Importance of mitochondrial haplotypes and maternal lineage in sprint performance among individuals of West African ancestry.

Mitochondrial DNA (mtDNA) is inherited solely along the matriline, giving insight into both ancestry and prehistory. Individuals of sub-Saharan ancestry are overrepresented in sprint athletics, suggesting a genetic advantage. The purpose of this study was to compare the mtDNA haplogroup data of elite groups of Jamaican and African-American sprinters against respective controls to assess any differences in maternal lineage. The first hypervariable region of mtDNA was haplogrouped in elite Jamaican athletes (N=107) and Jamaican controls (N=293), and elite African-American athletes (N=119) and African-American controls (N=1148). Exact tests of total population differentiation were performed on total haplogroup frequencies. The frequency of non-sub-Saharan haplogroups in Jamaican athletes and Jamaican controls was similar (1.87% and 1.71%, respectively) and lower than that of African-American athletes and African-American controls (21.01% and 8.19%, respectively). There was no significant difference in total haplogroup frequencies between Jamaican athletes and Jamaican controls (P=0.551 ± 0.005); however, there was a highly significant difference between African-American athletes and African-American controls (P<0.001). The finding of statistically similar mtDNA haplogroup distributions in Jamaican athletes and Jamaican controls suggests that elite Jamaican sprinters are derived from the same source population and there is neither population stratification nor isolation for sprint performance. The significant difference between African-American sprinters and African-American controls suggests that the maternal admixture may play a role in sprint performance.

Effect of magnitude and timing of maternal pregnancy blood lead (Pb) levels on birth outcomes.

OBJECTIVE: Associations between magnitude and timing of maternal pregnancy blood lead (Pb) levels (BLLs), birth weight, and total days of gestation were examined, as well as associations with related clinical diagnoses of low birth weight (LBW), preterm, and small-for-gestational-age (SGA) birth. STUDY DESIGN: Among a sample of 262 mother-infant pairs studied retrospectively, one-way analysis of variance and regression statistics were used to measure the relationship between level of maternal pregnancy BLLs and birth outcomes while controlling for key maternal and newborn factors. RESULTS: Women with maximum pregnancy BLLs (max-PBLLs) > or =10 microg/dl tended to give birth earlier and their babies were at substantially increased risk for preterm and SGA birth. By holding other explanatory factors constant, each unit increase in max-PBLL above 10 mug/dl was found to be associated with a decrease of -0.3 in total days of gestation. Compared to women with lower levels, women with max-PBLLs > or =10 microg/dl were at a threefold increased risk for preterm birth (adjusted OR=3.2, 95% CI 1.2-7.4) and more than a fourfold increased risk for having an SGA infant (adjusted OR=4.2, 1.3-13.9). Second trimester maximum BLLs > or =10 microg/dl were associated with a steep decrease in total days of gestation (a decrease of -1.0 days per each unit increase above 10 microg/dl). CONCLUSIONS: These data provide evidence of the adverse effects of maternal pregnancy BLLs, particularly when levels are > or =10 microg/dl. Prenatal Pb exposure at these levels was associated with significant decreases in total days of gestation and an increased risk of preterm and SGA birth.

Fetal intravenous nutritional supplementation ameliorates the development of embolization-induced growth retardation in sheep.

Since decreased transfer of nutrients into the fetus has been documented in many forms of intrauterine growth retardation, we evaluated whether increasing fetal nutrient availability would prevent the development of experimental growth retardation in fetal lambs. Fetuses were separated into three groups: E, animals growth retarded by repetitive uteroplacental embolization (n = 8); ES, animals treated as in E and given fetal femoral venous infusions of 5% glucose and 6.8% amino acids (n = 7); and C, controls (n = 8). The duration and density of embolization were the same in E and ES; initial physical and metabolic characteristics and gestation at delivery were similar in all groups. E birth weight was reduced 26% compared to C (2888 +/- 373 SEM g versus 3880 +/- 277 g, p less than 0.05); fetal/maternal weight ratio was decreased 35% (p less than 0.005) and ponderal index decreased 22% (p less than 0.005). Asymmetric growth retardation was indicated in E by an increased brain/body weight ratio (p less than 0.05). ES fetuses, in contrast, showed no differences from C in birth weight (3601 +/- 190 g) or body proportions. ES were larger than E, with a greater fetal/maternal weight ratio and ponderal index (p less than 0.05 for both). In E and ES, size at birth showed a positive relation to the amount of supplements received. The average daily supplementation rate correlated with the fetal/maternal weight ratio and with the ponderal index (for both r = 0.62, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of antipyrine on umbilical and regional metabolism in late gestation in the fetal lamb.

