Hyperglycemia and adverse pregnancy outcomes.
Level 3 - non-randomized controlled study
Prospective multicenter cohort study
PubMed 18463375 · doi:10.1056/NEJMoa0707943
What was done
In an international multicenter study across 15 centers in 9 countries, 25,505 pregnant women underwent a 75-g oral glucose-tolerance test at 24 to 32 weeks of gestation. Caregivers and participants were blinded to glucose results if fasting plasma glucose was 105 mg/dL (5.8 mmol/L) or less and 2-hour plasma glucose was 200 mg/dL (11.1 mmol/L) or less. In 23,316 participants with blinded data, researchers evaluated associations between maternal glucose levels and primary outcomes (birth weight >90th percentile, primary cesarean delivery, neonatal hypoglycemia, and cord-blood C-peptide >90th percentile) as well as secondary outcomes (delivery <37 weeks, shoulder dystocia or birth injury, neonatal intensive care, hyperbilirubinemia, and preeclampsia).
What was found
Adjusted odds ratios per 1 SD increase in fasting (6.9 mg/dL), 1-hour (30.9 mg/dL), and 2-hour (23.5 mg/dL) plasma glucose were: - Birth weight >90th percentile: 1.38 (95% CI, 1.32 to 1.44), 1.46 (95% CI, 1.39 to 1.53), and 1.38 (95% CI, 1.32 to 1.44). - Cord-blood C-peptide >90th percentile: 1.55 (95% CI, 1.47 to 1.64), 1.46 (95% CI, 1.38 to 1.54), and 1.37 (95% CI, 1.30 to 1.44). - Primary cesarean delivery: 1.11 (95% CI, 1.06 to 1.15), 1.10 (95% CI, 1.06 to 1.15), and 1.08 (95% CI, 1.03 to 1.12). - Neonatal hypoglycemia: 1.08 (95% CI, 0.98 to 1.19), 1.13 (95% CI, 1.03 to 1.26), and 1.10 (95% CI, 1.00 to 1.12). Risks increased continuously across the range of glucose levels without obvious thresholds. Significant, though weaker, associations were also observed for secondary outcomes.
Why it matters
This study demonstrated that risks of adverse perinatal outcomes increase continuously with maternal glycemia well below thresholds for overt diabetes. These findings provided the foundational evidence used internationally to establish diagnostic criteria for gestational diabetes.
Limits
As an observational cohort study, this work establishes association rather than demonstrating that treating mild hyperglycemia prevents adverse outcomes. Women with fasting glucose above 105 mg/dL or 2-hour glucose above 200 mg/dL were unblinded and excluded from the main analysis. Longer-term maternal and offspring metabolic outcomes were not captured in the primary study period.
Cited by
- supports Studies across tens of thousands of mothers show higher maternal glucose levels during pregnancy are associated with greater neonatal fat mass.