The Risk Factors And Safety Of Oral Iron Supplements For Iron Deficiency Anemia In Children: A Systematic Review

Objective In order to reduce the prevalence of iron deficiency anemia in 0 to 6 years old children, and to provide scientific basis for iron deficiency anemia(IDA) treatment guidelines, this study aimed at assessing the risk factors IDA among preschool children, comparing and evaluating the efficacy and safety of eight kinds of oral iron supplements,then select the best oral iron therapy for children IDA.Contents and methods(1) The CNKI, Wan Fang, VIP, China Biology Medicine disc, Pubmed, Science direct, Embase and Medline databases were searched. Literatures prior to November 2015 on the risk factors of children with IDA. Stata 12.0 was used for data analysis,Cochrane's Q and I2 statistics were used to evaluate heterogeneity among studies, subgroup analysis and sensitivity analysis were used to explore the heterogeneity sources. Publication bias was calculated by Begg rank correlation test and Egger linear regression test.(2) Searching and collecting domestic and foreign literature published before July 2015 about children with IDA and oral iron supplement from CNKI, Wan Fang,VIP, China Biology Medicine disc, Pubmed, Science direct, Embase Medline and Cochrane Library databases. We used random effects Bayesian models to statistical analysis in Win BUGS 1.4.3 which could be called by Net Meta XL macros in the Microsoft Excel software. The odds ratios(ORs) and mean ranking and the probability among eight kinds oforal irons were estimated. Forest plots and I2 statistics were used to evaluate heterogeneity among studies. Inconsistency models and nodal analysis were used to evaluate heterogeneity among studies.Results(1) Nineteen literatures involved 4061 participants were analyzed by the meta-analysis. The results of OR and 95% CI are as follows:residency(OR 1.630, 95% CI 1.136 to 2.339), Parents' education(OR 1.848, 95% CI 1.076 to 3.175),preterm(OR 12.370, 95% CI1.900 to 2.956), low birth weight children / huge child(OR 2.521, 95%CI 2.010 to 3.163), birth order(> 2 parities)(OR 4.794, 95% CI 1.562 to14.714), anemia in pregnancy(OR 13.267, 95% CI 2.208 to 4.833),unreasonable food supplement(OR 5.527, 95% CI 3.515 to 8.689), not timely complementary feeding(OR 5.194, 95% CI 3.138 to 8.597),recurrent respiratory infections(OR 3.363, 95% CI 1.945 to 5.816)and diarrhea(frequent or chronic)(OR 2.853, 95% CI 2.184 to 3.727).(2)We identified 48 eligible studies involved 5 085 children with IDA. In the total efficient respect, the results of OR and 95% CI compared with the ferrous sulfate were showed bellow:sodium iron chlorophyll(OR 12.52,95% CI 5.17 to 35.96), iron dextran(OR 10.46, 95% CI 4.68 to 27.04),multidimensional iron compounds(OR 6.73, 95% CI 2.39 to 20.89),ferrous fumarate(OR 6.10, 95% CI 2.06 to 19.99), ferrous succinate(OR5.06, 95%CI 2.03 to 16.43), iron polymaltose complex(OR 2.48, 95% CI1.01 to 6.98) and ferrous gluconate(OR 2.51, 95% CI 1.00 to 6.58)increased overall response rates. In the cure rate respect that multidimensional iron compounds(OR 3.74, 95% CI 1.77 to 8.12), iron dextran(OR 3.31, 95% CI 1.98 to 5.38), sodium iron chlorophyll(OR2.66, 95% CI 1.47 to 4.91) and ferrous succinate(OR 2.14, 95% CI 1.11 to 4.19) enhanced the cure rate when compared to ferrous sulfate. There were higher risk that ferrous sulfate(OR 0.00, 95% CI 0.00 to 0.03),sodium iron chlorophyll(OR 0.03, 95% CI 0.00 to 0.39), ferrous succinate(OR 0.02, 95% CI 0.00 to 0.23), ferrous gluconate(OR 0.01,95% CI 0.00 to 0.07), multidimensional iron compounds(OR 0.01, 95%CI 0.00 to 0.11), iron polymaltose complex(OR 0.02, 95% CI 0.00 to0.19) and ferrous fumarate(OR 0.01, 95% CI 0.00 to 0.12) prevented all side-effects when compared to iron dextran. There were higher risk that iron polymaltose complex(OR 0.02, 95% CI 0.00 to 0.23), ferrous fumarate(OR 0.01, 95% CI 0.00 to 0.14), multidimensional iron compounds(OR 0.01, 95% CI 0.00 to 0.14), ferrous gluconate(OR 0.01,95%CI 0.00 to 0.08) and ferrous sulfate(OR 0.00, 95% CI 0.00 to 0.04)prevented gastrointestinal side-effects when compared to iron dextran.Sodium iron chlorophyll has better overall response rates in treating children with IDA(SUCRA=0.8969), multidimensional iron compounds has better effect in cure rate(SUCRA=0.8651), and iron dextran has less risk in adverse event(SUCRA=0.9994) and gastrointestinal side-effects(SUCRA=0.9926) compared with eight kinds of oral irons, ferrous sulfate has the worst the efficacy and safety.Conclusion(1) Food supplement unreasonable, not timely complementary feeding, birth order(> 2 parities), recurrent respiratory infections, anemia in pregnancy, diarrhea(frequent or chronic), low birth weight children / huge child, preterm, parents' education and residency are the risk factors of 0 to 6 years old children with IDA.(2) Our results suggest that consumers and clinicians might be more cautious when using ferrous sulfate and ferrous gluconate to treat children with IDA, because of its highest risk among other oral iron supplements.(3) Iron dextran and sodium iron chlorophyll may be recommended as the best drug to treatchildren with IDA, however, due to the limited number and the poor quality of studies included, a large randomized controlled trial should be designed specially to confirm the results of our study.