Many HAPO Returns Maternal Glycemia and Neonatal Adiposity: New Insights from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study

Humans have the greatest fat content of anymammalian species at birth (1). It has beenknown for many years that abnormally highmaternal glucose (as is the case when the mother has type 1 or type 2 diabetes during pregnancy) is characteristically associated with increased fat deposition in utero. In pioneering work in the 1950s, Pedersen (2) suggested that in the offspring of mothers with diabetes, excess fetal insulin production was key in promoting fetal overgrowth. Specifically, maternal hyperglycemia led to excess exposure of the fetus to maternal glucose, fetal hyperinsulinemia, and excess growth. The Pedersen hy-pothesis was later modified by Freinkel and Metzger, who added a potential role of other nutrients to fetal over-growth in diabetic pregnancy (3); however, the central role of fetal hyperinsulinism and control of maternal glucose remained. The potential clinical importance of maternal glycemia and fetal overgrowth has increased, since i