Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction.

BACKGROUND: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. METHODS: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). RESULTS: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AAs that were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essential AAs were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels. CONCLUSION: We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate, which together reduce fetal AA demand.

Human breast milk sugars and polyols over the first 10 puerperium days.

OBJECTIVE: The transition from colostrum to mature breast milk during early puerperium is associated with significant concentration changes of numerous compounds. However, it is not known whether the free sugars, aminohexoses, and polyols are affected. Therefore, in this study, we aimed to determine their concentrations in human colostrum and milk during the first 10 days postpartum. METHODS: This prospective longitudinal study in a sample of normal consecutive obstetric patients was conducted as a collaboration between two academic centers-Polish and American. Participants were 13 women after uncomplicated pregnancy and delivery at term of a singleton, appropriate-for-gestational-age fetus. Lactose, galactose, glucose, mannose, galactosamine, glucosamine, glycerol, and myo-inositol concentrations were measured using high performance liquid chromatography. RESULTS: During the first 3 days postpartum, the concentrations of lactose and glucose increased significantly (P < 0.001), to steady-state values thereafter. In contrast, the concentrations of myo-inositol and glycerol decreased significantly (P < 0.001) over the first 4 days, to reach relatively low stable values. ANOVA analysis indicated that the postpartum day at which early changes ceased to be significantly different from their plateau values was Day 4. myo-Inositol concentrations were significantly higher (P = 0.022) in multiparas than in primiparas. CONCLUSIONS: The colostrum-to-milk transition is associated with significant changes in concentrations of free sugars and polyols, changes which are completed by the fourth postpartum day. Parity influences the concentrations of some compounds in the breast milk.

Placental TonEBP/NFAT5 osmolyte regulation in an ovine model of intrauterine growth restriction.

TonEBP/NFAT5 (the tonicity-responsive enhancer binding protein/nuclear factor of activated T cells) modulates cellular response to osmotic changes by accumulating inositol and sorbitol inside the cells. Our objective was to assess placental osmolytes, TonEBP/NFAT5 RNA and protein expression, and signaling molecules across gestation between control and intrauterine growth restriction (IUGR) ovine pregnancies. Pregnant sheep were placed in hyperthermic conditions to induce IUGR. Placental tissues were collected at 55, 95, and 130 days gestational age (dGA) to measure inositol, sorbitol, TonEBP/NFAT5 (NFAT5), sodium-dependent myo-inositol transporter (SMIT; official symbol SLC5A3), aldose reductase (AR), and NADPH (official symbol DE-CR1). Placental weight was reduced in IUGR compared to controls at 95 and 130 dGA. Osmolyte concentrations were similar between control and IUGR placentas, but both groups demonstrated a significant decrease in inositol concentration and an increase in sorbitol concentration with advancing gestation. Cytosolic NFAT5 protein decreased significantly from 55 to 95 dGA in both groups, and nuclear NFAT5 protein increased only at 130 dGA in the IUGR group, but no differences were seen between groups for either cytosolic or nuclear NFAT5 protein concentrations. DE-CR1 concentrations were similar between groups and increased significantly with advancing gestational age. AR was lowest at 55dGA, and SLC5A3 increased with advancing gestational age. We conclude that both placental osmolytes inositol and sorbitol (and their corresponding proteins SLC5A3 and AR) change with gestational age and are regulated, at least in part, by NFAT5 and DE-CR1 (NADPH). The inverse relationship between each osmolyte across gestation (e.g., inositol higher in early gestation and sorbitol higher in late gestation) may reflect nutritional needs that change across gestation.

Effect of antenatal betamethasone on maternal and fetal amino acid concentration.

OBJECTIVE: To determine the concentration of amino acids in women receiving the first course of antenatal betamethasone and to evaluate the umbilical venous and arterial amino acid concentrations at the time of elective cesarean section after betamethasone administration. STUDY DESIGN: Blood samples were collected from 34 pregnant women at risk of premature delivery before and 24 and 48 hours after the first course of betamethasone. In addition, maternal and cord blood samples were collected in 13 women undergoing an elective cesarean section between 24 and 192 hours after betamethasone. RESULTS: Maternal amino acid concentrations were significantly increased after the first dose of betamethasone. Overall total amino nitrogen increased 17.5% 24 hours after betamethasone administration and 20.5% after 48 hours. The concentration of most amino acids was increased both in the umbilical vein and artery after maternal betamethasone administration. CONCLUSION: The concentration of maternal and fetal amino acids increases significantly after betamethasone administration.

