IRON IN PRETERM INFANTS--REQUIREMENTS, EFFICACY AND SAFETY

早产儿贫血的发病机制尚不完全 明白了。虽然早产儿有储存铁(Fe)，但它是 不确定他们是否能足够快地从存储中动员铁 红细胞生成以与生长相适应的速度进行。早产 婴儿摄入的蛋白质低于所需水平。 因此，蛋白质缺乏可能是贫血的一个致病因素。这个 这一建议总体假设是铁和/或 蛋白质缺乏限制早产儿红细胞的形成 优化铁的利用率或蛋白质摄入量将导致 临床相关的红细胞生成增强和改善 贫血，这反过来可能导致对红细胞需求的减少 输血。在六个具体目标中，有四个将在临床上实现 在动物研究方面有两个。目标1将测试假设，通过 将口服铁摄入量从目前的常规水平提高到以下两种水平之一 更高水平，促进红细胞生成，改善铁 将达到营养状态，而不会招致毒性影响。至 定量测定铁的吸收和利用在这些较高的 将测定铁的摄入量、吸收率和红细胞掺入铁 使用非放射性同位素58Fe。在另一个子集中，我们 将检查红细胞输注对铁吸收和/或 排泄物。自由基损伤的证据将会被完全获得 铁的摄入量。目标#2将检验以下假设： 蛋白质摄入量与预计需要量更接近 目前的常规喂养将增强红细胞生成，导致 更好的增长。目标3将检验这样一种假设，即用r- 护红细胞和铁导致红细胞寿命缩短和/或导致 红血球肿块或血容量的扩大。这一目的旨在澄清 在之前的研究中所做的观察表明，这种不利的 在r-HuEPO和Fe处理过程中确实会产生影响。父母 与肠内注射相比，口服铁剂可能会提供实质性的优势 政府，但潜在的毒性更大。特定目标#4将测试 对早产儿缓慢输注铁会导致 与快速输注相比，58Fe对红细胞的掺入更大。新生儿 贫血的羔羊将在目标5中被用来检验这样的假设 静脉注射铁单独给药或静脉注射铁均可刺激红细胞生成 与r-HuEPO联合应用。目标#6将检验假设 静脉注射铁可以刺激红细胞生成。目标#4、5和6，如果 成功，将为未来的临床试验提供基础 人类婴儿的非肠道注射铁。

The pathogenesis of the anemia of prematurity is incompletely understood. Although preterm infants possess storage iron (Fe), it is uncertain that they can mobilize Fe from storage rapidly enough for erythropoiesis to proceed at a rate commensurate with growth. Preterm infants receive protein intakes that are less than the requirements. Hence, protein deficiency may be a causative factor in anemia. The overall hypothesis of this proposal is that availability of Fe and/or protein deficiency limit RBC formation in preterm infants and that optimization of Fe availability or of protein intake will result in clinically relevant enhancement of erythropoiesis and amelioration of anemia which, in turn, may lead to a reduction of the need for RBC transfusions. Of the six Specific Aims, four will be pursued in clinical and two in animal studies. Aim #1 will test the hypothesis that, by raising oral Fe intake from the current routine level to one of two higher levels, enhancement of erythropoiesis and improvement of Fe nutritional status will be achieved, without incurring toxic effects. To determine quantitatively Fe absorption and utilization at these higher Fe intakes, absorption and RBC incorporation of Fe will be determined with use of the non-radioactive isotope, 58Fe. In another subset, we will examine the effect of RBC transfusion on Fe absorption and/or excretion. Evidence of free radical damage will be obtained at all levels of Fe intake. Aim #2 will test the hypothesis that provision of protein intakes that match estimated requirements more closely than current routine feedings will enhance erythropoiesis, leading to improved growth. Aim #3 will test the hypothesis that treatment with r- HuEpo and Fe leads to a shortening of RBC life span and/or to an expansion of RBC mass or blood volume. This aim intends to clarify observation made during a previous study suggesting that such adverse effects do occur during r-HuEPO and Fe treatment. Parental administration of Fe may offer substantial advantages over enteral administration, but is potentially more toxic. Specific Aim #4 will test the hypothesis that slow infusion of Fe to preterm infants leads to greater RBC incorporation of 58Fe than more rapid infusion. Newborn anemic lambs will be used in Aim #5 to test the hypothesis that intravenous Fe stimulates erythropoiesis when given alone or in combination with r-HuEPO. Aim #6 will test the hypothesis that intravenous Fe stimulates erythropoiesis. Aims #4,5 and 6, if successful, will provide the basis for future clinical trials of parenterally administered Fe in human infants.