Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial

Bouhouch, Raschida; El-Fadeli, Sana; Andersson, Maria; Aboussad, A.; Chabaâ, L.; Zeder, Christophe; Kippler, Maria; Baumgartner, Jeannine; Sedki, A.; Zimmermann, Michael

doi:10.3945/ajcn.115.129346

Cited by 38 publications

(51 citation statements)

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“…daily amount of fortified MN, determined as the daily difference between the intervention and control group); and study results (details on extracted data in the study protocol: http://www.crd.york.ac.uk/prospero/). For six studies with more than two intervention groups and one control group [24–29] we combined the intervention groups to create a single pairwise comparison (Cochrane Handbook; Chapter 16.5.4 [18]).…”

Section: Methodsmentioning

confidence: 99%

Health effects of micronutrient fortified dairy products and cereal food for children and adolescents: A systematic review

et al. 2019

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IntroductionMicronutrient (MN) deficiencies cause a considerable burden of disease for children in many countries. Dairy products or cereals are an important food component during adolescence. Fortification of dairy products or cereals with MN may be an effective strategy to overcome MN deficiencies, but their specific impact on health in this age group is poorly documented.MethodsWe performed a systematic review and meta-analysis (registration number CRD42016039554) to assess the impact of MN fortified dairy products and cereal food on the health of children and adolescents (aged 5–15 years) compared with non-fortified food. We reviewed randomised controlled trials (RCT) using electronic databases (MEDLINE, EMBASE, Cochrane library; latest search: January 2018), reference list screening and citation searches. Three pairs of reviewers assessed 2048 studies for eligibility and extracted data. We assessed the risk of bias and applied GRADE to rate quality of evidence.ResultsWe included 24 RCT (often multi MN fortification) with 30 pair-wise comparisons mainly from low- and middle income countries. A very small and non-significant increase of haemoglobin values emerged (0.09 g/dl [95%-CI: -0.01 to 0.18]; 13 RCT with iron fortification; very low quality of evidence). No significant difference was found on anaemia risk (risk ratio 0.87 [95%-CI: 0.76 to 1.01]; 12 RCT; very low quality), but a significant difference in iron deficiency anaemia favouring fortified food was found (risk ratio 0.38 [95%-CI: 0.18 to 0.81]; 5 RCT; very low quality). Similar effects were seen for fortified dairy products and cereals and different fortification strategies (mono- vs. dual- vs. multi-MN). Follow-up periods were often short and the impact on anthropometric measures was weak (low quality of evidence) Very low quality of evidence emerged for the improvement of cognitive performance, functional measures and morbidity.ConclusionsFortification of dairy products and cereal food had only marginal health effects in our sample population from 5–15 years. Further evidence is needed to better understand the health impact of fortified dairy products and cereals in this age group.Systematic review registrationThe study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 26 May 2016 (registration number CRD42016039554).

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Section: Methodsmentioning

confidence: 99%

Health effects of micronutrient fortified dairy products and cereal food for children and adolescents: A systematic review

et al. 2019

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“…It has been argued, however, that this ADI may have been set too low [56], and a recent trial in Moroccan children has shown that daily oral intake of EDTA can reduce blood lead concentrations [57], which is important in view of the enormous public health burden due to lead exposure in developing countries.…”

Section: Discussionmentioning

confidence: 99%

Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children

Teshome

Andang’o

Osoti

et al. 2017

BMC Med

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BackgroundWe aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12–36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results.MethodsWe gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home fortification for 30 days with either placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention.ResultsA total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α 1-acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I 2: 84.1%; p value for test of heterogeneity: <0.0001).ConclusionsIn this population, home fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our finding of heterogeneity between trial results should stimulate subgroup analysis or meta-regression to identify population-specific factors that determine efficacy.Trial RegistrationThe trial was registered with ClinicalTrials.gov (NCT02073149) on 25 February 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0839-z) contains supplementary material, which is available to authorized users.

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“…Iron and Na2EDTA each independently resulted in modest but statistically significant reductions in children's BLLs. 20 The trials in Mexico and India enrolled children with similar BLLs (mean of 11.4 and 12.0 mg/dL, respectively), and Moroccan children had lower BLLs (adjusted geometric mean of 4.3 mg/dL). In contrast, 12% of the Mexican children,~70% of the Indian children, and 32% of Moroccan children had iron deficiency.…”

Section: Iron Status Intake and Supplementationmentioning

confidence: 99%

“…The recent RCT of iron fortification is a notable exception. 20 There is an implicit assumption that the recommendations are appropriate for children with low or very low lead exposure; this assumption needs to be tested further.…”

Section: Tempering Expectationsmentioning

confidence: 99%

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The “Lead Diet”: Can Dietary Approaches Prevent or Treat Lead Exposure?

Kordas

2017

The Journal of Pediatrics

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lthough blood lead levels (BLLs) have been declining in the US for decades, pediatric lead exposure is an ongoing public health issue. 1 Given the welldocumented cognitive deficits at BLLs <10 mg/ dL, in 2012 the Centers for Disease Control and Prevention (CDC) called for renewed efforts for the primary prevention of any lead exposure in children. 2 Recent events in Flint, Michigan, also have served to refocus the public and health professionals on the seriousness of lead exposure. According to CDC statistics for years 2010-2014, 0.5%-0.6% of children (13 000-26 000) had confirmed BLLs ≥10 mg/dL and 4%-6% (106 000-282 000) ≥5 mg/dL. 3 Only 10%-18% of all children in the US aged <6 years, however, had a BLL test during that period. A recent study based on a national clinical laboratory database reported an overall prevalence of BLLs ≥10 mg/dL at 0.58% and ≥5 mg/dL at 2.95% for the years 2009-2015, with certain US states and cities particularly affected. 4 Whether through contaminated water, lead-based paint, or a combination of sources, the problem of lead exposure resurfaces periodically in US municipalities like Flint, Michigan, Washington, DC, or Buffalo, New York, 5-7 highlighting issues of aging infrastructures, under-resourced communities, poor decision making, and environmental injustice. Overlaid on these systemic causes are personal poverty and complex family situations, potentially creating multiple threats to optimal child health and development, including factors such as poor diet or low developmental stimulation. Parents and frontline health workers often are left to figure out how to help affected children, posing questions regarding effective interventions. Because dietary approaches seem relatively easy to implement compared with, for example, lead abatement or replacing old plumbing infrastructure, the conversation often turns to dietary recommendations. The 2012 CDC report highlights the role of pediatricians in educating families on nutrition as one primary prevention approach. 2 It should be emphasized that the prevention of lead exposure among vulnerable populations is the best solution to this problem and that intervening in exposure via dietary approaches does not address the root cause. Furthermore, careful examination of the links between nutrition (nutritional status, nutrients, diet) and lead exposure reveals limited and tenuous evidence. BLL Blood lead level CaT1 Calcium transport protein 1 CDC Centers for Disease Control and Prevention DMT1 Divalent metal transporter 1 RCT Randomized controlled trials See related article, p 218

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Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial

Abstract: Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.

Cited by 38 publications

References 40 publications

Health effects of micronutrient fortified dairy products and cereal food for children and adolescents: A systematic review

Health effects of micronutrient fortified dairy products and cereal food for children and adolescents: A systematic review

Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children

The “Lead Diet”: Can Dietary Approaches Prevent or Treat Lead Exposure?

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