Normal OGTT does not imply uniform risk: association of area under the curve percentiles with adverse perinatal outcomes

OBJECTIVES: Although the 75 g oral glucose tolerance test (OGTT) is the standard diagnostic tool for gestational diabetes mellitus (GDM), women with normal OGTT results may still show differences in glucose metabolism. The area under the glucose curve (AUC) reflects the overall glycemic response during the OGTT and may help identify differences in perinatal risk not captured by conventional thresholds. We aimed to evaluate perinatal outcomes across OGTT-AUC quartiles in pregnancies with normal glucose tolerance. METHODS: In this retrospective cohort study, 11,607 pregnant women with normal 75 g OGTT results at 24-28 weeks of gestation were stratified into quartiles (Q1-Q4) according to OGTT AUC. Maternal characteristics and obstetric and neonatal outcomes were compared across AUC quartiles using appropriate statistical tests and post-hoc analyses. Multivariable logistic regression analyses were performed to identify independent associations between OGTT-AUC quartiles and selected adverse perinatal outcomes. RESULTS: Among 11,607 normoglycemic pregnancies, increasing OGTT-AUC quartiles were associated with higher cesarean delivery rates, birth weight, LGA, macrosomia, polyhydramnios, preterm birth and NICU admission, whereas SGA rates decreased (all p≤0.001). In multivariable analyses adjusted for maternal age, parity, BMI, fetal sex, smoking, and mode of conception, higher AUC was independently associated with increased odds of LGA, macrosomia, polyhydramnios, preterm birth, and NICU admission, while SGA odds decreased. No independent association was observed with preeclampsia. CONCLUSIONS: Among women with normal glucose tolerance, higher OGTT-AUC was independently associated with a distinct pattern of adverse perinatal outcomes, characterized by increased risks of LGA, macrosomia, polyhydramnios, preterm birth, and NICU admission, alongside a lower risk of SGA. These findings support a continuum of maternal glycemic exposure below the diagnostic threshold for GDM and suggest that OGTT-AUC may provide additional prognostic information beyond conventional OGTT-based classification.