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A better understanding of the determinants of placental growth is needed. Our primary aim was to explore associations between maternal ethnic origin and cardio-metabolic factors during pregnancy, and placental weight, surface area, shape and thickness. A multi-ethnic population-based cohort study of 474 pregnant women examined at mean 15 and 28 weeks' gestation. Placentas were inspected after birth by a placental pathologist. Outcome measures were trimmed placental weight and three uncorrelated placental components; surface area, shape (oval vs round) and thickness, created through a principal components analysis. Multivariate linear regression models were used to explore the associations with maternal factors. Compared with ethnic European women, mothers with South- and East Asian ethnicity had placentas with lower weight (−51 g (95% CI: 75, −27) and −55 g (−95, −14) respectively), primarily due to a smaller surface area. The association between South Asian ethnicity and placental surface area was still significant after adjusting for maternal characteristics and cardio-metabolic factors. Fat mass index in early pregnancy was associated with higher placental weight and thickness. Placental surface area was positively associated with mid-gestational increases in fat mass, fasting glucose and triglycerides and with the 2-h glucose value at the 28 week oral glucose tolerance test, and inversely with a mid-gestational increase in HDL-cholesterol. Mid-gestational changes in fat mass, glucose, triglycerides and cholesterol were associated with, but only partly explained ethnic differences in placental surface area, while maternal fat mass in early pregnancy was associated with placental thickness. • We report placental characteristics from a multi-ethnic, population-based cohort. • Mothers with Asian ethnic origin had smaller placental surface area. • Placental thickness was associated with maternal fat mass in early pregnancy. • Placental surface area was related to mid-gestational cardio-metabolic changes. [ABSTRACT FROM AUTHOR]

Glucose from placenta is the predominant energy source for the fetus. Individual placentas exhibit a range of glucose handling from apparent net production to high consumption, presumably reflecting an ability of placenta to secure both own and fetal energy needs. A dependency of placenta on glucose as the main energy source could impede fetal supply. Placenta seems to release lactate to maternal side implying loss of energy. Whether placenta takes up ketones is unclear. Our main hypothesis was that the human placenta can release lactate to the maternal side but take up maternal ketones. An in vivo study of term uncomplicated pregnancies including 56 women delivered by cesarean section. We measured uterine and umbilical blood flow by Doppler ultrasonography, combined with blood sampling from maternal radial artery, uterine vein, umbilical artery and vein. Lactate and ketones were determined by quantitative nuclear magnetic resonance. Placenta released lactate to the maternal side (median −36.65 μmol/min. Q1, Q3: 78.53, 13.29), p < 0.001), but not to the fetal side. A net uptake of maternal ketones was found (median (Q1, Q3): 59.12 (30.64, 131.46) μmol acetate equivalents/min, p < 0.001) which largely was metabolized by the uteroplacenta. The uptake of ketones was comparable in energy to the loss of lactate. Placenta may release lactate to the maternal side. The energy lost by lactate may be compensated by uptake of maternal ketones. This lactate-ketone trade could benefit both placenta and the fetus by providing lactate for maternal gluconeogenesis and ketones for uteroplacental oxidative energy production. [Display omitted] • The placenta may release around 60 % of consumed glucose to the maternal blood as lactate. • The mass of lactate released was related to the placenta's own glucose consumption. • In energy terms a comparable mass of maternal ketones were taken up and consumed. • The limited placental use of glucose may be compensated by consumption of ketones. • This lactate-ketone trade limits placental use of glucose to the benefit of the fetus. [ABSTRACT FROM AUTHOR]

