静脉注射二糖铁对产后缺铁性贫血治疗效果的Meta分析

2020-08-31 11:39:23 中国当代医药 2020年21期

邱文文 魏莉莉 李海鸿 仇杰 练芮含 虎亚光 柳雨雨 杨克虎

[摘要]目的 系統评价静脉注射二糖铁与口服硫酸亚铁对产后缺铁性贫血患者的有效性和安全性。方法 计算机检索PubMed、Cochrane Library、Web of Science、EMbase、CBM、WanFang Data、CNKI、VIP数据库,同时追溯相关的参考文献,搜集试验组静脉注射二糖铁(蔗糖铁、羧麦芽糖铁)及对照组口服硫酸亚铁对产后缺铁性贫血治疗后血红蛋白和铁蛋白效果的随机对照试验(RCTs),检索时限为建库至2019年6月。依据纳入标准和排除标准由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果 最终纳入10篇RCTs文献,共1877例患者。Meta分析结果显示,试验组治疗后14、28 d血红蛋白水平均高于对照组,差异有统计学意义[SMD=0.39,95%CI(0.18,0.60),P=0.0003;SMD=0.78,95%CI(0.59,0.96),P<0.000 01]。两组治疗后的铁蛋白和24 h血红蛋白水平比较,差异无统计学意义[SMD=0.47,95%CI(-0.56,1.50),P=0.37;SMD=0.31,95%CI(-0.32,0.94),P=0.33]。结论 静脉注射二糖铁可改善14、28 d的血红蛋白水平,提高临床有效性,但受纳入研究数量和质量的限制,上述结论尚需开展更多高质量随机对照研究予以验证。

[关键词]静脉注射;二糖铁;产后;缺铁性贫血;Meta分析

[中图分类号] R556.3          [文献标识码] A          [文章编号] 1674-4721(2020)7(c)-0016-06

Meta-analysis of the effect of intravenous injection of iron disaccharide in the treatment of postpartum iron deficiency anemia

QIU Wen-wen1,2   WEI Li-li3,4   LI Hai-hong1,2▲   QIU Jie5   LIAN Rui-han1   HU Ya-guang5   LIU Yu-yu1,2   YANG Ke-hu3,4

1. School of Nursing, Gansu University of Chinese medicine, Gansu Province, Lanzhou   730000, China; 2. Department of Nursing, Gansu Provincial Maternity and Child-care Hospital, Lanzhou   730050, China; 3. Center for Evidence-based Medicine, Lanzhou University, Gansu Province, Lanzhou   730030, China; 4. Key Laboratory of Evidence-based Medicine and Clinical Translational Medicine in Gansu Province, Lanzhou   730030, China; 5. Department of Administration, Gansu Provincial Maternity and Child-care Hospital, Lanzhou   730050, China

[Abstract] Objective To systematically evaluate the effectiveness and safety of intravenous injection of iron disaccharide and oral ferrous sulfate in patients with postpartum iron deficiency anemia. Methods PubMed, Cochrane Library, Web of Science, EMbase, CBM, WanFang Data, CNKI, VIP database were searched by the computer. At the same time, the relevant references were traced, and the randomized controlled trials (RCTs) of the effect of the intravenous injection of iron disaccharide (iron sucrose, iron carboxymaltose) in the experimental group and the oral ferrous sulfate in the control group on hemoglobin and ferritin after postpartum iron deficiency anemia were collected. The retrieval period was from database construction to June 2019. According to the inclusion criteria and exclusion criteria, two researchers independently screened the literature, extracted the data and evaluated the risk of bias in the included study. Then, RevMan 5.3 software was used for Meta-analysis. Results A total of 1877 patients were included in 10 RCTs. Meta-analysis results showed that the hemoglobin levels of the experimental group were higher than those of the control group on 14 and 28 days after treatment, and the differences were statistically significant (SMD=0.39, 95%CI[0.18, 0.60], P=0.0003; SMD=0.78, 95%CI [0.59, 0.96], P<0.000 01). There were no statistically significant differences in ferritin and 24 h hemoglobin levels between the two groups after treatment (SMD=0.47, 95%CI[-0.56, 1.50], P=0.37; SMD=0.31, 95%CI[-0.32, 0.94], P=0.33). Conclusion Intravenous injection of iron disaccharide can improve the hemoglobin levels at 14 and 28 days and improve the clinical effectiveness. However, due to the limitations of the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality randomized controlled studies.

[Key words] Intravenous injection; Iron disaccharide; Postpartum; Iron deficiency anemia; Meta-analysis

产后贫血是产褥期最常见的并发症之一,发病率为4.27%[1]。缺铁是贫血最常见的原因,且产后贫血以缺铁性贫血最为常见[2]。缺铁性贫血的产妇在产后会出现心悸、虚弱等现象,甚至带来严重的心血管问题[3],以致发病率增加,住院时间延长。静脉铁剂是一种胶质溶液,其吸收好,利用率高[4],近年来被广泛应用于临床。怀孕期间补充铁剂是对抗贫血的常见策略,当前证据表明,这种策略可以将足月贫血和产后缺铁性贫血的发生率降低近2/3,并改善其分娩结果[5]。静脉给予铁剂不仅能快速有效地补充患者体内铁的储备情况,而且能增加铁在骨髓中的沉积,可较好地改善患者的贫血状况。为了更全面地探讨静脉注射二糖铁对产后缺铁性贫血的有效性,本研究采用Meta分析的方法对产后缺铁性贫血患者静脉注射二糖铁的效果进行综合评价,以期为产后缺铁性贫血患者的治疗提供相关依据。

