Iron Therapy Reduces Oxidative Stress in Pregnant Women with Anemia: A Prospective Study

Background Iron deficiency anemia (IDA) affects approximately 40% of pregnant women worldwide, regarding increased oxidative stress (OS) and adverse pregnancy outcomes. Recent advances identified hepcidin as the master regulator of iron homeostasis and erythroferrone (ERFE) as a key erythroid regulator, yet their responses to iron supplementation and relationships with OS markers during pregnancy remain poorly understood. Objective To investigate whether oral iron supplementation reduces OS-related molecular damage in pregnant women with IDA and characterize relationships between iron regulatory molecules (hepcidin, ERFE) and OS biomarkers. Methods This prospective observational study enrolled 40 pregnant women with IDA (mean age 29.23 ± 6.33 years) across all trimesters. Participants received 200 mg elemental iron daily for one month. Pre- and post-treatment measurements included hematologic parameters, iron metabolism markers (ferritin, hepcidin, ERFE), and OS biomarkers (total antioxidant status [TAS], total oxidant status [TOS]). Results Iron supplementation produced very large improvements in TAS (0.96 ± 0.36 to 1.64 ± 0.37 mmol/L; Cohen's d = 1.87, p < 0.001), exceeding hematological improvements in hemoglobin (10.10 ± 0.72 to 11.61 ± 0.97 g/dL; d = 1.76, p < 0.001) and hematocrit (30.93 ± 1.79% to 35.24 ± 3.01%; d = 1.74, p < 0.001). The TOS/TAS ratio decreased substantially (14.53 ± 15.98 to 4.10 ± 3.14; d=-0.91, p < 0.001). Hepcidin increased appropriately (2214.62 ± 1444.27 to 3492.65 ± 1640.51 pg/mL; d = 0.83, p < 0.001) while ERFE decreased (470.75 ± 170.75 to 345.25 ± 112.96 pg/mL; d=-0.87, p < 0.001), confirming successful iron repletion. TAS improvements showed minimal correlation with iron parameters (all |r|<0.25), suggesting independent mechanisms. Conclusions Iron supplementation effectively reduces OS in pregnant women with IDA through mechanisms independent of iron parameter changes. The coordinated hormonal responses confirm appropriate iron repletion while suggesting additional therapeutic benefits beyond anemia correction.