IntroductionThe significant maternal and neonatal outcomes of gestational diabetes mellitus (GDM) make it a major public health concern. Mothers with GDM are at greater risk of pregnancy complications and their offspring are at higher risk of diabetes and obesity. Currently, GDM is diagnosed with glucose load methods which are time-consuming and inconvenient to administer more than once during pregnancy; for this reason, there is a recognised need for a more accurate and simpler test for GDM. Previous studies indicate that plasma-glycated CD59 (pGCD59) is a novel biomarker for GDM. We present here the protocol of a prospective cohort study designed to (1) determine the accuracy of pGCD59 as an early, first trimester predictor of GDM and gestational impaired glucose tolerance and (2) assess the associations between pGCD59 levels and adverse maternal and neonatal outcomes.Methods and analysisWe will obtain discarded plasma samples from pregnant women at two time points: first prenatal visit (usually <14 weeks gestation) and gestational weeks 24–28. A study-specific medical record abstraction tool will be used to obtain relevant maternal and neonatal clinical data from the EPIC clinical database. The prevalence of GDM will be determined using standard of care glucose load test results. We will determine the sensitivity and specificity of pGCD59 to predict the diagnosis of GDM and gestational impaired glucose tolerance, as well as the associations between levels of pGCD59 and the prevalence of maternal and neonatal outcomes.Ethics and disseminationThis study has been approved by the Mass General Brigham Institutional Review Board (protocol 2011P002254). The results of this study will be presented at international meetings and disseminated in peer-reviewed journals.

OBJECTIVE The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycaemia (NH). MATERIALS and METHODS This is an observational study of pregnant women with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59, were measured in fasting maternal samples taken at the time of a 75 g, 2-hour oral glucose tolerance test (OGTT) performed in early pregnancy (&lt;20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 h of delivery. RESULTS We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy, were positively associated with the prevalence of NH (ANOVA one-way, p-value &lt;0.001). The odds of NH were higher in infants from mothers in the Tertile 3 of pGCD59 levels as compared to those from mothers in Tertile 1 (OR: 2.41, 95% CI: 1.03–5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28 (95% CI: 0.96–5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI: 0.54–0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI: 0.56–0.78). CONCLUSION Although pGCD59 levels in early pregnancy in women with BMI ≥29 kg/m2 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH.