Metabolomic identification of novel diagnostic biomarkers in ectopic pregnancy.

INTRODUCTION: Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture. OBJECTIVES: To identify putative plasma biomarkers for the detection of tubal EP and elucidate altered biochemical pathways in EP compared to intrauterine pregnancies. METHODS: This case-control study included prospective recruitment of 39 tubal EP cases and 89 early intrauterine pregnancy controls. Plasma samples were biochemically profiled using proton nuclear magnetic resonance spectroscopy (1H NMR). To avoid over-fitting, datasets were randomly divided into a discovery group (26 cases vs 60 controls) and a test group (13 cases and 29 controls). Logistic regression models were developed in the discovery group and validated in the independent test group. Area under the receiver operating characteristics curve (AUC), 95% confidence interval (CI), sensitivity, and specificity values were calculated. RESULTS: In total 13 of 43 (30.3%) metabolite concentrations were significantly altered in EP plasma (p < 0.05). Metabolomic profiling yielded significant separation between EP and controls (p < 0.05). Independent validation of a two-metabolite model consisting of lactate and acetate, achieved an AUC (95% CI) = 0.935 (0.843-1.000) with a sensitivity of 92.3% and specificity of 96.6%. The second metabolite model (D-glucose, pyruvate, acetoacetate) performed well with an AUC (95% CI) = 0.822 (0.657-0.988) and a sensitivity of 84.6% and specificity of 86.2%. CONCLUSION: We report novel metabolomic biomarkers with a high accuracy for the detection of EP. Accurate biomarkers could potentially result in improved early diagnosis of tubal EP cases.

Inflammation and glycemic tolerance status in pregnancy: the role of maternal adiposity.

BACKGROUND/AIMS: Although the association between inflammation and insulin resistance is well known, the data related to the role of inflammation in gestational diabetes mellitus (GDM) are conflicting. The aim of this study was to investigate the association of several inflammatory mediators with the glycemic status in pregnancy. METHODS: Leukocyte count, ferritin, C-reactive protein (CRP), fibrinogen and interleukin-6 levels were measured in 70 patients with normal glucose tolerance, in 57 patients with impaired glucose tolerance and in 35 patients with GDM as determined based on 50-gram oral glucose tolerance test (OGTT) and 100-gram OGTT results. RESULTS: A significant difference among the groups was seen only with regard to CRP and fibrinogen levels; however, no significant differences were observed after adjustment for body mass index (BMI). CRP was found to be strongly associated with current BMI in all three groups. CONCLUSION: Maternal serum levels of inflammatory mediators are not related to GDM at the time of the glucose challenge test in the late second or early third trimester. The significant difference in the levels of CRP in different strata of glycemic tolerance was not observed after adjustment for BMI. Adiposity may have a central role in GDM, causing an inflammatory response.