Maternal Hepcidin Is Associated with Placental Transfer of Iron Derived from Dietary Heme and Nonheme Sources4

Abstract

The determinants of placental transport of dietary iron remain largely uncharacterized. The objective of this research was to elucidate determinants of fetal Fe transfer from maternally ingested dietary heme and non-heme Fe. The study was undertaken in 19 pregnant females (16-32 y) who ingested intrinsically labeled (58)Fe-heme and a nonheme Fe source ((57)FeSO(4)) during the third trimester of pregnancy. At delivery, maternal and cord blood was obtained to assess neonatal (57)Fe and (58)Fe enrichment as a function of maternal/neonatal Fe status [serum ferritin (SF), transferrin receptor, hemoglobin (Hb), total body Fe, and hepcidin]. There was a greater percentage of maternally absorbed (58)Fe tracer present in the neonates compared to the (57)Fe tracer (5.4 ± 2.4 vs. 4.0 ± 1.6; P < 0.0001). Net dietary nonheme Fe (mg) and heme Fe (mg) transferred to the fetus were both inversely correlated with measures of maternal serum hepcidin (P = 0.002, r(2) = 0.43; P = 0.004, r(2) = 0.39) and SF (P = 0.0008, r(2) = 0.49; P = 0.003, r(2) = 0.41) and directly associated with neonatal Hb (P = 0.004, r(2) = 0.39; P = 0.008, r(2) = 0.35). The results of this study suggest that during pregnancy there appears to be preferential fetal use of maternally ingested Fe derived from a dietary, animal-based heme source compared to Fe ingested as ferrous sulfate. Maternal serum hepcidin and maternal/neonatal Fe status may play a role in placental uptake of dietary heme and nonheme Fe.

A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort

“…In response to high body iron stores, increased hepatic secretion of hepcidin inhibits iron absorption from three main sources: dietary absorption in the gut, recycled iron from macrophages and stored iron released from hepatocytes [16]. In pregnancy, hepcidin may also play a critical role in the active transport of iron to the fetus [17]. To our knowledge, only one prior study has examined serum hepcidin levels in relation to GDM [18].…”

Prevalence of anemia and associations between neonatal iron status, hepcidin, and maternal iron status among neonates born to pregnant adolescents

“…Hepcidin is the master regulator of iron homeostasis, and the production of this hormone is known to be regulated by iron stores, inflammation, hypoxia, and erythropoietic activity (9). Despite its crucial role in regulation of iron homeostasis, currently, little is known about fetal hepcidin production and its regulatory function, and few normative hepcidin data are available in maternal-neonatal pairs at birth (10)(11)(12).…”

The placenta: the forgotten essential organ of iron transport

“…102 Thus, available evidence suggests that TFR1-mediated iron uptake may be the primary target of hepcidin action in the placenta, although it cannot be ruled out that hepcidin also affects iron efflux by regulating subcellular localization of FPN1. 102 Interestingly, recent human studies failed to find significant relationships between cord hepcidin levels and either placental TFR1 expression 103 or placental transfer of maternal dietary iron, 104 suggesting differences between humans and rodents in hepcidin regulation of placental iron transfer. More research is needed to clarify the role of hepcidin in regulating iron homeostasis during the prenatal period and to identify other fetal factors regulating placental iron transport, such as those related to growth and development.…”

“…Stable isotope data in human pregnancies has shown that more iron in the maternal diet is transferred to the fetus when the maternal stores are low. 104,105 This is likely accomplished by upregulation of intestinal and placental iron transporters. Elevated placental TFR1 expression has been consistently observed in human and animal models of gestational iron deficiency 97,103,106,107 and is perhaps the best-known compensatory change in maternal deficiency.…”