on Day 21 of pregnancy. Fetal body weight positively correlated with maternal mean blood glucose (MBG) during pregnancy in the groups of diabetic mothers whose MBG was less than 220 mg/dl, whereas a negative correlation was observed in the groups whose MBG was more than 220 mg/dl. In addition, a similar correlation between hepatic glycogen content, serum concentrations of insulin or IGF-I and maternal MBG was observed. On the other hand, in the culture of fetal rat hepatocytes, glycogen content indicated a dose-related increase according to the increase in glucose concentration in the medium. These results suggest that the growth retardation observed in rats whose maternal mean glucose level is higher than 220 mg/dl is not caused by abnormalities in the metabolic function of the fetal metabolic organ (liver), but it is caused by a decrease in the production and/or secretion of growth-promoting factors (for example insulin and IGF-I) in the fetuses.     

Fetal hyperinsulinism and maternal one-hour postload plasma glucose level

OBJECTIVE: Fetal insulin concentrations reflect the intrauterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160-179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. RESULTS: Of the 930 patients who entered the study, 570 (61.3%) were assigned to group I, 76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL; range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 microU/mL; range, < 3-61 microU/mL). CONCLUSION: Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL.     

Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation

Maternal and fetal glucose concentrations were measured simultaneously in 54 pregnancies in which fetal blood sampling was conducted between 18 and 34 weeks gestation. Twenty-five pregnancies were normal (group 1), 13 were complicated by fetomaternal alloimmunization (group 2), and 16 by intrauterine growth retardation (group 3). The maternal glucose concentration was similar in the three groups. The fetal glucose level was significantly lower in growth-retarded (mean = 2.7 mmol/L) than in normal pregnancies (mean = 3.5 mmol/L). There was a statistically significant gradient between maternal and fetal glucose concentrations in groups 1 and 3, but no gradient was found in group 2. Maternal and fetal glucose concentrations were significantly correlated in all groups, but the correlations were distinct. For a given maternal glucose concentration, fetal glucose was higher in patients with alloimmunization and lower in patients with intrauterine growth retardation than in normal pregnancies. In patients with intrauterine growth retardation, fetal PO2 correlated positively with fetal glucose and inversely with maternal fetal glucose gradient.     

Second trimester maternal plasma and amniotic fluid adipokines in women who will develop gestational diabetes mellitus

Abstract

Objective: To study the adipokines concentration and glucose homoeostasis in the early-second trimester of women who will develop gestational diabetes mellitus (GDM).

Materials and methods: Maternal plasma and fetal amniotic fluid samples were prospectively collected between 2006 and 2007 at the time of mid-trimester amniocentesis. Eight patients found to be affected by GDM were compared with 10 control patients with a normal pregnancy course. Adipokines leptin and adiponectin, as well as insulin and glucose concentration both in amniotic fluid and maternal plasma were compared between cases and controls. HOMA-IR (homeostatic model assessment for insulin resistance) was also calculated both for amniotic fluid and maternal serum.

Results: The amniotic fluid adiponectin concentration was higher in women who would develop GDM than in controls (29.9?ng/ml, 95% CI 26.7–49.8 ng/ml, versus 14.9 ng/ml, 95% CI 13.5–18.8 ng/ml), p?<?0.05). No difference was shown for leptin both in amniotic fluid and maternal serum. Insulin concentrations in the amniotic fluid were found to be lower in GDM than in controls, while HOMA-IR-index resulted lower in amniotic fluid and higher maternal serum (p?<?0.05).

Conclusions: Our data suggests that an earlier alteration in the fetal glucose metabolism will precede the glucose dysmetabolism in pregnancies later complicated by GDM.     

The effect of maternal hypoaminoacidaemia on placental uptake and transport of amino acids in pregnant sheep

We developed a model of maternal hyperglycaemia with secondary hyperinsulinaemia and hypoaminoacidaemia in pregnant sheep (H) to determine the effect of these conditions on uterine, uteroplacental and fetal amino-acid uptake rates and fetal amino-acid concentrations [AA]. Results were compared with normal pregnant ewes (C). Plasma glucose concentrations were greater in H versus C animals: 7.7+/-0.3 versus 3.9+/-0.1 mmol/l maternal, P< 0.005; 2.6+/-0.1 versus 1.1+/-0.1 mmol/l fetal, P< 0.005. Maternal insulin concentrations [I] were greater in the H group (132+/-30 H versus 31+/-5 C microU/ml, P< 0.005); fetal [I] were not different (15+/-2 H versus 16+/-2 C microU/mL). Maternal [AA] were lower in H than C groups except for SER (P=ns) and GLY (approx twofold higher, P< 0.01). Uterine, uteroplacental and fetal uptake rates of several AA, particularly the branch chain AA, were lower in H than C animals, producing lower total fetal nitrogen uptake rates (270+/-64 mg N/kg fetus/day H, 696+/-75 mg N/kg fetus/day C, P=0.001) and lower fetal plasma concentrations for the branch chain AA. Most fetal [AA], however, remained at control values, which could occur by relative increase in fetal amino-acid production and/or decrease in utilization, but not by increased uteroplacental transport rates.     

