Physiologically Based Ferritin Thresholds to Redefine Early Pregnancy Iron Screening: A Cross-Sectional Study

Background Iron deficiency in early pregnancy is common yet frequently missed because current screening strategies rely on ferritin cutoffs designed to detect iron deficiency anemia. We aimed to establish physiologically based ferritin functional reference limits (FRLs) in healthy, non-anemic pregnant women to improve early identification of iron deficiency. Methods The study was conducted at a maternity hospital in Ho Chi Minh City, Vietnam, enrolling first-trimester pregnant women. Participants were included if they had hemoglobin ≥ 11 g/dL, no evidence of infection, body-mass index < 30 kg/m², no microcytosis or hypochromia. The primary outcome was the ferritin FRLs, defined using restricted cubic spline modelling of blood indices. Diagnostic performance was assessed against TSAT. Findings 452 patients had complete data for validation. The final suggested ferritin FRL is 59 ng/mL, identified more women with non-anemic iron deficiency compared with traditional cutoffs. Validation against TSAT showed excellent rule-out performance with negative predictive value of 95.8%. A four-zone classification for iron deficiency emerged, including absolute deficiency (< 15 ng/mL), deficiency (15–26 ng/mL), indeterminate status (26–59 ng/mL), and physiologic sufficiency (≥ 59 ng/mL). Interpretation Physiologically derived ferritin thresholds identify early iron deficiency more effectively than conventional cutoffs and provide a grounded framework for screening in first trimester.