OBJECTIVE: Antipyrine has been used extensively in fetal metabolic studies and is now known to inhibit prostaglandin synthesis; therefore we wished to determine the effects of antipyrine on fetal umbilical and regional metabolism. STUDY DESIGN: Chronically catheterized fetal lambs were randomly assigned to antipyrine (n = 6) or control (n = 5) groups. Animals in the antipyrine group were infused with antipyrine (mean +/- SD 9.6 +/- 0.9 mg/min for 165 +/- 38 minutes), and control group animals were not infused. Measurements were made of fetal blood gases, oxygen content, glucose, lactate, lower-body blood flow, upper-body flow distribution, and substrate uptakes across the umbilical and hind limb circulations. The unpaired t test, correlation coefficient, and regression analysis were used for comparisons. RESULTS: There were no differences in antipyrine and control group animals with respect to blood gases, metabolite levels, umbilical blood flow, or umbilical uptakes. Hind limb blood flow (p < 0.10) and oxygen uptake (p < 0.05) were lower and lactate production was higher (p < 0.01) in antipyrine animals than in control group animals. Duration of antipyrine exposure correlated directly with hind limb lactate production (r = 0.85, p < 0.001) and inversely with hind limb oxygen uptake (r = -0.65, p < 0.05). The distribution of blood flow within the fetal upper body also differed between groups, with higher cardiac distribution in the antipyrine group (p < 0.025). CONCLUSIONS: Antipyrine does not affect umbilical metabolism but does affect carcass metabolism and fetal blood flow distribution.

Nutrient and waste product concentration differences in upper and lower body arteries of fetal sheep.

Well oxygenated blood returning from the placenta is preferentially shunted into the left side of the fetal heart and the ascending aorta. This results in higher oxygen saturation in arterial blood supplying the fetal upper body than in blood supplying the lower body. Since the placenta is also the site of nutrient and waste exchange, we evaluated differences in arterial concentrations of nutrients and waste products in fetal upper and lower body. Studies were carried out on ten, chronically catheterized, third trimester, fetal sheep. Blood samples, drawn simultaneously from the carotid and femoral arteries, were analyzed for glucose, oxygen saturation, oxygen content, total amino acids, lactate, urea nitrogen, and hydrogen ion concentration. Carotid arterial blood had higher levels of glucose (1.4 +/- 0.1 mg/dl (SEM); P less than 0.001), of alpha-amino nitrogen (0.4 +/- 0.1 mg/dl, equivalent to amino acid concentration difference of 2.5 mg/dl, P less than 0.025), of oxygen saturation (9.9 +/- 0.5%, P less than 0.001), and of oxygen content (1.0 +/- 0.1 ml/dl; P less than 0.001). Carotid values exceeded femoral by an average of 10% for glucose, 4% for amino nitrogen, 29% for oxygen saturation and 23% for oxygen content. Carotid arterial blood had lower urea nitrogen, (-0.5 +/- 0.2 mg/dl; P less than 0.05) and hydrogen ion (-1.1 +/- 0.1 nM/L; P less than 0.001) concentrations, but these differences averaged only 2% between vessels. Lactate concentration in the carotid and femoral arteries was the same. Fetal glucose and oxygen levels were closely related.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intrauterine nutritional supplementation on fetal growth retardation.

