重组人类促红细胞生成素治疗极低出生体重早产儿贫血的近期疗效观察

目的:应用重组人类促红细胞生成素(rhu-EPO)治疗极低出生体重早产儿贫血并随访至出生后4个月,观察其疗效。方法：将56例极低出生体重早产儿按随机抽样原则分为对照组(26例)、治疗组(30例)。治疗组于生后第8天即予rhu-EPO,每次300 IU/kg,皮下注射,每周2次,共4周;第3周开始口服铁剂(每日5～10 mg/kg)。两组均于生后7 d内口服维生素E(每日5 mg/kg)、叶酸片(5 mg/d)。随访至出生后4个月。结果：随年龄增大两组血红蛋白、红细胞数、红细胞压积均逐渐下降,在7 d, 14 d, 21 d,28 d,35 d时,治疗组上述指标均较对照组高,差异有显著性意义(P<0.01或0.05);治疗结束后,两组的血清铁蛋白［(103±25 μmol/L vs (123±24) μmol/L)差异有显著性(P<0.01);治疗组较对照组出现贫血率低(43% vs 89%),两组比较差异有显著性(P<0.01)。结论：早期大剂量rhu-EPO能减轻早产儿贫血的程度,可减少甚至替代输血。     

促红细胞生成素加大剂量铁剂防治极低出生体重儿贫血临床观察

目的　观察重组人类促红细胞生成素(rH -EPO)加大剂量铁剂防治极低出生体重儿贫血的疗效。方法　将3 4例极低出生体重儿随机分为治疗组1 6例和对照组1 8例;两组观察对象均于出生第四天起开始口服葡萄糖酸亚铁糖浆(按元素铁9mg/kg·d计算)、VitC 0. 2g/d、VitE 1.5mg/d ,治疗组在上述常规治疗的基础上加rH -EPO每周60.0IU/kg ,分三次皮下注射,疗程满6周结束。结果　治疗组治疗后网织红细胞计数(Ret)较同日龄对照组明显升高(P <0.0 1 ) ;两组血红蛋白(Hb)及红细胞压积(Hct)均于出生后逐渐下降,但治疗组下降缓慢,两组在治疗后第1、3、5、7周相比均有极显著性差异(P <0.0 1 ) ;治疗组疗程结束后存在贫血者4例( 2 5 .0 0 % ) ,对照组1 3例( 72. 2 2 % ) ,两组相比x2 =7.5 6,P <0.0 1 ,有极显著性差异;治疗组输血2例,而对照组输血1 1例。结论　rH -EPO加大剂量铁剂能有效防治极低出生体重儿贫血,能最大限度地减少输血治疗,可作为极低出生体重儿的一项常规治疗     

重组红细胞生成素在极低出生体重儿中应用

为探讨重组红细胞生成素(rEPO)治疗极低出生体重儿(VLBW)贫血的疗效，对28例极低出生低体重儿予以rEPO治疗，疗效满意，现报道如下。     

重组人类促红细胞素和铁剂在极低出生体重儿中的应用研究

目的评价重组人类促红细胞素(rhEPO)和铁剂对极低出生体重儿(VL-BW)输血的影响及预防早产儿贫血的效果。方法对59例出生体重≤1500g,胎龄≤34周的早产儿进行研究,其中治疗组31例于生后第5-7天开始予以rhEPO治疗(250U/kg·次,皮下注射,每周2次),共6周,同时补充铁剂和多种维生素;对照组28例未给予rhEPO和铁剂治疗。比较两组的血液学指标、输血的量和次数。结果组间胎龄、出生体重、生后第1周的血红蛋白(Hb)、抽血的量和次数、并发症、机械通气的天数无差别。每个病人的输血次数和量,rhEPO治疗组为(0.7±1.0)次/人、(8.4±13.4)ml/kg,对照组为1.6±1.2)次/人、(20.8±15.9)ml/kg;两组对比,差异有非常显著性(P<0.001)。治疗组74.19%不需输血,而对照组32.14%不需输血(P<0.001)。两组生后Hb均逐渐下降,但对照组下降较治疗组明显(P<0.005);最低的Hb均值,治疗组为(98.5±16.1)g/L,对照组为(84.9±19.3)g/L。治疗组网织红细胞于rhEPO治疗1周后即较对照组明显升高(P<0.001),治疗组第2周达高峰。两组血清铁(SI)生后均呈下降趋势,但治疗组下降较对照组明显(P<0.001)。结论rhEPO预防性治疗早产儿贫血效果显著,可减少VLBW的输血量和次数。     

