Abstract
BACKGROUND: Gestational diabetes mellitus (GDM) poses significant risks, particularly for nulliparous women of advanced maternal age (AMA ≥35 years), a growing demographic due to delayed childbirth. However, effective early-pregnancy prediction tools tailored for this high-risk subgroup are lacking. This study aimed to identify readily available early biomarkers for GDM risk stratification in AMA nulliparous women. METHODS: This retrospective cohort study analyzed 354 AMA nulliparous women (140 GDM, 214 non-GDM). GDM was diagnosed by a 75g oral glucose tolerance test at 24-28 weeks using IADPSG criteria (fasting ≥5.1 mmol/L, 1-h ≥10.0 mmol/L, 2-h ≥8.5 mmol/L). Clinical and laboratory data at 10-13 gestational weeks were compared. Multivariate logistic regression identified independent risk factors. RESULTS: The GDM group had significantly higher body mass index (BMI), fasting blood glucose (FBG), white blood cell (WBC) count, neutrophil count (NEU), and urinary glucose (U-GLU) positivity (P< 0.05). Assisted reproductive technology (ART) use did not differ significantly in univariate analysis (P = 0.083). Multivariable analysis identified U-GLU positivity (adjusted odds ratio [aOR] = 7.91; 95% CI: 2.67-23.46), elevated FBG (aOR = 2.23 per mmol/L; 95% CI: 1.13-4.38), elevated NEU (aOR = 1.21 per 10(9)/L; 95% CI: 1.05-1.40), elevated WBC (aOR = 1.15 per 10(9)/L; 95% CI: 1.01-1.30), and ART use (aOR = 1.63; 95% CI: 1.02-2.59) as independent risk factors for GDM. The multivariable model achieved an AUC of 0.70 (95% CI 0.65 - 0.76), with sensitivity of 57.1% and specificity of 76.2% at the optimal cutoff. CONCLUSIONS: In this single-center retrospective cohort of AMA nulliparous women, early-pregnancy urinary glucose positivity, elevated fasting blood glucose, neutrophilia, leukocytosis, and the use of assisted reproductive technology were independently associated with an increased risk of GDM, with urinary glucose showing the strongest association. These findings suggest that a tiered screening strategy incorporating these readily available biomarkers might be explored for early risk stratification between 10-13 weeks' gestation. Their clinical utility requires prospective validation in larger, multicenter cohorts.