Inositol and mannose utilization rates in term and late-preterm infants exceed nutritional intakes.

Nonglucose carbohydrates such as mannose and inositol are important in early growth and development, although little is known about their metabolism. Our aim in this study was to determine the plasma appearance rates (Ra) for mannose and inositol in newborns as an index of utilization and as an improved guide to supplementation practices. We studied late-preterm (n = 9) and term (n = 5) infants (median 34 wk gestation, range 33-41 wk) using a multiple isotope infusion start time protocol to determine Ra for each carbohydrate. The plasma mannose concentration [median (range)] was 69.83 (48.60-111.75) micromol/L and the Ra was 0.59 (0.42-0.98) micromol x kg(-1) x min(-1) (854 micromol x kg(-1) x d(-1)). The plasma inositol concentration was 175.74 (59.71-300.60) micromol/L and Ra was 1.06 (0.33-1.75) micromol x kg(-1).min(-1) (1521 micromol x kg(-1) x d(-1)). The Ra for mannose and inositol are >10-fold higher than the amounts a breast-fed infant typically ingests, which are approximately 6 micromol x kg(-1) x d(-1) mannose and 150 micromol x kg(-1) x d(-1) inositol. Thus, for both mannose and inositol, the newborn infant must produce these compounds from glucose at rates sufficient to meet nutritional requirements.

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.

Comparison of fetal and neonatal growth curves in detecting growth restriction.

OBJECTIVE: To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. METHODS: We analyzed 53 pregnancies with severe IUGR classified as group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age (appropriate for gestational age [AGA] group). Differences were analyzed with the chi(2) test and the Student t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P<.05 was considered significant. RESULTS: At delivery, using the neonatal standards, 25 of 53 (47%) IUGR showed a birth weight above the 10th percentile (IUGR(AGA)), whereas in 28, birth weight was below the 10th percentile (IUGR small for gestational age [SGA]-IUGR(SGA)). All body size measurements were significantly higher in AGA than in IUGR(AGA) and IUGR(SGA). Forty-nine of 79 (62%) AGA and 49 of 53 (92%) IUGR were admitted to the neonatal intensive care unit (P<.001). One of 79 (1%) AGA and 6 of 53 (11%) IUGR newborns died within 28 days (P<.02). Major and minor morbidity was not different. CONCLUSION: This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birth weight infants and should be used only when obstetric data are unavailable. LEVEL OF EVIDENCE: II.

Placental transport: a function of permeability and perfusion.

Studies in ovine fetus and placenta have pointed to an interaction between the fetal liver and the placenta. The supply of amino acids and carbohydrates depends on this interaction. These studies have led to clinical studies in normal and high-risk pregnancies. The objective of the present review was to compare changes in fetal circulation, in terms of both velocimetry and actual blood flow measurements, and to couple such data with data on the placental transport of amino acids. Flow studies were carried out on the umbilical vein with measurements of time-averaged velocity and venous diameter. A similar approach was used for measurements of ductus venosus flow. Stable-isotope-labeled amino acids were used to study placental transport by the non-steady state approach. The studies of flow showed a marked reduction in umbilical blood flow even when expressed per kilogram fetal body weight in fetal-growth-restricted pregnancies. This may be coupled with an increased ductus venosus shunt, the combination leading to a marked reduction in fetal hepatic blood flow. The placental transport of some amino acids is reduced in fetal-growth-restricted pregnancies. Furthermore, nonglucose carbohydrates and polyols are found in fetal blood, some in concentrations higher than maternal concentrations. There is significant uptake of several polyols and of mannose across the umbilical circulation in normal pregnancies. In conclusion, both perfusion and permeability can now be studied in both normal and high-risk pregnancies.

Concentrations of monosaccharides and their amino and alcohol derivatives in human preovulatory follicular fluid.