重组人类促红细胞素和铁剂在极低出生体重儿中的应用研究

目的评价重组人类促红细胞素(rhFPO)和铁剂对极低出生体重儿(VL-BW)输血的影响及预防早产儿贫血的效果.方法对59例出生体重≤1500 g,胎龄≤34周的早产儿进行研究,其中治疗组31例于生后第5～7天开始予以rhEPO治疗(250 U/kg·次,皮下注射,每周2次),共6周,同时补充铁剂和多种维生素;对照组28例未给予rhEPO和铁剂治疗.比较两组的血液学指标、输血的量和次数.结果组间胎龄、出生体重、生后第1周的血红蛋白(Hb)、抽血的量和次数、并发症、机械通气的天数无差别.每个病人的输血次数和量,rhEFO治疗组为(0.7±1.0)次/人、(8.4±13.4)ml/kg,对照组为1.6±1.2)次/人、(20.8±15.9)ml/kg;两组对比,差异有非常显著性(P＜0.001).治疗组74.19%不需输血,而对照组32.14%不需输血(P＜0.001).两组生后Hb均逐渐下降,但对照组下降较治疗组明显(P＜0.005);最低的Hb均值,治疗组为(98.5±16.1)g/L,对照组为(84.9±19.3)g/L.治疗组网织红细胞于rhEPO治疗1周后即较对照组明显升高(P＜0.001),治疗组第2周达高峰.两组血清铁(SI)生后均呈下降趋势,但治疗组下降较对照组明显(P＜0.001).结论rhEPO预防性治疗早产儿贫血效果显著,可减少VLBW的输血量和次数.     

重组人促红细胞生成素对极低出生体重儿神经智能发育的影响

目的 评估早期给予重组人促红细胞生成素（rhEPO）对极低出生体重儿（VLBWI）神经智能发育的临床疗效。方法 选取VLBWI 78例,根据患儿父母的选择分为rhEPO治疗组（n=35）与对照组（n=43）。治疗组生后4~5 h内给予rhEPO（250 IU/kg,每周3次,连用4周）。纠正胎龄40周时行新生儿神经行为检测（NBNA）,纠正胎龄3月、6月、12月时进行Gesell发育量表评估,并比较纠正胎龄6月时脑干诱发电位（ABR）及头颅B超的异常率。结果 治疗组纠正胎龄40周的NBNA评分高于对照组（P<0.05）。治疗组纠正胎龄3月时的适应能力优于对照组,纠正胎龄6月时的大运动、适应能力、社交能力优于对照组,纠正胎龄12月时的大运动、适应能力、精细动作、社交能力、语言明显优于对照组,差异均具有统计学意义（均P<0.05）。治疗组纠正胎龄6月时的ABR异常率、头颅B超异常率明显低于对照组（P<0.05）。结论 早期rhEPO治疗可以促进VLBWI神经系统症状早期恢复,改善患儿的认知、运动及语言能力,对神经系统具有一定的保护作用。     

重组人类促红细胞生成素防治早产儿贫血的临床研究

目的探讨重组人类促红细胞生成素(rHu-Epo)防治早产儿贫血的疗效.方法将33例早产儿按入院次序分成治疗组17例,对照组16例.治疗组出生第1周即予rHu-Epo500IU*kg-1*w-1,隔日1次,每周3次皮下注射,共5周;对照组未予rHu-Epo治疗.两组早产儿生后第3周开始口服铁剂[元素铁5mg*kg-1*d-1],必要时输血,共观察7周.结果治疗组第2周开始网织红细胞较对照组明显升高(P＜0.01),第3周后渐下降但与对照组比较仍有显著差异(P＜0.05);两组患儿出生后Hb均渐下降,但治疗组程度较轻,最低Hb值较对照组高(P＜0.01),达最低Hb值的时间较对照组早(P＜0.01).治疗组血清铁蛋白第2周开始较对照组低(P＜0.01).治疗组输血率与对照组比较明显减少(P＜0.05).观察期末治疗组早产儿体重增长的速率较对照组高(P＜0.05).结论早期大剂量rHu-Epo能减轻早产儿贫血的程度,减少或避免输血;体内充足的铁储备是确保rHu-Epo疗效的重要因素.     

