The HAPO Study, a multinational research project, investigated the relationship between maternal glucose levels and neonatal adiposity. The study involved 23,316 pregnant women who underwent a 75-g oral glucose tolerance test between 24 and 32 weeks of gestation. Neonatal anthropometric data, including skin fold measurements and percent body fat, were collected. Cord serum C-peptide levels were also measured to assess fetal insulin production. The study aimed to test the Pedersen hypothesis, which suggests that maternal hyperglycemia leads to fetal hyperinsulinemia, resulting in neonatal adiposity. Results showed strong, statistically significant associations between increasing maternal glucose levels and neonatal adiposity, even after adjusting for potential confounders. Odds ratios for neonatal adiposity increased with higher levels of maternal fasting, 1-hour, and 2-hour plasma glucose. Similarly, higher cord serum C-peptide levels were associated with increased neonatal adiposity. These findings support the link between maternal glycemia and neonatal adiposity, suggesting that fetal insulin production mediates this relationship. The study also found that maternal glucose levels were continuously associated with increased birth weight, cesarean delivery, and neonatal hypoglycemia. However, the associations with cesarean delivery and neonatal hypoglycemia were weaker. The study confirmed that maternal hyperglycemia, even in the absence of overt diabetes, can lead to fetal hyperinsulinemia and neonatal adiposity. The findings suggest that the Pedersen hypothesis describes a fundamental biological relationship influencing fetal growth. The study's results highlight the importance of managing maternal glucose levels during pregnancy to prevent adverse outcomes in neonates. The findings also emphasize the need for further research to understand the long-term effects of maternal hyperglycemia on fetal growth and obesity risk. The study's multicenter design and consistent results across multiple measures of growth and adiposity make the findings robust. The study's limitations include the absence of cord C-peptide data for 15% of neonates and incomplete skin fold measurements for some participants. Despite these limitations, the study provides strong evidence supporting the link between maternal glycemia and neonatal adiposity.The HAPO Study, a multinational research project, investigated the relationship between maternal glucose levels and neonatal adiposity. The study involved 23,316 pregnant women who underwent a 75-g oral glucose tolerance test between 24 and 32 weeks of gestation. Neonatal anthropometric data, including skin fold measurements and percent body fat, were collected. Cord serum C-peptide levels were also measured to assess fetal insulin production. The study aimed to test the Pedersen hypothesis, which suggests that maternal hyperglycemia leads to fetal hyperinsulinemia, resulting in neonatal adiposity. Results showed strong, statistically significant associations between increasing maternal glucose levels and neonatal adiposity, even after adjusting for potential confounders. Odds ratios for neonatal adiposity increased with higher levels of maternal fasting, 1-hour, and 2-hour plasma glucose. Similarly, higher cord serum C-peptide levels were associated with increased neonatal adiposity. These findings support the link between maternal glycemia and neonatal adiposity, suggesting that fetal insulin production mediates this relationship. The study also found that maternal glucose levels were continuously associated with increased birth weight, cesarean delivery, and neonatal hypoglycemia. However, the associations with cesarean delivery and neonatal hypoglycemia were weaker. The study confirmed that maternal hyperglycemia, even in the absence of overt diabetes, can lead to fetal hyperinsulinemia and neonatal adiposity. The findings suggest that the Pedersen hypothesis describes a fundamental biological relationship influencing fetal growth. The study's results highlight the importance of managing maternal glucose levels during pregnancy to prevent adverse outcomes in neonates. The findings also emphasize the need for further research to understand the long-term effects of maternal hyperglycemia on fetal growth and obesity risk. The study's multicenter design and consistent results across multiple measures of growth and adiposity make the findings robust. The study's limitations include the absence of cord C-peptide data for 15% of neonates and incomplete skin fold measurements for some participants. Despite these limitations, the study provides strong evidence supporting the link between maternal glycemia and neonatal adiposity.