The study purpose was to compare sugar and polyol concentrations in preovulatory ovarian follicular fluid (FF) with those in the circulation. Samples of FF and peripheral venous blood were obtained after an overnight fast from 14 women attending an IVF program. High performance liquid chromatography measurements of seven polyols, two aminohexoses and four hexoses were the main outcome measures. Glucose concentrations in FF and plasma were 2781.26 +/- 205.64 and 4431.25 +/- 65.17 microM, respectively (P < 0.001). Mannose concentration in FF was 38.99 +/- 3.33 microM, significantly lower than plasma concentration (55.38 +/- 2.29 microM; P < 0.001). A concentration gradient from plasma to FF was also significant for glycerol (99.41 +/- 8.47 versus 74.32 +/- 6.54 microM; P < 0.002), galactose (31.69 +/- 1.58 versus 26.73 +/- 1.93 microM; P < 0.01) and galactosamine (11.49 +/- 0.69 versus 6.38 +/- 0.59 microM; P < 0.001). The plasma-to-FF concentration difference was greatest for glucose (1649.99 +/- 204.09 microM). There was a significant correlation between plasma and FF concentrations for galactose and glycerol. This study supports a substantial utilization of glucose by the oocyte/granulosa cells complex, and documents a significant concentration gradient from plasma to FF for glycerol, mannose, galactose and galactosamine. These plasma-FF differences may reflect both utilization of these carbohydrates by the cells of the preovulatory ovarian follicle and/or transport characteristics of these cells.

Competitive inhibition of amino acid transport in human preovulatory ovarian follicles.

To date we have yet to examine whether amino acid (AA) transport in human ovarian follicles is affected by competitive inhibition. In contrast, transplacental transfer of AAs in late-gestation sheep is characterized by reciprocal competition. This phenomenon has been described by algebraic equations of umbilical uptake of AAs based on maternal arterial concentrations. In the present translational study at a university teaching hospital, we verified whether these equations apply to the transport of AAs from blood to follicular fluid (FF) in human preovulatory follicles. For this purpose we used our data on AA concentrations in blood and FF measured earlier by high-performance liquid chromatography in specimens from 14 patients undergoing oocyte retrieval for in vitro fertilization after controlled ovarian stimulation. The main outcome measure was statistical significance of Spearman correlation coefficients for measured versus calculated concentrations of 8 AAs: isoleucine, leucine, valine, phenylalanine, methionine, threonine, lysine, and arginine. Equations for umbilical uptake provided a highly accurate description of blood-to-FF transport for 7 AAs with the exception of lysine: R ≥ 0.899 (p < 0.0001) for the branched-chain AAs, R = 0.829 (p = 0.0003) for threonine, R = 0.754 (p = 0.0019) for arginine, and R = 0.631 (p = 0.0156) for phenylalanine and methionine. We conclude that these equations indicate competitive inhibition between the AAs studied. Our study strongly suggests that many AA transport systems operating in the placenta should also be active in the cells of the preovulatory follicle. Future studies on AA fluxes in human ovarian follicles must consider possible competitive inhibition. ABBREVIATIONS: AA: amino acid; FF: follicular fluid; HPLC: high-performance liquid chromatography.

Polyol concentrations in the fluid compartments of the human conceptus during the first trimester of pregnancy: maintenance of redox potential in a low oxygen environment.

Polyols are sugar alcohols formed by the reduction of aldoses and ketoses. Production is favored under conditions of low oxygenation, when it may provide an alternative means to production of lactate for regulating the oxidation-reduction balance of pyridine nucleotides. Polyols also act as important organic osmolytes and as precursors of cell membrane components. We measured free sugar and polyol concentrations in matched samples of maternal serum, intervillous fluid, coelomic fluid, and amniotic fluid from normal human pregnancies at 5-12 wk gestational age. The concentrations of fructose, inositol, sorbitol, erythritol, and ribitol were significantly higher in coelomic and amniotic fluids than in maternal serum, but the reverse was the case for glucose and glycerol. Intervillous fluid concentrations of inositol, mannitol, and sorbitol were also significantly higher than those in maternal serum. These results demonstrate that the polyol pathway, considered vestigial in adult tissues, is highly active in the human conceptus during early pregnancy. The pathway may serve to maintain ATP concentrations and cellular redox potential while the embryo develops in a low oxygen environment. Polyols may also play important physiological roles in development of the human conceptus, possibly drawing water and solutes across the placenta and expanding the gestational sac.

Transplacental carbohydrate and sugar alcohol concentrations and their uptakes in ovine pregnancy.