不同剂量重组人类促红细胞生成素防治早产儿贫血的疗效观察

目的　探讨重组人类促红细胞生成素(rhEpo)治疗早产儿贫血的疗效及最适剂量。方法　予rhEpo750IU/(kg*w)(Ⅰ组)、600IU/(kg*w)(Ⅱ组)、450IU/(kg*w)(Ⅲ组)、300IU/(kg*w)(Ⅳ组),分别治疗15例胎龄35周以下、出生体重<1800g的早产儿,并与15例同胎龄、同出生体重的早产儿(Ⅴ组)对照。结果　①5组早产儿生后血红蛋白(Hb)、红细胞压积比(ΦRBC)均逐步下降,但Ⅰ组下降程度最轻,对照组下降程度最明显。治疗结束时,经方差分析,除了Ⅲ组与Ⅳ组之间无显著性差异外,其余各剂量组之间差异有显著性意义。②Ⅰ～Ⅳ组第2周起网织红细胞(Ret)较对照组升高(P均<0.01),并且与剂量有关;治疗结束时,各剂量组差异已不显著,但仍高于对照组(P<0.01)。③Ⅰ～Ⅳ组第2周血清铁明显低于对照组,第4周更甚;治疗结束时,治疗组血清铁上升,但Ⅰ～Ⅲ组仍低于对照组(P<0.01)。结论　rhEpo可提高Hb、ΦRBC及Ret,并且疗效与剂量有关,750IU/(kg*w)组疗效最显著。     

重组人类红细胞生成素预防早产儿贫血临床观察

目的　评价不同剂量的重组人类红细胞生成素 (rHuEPO)预防早产儿贫血的效果。方法　选择2 0 0 0～ 2 0 0 2年广州医学院荔湾医院收治的 6 7例胎龄≤ 34周 ,出生体重≤ 2 0kg早产儿 ,随机分为大剂量组、小剂量组和对照组。大、小剂量组分别于生后 3～ 7d接受rHuEPO每周 5 0 0IU/kg和每周 15 0IU/kg ,每周分 2次 ,皮下注射 ,共 6周 ;3组治疗期间均予 3～ 8mg·kg-1·d-1元素铁口服。分别于生后 1～ 8周、12周、16周观察各项血液学指标。结果　完成 16周研究的早产儿共 5 8例 ,3组生后血红蛋白、红细胞压积比均逐渐下降 ,大剂量组下降幅度最小 ,对照组下降最明显 (均P <0 0 1) ;大、小剂量组较对照组血红蛋白和红细胞压积比达最低值的时间提前。大、小剂量组网织红细胞于rHuEPO治疗 1周后即较对照组明显升高 ,尤以大剂量组上升幅度最明显 (P <0 0 1) ,治疗第 2～ 3周达高峰。 3组血清铁生后均呈下降趋势 ,但治疗期间治疗组下降较对照组明显 (P <0 0 1)。结论　rHuEPO辅以铁剂治疗可有效地预防早产儿贫血 ,且rHuEPO每周 5 0 0IU/kg优于每周 15 0IU/kg。     

重组人促红细胞生成素对早产儿贫血和细胞免疫功能的影响

目的　观察重组人促红细胞生成素 (rHu Epo)对早产儿贫血的预防和细胞免疫功能的影响。 方法　将 6 0例早产儿随机分为治疗组和对照组各 30例 ,治疗组用rHu Epo 6 0 0IU/kg ,隔日一次× 6周 ,加常规治疗[速力菲 8mg/ (kg·d) ,VitC 0 .1Bid ;VitE 10mg ,qd],对照组仅用常规治疗。两组同时监测红细胞计数 (RBC)、血红蛋白 (Hb)、网织红细胞 (Ret) )、血清铁和细胞免疫功能的变化。结果　疗程结束后治疗组Ret 2 .0 7% ,对照组 0 .80 9% ,两组Ret相差 10个百分点左右。治疗组血清铁 13μmol/L ,对照组 2 2 .13μmol/L ,P<0 .0 1。治疗组贫血发生率 3.3% ,对照组 6 3.4% ,P <0 .0 1,两组贫血症状有明显差异。结论　rHu Epo能预防早产儿贫血     

