Pregnancy and iron: Bridging metabolic demands and supplementation needs

Maternal iron requirements increase during pregnancy. Placental transfer is unidirectional via transferrin receptor 1 and ferroportin, and most fetal iron accumulation occurs in the third trimester. Iron deficiency during pregnancy is associated with maternal fatigue, reduced work capacity, and increased risk of anemia, as well as adverse outcomes such as preterm birth, low birthweight, and impaired neonatal iron stores, which may affect early neurodevelopment. Oral iron supplementation reduces anemia and improves iron status. In women at risk of deficiency, lower prophylactic doses are commonly used. Intravenous iron is effective and generally safe from the second trimester in women who do not respond to or tolerate oral therapy. However, iron status shows a U-shaped association with outcomes: elevated maternal iron has been associated with preterm birth, low birthweight, and possible neurodevelopmental effects. Excess iron may induce oxidative stress and placental iron loading. Hepcidin suppression in the second and third trimesters enhances iron absorption. Important gaps remain regarding hepcidin regulation, placental transport mechanisms, safe upper supplementation limits, and optimal dosing strategies. While supplementation clearly benefits iron-deficient women, current evidence supports screening-based rather than universal supplementation in iron-replete populations. Herein, we discuss the need for iron during pregnancy, the impact of dysmetabolism, and the molecular actors at the cellular and systemic levels to build a translational bridge between clinical unmet needs and fundamental knowledge.