Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review

Abstract

Background: Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy.

Objective: To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy.

Search strategy: An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords.

Selection criteria: We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

Data collection and analysis: Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328.

Main results: Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group.

Conclusions: Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.

Keywords: iron deficiency anemia; pregnancy; prenatal care; recombinant erythropoietin; treatment.

FIGURE 1

Flow diagram of studies identified in the meta‐analysis according to the PRISMA statement.

FIGURE 2

Assessment of risk of bias of randomized trials (RoB2.0). A summary of risk of bias for each trial. Plus sign indicates low risk of bias, minus sign indicates some concerns of bias, and x mark indicates high risk of bias.

FIGURE 3

Assessment of risk of bias of nonrandomized trials (ROBINS‐I). A summary of risk of bias for each trial. Plus sign indicates low risk of bias and minus sign indicates moderate risk of bias.