Utility of metabolic profiling of serum in the diagnosis of pregnancy complications.

Introduction: Currently there are no clinical screening tests available to identify pregnancies at risk of developing preeclampsia (PET) and/or intrauterine growth restriction (IUGR), both of which are associated with abnormal placentation. Metabolic profiling is now a stable analytical platform used in many laboratories and has successfully been used to identify biomarkers associated with various pathological states.

Methods: We used nuclear magnetic resonance spectroscopy (NMR) to metabolically profile serum samples collected from 143 pregnant women at 26-41 weeks gestation with pregnancy outcomes of PET, IUGR, PET IUGR or small for gestational age (SGA) that were age-matched to normal pre/term pregnancies.

Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined.

High maternal serum ferritin in early pregnancy and risk of spontaneous preterm birth.

Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and the risk of spontaneous preterm birth (sPTB). The aim of the present study was to examine the association between Fe biomarkers, including serum ferritin concentrations, and the risk of total ( 75th percentile ( ≥ 43 μg/l) (OR 1.49, 95% CI 1.

Maternal body weight and first trimester screening for chromosomal anomalies.

Prenatal risk ratios for Down syndrome adjust for maternal weight because maternal serum biomarker levels decrease with increasing maternal weight. This is accomplished by converting serum biomarker values into a multiple of the expected median (MoM) for women of the same gestational age. Weight is frequently not recorded, and the impact of using MoMs not adjusted for weight for calculating risk ratios is unknown.

Evaluation of first trimester serum soluble endothelial cell-specific tyrosine kinase receptor in normal and affected pregnancies.

Aims: To assess soluble endothelial cell-specific tyrosine kinase receptor (sTie-2) levels in the first trimester of pregnancy and its association with adverse pregnancy outcomes; and examine the predictive accuracy.

Study Design: In this nested case-control study, serum sTie-2 levels were measured in 2616 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum sTie-2 with subsequent adverse pregnancy outcomes.

Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population.

Background: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy have been associated with adverse pregnancy outcomes in a few studies but not in other studies.

Objectives: We assessed the serum 25(OH)D concentration at 10-14 wk of pregnancy and its association with adverse pregnancy outcomes and examined the predictive accuracy.

Design: In this nested case-control study, we measured serum 25(OH)D in 5109 women with singleton pregnancies who were attending first-trimester screening in New South Wales, Australia.

Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes.

Objective: To assess angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes, and their predictive accuracy.

Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks, and stillbirth).

First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy.

Objective: To assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.

Study Design: In this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.

Main Outcome Measures: Prediction of pregnancy hypertension and pre-eclampsia.

Association and predictive accuracy of high TSH serum levels in first trimester and adverse pregnancy outcomes.

Context: High serum levels of TSH have been associated with adverse pregnancy outcomes by some studies, and not by others.

Objective: The aim of the study was to assess the association between high levels of TSH in the first trimester of pregnancy and adverse pregnancy outcomes; and to examine the predictive accuracy as a screening test.

Setting And Participants: Serum levels of TSH were measured in a cohort of 2801 women with a singleton pregnancy attending first trimester Down syndrome screening.

Record linkage to obtain birth outcomes for the evaluation of screening biomarkers in pregnancy: a feasibility study.

Background: Linking population health data to pathology data is a new approach for the evaluation of predictive tests that is potentially more efficient, feasible and efficacious than current methods. Studies evaluating the use of first trimester maternal serum levels as predictors of complications in pregnancy have mostly relied on resource intensive methods such as prospective data collection or retrospective chart review. The aim of this pilot study is to demonstrate that record-linkage between a pathology database and routinely collected population health data sets provides follow-up on patient outcomes that is as effective as more traditional and resource-intensive methods.

PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth.

Follicular thyroid carcinomas are associated with a chromosomal translocation that fuses the thyroid-specific transcription factor paired box gene 8 (PAX8) with the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). This study investigated the transcriptional mechanisms by which PAX8-PPARgamma regulates follicular thyroid cells. In HeLa cells, rat follicular thyroid (FRTL-5) cells, or immortalized human thyroid cells, PAX8-PPARgamma stimulated transcription from PAX8-responsive thyroperoxidase and sodium-iodide symporter promoters in a manner at least comparable with wild-type PAX8.

Bioactivity of PTH/PTHrP analogs lacking the 1-14 N-terminal domain.

The N-terminal regions of 1-34 parathyroid hormone (PTH) and 1-34 parathyroid hormone related protein (PTHrP) are thought to be required for full agonist activity of these molecules and for signal transduction by cyclic AMP (cAMP). The C-terminal regions are thought to be involved in receptor binding and protein kinase C activation. In this study, two analogs of PTH/PTHrP lacking the segment 1-14 exhibited agonist activity in opossum kidney (OK) 3B2 cells.