The Use of Early Pregnancy HbA1c in Predicting Excessive Fetal Growth in Women at Risk of Glucose Intolerance

The association of hyperglycaemia in pregnancy (gestational diabetes mellitus; GDM) with adverse maternal and fetal outcomes is clearly recognised. Traditionally the diagnosis is made at 28 weeks gestation at which stage children of affected women already have a two-fold rate of excessive weight gain (abdominal circumference > 90th percentile). This is attributed to fetal exposure to undiagnosed high blood glucose earlier in pregnancy. Indeed almost 25% of women with GDM develop the condition before 20 weeks gestation. Interventional studies in women diagnosed in the late second trimester have shown benefits in reducing fetal macrosomia. It is unknown whether screening in the first trimester would predict fetal macrosomia and allow more timely and effective intervention. To examine this question, we propose a prospective cohort study of 1,662 women at increased risk of GDM to determine if an elevated HbA1c (39-48mmool/l) in early pregnancy (<14 weeks) can identify babies at risk of excessive weight gain in later pregnancy, as determined by ultrasound measurement of abdominal circumference at 28 weeks gestation. The study will be largely integrated into routine clinical practice enabling a large number of women to participate. Study participants will all undergo formal screening (75g oral glucose tolerance test) for GDM at 28 weeks gestation. Secondary outcomes, namely the ability of early pregnancy HbA1c to predict later maternal GDM, and fetal and maternal complications of pregnancy will also be evaluated. The results of this study, if positive, are likely to impact upon patient care almost immediately following study completion. In addition, given the stability of the Northern Ireland population, the relatively unique data set will facilitate future work on predictive markers for cardiovascular disease, and prospective studies on the cardiovascular consequences of GDM on both mother and baby.