The effects of fetal nutritional supplementation on experimentally induced growth retardation were investigated in third-trimester sheep. The control group, C, was fed ad libitum (n = 8). Group R received a protein- and calorie-restricted diet over the last 3 weeks of gestation (n = 8). Group RS was given the same restricted diet as group R, and fetal, intragastric supplements of amino acids and glucose (n = 7). Over the experimental period, maternal weight increased 4.1 +/- 0.6 kg in C but was stable in R and RS (p less than 0.01). R and RS ewes and fetuses showed biochemical evidence of malnutrition but the changes were less severe in the RS group (p less than 0.05). Nutrient levels did not change in group C ewes and fetuses. At delivery, R lambs were smaller in weight and length than RS or C (p less than 0.05); gestational ages were the same. Weights were: R, 2,702 +/- 182 g; RS, 3,235 +/- 121 g; and C, 3,290 +/- 297 g. R also had lower fetal to maternal weight ratios and higher brain to body weight ratios than RS or C (p less than or equal to 0.05). Placental size was reduced 28% in R compared to C (p less than 0.05) and was intermediate in RS. The disparity in fetal size was explained by differences in nutrient acquisition between groups. Over the experimental period, caloric intake rose 24% in C fetuses; near delivery, they had the highest umbilical uptakes of carbohydrate and alpha-amino nitrogen. After maternal diet was limited, R and RS fetuses had dramatic decreases in umbilical uptake of alpha-amino nitrogen and static umbilical uptakes of carbohydrate. Caloric intake fell 42% in R. RS fetuses, however, were receiving sufficient gastric supplementation so that umbilical + gastrointestinal carbohydrate uptake equalled that of controls, and entry of alpha-amino nitrogen and calories was intermediate, between those of R and C. Fetal oxygen consumption reflected the differences in nutrient uptake, being greatest in C, lowest in R and intermediate in RS. Fetal supplementation lessened the drain on maternal nutrients and promoted more normal fetal growth and metabolism.

Substrate utilization by the fetal sheep lung during the last trimester.

In vivo substrate utilization has not been described for the maturing fetal lung. We, therefore, studied pulmonary delivery and use of major fetal substrates in six chronically catheterized fetal lambs over 119-141 days gestation. Oxygen, glucose, lactate, and alpha-amino nitrogen concentrations were measured in the pulmonary artery and pulmonary vein whereas lung blood flow was determined using labeled microspheres. We found that lung oxygen availability and use increased near term. Oxygen delivery averaged 4960 +/- 480 (SEM) microliters/min and rose with fetal age (p less than 0.05); uptake averaged 708 +/- 111 microliters/min and increased 93% near term (p less than 0.05). In contrast, glucose availability and use fell with gestation. Pulmonary artery glucose decreased with time (p less than 0.001), with a mean drop of 5.05 +/- 1.71 mg/dl in individual animals (p less than 0.05). Average glucose uptake was 844 +/- 225 micrograms/min and fell near term (p less than 0.05). Lactate was produced by the lung at a mean rate of 534 +/- 176 micrograms/min; this did not change with gestation. Lung amino nitrogen availability increased with fetal age. Pulmonary artery amino nitrogen rose by 1.35 mg/dl, or 43% (p less than 0.001) and lung delivery of amino nitrogen increased (p less than 0.05). The mean pulmonary glucose/O2 ratio was 1.48 +/- 0.26 and decreased with gestation (p less than 0.05), being less than 1.0 near term. The glucose-lactate/O2 ratio was 0.67 +/- 0.26, implying that 30% of lung oxidative metabolism is still unaccounted for. The alterations in delivery of substrates to the lung which were identified may serve as signals for pulmonary maturation, inducing the changes in lung metabolism that were found near term.

Effects of gastric nutritional supplementation on fetal umbilical uptake of nutrients.

Intrauterine nutritional supplementation may be of therapeutic benefit to the malnourished, growth-retarded fetus. Using 14 chronically catheterized, third trimester fetal lambs, we evaluated the effects of gastric infusions of amino acids and glucose on umbilical uptake of alpha-amino nitrogen, glucose, lactate, and oxygen. When amino acids were infused, amino nitrogen was gained through the intestine at an average rate equal to 45% of fetal umbilical uptake of amino nitrogen. There were no consistent changes in umbilical uptake of the measured nutrients, except for a small decrease in umbilical uptake of oxygen (P less than 0.05). No relationship were found between changes in fetal amino nitrogen levels or changes in fetal-maternal amino nitrogen concentration gradients and umbilical uptake of amino nitrogen. When glucose was infused, glucose was absorbed through the intestine at an average rate equal to 42% of fetal umbilical uptake of glucose. There were no changes in umbilical uptake of amino nitrogen, lactate, or oxygen. Umbilical uptake of glucose decreased, however, in inverse proportion to both the glucose infusion rate (P less than 0.005) and the rise in fetal glucose concentration (P less than 0.025). This limited the quantity of glucose that could be gained by the fetus, via gastrointestinal supplementation. During the infusions, we also observed a change in the pattern of fetal lower body blood flow. There was a 12% decrease in the mean umbilical blood flow (P less than 0.005) and a 22% increase in mean intestinal flow (P less than 0.05).

