Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia

The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995-2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT). Measured weight in offspring (n = 9,439) was ascertained 5-7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963-1994 standard) and then classified by maternal positive GCT (1 h >or= 7.8 mmol/l) and OGTT results (1 or >or=2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). There was a positive trend for increasing childhood obesity at age 5-7 years (P < 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (<or=4,000 g). These results in a multiethnic U.S. population suggest that increasing hyperglycemia in pregnancy is associated with an increased risk of childhood obesity. More research is needed to determine whether treatment of GDM may be a modifiable risk factor for childhood obesity.