***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To compare the neurodevelopmental outcome of premature infants treated with recombinant human erythropoietin  with that of control infants . STUDY DESIGN : A total of 20 treated infants and 20 control infants who had completed r and omized , double-blind , placebo-controlled studies of recombinant human erythropoietin as treatment for anemia of prematurity were followed for growth and developmental outcome in an intensive care nursery follow-up program . Infants were assessed by st and ard developmental tests . RESULTS : No differences were found between groups for neurologic outcome , cognitive outcome , or growth patterns . All infants treated with recombinant human erythropoietin were neurologically normal . The rate of cognitive deficits was similar in the two groups . CONCLUSION : In this small sample we did not see differences in neurodevelopmental outcome between infants treated with recombinant human erythropoietin and control infants Backgroud : The aim of the study was to evaluate the effect of early parenteral iron supplementation combined erythropoietin for prevention of anemia in preterm infants . Methods : In total , 96 preterm infants were r and omly assigned to 3 groups : a control group receiving st and ard parenteral nutrition ( group 1 : n = 31 ) , an iron-supplemented group ( group 2 : IS , n = 33 ) , and an iron-supplemented combined erythropoietin group ( group 3 : IS+EPO , n = 32 ) . The primary objective was to assess hemoglobin ( Hb ) levels . The secondary objectives included assessment of red blood cell counts ( RBC ) , mean cell volume ( MCV ) , serum iron , ferritin , percentages of reticulocyte ( RET ) , total iron binding capacity ( TIBC ) and oxidative stress , which was assessed by measuring plasma levels of malondialdehyde and superoxide dismutase at baseline and at 2 weeks . The blood routine indices including Hb , RBC , MCV , and percentages of RET were measured at corrected age of 1 and 3 months . Results : At 2 weeks of life , the percentages of reticulocyte in group 2 and group 3 were significantly higher than those in group 1 ( 2.1±0.4 , 2.5±0.3 , and 1.7±0.3 , respectively , P < 0.001 , P<0.001 ) , whereas TIBC were significantly lower than those in group 1 ( 36.7±4.6 , 36.0±4.7 , and 41.6 ± 5.2 respectively , P = 0.011 , P = 0.006 ) . There were no significant differences in RBC counts , the levels of hemoglobin , ferritin , malondialdehyde , and superoxide dismutase among the 3 groups at 2weeks of life . RBC , Hb , MCV , body weight , body length , and head circumference at a corrected age of 1 month did not differ among 3 groups . At corrected age of 3months , more infants in the control group had abnormal Hb and MCV levels ( Hb levels : 114.3 ± 21.3 , 123.7 ± 31.6 , and 125.1 ± 21.2 , P = 0.021 , P = 0.034 , respectively ; MCV : 74.1 ± 3.5 , 78.3 ± 4.7 and 79.1 ± 5.2 , P = 0.017 , P = 0.012 , respectively ) , whereas cases of oral iron , cases of breastfeeding , RBC , body weight , body length , and head circumference were not different among 3 groups . Conclusion : Early parenteral iron supplementation combined erythropoietin in preterm infants improved the percentages of reticulocyte , decreased total iron binding capacity , and improved the Hb and MCV levels at 3 months of age . Early parenteral iron supplementations with EPO were beneficial for the preterm infants In vitro and animal studies suggest that high concentrations of recombinant human erythropoietin ( rHuEPO ) might divert multipotent progenitors into erythroid maturation at the expense of granulocyte production . We determined whether changes of number and lineage commitment of peripheral blood progenitor cells occur in premature infants during therapy with rHuEPO .  Thirty preterm infants were r and omly assigned either to receive 300 IU of eopoetin alpha s.c . per kilogram body weight three times a week for four weeks or to a control group . At study entry and after two weeks of treatment the numbers of circulating BFU-E , granulocyte-macrophage colony-forming units ( CFU-GM ) and granulocyte-erythrocyte-macrophage-megakaryocyte CFU ( CFU-GEMM ) were analyzed by semisolid culture technique , CD34 + cells and early myeloid CD34+CD45RA- progenitors by flow cytometry . As compared with the control group , rHuEPO treatment did not exert any significant modulatory effect on numbers of CFU-GM , nor was there a significant change in numbers of BFU-E , CFU-GEMM , total-CFU , percentage of CD34 + or CD34+CD45RA- cells . Mean neutrophil count was not significantly reduced at any period during the study . Compared with the control group , the infants receiving rHuEPO had higher hematocrit values ( p = 0.003 ) and absolute reticulocyte counts ( p < 0.001 ) . The median cumulative volume of blood transfused per kilogram per day was 0.86 ml ( first quartile 0.5 ml ; third quartile 1.1 ml ) in the control group and 0 ml ( first quartile 0 ml ; third quartile 0.47 ml ) in the rHuEPO group ( p = 0.038 ) . We conclude using a relatively high dose of rHuEPO in premature infants , no significant in vivo effect on circulating peripheral blood progenitor or neutrophil count could be detected Despite improved survival , many preterm infants undergo subsequent neurodevelopmental impairment . To date , no neuroprotective therapies have been implemented into clinical practice . Erythropoietin , a haematopoietic cytokine used for treatment of anaemia of prematurity , has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies . The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age . A r and omized , double-blind placebo-controlled , prospect i ve multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled ' Does erythropoietin improve outcome in preterm infant ' was conducted in Switzerl and ( NCT00413946 ) . Preterm infants were given recombinant human erythropoietin ( 3000 IU ) or an equivalent volume of placebo ( NaCl 0.9 % ) intravenously before 3 h of age after birth , at 12 - 18 h and at 36 - 42 h after birth . High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean ( st and ard deviation ) gestational age at birth 29.75 ( 1.44 ) weeks , and at scanning at 41.1 ( 2.09 ) weeks . Imaging was performed at a single centre . Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model , covarying for the gestational age at birth and the corrected gestational age at the time of the scan . Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum , the anterior and posterior limbs of the internal capsule , and the corticospinal tract bilaterally . Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo ( P < 0.001 ) . We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics OBJECTIVE To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor ( rhG-CSF ) and recombinant human erythropoietin ( rhEPO ) in preventing feeding intolerance . STUDY DESIGN An interventional r and omized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age . The neonates were assigned to 4 groups ; 20 received rhG-CSF , 20 received rhEPO , 20 received both , and 30 received distilled water ( placebo control ) . The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days , whichever came first . Feeding tolerance and adverse effects of treatment were assessed . Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment . RESULTS All neonates  tolerated the treatment without side effects . Neonates who received rhG-CSF and /or rhEPO had better feeding tolerance , as reflected by earlier achievement of 75 mL/kg/day , 100 mL/kg/day , and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay ( P < .05 ) . The risk of necrotizing enterocolitis was reduced from 10 % to 0 % in all treatment groups ( P < .05 ) . There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo ( P < .05 ) . Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups . CONCLUSIONS Enteral administration of rhG-CSF and /or rhEPO  improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates . The mechanism may involve the prevention of villous atrophy BACKGROUND : We previously reported decreased transfusions and donor exposures in preterm infants r and omized to Darbepoetin ( Darbe ) or erythropoietin ( Epo ) compared with placebo . As these erythropoiesis-stimulating agents ( ESAs ) have shown promise as neuroprotective agents , we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants r and omized to receive ESAs . METHODS : We performed a r and omized , masked , multicenter study comparing Darbe ( 10 μg/kg , 1 × /week subcutaneously ) , Epo ( 400 U/kg , 3 × /week subcutaneously ) , and placebo ( sham dosing 3 × /week ) given through 35 weeks ’ postconceptual age , with transfusions administered according to a st and ardized protocol . Surviving infants were evaluated at 18 to 22 months ’ corrected age using the Bayley Scales of Infant Development III . The primary outcome was composite cognitive score . Assessment s of object permanence , anthropometrics , cerebral palsy , vision , and hearing were performed . RESULTS : Of the original 102 infants ( 946 ± 196 g , 27.7 ± 1.8 weeks ’ gestation ) , 80 ( 29 Epo , 27 Darbe , 24 placebo ) returned for follow-up . The 3 groups were comparable for age at testing , birth weight , and gestational age . After adjustment for gender , analysis of covariance revealed significantly higher cognitive scores among Darbe ( 96.2 ± 7.3 ; mean ± SD ) and Epo recipients ( 97.9 ± 14.3 ) compared with placebo recipients ( 88.7 ± 13.5 ; P = .01 vs ESA recipients ) as was object permanence ( P = .05 ) . No ESA recipients had cerebral palsy , compared with 5 in the placebo group ( P < .001 ) . No differences among groups were found in visual or hearing impairment . CONCLUSIONS : Infants r and omized to receive ESAs had better cognitive outcomes , compared with placebo recipients , at 18 to 22 months . Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants ABSTRACT : To assess whether erythropoietin ( EPO ) treatment is safe and reduces the need for transfusion , we r and omized 44 preterm infants to an EPO group and a comparable control ( CON ) group .  EPO 150 U/kg was given s.c . twice weekly for 6 wk from the 1st wk of life . Hematologic parameters , transfusion requirements , and growth were followed during therapy and for 6 mo thereafter . To better assess in which neonates EPO treatment was effective , we classified retrospectively the EPO and CON groups into uncomplicated neonates ( EPO A : n = 9 , birth weight = 1247 ± 126 g , gestational age = 29.8 ± 1.5 wk ; CON A : n = 7 , birth weight = 1217 ± 145 g , gestational age = 29.9 ± 1. 
    Output:
    
The number of RBC transfusions per infant was minimally reduced , but the number of donors to whom infants who were transfused were exposed was not significantly reduced .
Early administration of ESAs reduces the use of red blood cell ( RBC ) transfusions , the volume of RBCs transfused , and donor exposure after study entry .
Small reductions are likely to be of limited clinical importance .
This up date found no significant difference in the rate of ROP ( stage ≥ 3 ) for studies that initiated EPO treatment at less than eight days of age , which has been a topic of concern in earlier versions of this review .
Early EPO treatment significantly decreased rates of IVH , PVL , and NEC .