Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia
Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia
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DOI：
10.1542/peds.2004-1601
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发表时间：
2005-08-01
期刊：
影响因子：
8
通讯作者：
Widness, JA
中科院分区：
文献类型：
--
作者：
Lott, DG;Zimmerman, MB;Widness, JA
目标。目的探讨红细胞锌原卟啉/血红素比值(锌原卟啉/血红素比值)作为胎儿铁状态指标的应用价值，因为低血清铁蛋白提示出生时铁状态差与神经发育不良有关，而且几乎没有可靠的胎儿和早期新生儿铁状态指标。分娩时连续研究的早产儿和足月儿包括：(1)非缺氧组，(2)胎儿宫内生长迟缓(IUGR)，(3)胰岛素治疗母亲的胎儿(FDM)。我们假设(1)正常胎儿的快速生长速度伴随着红细胞生成的加速将导致向快速扩张的红细胞质量和更高的脐带血RBC的铁供应减少；以及(2)暴露于病理性/低氧血症的胎儿将经历额外的红细胞生成增加和更高的脐血ZPP/H。用血液荧光法测定生理盐水洗涤的脐血红细胞上的ZNPP/H，并检查其与临床因素和脐血实验室指标(组织氧合(血浆促红细胞生成素和网织红细胞计数)和铁状态(血浆铁蛋白和红细胞指数)的关系。统计检验包括单因素方差分析、有协变量的双因素方差分析、一元线性回归和多元回归分析。在对照组中，出生时胎龄与RBC、ZPP/H、网织红细胞数呈负相关，与铁蛋白、EPO呈正相关。与对照组相比，IUGR和FDM胎龄在特定胎龄分组的胎儿具有更高的ZPP/H、更低的血浆铁蛋白和更高的血浆EPO水平。对所有研究组中的锌蛋白/氢和血浆铁蛋白的关系的统计模型显示，胎龄、血浆促红细胞生成素、母亲高血压和母亲吸烟对其有显著影响。在对照组中，胎儿ZPP/H与出生时胎龄的负相关可归因于红细胞生成刺激，这可能是由于在最早胎龄时生长速度增加的结果。IUGR组和FDM组中观察到的相对较高的ZnPP/H可能归因于病理性低氧血症继发的红细胞生成活性增加。在IUGR组，胎盘铁转移减少也可能限制了铁的可获得性，并导致了ZPP/H的升高。这些数据支持这一概念，即红细胞生成活动增加和/或铁运输受限可能会使糖尿病母亲的婴儿和生长迟缓婴儿在婴儿期后期和儿童早期出现全身性铁缺乏症的风险。
Objective. To examine the utility of red blood cell (RBC) zinc protoporphyrin/heme ratio (ZnPP/H) as an indicator of fetal iron status, because unfavorable neurodevelopmental outcomes have been associated with poor iron status at birth, as indicated by low serum ferritin, and because few reliable indicators of fetal and early neonatal iron status exist.Methods. Consecutively studied preterm and term fetuses at delivery included the following groups: (1) control nonhypoxic, (2) fetuses with intrauterine growth retardation (IUGR), and (3) fetuses of insulin-treated mothers (FDM). We hypothesized (1) that rapid growth velocity associated with an accelerated erythropoiesis among normal fetuses will lead to reduced iron delivery to a rapidly expanding RBC mass and higher umbilical cord blood RBC ZnPP/H and (2) that fetuses that are exposed to pathologic/hypoxemia will experience an additional increase in erythropoiesis and higher cord ZnPP/H. ZnPP/H was determined on saline-washed cord blood erythrocytes by hematofluorometry and was examined for its relationship with clinical factors and cord blood laboratory measurements indicative of tissue oxygenation (plasma erythropoietin [EPO] and reticulocyte count) and iron status (plasma ferritin and erythrocyte indices). Statistical testing included 1-way analysis of variance, 2-way analysis of variance with covariates, simple linear regression, and multiple regression analysis.Results. Among control group subjects, gestational age at birth was inversely correlated with RBC ZnPP/H and reticulocyte count and positively correlated with ferritin and EPO. Relative to control subjects, IUGR and FDM fetuses at specified gestational age groupings had higher ZnPP/H, lower plasma ferritin, and higher plasma EPO. Statistical modeling of the relationship between ZnPP/H and plasma ferritin among all study groups demonstrated significant impacts of gestational age, plasma EPO, maternal hypertension, and maternal smoking.Conclusions. The inverse association of fetal ZnPP/H with gestational age at birth among control subjects is attributable to erythropoietic stimulation likely as a result of increasing growth velocity at the earliest gestational ages. The relatively higher ZnPP/H observed among fetuses in the IUGR and FDM groups likely is attributable to increased erythropoietic activity secondary to pathologic hypoxemia. Decreased placental iron transfer may also have limited iron availability and contributed to elevated ZnPP/H in the IUGR group. These data support the concept that increased erythropoietic activity and/or limited iron transport may place infants of diabetic mothers and infants with growth retardation at risk for developing systemic iron deficiency later in infancy and in early childhood.