The concentrations of glucose, fructose, sorbitol, glycerol, and myo-inositol in sheep blood and tissues have been reported previously (1--5). However, the other polyols that are at low concentrations have not been investigated in pregnant sheep due to technical difficulties. By using HPLC and gas chromatography-mass spectrometry, seven polyols (myo-inositol, glycerol, erythritol, arabitol, sorbitol, ribitol, and mannitol) and three hexoses (mannose, glucose, and fructose) were identified and quantified in four blood vessels supplying and draining the placenta (maternal artery, uterine vein, fetal artery, and umbilical vein). Uterine and umbilical blood flows were measured, and uptakes of all the polyols and hexoses in both maternal and fetal circulations were calculated. There was a significant net placental release of sorbitol to both maternal and fetal circulations. Fructose was also taken up significantly by the uterine circulation. Maternal plasma mannose concentrations were higher than fetal concentrations, and there was a net umbilical uptake of mannose, characteristics that are similar to those of glucose. Myo-inositol and erythritol had relatively high concentrations in fetal plasma (697.8 plus minus 53 microM and 463.8 plus minus 27 microM, respectively). The ratios of fetal/maternal plasma arterial concentrations were very high for most polyols. The concentrations of myo-inositol, glycerol, and sorbitol were also high in sheep placental tissue (2489 plus minus 125 microM/kg wet tissue, 2119 plus minus 193 microM/kg wet tissue, and 3910 plus minus 369 microM/kg wet tissue), an indication that these polyols could be made within the placenta.

Clinical studies linking fetal velocimetry, blood flow and placental transport in pregnancies complicated by intrauterine growth retardation (IUGR).

Our research has focused on two aspects of IUGR pregnancies: first, the changes in the fetal circulation which progress to fetal circulatory failure, and second, to reduced placental transport for amino acid and carbohydrate. There are sequential changes in fetal velocimetry for 8 different velocimetric indices. Measurements of blood flows in the fetal ductus venosus and in the umbilical vein have identified a subset of IUGR fetuses with significantly reduced umbilical blood flow, increased ductal shunt and reduced hepatic flow. Studies of placental amino acid transport in vivo have shown differences between normal and IUGR pregnancies which can be related to the velocimetry data. Clinical severity in FGR pregnancies can be related to 2 different sets of metabolic data. One is that of the glucose gradients across the placenta and another is the fetal/maternal enrichment ratios for amino acids. The implication and extension of these studies will be discussed.

Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep.

BACKGROUND: The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short (2-wk) and long (8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. RESULTS: A maternal insulin infusion resulted in lower maternal (50%, P < 0.01) and fetal (35-45%, P < 0.01) mannose concentrations, which were highly correlated (r(2) = 0.69, P < 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose (P < 0.05). Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose (P < 0.01). CONCLUSIONS: Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.

Review of studies in human pregnancy of uterine and umbilical blood flows.

Uterine and umbilical blood flow measurements are reviewed in terms of studies carried out in uncomplicated human pregnancies. The review includes the perspective of how those estimates of flow fit with current knowledge of human fetal O2 consumption and uterine O2 and glucose consumption. From the consideration of both the O2 data and the flow measurements, we conclude that the best estimates for mean umbilical blood flow at term range between 120 and 145 ml•min-1•(kg fetus)-1. The uterine flow estimate from physiologic data would equate to ~270 ml•min-1•(kg fetus)-1. This estimate, based upon estimates of uterine O2 and glucose consumption, is much higher than some estimates made by imaging techniques. The reasons for this discrepancy are not yet established. However, given the enormous variability in uterine flow measurements made with imaging techniques, it is clear that more research into improvement in these non-invasive approaches is still required and all current estimates of uterine flow must be regarded as rather crude trials.

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 tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation.

In an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of glucose and mannose were greater in the PI-IUGR fetus; glucose: C (n = 7), 2.68 +/- 0.14 mmol/L versus PI-IUGR (n = 9), 3.18 +/- 0.16 mmol/L (P < 0.02) and mannose: C, 42.9 +/- 8.1 micromol/L versus PI-IUGR, 68.5 +/- 19.1 micromol/L (P < 0.001). For PI-IUGR fetuses, fetal arterial plasma myo-inositol concentrations were significantly increased (P < 0.001). The concentrations of sorbitol, glucose and fructose were significantly reduced (P < 0.03, 0.01, 0.02, respectively). The cotyledons of IUGR placentas had a significantly increased concentration of myo-inositol (P < 0.003) and decreased concentrations of sorbitol, fructose and glycerol (P < 0.01, 0.02, 0.01, respectively). Fetal hepatic concentrations of sorbitol (P < 0.001) and fructose (P < 0.03) were also significantly reduced. These profound changes in both placental and fetal concentrations of polyols and sugars in sheep PI-IUGR pregnancies support the conclusion that within the PI-IUGR placenta there is an increased flux through the glucose 6-P:inositol 1-P cyclase system and decreased flux through the polyol dehydrogenase system, leading to increased placental myo-inositol production and decreased sorbitol production. The decreased placental supply of sorbitol to the fetal liver may lead to decreased fetal hepatic fructose production. These observations highlight that, in association with hypoxic and hypoglycemic PI-IUGR fetuses, there are major placental and fetal alterations in polyol production. The manner in which these alterations in fetoplacental carbohydrate metabolism contribute to the pathophysiology of PI-IUGR is currently unknown.