Does fetal acidosis develop with maternal glucose infusion during normal labor?

The actual effects of glucose infusion on fetal acid-base status were studied during 125 normal deliveries in which plasma glucose and acid-base parameters were determined after maternal infusion of either 10% glucose or Ringer's solution. After 80 minutes, mean (+/- SD) plasma glucose levels were significantly higher in the glucose group (N = 59) than in the Ringer's group (N = 66), both for the mother (183.6 +/- 46.8 versus 95.3 +/- 18.0 mg/dL) and the fetus (108.4 +/- 41.4 versus 64.8 +/- 16.2 mg/dL). Fetal plasma lactate concentrations did not differ between the glucose and the Ringer's groups, but were significantly lower in the fetuses delivered by elective cesarean section in both groups. With glucose administration, fetal pCO2 was higher and pH values were lower than in the Ringer's group. However, the magnitude of acid-base status changes, indicated by both pH and pCO2 shifts (ie, the difference between umbilical artery and scalp values), failed to differ between the two groups. In fetuses with progressing hypoxia, no differences in any of the acid-base parameters were observed between glucose and Ringer's administration. These data indicate that at a glucose infusion rate of 30 g/hour, fetal acidosis, when it occurs, results from hypoxia rather than from maternal glucose administration.     

Fetal and maternal energy metabolism during labor in relation to the available caloric substrate.

AIM: To discuss maternal and fetal metabolic events during labor and the possible role of glucose administration. RESULTS: The oxidative pathway covers the largest part of the energy demand of labor, although in the second stage or, in polysystolic labor, the non-oxidative pathway becomes important as well. Glucose is the main maternal energy source, but the rise in ketobodies, even during normal labor, suggests a relative shortage. In the first stage of labor, a combination of a respiratory alkalosis, and to a lesser extent, a metabolic acidosis, result in a rise in the maternal pH. In the second stage of labor, the maternal pH decreases due to an increasing metabolic acidosis. Glucose is also the main fetal energetic fuel. In fetal hypoxia, lactate is produced, which in most cases is transferred to the maternal circulation. High maternal lactate concentrations, however, may interfere with this process. Furthermore, fetal hyperglycemia may lead to an increased fetal lactate production. CONCLUSIONS: Maternal hyperglycemia, may lead to an increase in maternal and fetal lactate production resulting in metabolic acidosis. Unlike high dosage intravenous glucose administration, it is not likely that oral intake of carbohydrates leads to maternal and fetal hyperglycemia and subsequently to metabolic acidosis, but studies are rare.     

Decreased fetal movements with sustained maternal hyperglycemia using the glucose clamp technique

The purpose of this study was to evaluate the effect of sustained maternal hyperglycemia (120 mg/dl) on fetal activity. The glucose infusion study group was comprised of nine healthy gravidas between 36 and 40 weeks' gestation, and six patients served as controls. The protocol design included an overnight fast for all patients. Fetal movements were evaluated by external fetal monitoring. A 2-hour preinfusion evaluation of fetal activity served as the baseline control for each patient studied. Study patients then received a glucose infusion by a glucose clamp technique to maintain a sustained hyperglycemia of 120 mg/dl for 3 hours. After the glucose infusion, fetal movements were observed for 1 hour. Control patients received a saline infusion for 2 hours after a 2-hour baseline evaluation. Maternal hyperglycemia was associated with a significant decrease of fetal movements greater than 1 second duration during the first hour of glucose infusion. Fetal movements returned to baseline during the second and third hours of glucose infusion. Saline infusion was not associated with a decrease in fetal activity. We conclude that sustained maternal hyperglycemia is associated with a transient decrease in fetal movement during the first hour of glucose infusion followed by a return to the control (preinfusion) level of fetal activity. These data may have implications in the study of fetal behavior in diabetes mellitus.     

Chronic hyperglycemia and insulin concentrations in fetal lambs

Insulin concentrations were measured in 20 chronically instrumented fetuses of 10 sheep with alloxan-induced chronic hyperglycemia and 10 control sheep to examine if the hyperglycemia resulted in high fetal insulin concentration. Additionally, in six neonatal lambs of three chronically hyperglycemic ewes and three control sheep, insulin concentrations were measured after intravenous glucose injection. After a 2-month period of significant maternal hyperglycemia, no relationship between concentrations of fetal glucose and insulin could be detected. The mean fetal glucose concentration was 3.5 +/- 0.5 mmol/L in the hyperglycemic group and 0.6 +/- 0.1 mmol/L in the control group. Mean fetal insulin levels were 12.5 +/- 1.4 and 10.7 +/- 1.3 microU/ml, respectively. The neonatal lambs of the hyperglycemic and control ewes showed comparable concentrations of glucose and insulin after infusion of glucose. It is presumed that persistent high glucose levels depress the insulin secreting capacity of the fetal pancreas.     

