AbstractObjectivesThis work aimed to assess the diagnostic validity of two approaches for the screening of gestational diabetes mellitus (GDM) with less discomfort for pregnant women.MethodsA prospective diagnostic validation study was conducted with 2007 pregnant women. According to risk factors for GDM, women were classified into high-risk and low-risk groups. The current diagnostic procedure, based on oral glucose overload, was followed; simultaneously HbA1cwas tested and an algorithm combining both biomarkers was applied.ResultsIn the low-risk group, the Glucose challenge test (GCT) showed a higher area under the curve (AUC 0.953; 95% CI 0.915–0.992) than the HbA1ctest (0.688; 95% CI 0.541–0.834). The best GCT cut-off, 153.5 mg/dL (8.52 mmol/L), showed higher diagnostic validity than that for HbA1c, 28 mmol/mol (4.75%), and that the algorithm using both tests. In the high-risk group, the GCT showed better diagnostic performance than the HbA1cand the algorithm; the optimal GCT cut-offs were higher than those recommended in current protocols. 13th week: GCT AUC 0.882 (95% CI 0.843–0.921), HbA1cAUC 0.624 (95% CI 0.562–0.686), GCT cut-off 140.5 mg/dL (7.8 mmol/L), HbA1ccut-off 33 mmol/mol (5.15%). 24th week: GCT AUC 0.944 (95% CI 0.925–0.962), HbA1cAUC 0.642 (95% CI 0.575–0.709), GCT cut-off, 145.5 mg/dL (8.08 mmol/L), HbA1ccut-off 29 mmol/mol (4.85%).ConclusionsThe GDM diagnostic approach using as the first step the GCT with higher cut-offs showed the best diagnostic validity. Applying these thresholds, 55.6 and 13.7% of 100 g. Oral glucose overloads would have been avoided in low-risk and high-risk pregnant women.