Serum maternal hepcidin levels 3 days after delivery are higher compared to those measured at parturition

Gyarmati, Béla; Szabó, Eszter; Szalay, Balázs; Czuczy, Noémi; Toldi, Gergely; Aron, C; Vásárhelyi, Barna; Takáts, Zoltán

doi:10.1111/j.1447-0756.2011.01586.x

Cited by 14 publications

(23 citation statements)

References 13 publications

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“…However, the uniform direction of the results obtained, as confirmed in a subanalysis of women whose blood samples were available during all time points, provide confidence in results obtained. In addition, our findings on gestational serum hepcidin levels were in agreement with previously assessed hepcidin concentration in first, second and third trimester [ 12 ] as were the increased hepcidin levels directly postpartum [ 11 ]. Another limitation is that we were not informed about the use of over-thecounter iron supplements.…”

Section: Discussionsupporting

confidence: 89%

The iron regulatory hormone hepcidin is decreased in pregnancy: a prospective longitudinal study

Santen¹,

Kroot

Zijderveld

et al. 2013

Clinical Chemistry and Laboratory Medicine

103

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Section: Discussionsupporting

confidence: 89%

The iron regulatory hormone hepcidin is decreased in pregnancy: a prospective longitudinal study

Santen¹,

Kroot

Zijderveld

et al. 2013

Clinical Chemistry and Laboratory Medicine

103

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“…This review reveals a significant paucity of studies assessing hepcidin during pregnancy. Ten human [47,48,49,50,51,52,53,54,55,56] and six animal studies [57,58,59,60,61,62] met the inclusion criteria with findings reported in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Six of the ten human studies utilized a cross-sectional study design [47,48,49,50,51,52] and four were longitudinal [53,55,56,68]. Sample size for the human studies ranged from 19 [52] to 191 subjects [48].…”

Section: Resultsmentioning

confidence: 99%

Hepcidin and Iron Homeostasis during Pregnancy

Koenig

Tussing‐Humphreys

Day³

et al. 2014

Nutrients

149

147

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Hepcidin is the master regulator of systemic iron bioavailability in humans. This review examines primary research articles that assessed hepcidin during pregnancy and postpartum and report its relationship to maternal and infant iron status and birth outcomes; areas for future research are also discussed. A systematic search of the databases Medline and Cumulative Index to Nursing and Allied Health returned 16 primary research articles including 10 human and six animal studies. Collectively, the results indicate that hepcidin is lower during pregnancy than in a non-pregnant state, presumably to ensure greater iron bioavailability to the mother and fetus. Pregnant women with undetectable serum hepcidin transferred a greater quantity of maternally ingested iron to their fetus compared to women with detectable hepcidin, indicating that maternal hepcidin in part determines the iron bioavailability to the fetus. However, inflammatory states, including preeclampsia, malaria infection, and obesity were associated with higher hepcidin during pregnancy compared to healthy controls, suggesting that maternal and fetal iron bioavailability could be compromised in such conditions. Future studies should examine the relative contribution of maternal versus fetal hepcidin to the control of placental iron transfer as well as optimizing maternal and fetal iron bioavailability in pregnancies complicated by inflammation.

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“…Consistent with prior studies (23,46), high iron demand during lactation has no profound effect on the expression of iron transporters in the mammary gland or liver hepcidin. Indeed, serum hepcidin levels return to normal levels immediately after delivery (15), where intestinal HIF-2α signaling uncouples a repressive effect of hepcidin on intestinal iron absorption. The present work shows that intestinal HIF-2α is not only a critical regulator, but also an essential sensor of maternal iron demand during lactation and essential to maintain adequate levels of iron in breast milk by enhancing the expression of intestinal iron absorption genes.…”

Section: Discussionmentioning

confidence: 99%

“…This is a highly conserved process observed in humans and animal models (12)(13)(14). However, hepcidin levels are restored after parturition or early lactation period during which the maternal iron requirement is still at its peak (15,16). This suggests alternative mechanisms exist during late pregnancy and lactation that allow efficient intestinal iron absorption independent of hepcidin levels.…”

mentioning

confidence: 99%

Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice

Ramakrishnan

Anderson

Martin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The mechanisms that are essential for the maintenance of nutrient status in breast milk are unclear. Our data demonstrate that the intestine via hypoxia-inducible factor (HIF)-2α is an essential regulatory mechanism for maintaining the quality of breast milk. During lactation, intestinal HIF-2α is highly increased, leading to an adaptive induction of apical and basolateral iron transport genes. Disruption of intestinal HIF-2α (but not HIF-1α) or the downstream target gene divalent metal transporter (DMT)-1 in lactating mothers did not alter systemic iron homeostasis in the mothers, but led to anemia, decreased growth, and truncal alopecia in pups which was restored following weaning. Moreover, pups born from mothers with a disruption of intestinal HIF-2α led to long-term cognitive defects. Cross-fostering experiments and micronutrient profiling of breast milk demonstrated that the defects observed were due to decreased maternal iron delivery via milk. Increasing intestinal iron absorption by activation of HIF-2α or parenteral administration of iron-dextran in HIF-2α knockout mothers ameliorated anemia and restored neonatal development and adult cognitive functions. The present work details the importance of breast milk iron in neonatal development and uncovers an unexpected molecular mechanism for the regulation of nutritional status of breast milk through intestinal HIF-2α.iron homeostasis | anemia | HIF-2α | pregnancy | lactation I ron is the most abundant trace element involved in numerous biological processes such as oxygen delivery, mitochondrial respiration, and metabolism. Under normal circumstances, dietary iron provides 1-3% of the systemic iron requirement, due to an efficient recycling of iron from senesced red blood cells (1). During conditions of high iron demand, iron homeostasis relies on intestinal iron absorption (2, 3). A major systemic regulator of intestinal iron absorption is the liver-derived peptide hormone hepcidin. Hepcidin expression is regulated by systemic iron levels and in turn can regulate the only known iron exporter ferroportin (FPN) (4). This adaptive mechanism is essential for systemic iron homeostasis as evidenced in patients with iron-related disorders exhibiting decreased hepcidin expression or function (5). Moreover, mouse models with disruption of hepcidin expression, intestine specific disruption of FPN, or mice with a specific mutation of FPN with decreased hepcidin binding results in robust iron-related disorders, detailing the importance of the hepcidin-FPN axis in iron homeostasis (6-8).During pregnancy, the systemic iron requirement increase by 10-fold to support placental and fetal growth (9). Fetal and neonatal iron deficiency results in decreased growth, immunological dysfunction, anemia, and irreversible cognitive defects (10). Iron supplementation is highly recommended to prevent iron deficiency anemia during pregnancy (11). The increase in iron demand during pregnancy is met by an adaptive decrease in maternal hepcidin levels leading to enhanced iron absorption...

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Serum maternal hepcidin levels 3 days after delivery are higher compared to those measured at parturition

Abstract: Factors triggering hepcidin synthesis dominate 3 days after delivery. Studies are needed to assess the contribution of hepcidin to iron homeostasis during the periparturition period.

Cited by 14 publications

References 13 publications

The iron regulatory hormone hepcidin is decreased in pregnancy: a prospective longitudinal study

The iron regulatory hormone hepcidin is decreased in pregnancy: a prospective longitudinal study

Hepcidin and Iron Homeostasis during Pregnancy

Maternal intestinal HIF-2α is necessary for sensing iron demands of lactation in mice

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