Abstract】Objective:To investigate the efficacy of recombinant human erythropoietin (rhu-Epo) in the prevention and treatment of anemia of preterm infants. Methods:Sixty cases of preterm anemic infants were randomly divided into 30 cases in the treatment group and 30 cases in the control group. The preterm infants in both groups were given oral vitamin E, elemental iron and folic acid tablets from the 1st w of birth and vitamin B12 intramuscularly at the 4th w. In the treatment group, recombinant human erythropoietin was given once every other day, 3 times/w, subcutaneously at the 7th d of birth for 4 w. RESULTS: The reticulocyte count, hemoglobin and erythrocyte pressure volume were significantly higher in the treatment group than in the control group (P<0.05). CONCLUSION: Early application of recombinant human erythropoietin can effectively prevent and treat anemia in preterm infants, and the drug is safe and has no significant toxic side effects.
Anemia in preterm infants is a relatively common clinical phenomenon that brings significant negative effects to preterm infants, which can lead to growth retardation, susceptibility to infectious diseases, developmental delays, and an increased risk of mortality. Low levels of erythropoietin and its response to anemia are one of the main causes of anemia in preterm infants [1]. Therefore, in this study, recombinant human erythropoietin (rhu-EPO) was given subcutaneously to preterm infants in addition to conventional treatment to prevent and treat anemia in preterm infants, with good results. The results are reported as follows.
1 Subjects and methods
1.1 Subjects
Children with preterm anemia who were hospitalized in the pediatric department of our hospital from June 2008 to May 2011 were selected as the study subjects. Inclusion criteria: (1) gestational week <35w. (2) birth weight <2500g. (3) no anemia at birth, hemoglobin (Hb) <145g/L and >110g/L within 1 week after birth. 60 cases were enrolled, including 32 males and 28 females. There were no significant differences in gestational age, birth weight, sex composition, red blood cell count (RBC) at 24 hours of birth, hemoglobin amount (g/L), and red blood cell pressure product (HCT) between the two groups (P>0.05).
1.2 Methods
1.2.1 Treatment Both groups received oral vitamin E 5mg/(kg.d), elemental iron 4mg-6mg/(kg.d), folic acid tablets 5mg/(kg.d) from the 1st w of birth, and vitamin B12 100μg/w intramuscularly from the 4th w for 4 w. In the treatment group, recombinant human erythropoietin (rhu-Epo) was given on the 7th d after birth 250IU/ kg.times, 3 times/w, for 4 w. Reticulocytes (Ret), hemoglobin (Hb) and red blood cell pressure (HCT) were checked before treatment, 1 w after treatment, 2 w after treatment, 3 w after treatment and 4 w after treatment in both groups of preterm infants.
1.2.2 Statistical treatment Statistical analysis was performed using spss11.0 statistical software.
2 Results
The changes of peripheral blood Hb, Ret and HCT in the two groups after treatment are shown in Tables 1, 2 and 3.
Table 1 Changes of Hb in children in the two groups (g/L ± s)
Group n Post-treatment Post-treatment Post-treatment Post-treatment
1 w 2 w 3 w 4 w
Treatment group 30 156±16.4 150±11.4 141±13.6 135±14.2
Control group 30 158±17.2 148±12.2 134±11.3 118±10.4
P value P>0.05 P>0.05 P<0.05 P<0.05
Table 2 Changes in Ret in children in both groups (% ± s)
Group n Post-treatment Post-treatment Post-treatment Post-treatment
1 w 2 w 3 w 4 w
Treatment group 30 2.8±0.5 3.2±0.4 4.0±0.8 4.3±0.2
Control group 30 2.9±0.5 3.0±0.7 3.3±0.3 3.1±0.5
P value P>0.05 P>0.05 P<0.05 P<0.05
Table 3 Changes in HCT in children in both groups (% ± s)
Group n Post-treatment Post-treatment Post-treatment Post-treatment
1 w 2 w 3 w 4 w
Treatment group 30 55.1±2 49.3±5 41.2±4 40.4±5
Control group 30 51.3±4 44.6±3 36.4±6 31.2±4
P-value P>0.05 P>0.05 P<0.05 P<0.05
Tables 1, 2 and 3 show that the peripheral blood Hb, Ret and HCT were significantly higher in the treated group than in the control group after treatment, and all differences were significant (P<0.05).
3 Discussion
Recent studies have shown that low levels of EPO in preterm infants are the main cause of anemia in preterm infants, and the factors that cause low levels of EPO [2]: ① the postnatal fetal hemoglobin synthesis in preterm infants is reduced and the curve is shifted to the left, so tissue hypoxia is not obvious, thus failing to adequately stimulate the production of EPO; ② increased clearance of EPO from the blood circulation in preterm infants; ③ a larger proportion of EPO is synthesized by the liver in preterm infants, and the liver is less sensitive to hypoxia than the kidneys, and thus produces less EPO. Studies have shown that precursor cells of the erythroid cell lineage can be present in the bone marrow and circulation of preterm infants if rhu EPO is given and show normal proliferation and differentiation; this provides a theoretical basis for the application of exogenous rhu-Epo for the treatment of preterm anemia [3]. The present results showed that the blood reticulocyte count, hemoglobin and erythrocyte pressure volume were higher in the treated group than in the control group, and the treatment effect was significantly higher than in the control group, which is consistent with the literature [4].
During the application of rhu-Epo treatment in our children, it was found that peripheral hemoglobin and erythrocytes had a tendency to decrease in the 2ndw of treatment and gradually increased after continuing treatment, probably because the hematopoietic raw materials such as folic acid, vitamin B12 and iron reserves were relatively insufficient in preterm infants, which affected erythropoiesis; secondly, the body mass grew rapidly during the neonatal period, and blood volume increased and blood was relatively diluted. The children in this treatment group were all applied from the 7th d after birth, and no significant adverse effects were found during the treatment. It is suggested that early application of rhu-Epo can effectively prevent and treat anemia in preterm infants, which can reduce blood transfusion, and the drug is safe and closer to the physiological pathway.