A first trimester prediction model for gestational diabetes utilizing aneuploidy and pre-eclampsia screening markers

Objective: We examined whether first trimester aneuploidy and pre-eclampsia screening markers predict gestational diabetes mellitus (GDM) in a large multi-ethnic cohort and the influence of local population characteristics on markers. Methods: Clinical and first trimester markers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), pregnancy associated plasma protein A (PAPP-A), free-β human chorionic gonadotropin (free-hCGβ)) were measured in a case-control study of 980 women (248 with GDM, 732 controls) at 11 to 13 + 6 weeks’ gestation. Clinical parameters, MAP-, UtA PI-, PAPP-A-, and free-hCGβ-multiples-of-the-median (MoM) were compared between GDM and controls; stratified by ethnicity, parity, and GDM diagnosis <24 versus ≥24 weeks’ gestation. GDM model screening performance was evaluated using AUROC. Results: PAPP-A- and UtA PI-MoM were significantly lower in GDM versus controls (median ((IQR) PAPP-A-MoM 0.81 (0.58–1.20) versus 1.00 (0.70–1.46); UtA PI-MoM 1.01 (0.82–1.21) versus 1.05 (0.84–1.29); p <.05). Previous GDM, family history of diabetes, south/east Asian ethnicity, parity, BMI, MAP, UtA PI, and PAPP-A were significant predictors in multivariate analysis (p <.05). The AUC for a model based on clinical parameters was 0.88 (95%CI 0.85–0.92), increasing to 0.90 (95%CI 0.87–0.92) with first trimester markers combined. The combined model best predicted GDM <24 weeks’ gestation (AUC 0.96 (95%CI 0.94–0.98)). Conclusions: Addition of aneuploidy and pre-eclampsia markers is cost-effective and enhances early GDM detection, accurately identifying early GDM, a high-risk cohort requiring early detection, and intervention. Ethnicity and parity modified marker association with GDM, suggesting differences in pathophysiology and vascular risk.