Iron Fortification Trail Using NaFeEDTA in Iron Deficient Lead-exposed Children
Condition: Iron Deficiency; Lead Poisoning
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies; Poisoning; Lead Poisoning
Study type: Interventional

Summary: 
      In a cross-sectional study allotted by the ethical committee of the ETH Zurich, we are
      investigating the extent of anemia, iron deficiency and lead intoxication in young children.
      For this purpose an assessment of body lead burden and iron status was conducted in a cohort
      of individuals residing in areas of presumed high lead exposure. Associations between lead
      burden and iron status will be investigated in the near future (current status of the study).

      In a follow-on intervention study, the effect of iron fortification with and without NaEDTA
      on blood lead levels in lead-exposed children will be evaluated; and the relative impact of
      these two strategies on child growth, motor and cognitive test performance will be compared.

      This study will investigate the potential use of iron fortification to not only combat anemia
      but also reduce body lead burden in lead-exposed populations; it specifically investigates
      whether iron fortification with NaFeEDTA could have additional beneficial effects to iron
      alone.
    

Detailed description: 
      Introduction Coexisting chronic lead poisoning and iron deficiency anemia (IDA) are common in
      urban areas in developing regions, particularly in young children. In urban Morocco, anemia
      affects more than 1/3rd of schoolchildren and lead exposure is high. Lead poisoning and IDA
      both impair cognitive development and educability and may therefore have substantial health,
      social and economic costs on developing countries.

      Iron status alters susceptibility to gastrointestinal lead exposure; absorption of lead is
      sharply increased in children with IDA. IDA upregulates the divalent metal transporter
      trans-port protein (DMT-1) and increases lead absorption. Thus, iron fortification to reduce
      IDA may also reduce lead absorption and be an effective strategy to accompany environmental
      lead abatement. The optimal iron compound for wheat flour is currently debated, and although
      elemental iron compounds are commonly used, they may be only poorly absorbed in the face of
      inhibitory compounds found in wheat flour.

      A form of chelated iron, NaFeEDTA, is a promising iron fortificant that is recommended for
      wheat flour fortification. It is also a lead chelator. It may be superior to other iron
      fortificants in its ability to reduce body lead burden, due to:

        1. its iron is highly bioavailable in the face of dietary inhibitors (such as phytic acid
           in wheat flour); and

        2. potentially, its ability to chelate lead in the gut and bloodstream. Thus, it may be a
           good choice for fortification of wheat flour in Morocco, particularly in urban areas, to
           both reduce IDA and lower body lead.

      Study aims and objectives:

        1. Assessment of body lead burden and iron status in a cohort of individuals residing in
           areas of presumed high lead exposure. Investigation of associations between lead burden
           and iron status.

        2. Comparison of effect of iron fortification with and without NaEDTA on body lead and iron
           status in lead-exposed children; and the relative impact on cognition.

      Study hypotheses:

      The prevalence of iron deficiency and elevated blood lead will be high in children in this
      region.

      2) Body lead burden, as assessed by blood lead levels and urinary lead and
      delta-aminolevulinic acid (ALA), will be higher in individuals with poorer iron status.

      3) Poor iron status will be associated with low intakes of bioavailable iron. 4) Greater
      severity of iron deficiency and/or higher body lead in children will predict poorer
      performance on cognitive and motor tests, and these conditions will interact to predict
      poorer performance.

      Study design:

      Our studies will be carried out in one of the four sub-economic areas, that were previously
      used in the baseline assessment in and near Marrakesh, Morocco (exact site still needs to be
      determined according to extend of lead contamination on the level of human population). Body
      lead burden and iron status will be determined, and associations between these examined using
      a cross-sectional design. For this purpose, blood and urine samples will be collected from
      two groups (preschool and school-aged children), residing in an area of high lead exposure.

      Study design:

      An 8-month intervention study in iron deficient, lead-exposed school children (n=500) will be
      designed to investigate whether iron fortification to reduce IDA may also reduce lead
      absorption and be an effective strategy to accompany environmental lead abatement.

      For this purpose these children will be divided into four groups to receive a daily fortified
      baked snack containing either: 1) 66.4 mg NaFeEDTA ; 2) 52.2 mg Na2EDTA dehydrate; 3) 27.1 mg
      FeSO4 ; or 4) no fortificants.
    

Intervention name(s): iron fortified biscuits; iron fortified biscuits; iron fortified biscuits; iron fortified biscuits
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 10 mg of iron per day for 8 months, either in the form of NaFeEDTA; 10 mg of iron per day for 8 months, in the form of FeSo4; EDTA fortified biscuit on a daily basis for 8 months; control biscuit on a daily basis for 8 months
Intervention MeSH terms: Iron
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Health Services Research
Keywords: iron deficiency; Lead poisoning; cognitive development; motor activity