重组人红细胞生成素对于早产儿神经发育保护作用的Meta分析

目的 采用Meta分析方法评价重组人红细胞生成素（rhEPO）对早产儿神经发育的保护作用。方法制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、Cochrane图书馆、中国期刊全文数据库、万方数据库、维普中文科技期刊数据库及中国生物医学文献数据库等,获得rhEPO对早产儿神经发育保护的RCT或半随机对照试验（quasi-RCT）文献。使用Jadad量表对纳入文献进行质量评价,采用RevMan 5.0软件进行Meta分析。以智力发育指数(MDI)、神经运动发育指数(PDI)、新生儿行为神经评估（NBNA）评分、严重神经系统后遗症（脑瘫、失明和听力受损）发生率以及严重早产儿视网膜病（ROP,≥3级）、严重脑室内出血（IVH,≥3级）、坏死性小肠结肠炎（NEC）和支气管肺发育不良（BPD）的发生率等作为观察指标,进行综合评估。结果 共检索到118篇文献,符合纳入标准的2篇RCT和3篇quasi-RCT文献（n=233）进入Meta分析,其中英文文献2篇,中文文献3篇。文献质量评价A级1篇,B级1篇,C级3篇。各研究间的基线水平有一定差异,出生体重、孕周、rhEPO剂量和治疗持续时间不尽相同。Meta分析结果显示,rhEPO治疗组MDI评分显著高于对照组（WMD=7.73,95%CI：3.45~12.01,P=0.000 4）;rhEPO治疗组PDI评分显著高于对照组（WMD=3.81,95%CI：0.59~7.02,P=0.02）;rhEPO治疗组NBNA评分显著高于对照组（WMD=1.95,95%CI：1.56~2.35,P＜0.000 01）。两组MDI评分<70发生率（OR= 0.70,95%CI:0.31～1.61）、PDI评分<70发生率（OR=2.46,95%CI:0.94～6.45）、脑瘫（OR=1.08,95%CI:0.39～2.99）、失明（OR=0.34,95%CI:0.01～8.56）和听力受损（OR=1.04,95%CI:0.06～17.15）的发生率差异均无统计学意义。两组严重ROP（OR=1.30,95%CI：0.50~3.43）、严重IVH（OR=2.91,95%CI:0.64～13.23）、NEC（OR=0.57,95%CI:0.13～2.54）和BPD（OR=1.06,95%CI:0.50～2.26）发生率的差异均无统计学意义。结论 应用rhEPO治疗可能改善早产儿神经系统预后,可能对于早产儿神经系统发育有保护作用,且不增加严重ROP的发生率。     

国产重组人类促红细胞生成素防治早产儿贫血的临床效果研究

为评价国产重组人类促红细胞生成素（rhEPO）防治早产儿贫血的效果和安全性，将40例胎龄≤34周的早产儿随机分为治疗组及对照组各20例。治疗组予国产rhEPO750IU／（kg.w），每周分3次皮下注射，用药6周；对照组未用rhEPO；两组早产儿均口服铁剂。结果显示治疗组用药后血清促工细胞生成素水平显著高于对照组（P＜0．01）；治疗组血红蛋白、红细胞压积比、网积红细胞显著高于对照组（P＜0．01）；血清铁蛋白水平在用药后治疗组明显低于对照组（P＜0．01）；治疗组输血率较对照组明显减少（P＜0．01）；治疗组体重增长指标高于对照组9P＜0．05）。研究提示，国产rhEPO能有效防治早产儿贫血，且用药安全，无明显副作用。     

Weekly intravenous administration of recombinant human erythropoietin in infants with the anaemia of prematurity

