The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study aimed to investigate the associations between maternal glucose levels and neonatal adiposity, as well as the role of fetal hyperinsulinemia in these relationships. The study included 23,316 participants, with data on glucose levels and cord serum C-peptide available for 19,885 babies. Neonatal anthropometrics, including skin fold thickness and percent body fat, were measured. The results showed strong, statistically significant gradients between increasing maternal glucose levels and neonatal adiposity, which persisted after adjusting for potential confounders. The odds ratios for neonatal adiposity measures (sum of skin folds >90th percentile or percent body fat >90th percentile) ranged from 1.35 to 1.44 for each 1 SD increase in fasting, 1-hour, and 2-hour plasma glucose levels. These findings support the Pedersen hypothesis, suggesting that maternal hyperglycemia leads to fetal hyperinsulinemia and neonatal adiposity. The study also found that cord serum C-peptide levels were positively associated with neonatal adiposity measures. The results highlight the importance of maternal glycemia in influencing fetal growth and adiposity, providing insights into the development of obesity and metabolic disorders in later life.The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study aimed to investigate the associations between maternal glucose levels and neonatal adiposity, as well as the role of fetal hyperinsulinemia in these relationships. The study included 23,316 participants, with data on glucose levels and cord serum C-peptide available for 19,885 babies. Neonatal anthropometrics, including skin fold thickness and percent body fat, were measured. The results showed strong, statistically significant gradients between increasing maternal glucose levels and neonatal adiposity, which persisted after adjusting for potential confounders. The odds ratios for neonatal adiposity measures (sum of skin folds >90th percentile or percent body fat >90th percentile) ranged from 1.35 to 1.44 for each 1 SD increase in fasting, 1-hour, and 2-hour plasma glucose levels. These findings support the Pedersen hypothesis, suggesting that maternal hyperglycemia leads to fetal hyperinsulinemia and neonatal adiposity. The study also found that cord serum C-peptide levels were positively associated with neonatal adiposity measures. The results highlight the importance of maternal glycemia in influencing fetal growth and adiposity, providing insights into the development of obesity and metabolic disorders in later life.