Cinzia L. Paolini

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.

Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term.

The objective of the present investigation was to determine fetal and maternal plasma concentrations of nonglucose carbohydrates and polyols in normal human pregnancies at term. Uncomplicated human pregnancies (n = 50) were studied at ≥37 wk gestation. Blood samples were obtained from umbilical artery, umbilical vein, and maternal peripheral blood at the time of elective cesarean section. Plasma concentrations of inositol, glycerol, erythritol, sorbitol, and mannose were determined by HPLC analysis. Differences between umbilical venous, umbilical arterial, and maternal concentration were tested by the two-tailed t test for paired samples. Correlations between umbilical and maternal concentration and between umbilical venoarterial concentration difference and umbilical arterial concentration were assessed by Pearsons correlation and multiple regression analysis. All newborns were appropriate for gestational age, and oxygenation and acid-base balance were within the normal range for all fetuses studied. For most of the polyols (inositol, sorbitol, and erythritol), the fetal concentration was significantly higher than the maternal concentration. The umbilical venoarterial concentration difference for inositol was −10.5 ± 3.6 μM, for glycerol was 10 ± 1.7 μM, for sorbitol was 3.8 ± 0.5 μM (p < 0.001), and for mannose was 7.6 ± 0.7 μM. There was a significant correlation between maternal concentration and umbilical venous concentration of mannose (UVMAN = 15.38 + 0.69 MMAN; R2 = 0.46; p < 0.001). These results indicate that in normal human pregnancies at term, inositol is produced by the fetus, sorbitol is produced by the placenta, and there is a significant umbilical uptake of mannose from the maternal circulation.

Nutrient Transport Across the Intrauterine Growth-Restricted Placenta

This chapter is a brief review of the current literature on nutrient transport across the intrauterine growth restricted placenta in human pregnancies in vivo. These studies, performed at the time of fetal blood sampling or elective cesarean section, show that the placenta plays a very important role in the pathophysiology of intrauterine growth restriction, clarifying the mechanisms of impaired nutrient placental transport. Further studies are needed though to open new perspectives in the clinical management and in the prevention of the disease.

Lactacidemia in Intrauterine Growth Restricted (IUGR) Pregnancies: Relationship to Clinical Severity, Oxygenation and Placental Weight

The aim of the study was to evaluate the impact of clinical severity and placental weight upon fetal lactacidemia in intrauterine growth restricted (IUGR) pregnancies. Seventy pregnancies complicated by IUGR were compared with 70 normal (appropriate for gestational age, AGA) pregnancies at the time of elective cesarean section. IUGR pregnancies were divided according to clinical severity in three groups: Group 1 had normal fetal heart rate (FHR) and normal pulsatility index of the umbilical artery (PI); Group 2 had normal FHR and abnormal PI; and Group 3 had abnormal FHR and PI. No cases with severe lactacidemia had placental weights ≥250 g. Forty-four fetuses had placental weight <250 g: Twenty-four had severe lactacidemia and all were Group 2 and 3, whereas 20 had normal umbilical artery lac (lactate) (and small placentas) regardless of the clinical severity. Gestational age, fetal and placental weights, F/P ratios, uv (umbilical vein) and ua lac and ua oxygen content and pH were significantly decreased in fetuses with small placentas and high lactate. There was a significant relationship between fetal and placental weight in AGA and IUGR. However, IUGR fetuses with placental weight ≥250 g exhibited an F/P ratio significantly lower than that in AGA fetuses suggesting that IUGR may be due to a reduction of placental function per gram of tissue.

Transplacental Supply of Mannose and Inositol in Uncomplicated Pregnancies Using Stable Isotopes

OBJECTIVE The aim of this study was to determine relative contributions of transplacental flux vs. fetal production for inositol and mannose in normal term pregnancies. STUDY DESIGN Seven term uncomplicated pregnancies undergoing cesarean section were infused with (13)C- and (2)H-labeled isotopes of glucose, inositol, and mannose until a steady state was achieved. Maternal and fetal concentrations of labeled and unlabeled glucose, mannose, and inositol were measured using gas chromatography/mass spectroscopy. The fetomaternal molar percentage excess ratio was calculated for each glucose, mannose, and inositol. RESULTS The fetomaternal molar percentage excess ratio of mannose in the fetal artery (F(artery)/M) was 0.99 [97.5% confidence interval (CI), 0.91-1.07] and in the fetal vein (F(vein)/M), 1.02 (97.5% CI, 0.95-1.10). Both were not significantly different from 1.0, consistent with transplacental supply. The fetomaternal ratios for glucose were similar to mannose (fetal artery, 0.95; 97.5% CI, 0.84-1.15; and fetal vein, 0.96; 97.5% CI, 0.85-1.07). The fetomaternal ratio for inositol was significantly less than 1.0 (fetal artery, 0.08; 97.5% CI, 0.05-0.12; fetal vein, 0.12; 97.5% CI, 0.06-0.18), indicating little transplacental flux and significant fetal production. CONCLUSION In normal term pregnancies, fetal mannose and glucose concentrations are dependent upon maternal transplacental supply. Fetal inositol is not dependent upon transplacental supply.

The transplacental transport of essential amino acids in uncomplicated human pregnancies

OBJECTIVE The purpose of this study was to assess the placental transport of the essential amino acids (EAAs) in normal pregnancies. STUDY DESIGN Nine ((13)C or (2)H) EAAs were infused simultaneously as a bolus into the maternal circulation of 12 patients with uncomplicated pregnancy before cesarean delivery. Maternal samples were collected before and after the bolus; umbilical blood was collected at delivery. The fetal/maternal molar percent enrichment for each EAA was calculated for both the umbilical vein and artery. Plasma amino acids enrichments were analyzed by gas chromatography mass spectrometry and concentrations by high performance liquid chromatography. Data were analyzed with paired and unpaired t-test. RESULTS The umbilical arterial enrichments were significantly lower than the venous. Fetal/maternal ratios for leucine, isoleucine, methionine, and phenylalanine were > 0.80, with no significant differences among their molar percent enrichment ratios, whereas fetal/maternal ratios of the other 5 EAAs were significantly lower (< 0.60). CONCLUSION The EAAs showed significant umbilical uptake and striking differences in their transport rates in vivo.