Determination of the NFAT5/TonEBP transcription factor in the human and ovine placenta.

Osmotic stress results in the accumulation of osmolytes in tissues. Synthesis of these osmolytes is mediated by the transcription factor NFAT5/TonEBP in the human kidney. We tested for the presence of NFAT5 mRNA and protein in the human and ovine placenta and confirmed sorbitol and inositol osmolyte concentrations in these tissues. To determine NFAT5 protein, human and ovine placenta were tested for inositol, sorbitol and glucose using high performance liquid chromatography (HPLC). Additionally, RNA was extracted and cDNA was made from these tissues. PCR was performed and products were sequenced. Western blotting was used to assess the expression of the NFAT5 protein. Human and ovine placenta demonstrated: 1) high concentrations of sorbitol and inositol, 2) presence of NFAT5 mRNA, 3) confirmation by NFAT5 sequence identity, and 4) presence of NFAT5 protein. NFAT5 is present in the ovine and human placenta at the RNA and protein levels that suggest a role for this protein in the induction of these osmolytes. Further trophoblast studies of osmotic stress effects on osmolytes are planned.

Neonatal morbidity and mortality in intrauterine growth restricted (IUGR) pregnancies is predicated upon prenatal diagnosis of clinical severity.

The objective of this work was to determine whether the prenatal determinates of clinical severity in intrauterine growth restricted pregnancies, established by abdominal circumference measures, correlates with neonatal morbidity and mortality. A total of 336 singleton pregnancies with intrauterine growth restriction were subdivided into group 1 (normal fetal heart rate and pulsatility index of the umbilical artery: 251 cases), group 2 (normal fetal heart rate and abnormal pulsatility index: 50 cases), and group 3 (abnormal fetal heart rate and pulsatility index: 35 cases). Gestational age, birth weight, body mass index, placental weight, and Apgar score were significantly related to the severity of intrauterine growth restriction (P < .001). Neonatal survival was 100%, 96%, and 57% in the 3 groups, respectively (P < .001). Greater than 80% of neonates of group 1 had no complications when compared to group 2 (54%) and group 3 (10%); P < .001. Gestational age was the only independent variable significantly associated with neonatal outcomes. The data confirm that the classification of clinical severity of intrauterine growth restriction based on biophysical parameters is clinically relevant to predict neonatal outcome.

Plasma concentrations of carbohydrates and sugar alcohols in term newborns after milk feeding.

Nonglucose carbohydrates such as galactose, mannose, and inositol play a clinically important role in fetal and neonatal nutrition, though little is known about their metabolism in the neonate. The aim of this study was to determine whether postprandial changes in plasma carbohydrate and sugar alcohol concentrations are affected by clinical variables such as postnatal age (PNA), milk type, feeding volume, or feeding duration in term newborns. Neonates (n = 26) taking intermittent enteral feedings were enrolled. Blood samples were obtained at baseline (immediately before the start of a feeding) and at 2-3 subsequent time points up to 110 min. Postprandial rise was only observed for plasma glucose concentrations [Glu] and plasma galactose concentrations [Gal] and clinical variables did not predict this change. Despite equimolar delivery in milk, the median of [Glu] rise minus [Gal] rise from baseline to second postprandial plasma sample was 674 microM (-38, 3333 microM; p < 0.0001), reflecting efficient hepatic first-pass metabolism of galactose. A significant PNA effect on [Gal] was observed such that for each day PNA there was an 18% decrease in [Gal] (p = 0.03). [Gal] are a function of PNA, suggesting maintenance of a significant ductus venosus shunt in term infants.