Placental hormones and maternal glucose metabolism. A study of fetal growth in normal pregnancy

The interrelations between three placental hormones (oestradiol, progesterone and hPL), maternal glucose metabolism, maternal anthropometry and fetal growth were studied in a sample of 52 carefully selected pregnant women. A relation was found between infant birthweight and both fasting blood glucose and t1/2 of glucose of an intravenous glucose tolerance test at week 37 of pregnancy. The serum concentrations of the placental hormones were not significantly related to the glucose variables. The correlation between birthweight and the maternal levels of hPL in late pregnancy (r = 0.60) persisted when fasting blood glucose and t1/2 of glucose were taken into account. Maternal fat mass was found to explain more of the variation in basal insulin levels around week 37 than did the placental hormones.     

Glucose gradients of maternal vein-umbilical vein and umbilical vein-umbilical artery in normally grown and growth-retarded fetuses.

The present study was designed to investigate the roles of maternal-fetal glucose transport and fetal glucose utilization in the regulation of fetal growth. Maternal venous blood, umbilical arterial and venous blood were sampled simultaneously in 60 full-term appropriate-for gestational age (AGA) fetuses and 48 small-for-gestational-age (SGA) fetuses. The cases were divided into four groups: group 1 consisted of 35 AGA fetuses, group 2 consisted of 25 AGA fetuses, group 3 consisted of 25 SGA fetuses, and group 4 consisted of 22 SGA fetuses. The mothers of group 1 and 3 were given 2.5% glucose in 0.9% normal saline and those of groups 2 and 4 by cesarean section received normal saline or Ringer's lactate at least one hour prior to delivery of the fetus SGA fetuses were found to have hypoglycaemia of umbilical venous blood, increased (maternal vein-umbilical vein) MV-UV and decreased UV-UA (umbilical vein-umbilical artery) glucose gradients, all of which disappeared after maternal glucose supplementation. However, hypoinsulinemia and lower insulin/glucose ratio in SGA fetuses persisted either with or without maternal parenteral glucose infusion. Increased MV-UV and decreased UV-UA glucose gradients suggests placental dysfunction and poor glucose utilization in SGA fetuses. The lower fetal insulin/glucose ratio may imply pancreatic dysfunction in SGA fetuses, which did not respond to glucose challenge from the maternal side. It seems that in SGA fetuses, placental dysfunction interferes with maternal-fetal transfer with resulting fetal hypoglycemia; on the other hand, pancreatic dysfunction leads to poor glucose utilization and retarded intrauterine growth. However, the mechanism that primarily accounts for pancreatic dysfunction in these fetuses remains to be resolved.     

Comparative effects of chronic exposure to glucose or sodium butyrate on surfactant development in fetal rabbits.

BACKGROUND: Infants of diabetic mothers (IDM) often have delayed lung development and are thus at an increased risk of Respiratory Distress Syndrome (RDS). Both hyperglycemia and/or hyperinsulinemia have been implicated in this delay but the precise mechanism has not been clarified. Another metabolite, sodium butyrate, which is increased in IDM has been shown to decrease surfactant production in vitro but its effects on the development of the fetal lung surfactant system in vivo have not been studied. AIM: To investigate the in vivo effects of high glucose and sodium butyrate treatment on maternal and fetal glucose and insulin levels and on fetal lung surfactant maturation using timed-pregnant New Zealand White rabbits. METHODS: On the 24th day of gestation the doe was implanted s.c. with time release pellets containing either glucose (300 mg), sodium butyrate (200 mg) or matching placebo. On the 27th or 30th day maternal (ear vein) and fetal (cardiac puncture) blood samples were drawn for glucose and insulin determinations. Fetal surfactant pools (both intra- and extracellular) were quantitatively harvested using differential and density gradient centrifugation and their phospholipid profiles determined. Data were statistically compared with ANOVA and Duncan's Multiple Range Test. RESULTS: Neither glucose nor sodium butyrate affected maternal plasma glucose or insulin. Both metabolites significantly increased fetal plasma insulin, decreased fetal plasma glucose but did not delay any of the parameters of surfactant maturation examined. CONCLUSIONS: Fetal hyperinsulinemia, whether attained by prolonged exposure to elevated glucose or sodium butyrate in vivo does not appear to be the causative agent for delayed lung maturity which frequently occurs in infants of diabetic mothers.     

