Recommendations for the treatment of iron deficiency and iron deficiency anemia during pregnancy based on patient blood management strategies

Clinical question What are the recommendations for the treatment of iron deficiency (ID) and iron deficiency anemia (IDA) based on patient blood management strategies? Recommendations Oral iron therapy: Oral iron therapy is the first choice for the treatment of ID and IDA during pregnancy (Good Practice Statement [GPS]). Intravenous iron therapy: For pregnant women who exhibit poor compliance, intolerance to oral iron preparations, an inadequate response to oral iron, or severe anemia, intravenous iron therapy is recommended during the second and third trimesters. Newer formulations of intravenous iron, which allow for the administration of larger doses, are considered viable and effective options (Evidence quality: Moderate [B], recommendation strength: Strong). Red blood cell (RBC) transfusion: Red blood cell transfusion is indicated for pregnant women whose hemoglobin (Hb) concentration is <70 g/L (GPS). Recommendation Explanation Patient blood management (PBM) is a patient-centered, systematic, evidence-based approach to optimizing patient outcomes by managing and preserving a patient’s own blood while promoting patient safety and empowerment.[1,2] PBM comprises a series of measures and methods to maintain the Hb concentration, optimize hemostasis, minimize blood loss, and limit blood transfusions.[3] Pregnancy, delivery, and the puerperium are associated with increased risks of anemia and blood loss, which correlate with worse maternal and fetal outcomes and place pregnant women at increased risk of blood transfusion. Therefore, pregnant and parturient women are important patient populations on which PBM focuses.[4,5] PBM in obstetrics should focus on different stages—pregnancy, peripartum, and postpartum—and the cornerstone of obstetric PBM lies in the timely correction of antenatal anemia, early detection of and intervention with hemorrhage risk factors, and, ultimately, achievement of blood conservation and avoidance of transfusion. Anemia during pregnancy represents a relatively common obstetric complication, with ID being the most common cause of anemia, resulting from increased erythropoiesis in the mother, fetal and placental iron consumption, and blood loss during delivery. In addition, many women of reproductive age are already iron deficient prior to pregnancy. Consequently, the treatment of ID and IDA represents a vital element in comprehensive obstetric PBM strategies. In China, the diagnostic criterion for anemia during pregnancy is Hb concentration <110 g/L. ID during pregnancy is indicated by a serum ferritin concentration of <20 µg/L, whereas anemia accompanied by a serum ferritin level below the established threshold is a diagnostic criterion for IDA.[6] In terms of dosage selection, pregnant women diagnosed with IDA are recommended to receive a daily dose of 100–200 mg of elemental iron. Hb levels should be monitored after 2 weeks to evaluate treatment efficacy. For nonanemic pregnant women whose serum ferritin concentration is less than 30 µg/L, a daily supplementation of 60 mg of elemental iron is necessary, with efficacy evaluation conducted after 8 weeks.[6] The management measures for ID during pregnancy primarily involve oral and intravenous (IV) iron supplementation. Oral iron therapy remains the first-line treatment for ID and IDA during pregnancy, given its cost-effectiveness, ease of administration, and well-demonstrated therapeutic efficacy. However, IV iron therapy should be prioritized in cases of intolerance to oral iron preparations, poor patient compliance, or severe anemia.[6–8] Notably, the first trimester is a critical period for fetal development and organ formation. Owing to the lack of sufficient evidence on the safety of IV iron during this stage, oral iron therapy is recommended during the first trimester. IV iron should be considered in the second and third trimesters for women with severe IDA or for those who exhibit an inadequate response to oral iron (Hb concentration increases by <1 g/dL or remains <10 g/dL after 2–3 weeks of treatment), have poor oral iron tolerance, or require rapid correction.[9] In terms of the efficacy and safety, a systematic review and meta-analysis comparing IV and oral iron therapies during pregnancy demonstrated a superior efficacy of IV iron, as evidenced by the following three key outcomes: (1) a higher likelihood of achieving the target Hb level (pooled OR 2.66, 95% CI 1.71–4.15); (2) a greater elevation in the Hb level at 4 weeks (pooled weighted mean difference (WMD) 0.84 g/dL, 95% CI 0.59–1.09 g/dL); and (3) a reduced incidence of adverse reactions (pooled OR 0.35, 95% CI 0.18–0.67).[10] These findings underscore the superior efficacy and tolerability of IV iron in managing iron deficiency during pregnancy. Furthermore, studies indicate that IV iron therapy does not appear to increase adverse outcomes.[11] However, it is crucial to emphasize that pregnant women receiving IV iron require close monitoring—including vital signs, symptomatic responses, and allergic reactions—for at least 30 minutes postinfusion to minimize risks.[12] Additionally, more well-coordinated research with standardized outcome measures and enhanced safety reporting for both intravenous and oral iron preparations is warranted. On the other hand, recent advances in IV iron therapy have demonstrated significant improvements over traditional preparations, particularly through the development of larger and more complex carbohydrate shells. These structural modifications facilitate the controlled release of free iron, enabling the administration of higher therapeutic doses. Randomized controlled trials have demonstrated that intravenous ferric carboxymaltose (1000–1500 mg) and ferric derisomaltose (1000 mg) significantly improve hemoglobin levels more effectively than oral iron does in pregnant women.[12,13] However, ferric carboxymaltose is associated with an increased risk of hypophosphatemia, necessitating close monitoring of serum phosphate levels in high-risk groups.[14] Furthermore, the current body of evidence is primarily drawn from international research; data specific to China are scant, indicating a clear need for further study. RBC transfusion is recommended for pregnant women with Hb concentrations <70 g/L, while in those with Hb concentrations between 70 and 100 g/L, transfusion should be guided by clinical symptoms and can be combined with oral or IV iron supplementation.[6] Oral iron should be continued for ≥3 months after normalization of Hb levels. However, a recent prospective multinational observational study revealed that both low (<100 g/L) and high (>145 g/L) maternal Hb levels were associated with elevated risks of adverse outcomes, including pregnancy-induced hypertension, preterm birth, and acute respiratory distress syndrome[15]. Similarly, a meta-analysis confirmed that abnormal Hb levels—both low (<110 g/L) and high (>130 g/L)—were linked to various complications. Specifically, low hemoglobin levels were associated with adverse birth outcomes (low birth weight, preterm delivery, small for gestational age (SGA), stillbirth, and perinatal/neonatal mortality) and maternal risks (postpartum hemorrhage, preeclampsia, and transfusion requirements). Additionally, high Hb levels were correlated with increased incidences of SGA, stillbirth, preeclampsia, and gestational diabetes.[16] Therefore, Hb levels should be closely monitored following treatment and should not exceed 130 g/L. Evidence Summary This rapid recommendation was developed in accordance with the standardized methodology framework outlined in the STAR Recommendations.[17] Comprehensive documentation of the evidence retrieval strategy, detailed search results, the GRADE methodology for quality assessment of evidence, and other information is available in the Supplementary Materials, https://links.lww.com/CM9/C717. Funding This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2024ZD0532100). Conflicts of interest None.