Anna Maria Marconi

Association between the Activity of the System A Amino Acid Transporter in the Microvillous Plasma Membrane of the Human Placenta and Severity of Fetal Compromise in Intrauterine Growth Restriction

Primarily, our objectives were to compare system A amino acid transporter activity in the microvillous plasma membrane (MVM) of placentas from normally grown (appropriate for gestational age, AGA) and intrauterine growth-restricted (IUGR) fetuses delivered during the third trimester, as a whole and in relation to the severity of IUGR. Ten AGA and 16 IUGR pregnancies were studied at the time of elective cesarean section performed between 28 and 40 wk of gestation. Severity of IUGR pregnancies was assessed primarily by Doppler velocimetry and fetal heart rate monitoring. Placental MVM vesicles were prepared, and system A activity in these was measured. The transporter activity was significantly lower in IUGR compared with AGA pregnancies. Within the IUGR group system A activity was only significantly lower, compared with AGA, in cases that presented with a reduction in umbilical blood flow. We conclude that placental MVM system A activity is lower in IUGR compared with AGA pregnancies delivered during the third trimester. System A activity is related to the severity of IUGR.

Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis

Fetal plasma amino acid concentrations were obtained by cordocentesis at midgestation in 11 normal (appropriate for gestational age) fetuses and at late gestation in 12 small-for-gestational-age fetuses, and at cesarean section in 14 normal term infants. In normal fetuses total molar amino acid concentrations and fetal/maternal total molar concentration ratios did not change significantly between the second and third trimesters. Fetal and maternal concentrations of most amino acids were significantly correlated at both midgestation and late gestation. Small-for-gestational-age fetuses had significantly lower concentrations of total alpha-aminonitrogen; this was mainly because of a reduction of the branched chain amino acids valine, leucine, and isoleucine, and of lysine and serine. Maternal arterial concentrations of phenylalanine, arginine, histidine, and alanine were elevated in small-for-gestational-age pregnancies. Thus there are only minor changes in amino acid concentrations between midgestation and late gestation in normal fetuses with a constant fetal/maternal ratio. In small-for-gestational-age infants a significant reduction in alpha-aminonitrogen and in most essential amino acids was demonstrable in utero weeks before delivery.

Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies.

OBJECTIVES Our purpose was to determine whether maternal amino acid concentration changes during gestation in pregnancies with intrauterine growth restriction as in normal pregnancies and to verify whether these changes are related to changes in fetal-maternal differences. STUDY DESIGN Amino acid concentrations were measured in 5 nonpregnant women, in 11 second-trimester and 10 third-trimester pregnant women with appropriate-for-gestational-age fetuses, and in 23 pregnant women with intrauterine growth restriction. Umbilical venous amino acids were measured at the time of fetal blood sampling. The severity of intrauterine growth restriction was assessed by Doppler velocimetry and fetal heart rate and by evaluation of oxygenation and acid-base balance. RESULTS In normal pregnant women the maternal concentration of most amino acids was significantly lower in both the second and third trimesters compared with nonpregnant women. In intrauterine growth restriction the maternal concentrations of most essential amino acids were significantly higher than in appropriate-for-gestational-age pregnancies. This observation, coupled with lower fetal amino acid concentrations in intrauterine growth restriction, leads to significantly lower fetal-maternal differences. CONCLUSIONS Normal pregnant women have a significant decrease in amino acid concentrations compared with nonpregnant women, whereas in intrauterine growth restriction maternal amino acids are reduced less, Significantly lower fetal-maternal concentration differences are present in intrauterine growth restriction, independent of the degree of severity.

Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies.

The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125 ± 7 min. Umbilical venous samples were obtained after 114 ± 42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.

Venous drainage of the human uterus: Respiratory gas studiesin normal and fetal growth-retarded pregnancies

OBJECTIVE To determine respiratory gas relationships between the uterine veins and umbilical vein in normal and pregnancies complicated by intrauterine growth retardation. STUDY DESIGN Respiratory gases were measured in both uterine veins and the umbilical vein in eight normal and 13 pregnancies with intrauterine growth retardation. RESULTS No significant differences were found in the placental versus nonplacental uterine veins. There was a significant correlation for umbilical and uterine venous values of PO2 (p less than 0.002) and PCO2 (p less than 0.004) in appropriate-for-gestational-age pregnancies, umbilical venous PO2 was always less than uterine venous PO2, and PCO2 always greater than uterine. The transplacental gradient was significantly higher in intrauterine growth retarded than appropriate-for-gestational-age pregnancies for both POC2 and PCO2. There was a lower uterine oxygen extraction in intrauterine growth retarded pregnancies (p less than 0.05). CONCLUSION There is no consistent relationship between placental venous drainage in each uterine vein and placental location. The human placenta simulates a relatively inefficient venous equilibrator and the larger transplacental gradients in intrauterine growth retarded pregnancies may reflect differences in both perfusion pattern and placental structure.