Late gestation alterations in fetal pulmonary lactate metabolism in vivo.

We have previously shown that lactate is produced by the ovine fetal lung. Inasmuch as factors that might affect lactate production, such as pulmonary glucose and oxygen uptake, change late in gestation we investigated whether pulmonary lactate metabolism also changes. Eleven chronically catheterized fetal lambs were studied over 119-141 d gestation. Lactate, glucose, and oxygen concentrations were measured in the pulmonary artery (PA) and vein while lung blood flow was determined using labeled microspheres. Between early studies (less than or equal to 127 d) and studies near term (greater than or equal to 134 d) PA lactate levels did not change, but due to increasing pulmonary blood flow, lung lactate delivery rose 51% (p less than 0.05). Because of a decline in PA glucose, lactate also made up a larger fraction of the major nonnitrogenous substrate in PA blood near term (p less than 0.001). Despite this, no net pulmonary uptake of lactate occurred. Lactate production continued, but decreased by 80% between early and late studies (p less than 0.05) and the maximum fraction of glucose uptake that could be accounted for by lactate production dropped from 0.78 to 0.20 (p less than 0.025). Correlations were found between lung lactate production and glucose uptake also correlated with PA glucose (p less than 0.05). No relationships were observed between lactate production and PA oxygen content, oxygen delivery, lactate concentration, or lactate delivery. The decreasing fraction of glucose uptake explained by lactate production suggests that metabolism of pulmonary glucose is altered near term. The correlation between decreasing glucose delivery and declining lactate production also suggests that glucose itself influences this change.

Effect of lactate and beta-hydroxybutyrate infusions on brain metabolism in the fetal sheep.

Brain uptake of substrates other than glucose has been demonstrated in neonatal but not fetal animals in vivo. This study was undertaken to investigate the ability of the fetal sheep brain to use potential alternative substrates when they were provided in increased amounts. Brain substrate uptake was measured in chronically catheterised fetal sheep during 2-h infusions of neutralised lactate (n = 12) or beta-hydroxybutyrate (n = 12). Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective infusions, no significant uptake of either substrate was demonstrated. However during both types of infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres (measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and the rise in lactate and butyrate concentrations during the butyrate infusions. Both substrates have metabolic actions that may inhibit brain glucose uptake. We speculate that the deleterious effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of brain glucose uptake.

Effects of beta-hydroxybutyrate infusion on hind limb metabolism in fetal sheep.

OBJECTIVES: This study investigated the effects of high ketone levels on fetal carcass metabolism. Specifically, we aimed to determine whether beta-hydroxybutyrate was taken up by fetal muscle and whether lactate production by the fetal hind limb contributed to the raised circulating lactate levels seen in high ketone states. STUDY DESIGN: Hind limb metabolism was studied in 10 chronically catheterized fetal sheep. Substrate/oxygen quotients were measured before and after 2 hour infusions of beta-hydroxybutyrate and compared with the Wilcoxon signed-rank test. RESULTS: beta-Hydroxybutyrate was taken up by hind limb tissues in large amounts (butyrate/oxygen quotient = 1.02 +/- 0.40). Lactate was produced by the hind limb (lactate/oxygen quotient = -0.96 +/- 0.52) in amounts almost equivalent to glucose uptake (glucose/oxygen quotient = 1.32 +/- 0.29). Hind limb oxygen consumption increased 35% and fetal arterial oxygen content fell 16%. CONCLUSION: beta-Hydroxybutyrate may be consumed by the fetal carcass in amounts sufficient to entirely substitute for glucose. Glucose may then be released as lactate for metabolism elsewhere. Ketones may be important fetal substrates during maternal starvation.

Consumption of carbohydrates, amino acids and oxygen across the intestinal circulation in the fetal sheep.

