营养性缺铁性贫血婴幼儿的治疗

　　缺铁性贫血累及世界各地数百万人，与婴幼儿神经发育障碍有相关性。该年龄组缺铁性贫血的最常见原因为饮食铁摄入量不足，其成因有喝牛奶过多、哺乳时间过长但又未补充恰当剂量的铁，或两者兼有。虽然多糖铁可能有更好的耐受性，但是硫酸亚铁仍然是最常处方的口服铁剂。

　　2017年6月13日，《美国医学会杂志》正式发表贝勒医学院、德克萨斯儿童医院、德克萨斯大学西南医学中心、达拉斯儿童医学中心、库克儿童医学中心的研究报告，对两种口服铁剂（硫酸亚铁、多糖铁）治疗婴幼儿营养性缺铁性贫血的效果进行了比较。

　　该单中心双盲优效随机临床研究（BESTIRON）于2013年9月至2015年11月从达拉斯儿童医学中心血液科门诊入组年龄9～48个月（中位22个月）营养性缺铁性贫血（根据病史和实验室标准评定）婴幼儿80例，随机分为两组，每天口服元素铁3mg/kg（硫酸亚铁滴剂或多糖铁滴剂）共12周，其中59例完成研究，硫酸亚铁组、糖铁组分别有28例（70%）、31例（78%）。

　　主要结局衡量指标为12周血红蛋白变化，次要结局衡量指标包括完全纠正缺铁性贫血（定义为12周时复查血红蛋白浓度＞11g/dL、平均红细胞体积＞70fL、网织红细胞血红蛋白当量＞25pg、血清铁蛋白水平＞15ng/mL、总铁结合能力＜425μg/dL）、血清铁蛋白水平、总铁结合力的变化、不良反应。

　　结果发现，经过12周治疗后，硫酸亚铁组与多糖铁组相比：

• 平均血红蛋白浓度增幅较大（4.0g/dL比3.4g/L，P＜0.001）

• 缺铁性贫血完全纠正率较高（29%比6%，P=0.04）

• 血清铁蛋白水平的增幅较大（12.6ng/mL比5.5ng/mL，P＜0.001）

• 平均总铁结合能力降幅较大（112μg/dL比89μg/dL，P＜0.001）

• 腹泻发生率较低（35%比58%，P=0.04）

　　因此，对于9～48个月的营养性缺铁性贫血婴幼儿，硫酸亚铁与多糖铁相比，12周时血红蛋白浓度显著较高。对于营养性缺铁性贫血的儿童，应该考虑每天口服一次低剂量硫酸亚铁。

　　不过，本研究的局限性包括：仅在单个三级医院进行；低收入和少数民族的严重贫血患者数量不成比例，将近23%入组前需要输血；12周期间失访率达25%；临床研究与标准社区实践相比，监测比较严格，故这些结果可能无法推广到普通儿科人群。如果通过选择使用简化给药方案，创建实用的治疗措施，那么即使在临床环境中应用，也有可能改善结局。

JAMA. 2017 Jun 13;317(22):2297-2304.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

Powers JM, Buchanan GR, Adix L, Zhang S, Gao A, McCavit TL.

Baylor College of Medicine, Houston, Texas; Texas Children's Hospital, Houston, Texas; University of Texas Southwestern Medical Center, Dallas, Texas; Children's Health, Dallas, Texas; Cook Children's Medical Center, Ft Worth, Texas.

IMPORTANCE: Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated.

OBJECTIVE: To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA.

DESIGN, SETTING, AND PARTICIPANTS: Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016.

INTERVENTIONS: Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks.

MAIN OUTCOMES AND MEASURES: Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects.

RESULTS: Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P<.001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P=.04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over 12 weeks, a greater difference of 10.2 ng/mL (95% CI, 6.2 to 14.1 ng/mL; P<.001) with ferrous sulfate. Mean total iron-binding capacity decreased from 501 to 389 μg/dL (ferrous sulfate) vs 506 to 417 μg/dL (iron complex) (a greater difference of -50 μg/dL [95% CI, -86 to -14 μg/dL] with ferrous sulfate; P<.001). There were more reports of diarrhea in the iron complex group than in the ferrous sulfate group (58% vs 35%, respectively; P=.04).

CONCLUSIONS AND RELEVANCE: Among infants and children aged 9 to 48 months with nutritional iron-deficiency anemia, ferrous sulfate compared with iron polysaccharide complex resulted in a greater increase in hemoglobin concentration at 12 weeks. Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01904864.

PMID: 28609534

DOI: 10.1001/jama.2017.6846