The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.

OBJECTIVE: The objective of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is to clarify unanswered questions on associations of maternal glycemia, less severe than overt diabetes mellitus, with risks of adverse pregnancy outcome. This report describes the background and design of the HAPO Study.
METHODS: HAPO is a 5-year investigator-initiated prospective observational study that will recruit approximately 25000 pregnant women in 10 countries. HAPO utilizes a Central Laboratory for measurement of key metabolic variables, a Clinical Coordinating Center, a Data Coordinating Center, and an independent Data Monitoring Committee. Glucose tolerance is assessed by a 75 g 2-h OGTT at 24-32 weeks' gestation. Results are unblinded to the woman and her caregivers if: fasting plasma glucose >5.8 mmol/l, 2-h plasma glucose >11.1 mmol/l or any plasma glucose <2.5 mmol/l. Random plasma glucose measurement is performed at 34-37 weeks or if symptoms suggest hyperglycemia; results are unblinded for values > or = 8.9 mmol/l. Sociodemographic and health history data are collected via questionnaire and medical record abstraction. Maternal blood is obtained for measurement of serum C-peptide and hemoglobin A1c (HbA(1C)), cord blood for serum C-peptide and plasma glucose, and a capillary specimen is taken between 1 and 2 h following delivery for neonatal plasma glucose. Neonatal anthropometrics are obtained, and follow-up data are collected at 4-6 weeks post-delivery. The primary outcomes to be assessed in relation to maternal glycemia are cesarean delivery, increased fetal size (macrosomia/LGA/obesity), neonatal morbidity (hypoglycemia), and fetal hyperinsulinism.