Prediction of late-onset preeclampsia using plasma proteomics: a longitudinal multi-cohort study.

Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling.

Protein biomarker signatures of preeclampsia - a longitudinal 5000-multiplex proteomics study.

We aimed to explore novel biomarker candidates and biomarker signatures of late-onset preeclampsia (LOPE) by profiling samples collected in a longitudinal discovery cohort with a high-throughput proteomics platform. Using the Somalogic 5000-plex platform, we analyzed proteins in plasma samples collected at three visits (gestational weeks (GW) 12-19, 20-26 and 28-34 in 35 women with LOPE (birth ≥ 34 GW) and 70 healthy pregnant women). To identify biomarker signatures, we combined Elastic Net with Stability Selection for stable variable selection and validated their predictive performance in a validation cohort.

Validity of self-reported hysterectomy and oophorectomy in a population-based cohort: The HUNT study.

Objective: To validate self-reported hysterectomy and bilateral oophorectomy.

Design: Validation study.

Setting: Large population-based cohort study in Norway: The Trøndelag Health Study (HUNT).

The effect of intravenous hyoscine butylbromide on slow progress in labor (BUSCLAB): A double-blind randomized placebo-controlled trial.

Background: Prolonged labor is a common condition associated with maternal and perinatal complications. The standard treatment with oxytocin for augmentation of labor increases the risk of adverse outcomes. Hyoscine butylbromide is a spasmolytic drug with few side effects shown to shorten labor when used in a general population of laboring women.

Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia.

Background: Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear.

Placental weight, surface area, shape and thickness - Relations with maternal ethnicity and cardio-metabolic factors during pregnancy.

Introduction: 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.

Methods: A multi-ethnic population-based cohort study of 474 pregnant women examined at mean 15 and 28 weeks' gestation.

Placental energy metabolism: Evidence for a placental-maternal lactate-ketone trade in the human.

Introduction: 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.

Maternal metabolic profiling across body mass index groups: An exploratory longitudinal study.

Introduction: Increased BMI has been identified as a risk factor for most pregnancy complications, but the underlying metabolic factors mediating the detrimental effects of BMI are largely unknown. We aimed to compare metabolic profiles in overweight/obese women (body mass index [BMI] ≥ 25 kg/m ) and normal weight/underweight women (BMI < 25 kg/m ) across gestation. We also explored how gestational weight gain (GWG) affected maternal metabolic profiles.

Maternal body mass index, birthweight, and placental glucose metabolism: evidence for a role of placental hexokinase.

Background: 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.

All-cause and cardiovascular mortality after hysterectomy and oophorectomy in a large cohort (HUNT2).

Introduction: Hysterectomy and bilateral oophorectomy are common major surgical procedures that have been associated with increased mortality risk. We aimed to assess the association of hysterectomy and/or bilateral oophorectomy with all-cause and cardiovascular mortality in a Norwegian population.

Material And Methods: Cohort study with data from The Trøndelag Health Study (HUNT2) linked to the Norwegian Cause of Death Registry, with follow-up from 1996 until 2014 or death.

Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study.

Introduction: Preeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures.

Uteroplacental versus fetal use of glucose in healthy pregnancies at term. A human in vivo study.

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.

Effect of a standardized maternal meal on fetal middle cerebral artery Doppler indices: A single-blinded crossover study.

Objective: Measures of Doppler blood flow velocity profiles are an integral part of monitoring fetal well-being during pregnancy. These examinations are performed at different times of the day and at different maternal meal states. In uncomplicated pregnancies, we assessed the effect of a standardized maternal meal on middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow velocity pulsatility indices (PIs) and MCA peak systolic velocity (PSV).

Placenta-derived proteins across gestation in healthy pregnancies-a novel approach to assess placental function?

Background: Placenta-derived proteins in the systemic maternal circulation are suggested as potential biomarkers for placental function. However, the identity and longitudinal patterns of such proteins are largely unknown due to the inaccessibility of the human placenta and limitations in assay technologies. We aimed to identify proteins derived from and taken up by the placenta in the maternal circulation.

Lipid and lipoprotein concentrations during pregnancy and associations with ethnicity.

Background: To describe ethnic differences in concentrations of lipids and lipoproteins, and their changes, during pregnancy to postpartum.

Methods: This was a population-based cohort study conducted in primary antenatal care in Norway. The participants (n = 806) were healthy, pregnant women, 59% were ethnic minorities.

Characterization of the Primary Human Trophoblast Cell Secretome Using Stable Isotope Labeling With Amino Acids in Cell Culture.

The placental villus syncytiotrophoblast, the nutrient-transporting and hormone-producing epithelium of the human placenta, is a critical regulator of fetal development and maternal physiology. However, the identities of the proteins synthesized and secreted by primary human trophoblast (PHT) cells remain unknown. Stable Isotope Labeling with Amino Acids in Cell Culture followed by mass spectrometry analysis of the conditioned media was used to identify secreted proteins and obtain information about their relative rates of synthesis in syncytialized multinucleated PHT cells isolated from normal term placental villus tissue ( = 4/independent placenta).

Insulin Increases Adipose Adiponectin in Pregnancy by Inhibiting Ubiquitination and Degradation: Impact of Obesity.

Context: Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood.

Objective: We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress.

Blood pressure and cardiac output during caesarean delivery under spinal anaesthesia: a prospective cohort study.

Objectives: We have previously established a method to measure transfer of nutrients between mother, placenta and fetus in vivo. The method includes measurements of maternal and fetal blood flow by Doppler ultrasound prior to spinal anaesthesia. Spinal anaesthesia affects maternal blood pressure and cardiac output.

Novel associations between parental and newborn cord blood metabolic profiles in the Norwegian Mother, Father and Child Cohort Study.

Background: More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring's cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied.

Mediators Linking Maternal Weight to Birthweight and Neonatal Fat Mass in Healthy Pregnancies.

Context: Lifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators.

Objective: We hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels (Ifv) and venous-arterial glucose difference (ΔGfva). Hypothesized confounders were maternal age, gestational age, and parity.

Risk of cardiovascular disease after preventive salpingo-oophorectomy.

Introduction: Breast cancer susceptibility gene (BRCA) mutation carriers are recommended to undergo early oophorectomy to prevent ovarian cancer. Premature loss of ovarian hormones may increase the risk of cardiovascular disease. Because women with preventive oophorectomy are mainly young and healthy, they rarely undergo specialized cardiological surveillance.