Derman Richard J, Bellad Mrutyunjaya B, Somannavar Manjunath S, Bhandari Sudhir, Mehta Sudhir, Mehta Seema, Sharma Dharmesh Kumar, Kumar Yogesh, Charantimath Umesh, Patil Amaresh P, Mallapur Ashalata A, Ramadurg Umesh, Sangavi Radha, Patil Praveen S, Roy Subarana, Vastrad Phaniraj, Shekhar Chander, Leiby Benjamin E, Hartman Rebecca L, Georgieff Michael, Mennemeyer Stephen, Aghai Zubair, Thind Simal, Boelig Rupsa C
Department of Global Affairs, Thomas Jefferson University, Philadelphia, PA.
Department of Obstetrics and Gynaecology, KLE Academy of Higher Education and Research's J N Medical College, Belagavi, Karnataka, India.
Am J Obstet Gynecol. 2025 Feb 3. doi: 10.1016/j.ajog.2025.01.037.
Maternal iron deficiency anemia is a persistent global health challenge with increased risk of adverse perinatal outcomes. Obstetric guidelines advocate for first-line treatment of moderate iron deficiency anemia with twice-daily oral iron; however, rates of iron deficiency anemia in pregnancy remain above global targets and are rising.
Determine whether single-dose intravenous iron for primary treatment of maternal iron deficiency anemia in the second trimester is superior to twice daily oral iron in reducing incidence of low birth weight infants and maternal anemia at delivery.
This is a parallel, 3-arm, semiblind superiority randomized controlled multicenter trial across 4 sites in India from March 15, 2021-May 12, 2023. Participants were singleton pregnancies at 14 to 17 weeks with moderate iron deficiency anemia (hemoglobin 7.0-9.9 g/dL) who were randomized 1:1:1 to (1) 60 mg oral ferrous sulfate twice daily; or single-dose infusion of (2) intravenous ferric derisomaltose or (3) intravenous ferric carboxymaltose. Two intravenous arms were selected as these are the only 2 intravenous iron formulations publicly available in India. All participants received folic acid supplementation throughout pregnancy and antihelminthic therapy, as recommended by national guidelines. The dual primary outcomes were: (1) low birth weight (<2500 grams) and (2) attainment of a maternal nonanemic state (hemoglobin ≥11.0 g/dL at 30-34 weeks or delivery) for each intravenous iron arm vs oral iron; intravenous iron arms were not compared to each other. Secondary outcomes included safety measures, and other maternal and infant outcomes. Participants with hemoglobin <7 g/dL or <1 g/dL improvement on therapy received rescue treatment with intravenous iron or blood transfusion as determined by their provider. Sensitivity analyses included defining nonanemic state as achieving hemoglobin ≥11.0 without need for additional IV iron or transfusion. Comparison of each intravenous iron arm to oral iron was conducted with a 2-sided alpha set at 0.0005 for achieving nonanemic state and 0.0245 for low birth weight for each intravenous iron arm using a Cochran-Mantel-Haenszel chi-square test stratified by enrollment site.
The oral iron, ferric derisomaltose, and ferric carboxymaltose arms included 1450, 1456, and 1462 participants respectively. There was a reduced rate of low birth weight with intravenous ferric carboxymaltose (25·2%, relative risk 0·87 [97·55% confidence interval 0.75, 0.99], P=.017), but not intravenous ferric derisomaltose (29.1%, relative risk 0.98 [97.55% confidence interval 0.86, 1.12], P=.71) vs oral iron (29.3%). Achievement of nonanemic state was not improved: intravenous ferric carboxymaltose (relative risk 1.05 [99.95% confidence interval 0.97-1.15]) and intravenous ferric derisomaltose (relative risk 1.06 [99.95% confidence interval 0.98, 1.16]) vs oral (69.7%). In sensitivity analysis, there was increased rate of achieving nonanemic state without use of additional IV iron or transfusion in both intravenous ferric derisomaltose (relative risk 1.25 (1.13-1.396), P<.0001) and intravenous ferric carboxymaltose (relative risk 1.24 (1.12-1.38), P<.0001) vs oral iron.
