Association of Three Selenium Biomarkers in Early and Late Pregnancy with Gestational Diabetes Mellitus and Large for Gestational Age Offspring: Odense Child Cohort

Background: To investigate the association of three established biomarkers of Se status with gestational diabetes mellitus (GDM), gestational glucose metabolism and large for gestational age offspring (LGA).Methods: This study included 1346 pregnant women with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity in early and late pregnancy and fasting insulin and glucose in late pregnancy were measured. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated and GDM definition was according to WHO13. A sub-cohort underwent Oral Glucose Tolerance Test (OGTT). Regression models adjusted for various confounders quantified dose-dependent associations.Findings: Se and SELENOP declined from first to third trimester. There was a dose-dependent inverse association of early GPx3 with late pregnancy GDM, HOMA-IR, fasting glucose, insulin, and glucose during OGTT. Odds ratio (OR) of GDM for one log-scale-increment in GPx3 activity was 0·33(95%CI=0·16-0·65). Third trimester SELENOP and GPx3 were inversely associated with GDM and HOMA-IR. OR of GDM for one log-scale-increment in SELENOP and GPx3 were 0·22(95%CI=0·12-0·38) and 0·50(95%CI=0·34-0·74). Decline in Se biomarkers from first to third trimester was associated with higher HOMA-IR and GDM. Low GPx3 activity was associated with higher risk of large for gestational age offspring, which was partly (~20%) mediated by fasting glucose levels (p=0·006).Interpretation: Low serum selenoprotein expression in pregnancy is independently associated with the risk of GDM and LGA. Se status screening in pregnancy may identify those at high risk for GDM.Funding Information: The research has been funded by the Deutsche Forschungsgemeinschaft (DFG), Research Unit FOR-2558 “TraceAge” (Scho 849/6–2), CRC/TR 296 “Local control of TH action” (LocoTact, P17).Declaration of Interests: LS holds shares of selenOmed GmbH, a company involved in Se status assessment; no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: OCC is being carried out according to the Declaration of Helsinki, and was approved by the Regional Scientific Ethical Committees for Southern Denmark (no. S-20090130), and the Danish Data Protection Agency (j.no. 2008-58-0035).