Introduction: Fetal glucose is thought to originate from maternal glucose driven across the placenta by a maternal-fetal glucose gradient. Still, there is no correlation between the mass of glucose taken up by the uteroplacenta and the fetal uptake. We propose a hypothesis that the uteroplacenta's own treatment of glucose affects the net mass of glucose taken up by the fetus, independent of the maternal-fetal gradient.Methods: We performed a human in vivo study of term uncomplicated pregnancies including seventy healthy women delivered by scheduled cesarean delivery. We measured uterine and umbilical blood flow by Doppler ultrasonography, and glucose concentrations in the maternal radial artery, uterine vein, umbilical artery and vein. We calculated Spearman's correlations between uteroplacental and fetal glucose uptake within tertiles of placental glucose consumption.Results: There were significant correlations between uteroplacental uptake and fetal uptake of glucose when determined within each tertile (Spearman's rho 0.76, (p < 0.001); 0.94 (p < 0.001) and 0.49 (p = 0.029) from lowest to highest tertile, respectively). The median (Q1, Q3) uteroplacental glucose consumption in each tertile was -88.8 (-140.3, 56.7), 29.7 (9.2, 47.4) and 174.7 (87.8, 226.1) (μmol/min). The corresponding median (Q1, Q3) fetal glucose uptake was 152.9 (94.2, 162.7), 110.8 (54.7, 167.2) and 66.6 (8.5, 122.1) (μmol/min).Discussion: The maternal fetal glucose gradients were similar in the tertiles of placental glucose consumption. Still, the net mass of glucose taken up by the fetus was markedly different between the tertiles. Placental treatment of glucose exhibited a large variation from apparent production to consumption. [ABSTRACT FROM AUTHOR]

The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta's glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose-6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown. This study aimed to test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birthweight. Overall, 67 healthy pregnant participants at term were included in this study at Oslo University Hospital, Oslo, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arteriovenous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptakes. The Spearman rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (milliunit per milligram of protein) with prepregnancy body mass index, maternal glucose and insulin, birthweight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (micromole per minute). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight. Hexokinase activity was detectable in all placental tissue samples. The mean activity was 19.6 (standard deviation, 4.64) mU/mg protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman rho=0.33; P =.006). On controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r =0.30; P =.01) and insulin (r =0.28; P =.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (Spearman rho=0.31; P =.01) and consumption (Spearman rho=0.28; P =.02). Hexokinase activity did not correlate with fetal glucose uptake. On controlling for placental weight, hexokinase activity showed a positive correlation with birthweight (r =0.31; P =.01). Our findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for disposition, is related to both maternal body mass index and birthweight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Surgical menopause may increase the risk of cardiovascular diseases (CVDs). The aim of this study was to determine the risk of metabolic syndrome in women who had undergone risk-reducing salpingo-oophorectomy (RRSO) because of increased risk of hereditary breast ovarian cancer (HBOC). A sample of 326 (65% of invited) women at risk of HBOC who had undergone RRSO was compared to 679 women from the general population. Mean follow-up after surgery was 6.5 years (standard deviations [SD] 4.4). RRSO was significantly associated with metabolic syndrome according to the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria (odds ratio [OR] 2.46 [95% confidence interval (CI) 1.63, 3.73]) and according to the International Diabetes Federation criteria (OR 2.49 [CI 1.60, 3.88]), as were increasing age and body mass index (BMI). RRSO in women at risk of HBOC is significantly associated with the metabolic syndrome, and the follow-up after RRSO should take these findings into consideration. [Copyright &y& Elsevier]

Background: The intrauterine environment and especially the fetal nutritional conditions affect lifelong health. There are few human in vivo studies on fetal nutrition. The importance to test experimentally based concepts of fetal nutrition in a human in vivo setting is becoming increasingly apparent. A way of testing nutrient transfer in human is 4-vessel sampling, which implies blood sampling from artery and vein on both sides of the placenta. Here we give a brief review of the studies using the 4-vessel sampling method.Method: We performed systematic searches in Ovid MEDLINE and EMBASE (Ovid) from 1946 to May 2016. The following search terms were used to identify eligible articles: [placenta] AND [glucose/blood glucose] OR [amino acids] OR [lipids] OR [cholesterol] OR [nutrient] AND [blood sample] OR [biological transport] OR [transport/transfer/exchange] OR [maternal-fetal exchange] AND [humans].Results: The search retrieved 623 studies. After abstract scanning 25 full text articles were evaluated and seven articles describing 