In Vivo Placental Transport of Glycine and Leucine in Human Pregnancies

ABSTRACT: L-[1-13C]Glycine and L-[l-13C]leucine were infused as a bolus into 12 pregnant patients carrying normal fetuses before fetal blood sampling at gestational ages ranging from 20 to 37 wk. Maternal venous samples were obtained every 2-3 min for 15 min after the bolus infusion. Fetal samples were obtained from the umbilical vein within 15 min of the bolus. Amino acid plasma enrichments (molar percent enrichment) were determined by gas chromatography-mass spectroscopy and their concentrations by ion exchange chromatography. The ratios of glycine and leucine transfer were assessed from fetal/maternal enrichment ratios for each amino acid. We now report that over the gestational age range of 20-37 wk, under relatively undisturbed fetomaternal conditions (fetal blood sampling), human placental glycine transfer is limited, with a glycine/leucine ratio = 0.16 ± 0.02. We hypothesize that, in human pregnancies, the relative rates of in vivo transplancental transport of amino acids can be assessed indirectly utilizing fetal blood sampling and stable isotope methodology. The application of this approach to leucine and glycine demonstrates that the transfer of leucine is rapid (demonstrable in seconds), whereas that of glycine is more limited.

An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies

The presence of fetal glucogenesis was evaluated in nine patients with pregnancies complicated by intrauterine growth retardation (IUGR) at the time of fetal blood sampling (FBS) between 29 and 35 weeks of pregnancy. Eight were singleton pregnancies and one was a twin pregnancy in which blood samples were obtained from both twins. A maternal primed-constant infusion of D(U-13C]glucose was performed, and the presence of fetal glucogenesis was assessed by a comparison of steady-state maternal and fetal glucose enrichments. No significant difference was present between maternal and fetal molar percent excess ([MPE] P = .97), and the mean fetal to maternal (F/M) MPE ratio (0.99 +/- 0.01) was not significantly different from 1 (P = .76). F/M MPE ratio was independent of the time of FBS and umbilical venous glucose and lactate concentrations. Thus fetal glucogenesis is not demonstrable in a group of fairly severe growth-retarded fetuses after an overnight fast with this relatively noninvasive approach.

Cord sampling for the evaluation of oxygenation and acid-base balance in growth-retarded human fetuses

In 14 pregnancies complicated by intrauterine growth retardation, the umbilical cord was sampled before delivery under ultrasonic guidance for rapid fetal karyotyping. Fetal blood was analyzed for respiratory gases, acid-base balance, and lactate concentrations. Two patients were excluded from the study because cord samples were diluted with amniotic fluid. In six patients (group 1), the clinical assessment warranted continuation of pregnancy. Cesarean sections were performed in the remaining eight patients (group 2) within 8 hours of cord sampling. The data from the two groups were compared with those obtained from umbilical venous blood at the time of elective repeat cesarean section in term appropriate for gestational age infants (controls). No significant difference in PO2 was found between groups 1 and 2 and controls. In contrast, there were significant differences in oxygen saturation and acid-base balance between groups 1 and 2. Lactate concentration was inversely correlated with pH and was elevated in five of six fetuses requiring a prompt cesarean section: In two of these five fetuses, nonstress fetal heart rate tracings were reactive. The results suggest that fetal blood biochemistry, and particularly lactate concentration, may represent an additional indicator of fetal well-being in pregnancies complicated by intrauterine growth retardation.

Autophagy in term normal human placentas

Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

Fetal amino acids in normal pregnancies and in pregnancies complicated by intrauterine growth retardation.

Plasma amino acid concentrations were measured in normal (AGA) and intrauterine growth retarded (IUGR) percutaneous umbilical blood sampling (PUBS) performed for prenatal diagnosis or at elective cesarean section. IUGR fetuses present significantly lower concentrations of most amino acids, with a significant reduction of the umbilical veno-arterial difference for total alpha-amino nitrogen. These findings are present early in growth retarded fetuses and may be potentially responsible for the growth retardation.