Impact of oral iron dosing regimens on iron biomarkers during pregnancy: insights from the PANDA trial.

Iron deficiency during pregnancy remains a global health burden, yet pregnancy-related physiological adaptations complicate the interpretation of iron biomarkers. Modified oral iron regimens are increasingly used to balance iron intake, absorption, and tolerability. This study evaluated the effects of daily, alternate-day, and 3-times-weekly oral iron supplementation on iron status biomarkers in nonanaemic pregnant participants. In the PANDA (Primary prevention of maternal Anemia to avoid preterm Delivery and other Adverse outcomes) dose-finding trial, nonanemic pregnant women were randomized to receive 200 mg of ferrous sulfate daily, on alternate days, or 3-times-weekly. Blood samples were collected at 9 to 13 and 26 to 30 weeks' gestation (N = 135 participants). Hepcidin and soluble transferrin receptor (sTfR) were measured by enzyme-linked immunosorbent assay, and serum iron, ferritin, transferrin, and C-reactive protein using automated biochemistry. Linear mixed-effects models assessed within- and between-group biomarker changes. Hepcidin, ferritin, and transferrin saturation declined significantly between baseline and follow-up in all groups (P< .001). sTfR increased in the alternate-day (P = .003) and 3-times-weekly groups (P< .001), but not in the daily group (P = .084). Despite supplementation and maintenance of hemoglobin levels, 69% to 72% of women were iron deficient (ferritin <30 μg/L) at 26 to 30 weeks' gestation. Iron status declined across pregnancy regardless of supplementation regimen, suggesting physiological adaptations may dominate over dosing effects. The absence of a significant rise in sTfR in the daily group suggests that daily dosing best meets the iron demand of pregnancy, though confirmation in larger, adequately powered studies is required. This trial was registered at the UK trial registry as #ISRCTN12911644.