4-vessel sampling were identified. The studies had from 14 to 77 participants and reported placental transfer of different nutrients (glucose, lactate, amino acids and arachidonic acid).Conclusion: Few studies have used 4 vessel sampling to study placental nutrient transfer in human pregnancies. Overall these studies indicate that the transfer of nutrients between the mother and the fetus is highly "dynamic," i.e. most nutrients may pass either way on both the maternal and fetal sides of the placenta. Furthermore, the concept that the placenta is a metabolically highly active organ affecting transfer of glucose, amino acids and lipids, fits the human in vivo data. The 4-vessel method can provide essential information on the transfer between the mother, placenta and fetus of virtually any compound. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is characterized by maternal endothelial dysfunction, which underlies a highly diverse clinical presentation. The pathophysiologic condition remains to be unraveled fully, but interplay between factors that are released from the placenta and maternal vascular vulnerability is likely. An imbalance in circulating angiogenic factors is a prominent feature of preeclampsia; placental growth factor and soluble Fms-like tyrosine kinase 1 have been implemented as biomarkers of placental function and preeclampsia. Their test accuracies are limited in a clinical setting, which urges better insight into their production and removal. Current data suggest that placental growth factor and soluble Fms-like tyrosine kinase 1 are released from the placenta. Both the circulating levels and the placental expression are altered in preeclamptic pregnancies. However, in vivo placental release has not been determined in human pregnancies. Moreover, there is evidence that extra-placental tissues might contribute to the circulating levels placental growth factor and soluble Fms-like tyrosine kinase 1 in normal and preeclamptic pregnancies.Objectives: We aimed to study the in vivo placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 by determining the uteroplacental arteriovenous differences in human pregnancies. Further, we investigated whether this release was altered in early-onset preeclampsia compared with control subjects and whether there was a release of placental growth factor and soluble Fms-like tyrosine kinase 1 from maternal systemic endothelium.Study Design: We conducted a case-control study at Oslo University Hospital and included 23 women with preeclampsia (diagnosis <34 weeks) and 20 control subjects. During cesarean delivery, we sampled blood from 3 vessels simultaneously (uterine vein, radial artery, and antecubital vein). We determined concentrations of placental growth factor and soluble Fms-like tyrosine kinase 1 and calculated the arteriovenous differences. A possible net placental and extra-placental release was evaluated with the use of a Wilcoxon signed rank test. Differences between groups were compared by a Mann-Whitney U-test.Results: The median gestational age at delivery was 33.4 weeks (Q1, 28.3; Q3, 34.4 weeks) in the preeclamptic group and 39.3 weeks (Q1, 39.0; Q3, 39.6 weeks) in the control subjects. Women with preeclampsia had lower plasma concentrations of placental growth factor and higher concentrations of soluble Fms-like tyrosine kinase 1 compared with control subjects (P<.001). There were significant uteroplacental arteriovenous differences of soluble Fms-like tyrosine kinase 1 in preeclampsia (P<.001), but not in the control subjects. The uteroplacental arteriovenous differences of placental growth factor were significant in both groups (P<.001). Despite lower concentrations of plasma placental growth factor in women with preeclampsia, the arteriovenous differences were not significantly different from normal pregnancies (P=.53), even when we corrected for placental weight (P=.79). We found no placental growth factor or soluble Fms-like tyrosine kinase 1 concentration differences between the radial artery and the antecubital vein.Conclusion: Our findings are consistent with a net release of soluble Fms-like tyrosine kinase 1 from the placenta in early-onset preeclampsia. This study demonstrated a placental release of placental growth factor to the maternal circulation but could not demonstrate that this release was impaired in the preeclamptic group. We could not find evidence of systemic endothelial release of placental growth factor and soluble Fms-like tyrosine kinase 1 by analyzing the arteriovenous differences in the forearm. This study contributes to the pathophysiologic understanding of preeclampsia by the use of the clinical setting to test current concepts in vivo and underscores that studies of in vivo degradation rates of placentally released compounds are needed. [ABSTRACT FROM AUTHOR]