Placental Iron Content Is Lower than Previously Estimated and Is Associated with Maternal Iron Status in Women at Greater Risk of Gestational Iron Deficiency and Anemia

Abstract

Background Based on limited data, it is estimated that the placenta retains 90 mg of iron (Fe). Little is known about determinants of placental Fe content. Animal data indicate that the placenta prioritizes Fe for its own needs, but this hypothesis has not been evaluated in humans. Objectives To characterize placental Fe content and placental Fe concentration (p[Fe]) in pregnant women at risk of Fe insufficiency and identify determinants of p[Fe]. Methods Placentae were collected from 132 neonates born to teens carrying singletons (≤18 y) and 101 neonates born to 48 women carrying multiples (20–46 y). Maternal and neonatal Fe status indicators (hemoglobin, SF, sTfR, serum Fe, TBI) and hormones (erythropoietin, hepcidin) were measured. P[Fe] was measured using ICP-MS. Correlation analyses and mixed-effects models were constructed to identify determinants of p[Fe]. Results Mean placental Fe content was 23 mg per placenta [95%CI 15–33] in the multiples and 40 mg [95%CI 31–51] in the teens (P = 0.03). Mean p[Fe] did not differ between the cohorts. P[Fe] was higher in anemic (175 [95%CI 120–254] μg/g) compared to non-anemic (46 [95%CI 26–82] μg/g) women carrying multiples (P = 0.009), but did not differ between anemic (62 [95%CI 40–102] μg/g) and non-anemic (73 [95%CI 56–97] μg/g) teens. In women carrying multiples, low maternal Fe status [lower SF (P = 0.002) and lower TBI (P = 0.01)] was associated with higher p[Fe], while in teens, improved Fe status [lower sTfR (P = 0.03) and higher TBI (P = 0.03)] was associated with higher p[Fe]. Conclusions Placental Fe content was ∼50% lower than previously estimated. P[Fe] is significantly associated with maternal Fe status. In women carrying multiples, poor maternal Fe status was associated with higher p[Fe], while in teens, improved Fe status was associated with higher p[Fe]. More data are needed to understand determinants of p[Fe] and the variable Fe partitioning in teens compared to mature women. Clinical Trial Registry: These clinical trials were registered at clinicaltrials.gov as NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902) and NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802).

The Trace Element Concentrations and Oxidative Stress Parameters in Afterbirths from Women with Multiple Pregnancies

“…Comparing these results with our previous research on Fe concentrations in afterbirths obtained from women with singleton pregnancies from the same study area, higher Fe concentrations were found in the placenta (640.73 mg/kg −1 dw), umbilical cord (640.73 mg/kg −1 dw), and fetal membrane (567.29 mg/kg −1 dw) [39]. However, Barad et al [40] reported lower Fe concentrations in the placenta obtained from teenage women with singleton pregnancies (71.1 mg/kg −1 ww; 106.7 mg/kg −1 dw after conversion) than in women aged 20-46 years with multiple pregnancies (84.6 and 78.6 mg/kg −1 ww; 126.9 and 117.9 mg/kg −1 dw after conversion, respectively, for twin and triplet placentas). De Angelis et al [41] reported that the Fe concentration in the placenta was higher in women with multiple pregnancies (26.05 µg/g −1 dw) than in those with singleton pregnancies (17.99 µg/g −1 dw), although this difference was not statistically significant.…”

Disordered Maternal and Fetal Iron Metabolism Occurs in Preterm Births in Human

“…However, a recent study conducted by Irwinda et al indicated that the placental iron stores in women with preterm births were much lower than that in women full-term births [ 28 ]. Besides, placental iron content in humans was reported ~50% lower than previously estimated in animal studies, and the placental iron concentrations were significantly associated with the maternal iron status, indicating that distinct mechanisms may be involved in different species [ 31 ]. In our work, in agreement with reduced iron concentrations in maternal and cord blood, the placental iron stores were reduced by >30% in the preterm group, compared to that in the full-term group ( Figure 1(e) ), P < 0.05).…”

“…However, in analogy to a recently reported study [ 28 ], the placental iron stores were apparently compromised under preterm condition ( Figure 1(e) ). These results indicate that distinct mechanism may account for the human preterm-related iron deficiency, different from animal model with pure iron deficiency condition [ 31 ], which warrants detailed studies to address the discrepancies further.…”

Iron Metabolism and Ferroptosis in Physiological and Pathological Pregnancy

“…Maintaining the iron hemostasis is essential to support trophoblast function, and severe placental iron deficiency could impair cellular oxidative phosphorylation [ 5 , 97 ]. All conclusions above were drawn with animal data, and further validation on the human placenta is needed [ 98 ].…”