First-line treatment of moderate maternal iron deficiency anemia with single-dose infusion of intravenous iron results in a reduced incidence of low birth weight infants (intravenous ferric carboxymaltose vs oral) and a higher incidence of attaining maternal nonanemic state without use of additional iron or blood transfusion (intravenous ferric carboxymaltose and ferric derisomaltose vs oral). Clinical guidelines should address the potential benefit of single-dose intravenous iron as the primary treatment of moderate iron deficiency anemia in pregnancy.
孕产妇缺铁性贫血是一项持续存在的全球健康挑战，会增加不良围产期结局的风险。产科指南提倡对中度缺铁性贫血进行一线治疗，采用每日两次口服铁剂；然而，孕期缺铁性贫血的发生率仍高于全球目标，且呈上升趋势。
确定孕中期单剂量静脉注射铁剂治疗孕产妇缺铁性贫血是否优于每日两次口服铁剂，以降低低出生体重儿的发生率和分娩时孕产妇贫血的发生率。
这是一项平行、三臂、半盲优效性随机对照多中心试验，于2021年3月15日至2023年5月12日在印度的4个地点进行。参与者为单胎妊娠，孕1�至17周，患有中度缺铁性贫血（血红蛋白7.0 - 9.9 g/dL），按1:1:1随机分为三组：（1）每日两次口服60 mg硫酸亚铁；或单剂量输注（2）静脉注射右旋糖酐铁或（3）静脉注射羧基麦芽糖铁。选择这两种静脉注射组是因为它们是印度仅有的两种可公开获得的静脉注射铁剂配方。所有参与者在整个孕期均按照国家指南的建议补充叶酸并接受抗蠕虫治疗。两个主要结局指标为：（1）低出生体重（<2500克）；（2）与口服铁剂相比，每种静脉注射铁剂组的孕产妇达到非贫血状态（孕30 - 34周或分娩时血红蛋白≥11.0 g/dL）；静脉注射铁剂组之间不进行比较。次要结局指标包括安全措施以及其他孕产妇和婴儿结局。治疗后血红蛋白<7 g/dL或改善<1 g/dL的参与者，由其医生决定接受静脉注射铁剂或输血的抢救治疗。敏感性分析包括将非贫血状态定义为无需额外静脉注射铁剂或输血即可达到血红蛋白≥11.0。使用按入组地点分层的Cochran - Mantel - Haenszel卡方检验，对每种静脉注射铁剂组与口服铁剂进行比较，设定双侧α值为0.0005以判断是否达到非贫血状态，设定双侧α值为0.0245以判断低出生体重情况。
口服铁剂组、右旋糖酐铁组和羧基麦芽糖铁组分别纳入1450、1456和1462名参与者。与口服铁剂组（29.3%）相比，静脉注射羧基麦芽糖铁组低出生体重发生率降低（25.2%，相对风险0.87 [97.55%置信区间0.75, 0.99]，P = 0.017），而静脉注射右旋糖酐铁组未降低（29.1%，相对风险0.98 [97.55%置信区间0.86, 1.12]，P = 0.71）。达到非贫血状态未得到改善：与口服铁剂组（69.7%）相比，静脉注射羧基麦芽糖铁组（相对风险1.05 [99.95%置信区间0.97 - 1.15]）和静脉注射右旋糖酐铁组（相对风险1.06 [99.95%置信区间0.98, 1.16]）均未改善。在敏感性分析中，与口服铁剂相比，静脉注射右旋糖酐铁组（相对风险1.25 [1.13 - 1.396]，P < 0.0001）和静脉注射羧基麦芽糖铁组（相对风险1.24 [1.12 - 1.38]，P < 0.0001）在不使用额外静脉注射铁剂或输血的情况下达到非贫血状态的发生率均增加。
单剂量静脉注射铁剂作为中度孕产妇缺铁性贫血的一线治疗，可降低低出生体重儿的发生率（静脉注射羧基麦芽糖铁与口服铁剂相比），并提高在不使用额外铁剂或输血的情况下达到孕产妇非贫血状态的发生率（静脉注射羧基麦芽糖铁和右旋糖酐铁与口服铁剂相比）。临床指南应提及单剂量静脉注射铁剂作为孕期中度缺铁性贫血主要治疗方法的潜在益处。
