Hepcidin as the Central Regulator in Pregnancy-Associated Iron Deficiency Anemia and Vitamin D Deficiency

Iron deficiency anemia (IDA) and vitamin D deficiency are among the most prevalent micronutrient deficiencies worldwide, particularly affecting pregnant women. The physiological demands for both iron and vitamin D increase significantly during pregnancy to support maternal health, fetal development, and placental function. Failure to meet these demands leads to adverse outcomes, including preterm birth, low birth weight, preeclampsia, and maternal infections. Hepcidin, a liver-derived peptide hormone, is central to systemic iron regulation. It modulates dietary iron absorption and mobilization from body stores through its interaction with ferroportin. In healthy pregnancy, hepcidin levels are physiologically suppressed to enhance iron bioavailability. However, inflammation or vitamin D deficiency may elevate hepcidin levels, exacerbating IDA and complicating its management. Vitamin D, primarily recognized for its role in calcium metabolism, is also a key regulator of hepcidin expression. Through receptor-mediated pathways, vitamin D suppresses hepcidin synthesis, improving iron absorption and mobilization. The coexistence of IDA and vitamin D deficiency during pregnancy creates a complex clinical scenario, compounded by overlapping risk factors like poor diet, limited sun exposure, and chronic inflammation. Emerging evidence highlights hepcidin as a dynamic biomarker capable of differentiating IDA from anemia of inflammation. This review explores the intricate relationship between vitamin D deficiency and IDA, with a focus on hepcidin as both a regulator and biomarker. We discuss physiological and pathological mechanisms, diagnostic applications of hepcidin, and therapeutic opportunities, including the synergistic role of vitamin D and iron supplementation. By addressing the dual burden of vitamin D deficiency and IDA, this review provides a comprehensive framework for improving maternal and neonatal outcomes through targeted interventions and biomarker-guided therapies. Future research should focus on refining diagnostic tools and exploring innovative therapies to optimize anemia management in pregnancy.