To study the safety and efficacy of administering human recombinant erythropoietin (rHuEPO) to infants with anaemia of prematurity, a combined phase I/II trial of weekly intravenous injections for 4 weeks was undertaken. We treated 16 infants with 10, 25, 50, 100 or 200 units/kg body weight in groups of two to four patients per dose level. They were all born prematurely (mean gestational age: 29 weeks; range 27–32), had a mean post-natal age of 42 days (range: 25–59) and haemoglobin concentration of 87 g/l (range: 72–94) when treatment was started. Four patients (25%) needed a transfusion during the trial, one at day 7 treated with 10 units/kg and 3 at days 15, 25, 29 with 100 units/kg. In the others, a progressive rise in mean haemoglobin values was seen in each group after 21 days of treatment, without a dosedependent effect. A positive change in absolute reticulocyte counts with a peak after 7–14 days of therapy was observed with low (25–50 units/kg) but not with higher doses, with a significant difference at day 14 between 25 and 100 units/kg (P<0.01). A dose-limiting severe neutropenia (absolute neutrophil count<0.5×10⁹/l) occurred transiently in five patients, with doses >25 units/kg. No infectious complication and no sign of iron deficiency were observed. Weekly low doses of rHuEPO appear safe, convenient to administer and able to induce a reticulocytic response in infants with anaemia of prematurity. A phase III placebo-controlled trial is needed to confirm these results. Neutropenia associated with rHuEPO administration in infants might be related to their stage of human ontogeny.     

No response to recombinant human erythropoietin therapy in patients with congenital dyserythropoietic anemia type I

Congenital dyserythropoietic anemia (CDA) type I is a rare inherited bone marrow disorder characterized by moderate to severe macrocytic anemia with pathognomonic cytopathology of nucleated red blood cells. Previous studies have suggested that serum erythropoietin levels in affected patients are lower than expected for the degree of anemia. An earlier study demonstrated a substantial increase in the number of CFU-E in CDA type I pattern on addition of exogenous erythropoietin. The present study reports on the response to recombinant human erythropoietin in 8 patients with CDA type I. Eighteen weeks of treatment, starting at 300 IU/kg twice a week and gradually increasing to 500 IU/kg three times a week, did not have a substantial effect on the mean hemoglobin value. These results indicate that recombinant human erythropoietin (rHuEpo) is not beneficial to patients with CDA type I and that the relatively low levels of serum erythropoietin probably play no major role in the pathogenesis of the disease.     

Effects of early human recombinant erythropoietin therapy on the transfusion in healthy preterm infants

Objective  Early recombinant erythropoietin therapy and iron therapy would decrease the need for red blood cells transfusions and prevents anemia of prematurity. Methods  Fifty-eight preterm infants in newborn services at Ghaem Medical Center randomly were assigned, among them 18 patients were excluded. A total of 40 preterm infants with gestational age 28–34 weeks, birth weight 1000–1750 g followed the study: 20 infants in treatment group and 20 infants in control group were randomized to treatment (rhu EPO, 500u per kg, per week, 2 times weekly, subcutaneous) and control (no treatment). Therapy was initiated 4 days after birth and continued throughout the 4 weeks. All infants on enteral feeds received supplements: iron 3 mg/kg/d, vitamins and folat. Complete blood cells and reticulocyte counts were measured weekly. Transfusions and phlebotomy data were recorded. Statistical significance was determined by chi-square test, student t test and Mann-Whitney. A P value of < 0.05 was considered statistically significant. Results  The reticulocyte counts were higher in treated infants during the study (p: 0.009). Final hematocrits were higher in treated infants (p: 0.02).The volume of packed red blood cells transfusions mililiter per infant significantly reduced (p: 0.05), the average number of transfusion per infant was also lower for treated infant than control [2 (10 % )vs 8 (40%) respectively]. No adverse effects of EPO or supplemental iron occurred. Conclusion  The combination of early rhu EPO and iron as administered in the present study stimulated erythropoiesis and decreased red blood cells transfusion in premature infants who were 1000–1750 g at birth. The enrollments of the larger and healthier preterm infants, who are at lower risk for transfusion, are limitation of the present study.     

Effect of recombinant human erythropoietin on transfusion needs in preterm infants

OBJECTIVE: To study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very low birthweight (VLBW) infants. METHODS: We conducted a non-blind randomized controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day 10. Transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g. RESULTS: VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. Of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant. Blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of VLBW infants. CONCLUSION: r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth.