Abstract:
Diabetes during pregnancy, mainly due to gestational diabetes mellitus (GDM), is common and associated with a higher risk of impaired neurodevelopment in the offspring in later life. Currently, there are no interventions to reduce the risk of neurodevelopmental impairment in children born to mothers with diabetes. The studies in this thesis aimed to determine if there were antenatal interventions that could reduce the incidence of GDM, if maternal glycaemic control during pregnancy and labour was associated with later neurodevelopment and if prophylactic dextrose gel one hour after birth to prevent neonatal hypoglycaemia improved neurodevelopment in early childhood. In a prospective cohort study of infants born to mothers with diabetes, glycaemic control in pregnancy was not associated with the children’s neurodevelopment at four and half years of age. This suggests that preventing the development of GDM may be a better alternative than interventions during pregnancy to improve neurodevelopmental outcomes. However, as part of our Cochrane overview investigating effective strategies for the prevention of GDM, we found no interventions that were of clear benefit in reducing the incidence of GDM. In particular, there were no trials of interventions before or between pregnancies to reduce the risk of GDM. The prospective follow-up of children from two randomised controlled trials of prophylactic oral dextrose gel to prevent neonatal hypoglycaemia, one of different doses of dextrose gel and one in children of diabetic mothers, showed that these interventions did not result in improved neurodevelopmental outcomes at age two years but, reassuringly, did not cause adverse effects. Neonatal hypoglycaemia in infants of diabetic mothers was associated with neurosensory impairment at age two years. These studies suggest that in children born to mothers with GDM the risk of neurosensory impairment is higher in the context of neonatal hypoglycaemia but is not associated with maternal glycaemic control in pregnancy or labour. Prophylactic oral dextrose gel, which previously has been shown to reduce neonatal hypoglycaemia, did not reduce the incidence of neurosensory impairment. Interventions to prevent GDM pre-conception should be tested in randomised controlled trials to reduce the number of children born at risk of impaired neurodevelopment.