Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study

While diabetes during pregnancy is associated with a significant risk of adverse perinatal outcomes, there is no consensus on the risks of adverse outcomes resulting from abnormal glucose levels below the established threshold for gestational diabetes. In response to this controversy, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study was established to clarify unanswered questions concerning the association of glucose with risks of adverse pregnancy outcomes. The prospective, observational HAPO Study enrolled 23,316 pregnant women who had no prior diagnosis of diabetes during or antedating pregnancy. Participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT) between 24 and 32 weeks’ gestation. Neonatal anthropometrics were obtained following delivery, and follow-up data, including hospital readmissions, were collected at 4-6 weeks post-delivery. The primary outcome measures assessed in relation to maternal glycemia included primary cesarean delivery, increased birthweight (defined as > 90th percentile for gestational age), neonatal hypoglycemia, and fetal hyperinsulinism. The study found that increased maternal glycemia was associated with both birthweight and cord serum C-peptide > 90th percentile. Greater maternal glucose levels were also associated with increased risk of primary cesarean delivery and clinical neonatal hypoglycemia. Subsequent to the conclusion of the HAPO Study, a follow-up study (HAPO-FUS) was initiated to determine whether elevated blood sugar during pregnancy, below the threshold for gestational diabetes, influences either development of type 2 diabetes mellitus in mothers or adiposity and disorders of glucose metabolism in offspring at 8-12 years of age. The HAPO Follow-Up Study enrolled 4800 mother-child pairs who originally participated in the HAPO Study. Mothers and children were required to undergo a single study visit for measurement of height, weight, blood pressure, body fat, insulin, and blood sugar and lipid levels. The primary outcome measures assessed in relation to maternal glycemia during pregnancy included development of diabetes in mothers, and obesity and altered glucose metabolism in children, as well as other metabolic abnormalities in both mothers and offspring.