Pharmacokinetic studies on fenoterol in maternal and cord blood

Fenoterol plasma concentrations were measured by radioimmunoassay in 38 pregnant women at different stages of preterm labor and in cord blood. Eight women were treated intravenously until delivery with 1.0 to 4 micrograms/min of fenoterol for periods ranging from 27 hours to 27 days; blood samples were taken at the same time as cord blood. In these women the fenoterol concentrations in cord blood ranged from 18 to 53% of the maternal concentrations. In eight women treated intravenously with 1.2 to 4.0 micrograms/min for 2 to 15 days, the infusion was stopped 1.3 to 38 hours before delivery. In these instances the concentrations in cord blood reached as much as 90% of the maternal, meaning that the rate of elimination from fetal plasma is lower than that from maternal plasma. Five women were treated daily with 20 to 30 mg per os for 3 to 17 days (three of these women had also had intravenous treatment before). The ratio of cord to maternal blood concentrations was higher than in women receiving the drug intravenously, the relative times of sampling being the same. The findings suggest that: (1) the placental transfer of fenoterol is higher than that found in previous studies in humans and animals with tritium-labeled substances; (2) the rate of fenoterol elimination from fetal plasma after intravenous and oral long-term therapy is lower than that from maternal plasma; (3) after oral administration, the ratios of fetal to maternal fenoterol concentrations are higher than after intravenous infusion.     

Adipokines and their relation to maternal energy substrate production,insulin resistance and fetal size

Objective

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

Study design

Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

Results

Median (range) rate of glucose production was 805 (653–1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110–576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (−0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5 mg/L and median level of leptin was 47.1 (9.9–58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5 mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r = −0.50, p < 0.035, r = −0.77, p < 0.001, r = −0.67, p < 0.002, and r = −0.51, p < 0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r = 0.76, p < 0.001 and r = 0.73, p < 0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

Conclusion

The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.     

Effect of variable long-term maternal feed allowance on the development of the ovine placenta and fetus

Maternal feed allowance during pregnancy can affect the development of the ovine placenta and fetus. The impact of variations in feed allowance prior to as well as throughout pregnancy has received less attention. Ewes were offered 0.6 (R), 1.2 (C) or 1.8 (AL) maintenance requirements from 89 days before conception until day 133 of pregnancy. Ewes were euthanised on days 50, 92 and 133 of pregnancy. Ewe live weight and body condition score, maternal and fetal metabolic and hormonal profiles, fetal body dimensions and organ weights, and the number, weight and morphology of placentomes were measured. Maternal live weight and condition score were lower in R compared to AL ewes at all stages of pregnancy (P<0.05). Plasma glucose and albumin concentrations of R ewes were significantly reduced (P<0.05) at mid and late gestation, respectively. Placental components were generally unresponsive to long term variations in maternal feed allowance. However, placental weight was significantly (P<0.05) correlated with fetal weight at days 50 (r=0.59) and 133 (r=0.69) of gestation. By late gestation growth-retarded singleton fetuses from R ewes were 19% lighter (P<0.05), with reduced abdominal (9%) and thoracic (10%) girths (P<0.05) but of similar crown-rump length compared with fetuses from AL ewes. These differences were associated with significantly reduced IGF-I concentrations in fetal plasma (P<0.05). In conclusion, maternal, placental and fetal adaptations to long established planes of variable maternal feed allowance were able to maintain fetal growth during early and mid-pregnancy while fetal growth restriction, associated with reduced fetal IGF-I levels, became apparent in late pregnancy.     

Effects of maternal antioxidant supplementation on maternal and fetal antioxidant levels: a randomized, double-blind study

OBJECTIVE: We sought to determine whether vitamins C and E could be delivered to the fetal-placental unit through maternal oral supplementation. STUDY DESIGN: In a randomized, double-blind study, 20 women received a daily prenatal vitamin with or without 400 IU of vitamin E and 500 mg of vitamin C, starting at 35 weeks' gestation. At randomization, a nutritional questionnaire, plasma vitamin C and E and red blood cell (RBC) vitamin E levels were determined. At delivery, concentrations of maternal and fetal plasma vitamin C and E, maternal and fetal RBC vitamin E, amniotic fluid vitamin C, and chorioamnion vitamin E and tensile strength were determined. RESULTS: Maternal plasma vitamin E levels increased in the supplemented women but not in the control subjects. No changes in maternal vitamin C levels were noted. Maternal plasma vitamin C concentrations at delivery correlated closely with amniotic fluid vitamin C levels. Similarly, maternal plasma vitamin E levels at delivery correlated with the chorioamnion concentration of vitamin E. CONCLUSIONS: Maternal plasma vitamin E levels are increased by oral supplementation. Maternal plasma vitamin C and E concentrations correlate with the concentration of vitamin C in the amniotic fluid and vitamin E in the chorioamnion, respectively.