1资料与方法

1.1纳入及排除标准

1.1.1纳入标准  ①比较静脉注射二糖铁与口服硫酸亚铁对产后缺铁性贫血患者有效性和安全性的随机对照试验(randomized controlled trials,RCTs);②经临床诊断为产后缺铁性贫血的患者;③试验组静脉注射二糖铁(羧麦芽糖铁或蔗糖铁),对照组口服硫酸亚铁;④结局指标,研究中至少报道1项结局指标,包括血红蛋白、铁蛋白。

1.1.2排除标准  ①重复发表的文献;②非中英文文献;③非RCTs;④干预措施不符的文献;⑤数据不全、影响分析的文献;⑥会议摘要、传统综述等。

1.2检索策略

计算机检索PubMed、Cochrane Library、Web of Science、EMbase、CBM、CNKI、VIP、WanFang Data数据库,此外,追溯纳入文献的参考文献,以补充获取相关文献,检索时限均为建库至2019年6月。英文检索词包括:Ferric Compounds,Maltose iron,Iron carboxymaltose,Ferric Oxide,Saccharated,Iron Saccharate,Iron-Saccharate,Iron Sucrose,Ferri-Saccharate,Ferri Saccharate,Postpartum,Postpartum Women,Puerperium,Iron-Deficiency Anemia*,Iron Deficiency Anemia*;中文检索词包括:静脉注射羧麦芽糖铁、静脉注射蔗糖铁、产后、缺铁性贫血。

1.3文献筛选与资料提取

由两名研究者独立筛选文献、提取资料并交叉核对信息,如遇分歧,则通过讨论或与第三方协助判断。筛选文献时,先阅读文题和摘要,在排除不相关的文献后,进一步阅读全文,以确定是否纳入。提取内容主要包括:①纳入研究的基本信息:第一作者、国家、发表时间等;②纳入研究的基线特征:患者的年龄、性别、种族等;③结局指标:血红蛋白、铁蛋白。

1.4纳入研究的偏倚风险评价

由两名研究员独立按照Cochrane手册5.1.0推荐的RCTs偏倚风险评价工具评价纳入研究的偏倚风险,并且对结果进行交叉核对;如遇分歧,则通过讨论或由第三方协助解决。

1.5统计学方法

采用RevMan 5.3软件进行统计分析,计數资料采用相对危险度(RR)为效应指标,计量资料采用标准化均差(SMD)为效应指标,各效应量均给出点估计值和95%CI。纳入研究结果的异质性采用χ2检验进行分析(检验水准为α=0.05),同时结合I2定量判断异质性的大小,若各研究结果间无统计学异质性,则采用固定效应模型进行Meta分析;反之,则采用随机效应模型进行Meta分析。Meta分析的检验水准设为α=0.05,即以P<0.05为差异有统计学意义。若存在明显的临床异质性,则采用亚组分析或敏感性分析等方法进行处理,或描述性分析。采用漏斗图对发表偏倚进行分析。

2结果

2.1文献筛选流程及结果

初步检索共获得381篇文献,经两名研究员逐层筛选后,最终纳入10篇RCTs[6-15],文献筛选流程及结果见图1。

“*”表示PubMed=43,Cochrane Library=4,EMbase=19,Web of Science=0,CBM=26,VIP=131,CNKI=169,WanFang Data=100

2.2纳入研究的基本特征与偏倚风险评价结果

纳入的10项RCTs[6-15],包括1877例患者,年龄、例数、干预措施等基本特征具体见表1。在纳入的研究中,只有1篇RCT[10]提供了相当充分的方法学信息,Bhandal等[9]研究仅提供了随机时间表和密封不透明的信封;Seid等[14]使用随机数字表和密封不透明的信封;其余研究未提供关于如何随机化方法、分配隐藏、及盲法的方法学信息,偏倚风险评价的详细信息见表2。

2.3 Meta分析

2.3.1血红蛋白水平的Meta分析

2.3.1.1 24 h血红蛋白水平的Meta分析  有4项RCTs[7-10]研究分析了治疗后24 h的血红蛋白水平,包括试验组413例和对照组289例,异质性检验结果为I2=92%,P<0.000 01,研究不具有同质性,故采用随机效应模型分析。Meta分析结果显示,两组的24 h血红蛋白水平比较,差异无统计学意义[SMD=0.31,95%CI(-0.32,0.94),P=0.33](图2)。

3.4对未来研究的意义

本研究共纳入10篇RCTs,干预时机均为产后,提示对于产后缺铁性贫血早期筛查需完善,WHO在2016年发布了产后妇女补铁的指南,条件性的推荐在妊娠期贫血为公共健康问题,基于当前研究证据表明,静脉注射二糖铁可减少产后缺铁性贫血的发生。受纳入研究数量和质量的影响,该结论需要更多高质量研究予以验证。同时,建议今后的研究尽可能参考相应的报告规范,从而降低研究的偏倚风险,为临床研究提供高质量的研究证据。

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(收稿日期:2020-02-19)

[作者简介]邱文文(1993-),女,甘肃中医药大学护理学院2018级在读硕士研究生,研究方向:妇科护理

▲通讯作者:李海鸿(1970-),女,甘肃兰州人,本科,研究方向:妇产科护理