Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Department of Pediatrics, Neonatology, University of Rochester School of Medicine, Rochester, NY, United States.
Am J Clin Nutr. 2024 Jan;119(1):76-86. doi: 10.1016/j.ajcnut.2023.10.022. Epub 2023 Oct 27.
Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting.
This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia.
Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone).
FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: β: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: β: 0.20; 95% CI: 0.03, 0.18; hepcidin: β: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (β-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (β: -0.02; 95% CI: -0.03, -0.003), EPO (β: 0.07; 95% CI: 0.01, 0.14), and sTfR (β: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (β: 0.08, 95% CI: 0.02, 0.14), TBI (β: 0.02; 95% CI: 0.009, 0.04), EPO (β: -0.10; 95% CI: -0.19, -0.01), sTfR (β: -0.16: 95% CI: -0.27, -0.06), and hepcidin (β: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05).
Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.
鼠类数据表明，当铁受到限制时，胎盘下调铁蛋白（FPN）以优先满足自身需求的铁。关于母体和新生儿铁状态对胎盘 FPN 表达的影响，人类数据存在矛盾。
本研究旨在确定胎盘 FPN 蛋白丰度的决定因素，并评估胎盘铁缺乏指数（PIDI）作为评估新生儿高危贫血的母体/胎儿铁状态的指标的效用。
通过蛋白质印迹法测量了 133 名青少年（17.4 ± 1.1 岁）携带单胎（分娩胎龄 [GA]：39.9 ± 1.3 周）的新生儿和 130 名 65 岁女性（30.4 ± 5.2 岁）携带多胎（分娩 GA：35.0 ± 2.8 周）的新生儿胎盘 FPN 蛋白丰度。评估了胎盘 FPN 和 PIDI（FPN：转铁蛋白受体 1）与新生儿和母体铁相关标志物（血红蛋白 [Hb]、血清铁蛋白 [SF]、可溶性转铁蛋白受体 [sTfR]、全身铁 [TBI]、hepcidin、促红细胞生成素 [EPO]、红细胞生成素）之间的关系。
在 25 至 42 周 GA 之间分娩的所有胎盘中均检测到 FPN 蛋白。胎盘 FPN 蛋白丰度与新生儿铁和红细胞生成标志物（EPO：β：0.10；95%置信区间 [CI]：0.06，0.35；sTfR：β：0.20；95%CI：0.03，0.18；hepcidin：β：-0.06；95%CI：-0.13，-0.0003；所有 P < 0.05）相关。母体 sTfR 仅与胎盘 FPN 间接相关，新生儿 sTfR 为中介物（β-间接：0.06；95%CI：0.03，0.11；P = 0.003）。PIDI 与新生儿 Hb（β：-0.02；95%CI：-0.03，-0.003）、EPO（β：0.07；95%CI：0.01，0.14）和 sTfR（β：0.13；95%CI：0.004，0.3）以及母体 SF（β：0.08，95%CI：0.02，0.14）、TBI（β：0.02；95%CI：0.009，0.04）、EPO（β：-0.10；95%CI：-0.19，-0.01）、sTfR（β：-0.16：95%CI：-0.27，-0.06）和 hepcidin（β：0.05；95%CI：0.002，0.11）相关（所有 P < 0.05）。
胎盘 FPN 丰度与新生儿红细胞生成活性增加和铁状态不佳的标志物呈正相关。PIDI 与母体和新生儿铁相关标志物相关，但方向相反。需要从风险较低的正常女性群体中获得更多数据，以评估研究结果的普遍性。这些试验在 clinicaltrials.gov 上注册为 NCT01019902 和 NCT01582802。
