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 any mammalian species at birth (1). It has been known for many years that abnormally high maternal 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 hypothesis was later modified by Freinkel and Metzger, who added a potential role of other nutrients to fetal overgrowth 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 it became apparent that exposure to maternal diabetes could exert long-term effects on the offspring, increasing the risk of type 2 diabetes and obesity (4,5).

Gestational diabetes—diabetes with first onset or recognition during pregnancy (6)—has long been a controversial clinical area. Methods of screening for gestational diabetes, the specific tests used, and even the biochemical definition of diabetes during pregnancy have varied between and indeed within countries. Such controversies usually flourish in the …