Research Partnership with Developing Countries
A Programme funded by Swiss National Science Foundation (SNSF) and Swiss Agency for Development and Cooperation (SDC)

Interactions of lead intoxication and iron deficiency in Morocco: lead source apportionment using stable isotopes and the effects of iron fortification with and without NaEDTA on lead burden, iron status and cognition in children

Background:
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. There are a large number of potential sources of dietary and environmental lead exposure in urban Morocco. The relative contribution of different routes or sources to human lead poisoning can be identified on the basis of the individual's blood lead isotope ratio; this can prioritize and target public health programs to reduce exposure.

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.

Objectives:

1. Assessment of body lead burden and iron status in a cohort of individuals residing in areas of presumed high lead exposure. Associations between lead burden and iron status will be investigated.
   
2. Investigation of nutritional risk factors for chronic lead poisoning in these groups, specifically, the contribution of low dietary iron intakes and identification of the most important environmental sources of lead exposure.
   
3. Comparison of effect on body lead and iron status of iron fortification with and without NaEDTA in lead-exposed children; and the relative impact on cognition.

Study design:
Our studies will be carried out in four sub-economic areas in and near Marrakesh, Morocco. 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 three groups (infants, school-aged children and lactating women), residing in areas of high lead exposure.

Furthermore lead isotopic ratio analysis will be used to identify lead sources and enable the apportionment of lead contamination from dietary and environmental sources in order to guide public health programs of lead abatement.

An 8-month intervention study in iron deficient, lead-exposed pre-school children 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) FeNaEDTA; 2) Na2EDTA dehydrate; 3) electrolytic iron (the iron compound often used in fortification programs); or 4) no fortificants.

Comparing among the groups at 8 months, the main biochemical outcome of the trial would be body lead burden, and functional outcomes of the trial would be child growth and cognitive and motor testing.

Expected outcomes
The results of this project will clarify the complex relationship between ID and lead poisoning.

Contact Addresses:

Swiss Coordinator:
Prof. Dr. med. Michael Zimmermann
Laboratory of Human Nutrition, Swiss Federal Institute of Technology (ETH) Zürich,ETH Zentrum, Schmelzbergstrasse 7, LFV E19
8092 Zürich, Switzerland
E-Mail: michael.zimmermann@ilw.agrl.ethz.ch

Main Foreign partner:

Prof. Dr.  Azzedine Sedki
Section of Ecotoxicology, Department of Biology
Faculty of Sciences Semlalia,
Marrakesh, Morocco
E-Mail: sedki@ucam.ac.ma