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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 absence of high-quality evidence, and in this case, the uncertainties have reflected a lack of large, suitably designed, observational, and randomized control trials. There have been particular problems with the interpretation of previous observational trials as the diagnosis of gestational diabetes itself likely alters medical and particularly obstetric practice, rendering outcomes such as rates of caesarean section difficult to assess (J). Happily, the evidence base has improved hugely in recent years. In 2005, Crowther et al. (8) provided clear evidence that diagnosis of glucose abnormality in pregnancy and management designed to lower blood glucose resulted in modification of birth weight and indeed improvement in perinatal outcomes. More recently, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) investigators have completed an extensive data collection examining the relationship of maternal glucose, measured by a 75-g oral glucose tolerance test, to neonatal...