Overt diabetes mellitus during pregnancy carries a significantly increased risk of adverse perinatal outcomes, but whether this is also true of less severe maternal hyperglycemia, or “gestational diabetes,” remains uncertain. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was planned to clarify the risk, if any, associated with less marked maternal glucose intolerance than is associated with overt diabetes. A standard oral glucose tolerance test using a 75-g dose of glucose was carried out at 24–32 weeks’ gestation (target date: 28 weeks) in 25,505 pregnant women aged 18 and over at 15 centers in nine countries. Patient information remained blinded for 23,316 women whose fasting plasma glucose level did not exceed 105 mg/dL (5.8 mmol/L), and whose 2-hour plasma glucose was 200 mg/dL (11.1 mmol/L) or less.
For women with blinded data, adjusted odds ratios (ORs) were calculated for adverse pregnancy outcomes associated with a 1-SD (standard deviation) increase in fasting plasma glucose (6.9 mg/dL or 0.4 mmol/L); a 1-SD increase in the 1-hour plasma glucose (30.9 mg/dL or 1.7 mmol/L); and a 1-SD increase in the 2-hour plasma glucose (23.5 mg/dL or 1.3 mmol/L). The respective ORs for birth weight above the 90th percentile were 1.38 (95% confidence interval, 1.32–1.44), 1.46 (1.39–1.53), and 1.38 (1.32–1.44). For a cord-blood serum C-peptide level above the 90th percentile the figures were 1.55 (1.47–1.64), 1.46 (1.38–1.54), and 1.37 (1.30–1.44). The ORs for primary cesarean delivery were 1.11 (1.06–1.15), 1.10 (1.06–1.15), and 1.08 (1.03–1.12); and for neonatal hypoglycemia, 1.08 (0.98–1.19), 1.13 (1.03–1.26), and 1.10 (1.00–1.12). No obvious thresholds were found at which risk levels increased. Nonadjusted analyses disclosed no increase in the risk of perinatal death with increasing glucose levels. Significant associations, although weaker, were found for secondary outcomes including premature delivery, shoulder dystocia or birth injury, the need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.
Finding significant associations between increased but not diabetic maternal blood glucose levels and several adverse pregnancy outcomes suggests the need to reconsider currently used criteria for diagnosing and treating hyperglycemia in pregnant women.
