Before the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study was carried out, it was controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is independently associated with increased risks of adverse pregnancy outcome. The HAPO Study found continuous associations of maternal glucose levels less than those diagnostic of diabetes with 4 primary outcomes (birth weight >90th percentile, primary Cesarean delivery, cord-blood serum C-peptide >90th percentile, clinically identified neonatal hypoglycemia). Associations with several secondary endpoints that included neonatal adiposity, preterm delivery, shoulder dystocia or birth injury and preeclampsia were also found. There were no obvious thresholds at which risks increased. These and other study results lead the International Association of Diabetes and Pregnancy Study Groups (IADPSG) to propose “outcome-based” criteria for the diagnosis of gestational diabetes mellitus (GDM). Questions about the application of these criteria in routine clinical care will be discussed elsewhere in this conference.
This presentation will focus on the HAPO Follow Up Study (HAPO FUS) that included examinations of mother-child pairs 10-14 years after participation in the original HAPO Study. The primary goal of the child component of HAPO FUS was to examine associations of maternal glycemia and GDM with childhood adiposity in a cohort treatment where treatment of maternal hyperglycemia was not a confounding factor. A second goal was to examine associations of maternal glycemia and GDM with childhood disorders of glucose metabolism (impaired glucose tolerance [IGT], & T2DM). HAPO FUS found highly significant associations of GDM with multiple measures of child adiposity at 10-14 years of age, i.e., BMI thresholds for obesity, % body fat, sum of skinfolds and waist circumference. However, the association of GDM with the BMI threshold for overweight/obesity combined was of borderline significance, confirming the common observation that not all children with a high BMI are obese. HAPO FUS also found highly significant associations of GDM with IGT/T2DM, but not with impaired fasting glucose. Offspring of HAPO FUS mothers retrospectively classified as GDM by IADPSG criteria were also more insulin resistant with a lower Disposition Index that those whose mothers did not have GDM.
In conclusion, the HAPO & HAPO FUS studies indicate that GDM by IAPDPSG criteria is associated with adverse perinatal and long-term outcomes that can contribute to the cycle of increasing obesity and metabolic disorders globally.