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We examined the influence of a moderately elevated serum ferritin level at entry to care on the risk of gestational diabetes mellitus (GDM) and a possible mechanism (increased iron stores versus inflammation).In a prospective observational study with 1,456 healthy pregnant women in Camden, New Jersey, serum ferritin and anthropometric measurements were determined. Serum C-reactive protein (CRP) concentration was measured in a nested case-control study of 172 subjects.Women who developed GDM had a higher concentration of serum ferritin than women who did not develop GDM (P < 0.001). Elevated serum ferritin level (highest quintile) was significantly and positively correlated with prepregnant BMI and skinfold measurements. Women in the highest quintile of serum ferritin had a twofold increased risk of developing GDM adjusted for several known risk factors (adjusted odds ratio, 2.02 [95% CI 1.04–3.92], P < 0.05). Similar results were obtained with a nested case-control study, in which women in the highest tertile of serum ferritin (2.35 [1.06–5.22], P < 0.05) or CRP (2.67 [1.16–6.17], P < 0.001) had a greater than twofold increased risk of GDM. However, these effects were modified and became nonstatistically significant after additional adjustment for prepregnant BMI.Elevated serum ferritin concentrations early in gestation are associated with an increased risk of GDM. The association, at least in part, is mediated by the maternal fat mass and obesity. These data suggest a possible link between elevated serum ferritin and low-grade inflammation.