Since large volumes of nutrient rich amniotic fluid are swallowed by the fetus, it has been suggested that intestinal digestion and absorption contribute significantly to fetal nutrition. To see if nutrients are being gained across the intestine, we measured blood flow and intestinal arteriovenous concentration differences of glucose, alpha-amino nitrogen, lactate, fructose and oxygen in eleven third trimester fetal sheep with chronically implanted vascular catheters. We found that in fetal blood circulating through the intestine nutrient concentration decreased significantly with arterio-venous concentration differences for glucose of 0.78 +/- 0.21 (SEM) mg/dl (P < 0.002), for alpha-amino nitrogen of 0.52 +/- 0.15 mg/dl (P < 0.005), for lactate of 0.68 +/- 0.24 mg/dl (P < 0.05) and for oxygen of 1.50 +/- 0.08 ml/dl (P < 0.001). Fructose concentration did not change. Blood flow to the fetal intestine averaged 89.92 +/- 7.16 ml/min and the intestine consumed 0.74 +/- 0.24 mg of glucose, 0.43 +/- 0.17 mg of alpha-amino nitrogen, 0.83 +/- 0.28 mg of lactate and 1.37 +/- 0.14 ml of oxygen per minute. Compared to previously published values for the umbilical uptake of nutrients the fetal intestine metabolizes about 4% of the glucose, 6% of the alpha-amino nitrogen, 13% of the lactate and 6% of the oxygen obtained across the umbilical circulation. Intestinal absorption does not appear to serve as a source of simple nutrients for the rest of the fetus, in fact intestinal metabolism extracts significant amounts of nutrients from fetal blood.

Carotid artery reconstruction following extracorporeal membrane oxygenation.

Right hemispheric brain injury has been noted in surviving infants treated with venoarterial extracorporeal membrane oxygenation (ECMO). This phenomenon may be secondary to permanent ligation of the right carotid artery. At our institution, conventional ventilatory therapy failed in five neonates with respiratory insufficiency, and they were treated successfully with ECMO. In four of the five neonates, the right carotid artery was reconstructed at the time of decannulation. At discharge, all newborns with carotid artery repair showed no signs of unilateral brain injury and had excellent antegrade flow in the right carotid artery as assessed by both duplex and transcranial Doppler ultrasound scanning. Carotid artery reconstruction after ECMO is a technically simple procedure that may reduce the incidence of right hemispheric brain injury and long-term consequences of marginal cerebral perfusion.

Selected indications for and applications of magnetic resonance angiography in children.

The purpose of this study was to investigate the efficacy and practicality of magnetic resonance angiography (MRA) in evaluating pediatric cerebrovascular disorders. A retrospective evaluation was performed of MR angiograms in 20 pediatric patients with cerebrovascular pathology. When appropriate, comparisons were made with duplex ultrasonography or conventional catheter angiography. MRA accurately assessed the patency of carotid reanastomoses in 8 babies who had previously undergone extracorporeal membrane oxygenation (ECMO). In 6 patients with moyamoya syndrome, MRA accurately evaluated stenotic intracranial carotid and circle of Willis arteries and progressive enlargement of the superficial temporal and middle cerebral arteries after revascularization procedures, and thus obviated the need for sequential angiograms. Thrombi and emboli were identified in 4 of 5 patients with symptoms and imaging evidence of an acute stroke. Two-dimensional time-of-flight MR venograms, acquired in both axial and coronal planes, were useful for preoperative venous mapping in a patient with an occipital encephalocele and detecting venoocclusive disease. MRA provided diagnostically useful information in a spectrum of pediatric cerebrovascular disorders. It can be used as the initial vascular imaging modality for patients with imaging evidence of acute cerebrovascular event, to evaluate progression of chronic vasoocclusive disease, to evaluate vessel patency following intracranial revascularization surgery, and for visualization of the venous circulation.

Gluten challenge in treated coeliac disease.

Thirty-two children with a past diagnosis of coeliac disease were reinvestigated by means of gluten challenge. They had received a gluten-free diet for a mean period of 6-5 years (range 0-25-11-0) before gluten challenge, and had a mean age of 9-9 years (range 3-0-15-3) at the onset of challenge. Small intestinal biopsies were performed before and after the gluten challenge (at least 10 g natural gluten per day for 3 months in the majority) and, as judged by light microscopy and morphometric techniques, coeliac disease was confirmed in 25 (78%) of the 32 patients; challenge was continued in the remaining 7 for a total period of 2 years when biopsies were repeated in 6 children and all were normal. Serum and RBC folate, serum iron, Hb level, and clinical symptoms were unpredictable variables in identifying children who developed gluten-induced enteropathies. The social and emotional effects of gluten challenge are discussed. The results highlight the importance of gluten challenge and intestinal biopsy in the diagnosis of coeliac disease and strongly suggest that a normal biopsy after a 3-month gluten challenge (as described above) excludes coeliac disease.