Messer J, Haddad J, Donato L, Astruc D, Matis J
Service de Neonatologie, University Hospital of Strasbourg, Hôpital de Hautepierre, France.
Pediatrics. 1993 Oct;92(4):519-23.
The specific objectives of this study were (1) to assess the safety and efficacy of recombinant human erythropoietin (rhEPO) in reducing postnatal hemoglobin decline in premature infants of less than 33 weeks' gestation, and thus reducing the need for transfusion; and (2) to determine the optimal dosage of rhEPO.
Three groups of premature infants of less than 33 weeks' gestation were treated with rhEPO: group 1 (n = 10) received 300 U/kg per week; group 2 (n = 11), 600 U/kg per week; and group 3 (n = 10), 900 U/kg per week. These three groups were compared to a reference group of 20 infants of the same gestational age and birth weight. Treatment started on the 10th day of life and lasted 6 weeks. All infants were given oral iron and vitamin E supplements.
Treated infants had significantly higher reticulocyte counts, and the effect was dose dependent (P = .009). Postnatal decline of hemoglobin and hematocrit was lessened in the treated groups; the percent of decrease of hemoglobin and hematocrit was significantly reduced in the treated infants at 35 days of age (P = .0025 and P = .0036, respectively). The need for blood transfusion was also reduced in the rhEPO-treated groups: 19% of treated vs 45% of reference infants received transfusions, and the treated infants received less blood. Serum iron and transferrin saturation percentage dropped significantly during the study and a dose-dependent relationship in treated infants was displayed, suggesting high iron consumption (P = .0008 and P = .006, respectively). No dose effect on hemoglobin level and the need for blood transfusion was found, possibly because of the higher degree of illness severity and iron consumption in groups 2 and 3. No side effects related to rhEPO therapy were observed.
It is concluded that rhEPO therapy is safe in premature babies when given in the three dosages used in this study; in addition, it enhances erythropoiesis and reduces the need for blood transfusions. rhEPO therapy seems more efficient when given in higher dosages; however, illness severity and iron consumption represent major limiting factors. Controlled, randomized studies are warranted to confirm these data and to determine precise modalities and indications of rhEPO therapy in premature infants.
本研究的具体目的为：（1）评估重组人促红细胞生成素（rhEPO）在减少孕周小于33周的早产儿出生后血红蛋白下降、从而减少输血需求方面的安全性和有效性；（2）确定rhEPO的最佳剂量。
三组孕周小于33周的早产儿接受了rhEPO治疗：第1组（n = 10）每周接受300 U/kg；第2组（n = 11），每周600 U/kg；第3组（n = 10），每周900 U/kg。将这三组与20名相同孕周和出生体重的婴儿组成的参照组进行比较。治疗从出生后第10天开始，持续6周。所有婴儿均给予口服铁剂和维生素E补充剂。
接受治疗的婴儿网织红细胞计数显著更高，且该效应呈剂量依赖性（P = .009）。治疗组出生后血红蛋白和血细胞比容的下降有所减轻；在35日龄时，治疗组婴儿血红蛋白和血细胞比容的下降百分比显著降低（分别为P = .0025和P = .0036）。rhEPO治疗组的输血需求也有所减少：接受治疗的婴儿中有19%接受了输血，而参照组婴儿中有45%接受了输血，且接受治疗的婴儿输血量更少。在研究期间，血清铁和转铁蛋白饱和度百分比显著下降，且在接受治疗的婴儿中呈现出剂量依赖性关系，提示铁消耗较高（分别为P = .0008和P = .006）。未发现对血红蛋白水平和输血需求有剂量效应，这可能是因为第2组和第3组疾病严重程度较高且铁消耗较多。未观察到与rhEPO治疗相关的副作用。
得出结论，在本研究使用的三种剂量下，rhEPO治疗对早产儿是安全的；此外，它可增强红细胞生成并减少输血需求。rhEPO治疗在给予较高剂量时似乎更有效；然而，疾病严重程度和铁消耗是主要限制因素。有必要进行对照随机研究以证实这些数据，并确定rhEPO治疗早产儿的确切方式和适应证。
