The recombinant human erythropoietin therapy for extremely and very low birth weight infants

Abstract

Anemia of prematurity is a common pathology in premature infants. The prevalence of anemia of prematurity is inversely proportional to the gestational age and body weight at birth. The pathogenetic importance of impaired erythropoietin (EPO) production in anemia of prematurity provides the rationale for therapy with erythropoiesis stimulating agents (ESAs) including recombinant EPO. A comparative analysis of the effectiveness of different regimens of recombinant human erythropoietin in extremely and very low birth weight infants (ELBW and VLBW) was studied. Research has been set as a prospective analysis of 133 VLBW and ELBW infants (in the period from December 2017 to February 2019). Gestational age (GA) of the children ranged from 26 to 33 weeks, of these, GA of 75 children (56%) was 30 weeks or less. Depending on the treatment of anemia of prematurity all infants were divided into 5 groups: group 1 (n = 26) – premature babies who were prescribed ESAs since 3 day of life 200 IU/kg 3 times per week subcutaneously; group 2 (n = 21) – premature babies who were prescribed ESAs since 3 day of life 400 IU/kg 3 times per week subcutaneously; group 3 (n = 37) – premature babies who were prescribed ESAs since 8 day of life 200 IU/kg 3 times per week subcutaneously; group 4 (n = 18) – premature babies who were prescribed ESAs since 8 day of life 400 IU/kg 3 times per week subcutaneously; group 5 (n = 31) premature infants who did not receive treatment with recombinant human erythropoietin (control group). Subgroups of children of gestational age ≤ 30 weeks were identified in each group. The groups and subgroups did not differ significantly in gestational age, weight, birth length, and Apgar score at 1 and 5 minutes of life, p > 0.05. Also, there were no statistically significant differences in the age of the 1st transfusion, the frequency and total volume of transfusions, the duration of respiratory therapy, the duration of hospitalization, including treatment in NICU, body weight and age at discharge. The frequency of retinopathy of prematurity stage ≥ 3, periventricular leukomalacia, bronchopulmonary dysplasia of moderate and severe severity, intraventricular hemorrhages of varying severity, necrotizing enterocolitis was not statistically significant in the study groups and subgroups. Statistically significant differences in the concentration of hemoglobin in the peripheral blood of premature infants were revealed at discharge. In the control group, children had a lower level of hemoglobin at discharge (94 g/l) compared with the groups with early appointment of ESAs (109 g/l and 107 g/l in groups 1 and 2, respectively, P0-1 = 0.048 and P0-2 = 0.047) due to newborn GA ≤ 30 weeks. It is preferable to use of the drug ESAs at a dose of 200 IU/kg 3 p/week p/, starting from the 3rd day of life. The effectiveness of erythropoietin therapy, the time of its start and various treatment regimens remain controversial issues that require further study. The study was approved by the Independent Ethics Committee of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov.

Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis

“…Table 1 shows the characteristics of the 14 RCTs included in our meta-analysis [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Although prophylactic intravenous or subcutaneous rhEPO treatment started within the first week of life in all included RCTs, the exact timing, dosing, and duration of rhEPO varied considerably.…”

“…Selection bias: As shown in online supplementary Figure 1, random sequence generation and allocation concealment were sometimes incompletely reported (unclear risk). Two studies lacked allocation concealment (high risk) [30,31] Performance bias: In 6 RCTs, parents and personnel were unblinded to the study intervention (high risk) [21,[28][29][30][31][32]. Detection bias: The ophthalmologists performing the ROP assessments were not blinded in 4 RCTs (high risk) [21,[30][31][32].…”

“…Fig. 1) [21,[28][29][30][31][32]. The issue was addressed by sensitivity analyses, omitting the latter studies (online suppl.…”

“…There was no effect of rhEPO, neither on any ROP nor on ROP stage ≥3 [5]. In comparison to these four meta-analyses [3,5,11,13], our meta-analysis not only included subsequently published RCTs [22,28,30,31] but also benefited from direct communication with the corresponding authors. This allowed us to clarify questions of study design, to prevent overlaps in study populations, and to get further stratified data [19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”