Fortification of staple cereal flours with iron and other micronutrients: cost implications of following World Health Organization-endorsed recommendations.

BACKGROUND: Wheat and maize flours are widely used delivery vehicles for mass fortification. In lower-income countries, most, if not all, national-level cereal flour fortification programs routinely fortify with iron; however, cofortification with other micronutrients is common. Little information is available on the cost implications programs face when considering current fortification practices versus what the World Health Organization (WHO) interim consensus statement recommends. OBJECTIVE: The objectives of the present paper are to provide information on the costs of adding different chemical forms of iron and/or other micronutrients to premix formulations, and to discuss some of the issues that should be considered regarding which micronutrients to include in the premix. METHODS: Nine countries in Latin America, Africa, and Asia (three countries per region) that currently cofortify with multiple micronutrients including iron were selected based on low (< 75 g/day), medium (75 to 149 g/day), and high (> or = 150 g/day) mean population flour consumption levels. Premix costs per metric ton of flour produced were estimated for improving iron formulations and for following WHO recommendations for other micronutrients. RESULTS: For the selected programs to maintain current premix formulations and improve iron compounds, premix costs would increase by between 155% and 343% when the iron compound was switched from electrolytic iron to sodium iron ethylenediaminetetraacetate (NaFeEDTA), by 6% to 50% when it was switched from electrolytic iron to ferrous sulfate, and by 4% to 13 when iron addition rates were adjusted without switching the compound. To meet WHO recommendations for other micronutrients, premix costs would increase the most when the amounts of vitamins B12 and A were increased. CONCLUSIONS: For programs that currently cofortify with iron and additional micronutrients, the quality of the iron fortificant should not be overlooked simply to be able to afford to add more micronutrients to the premix. Micronutrients should be selected according to population needs, costs, and potential beneficial synergistic reactions the added micronutrients may have.

The potential role of NaFeEDTA as an iron fortificant.

Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can combine with virtually every metal in the periodic table. CaNa2EDTA and Na2EDTA (ADI 2.5 mg EDTA/kg body weight/day) are widely used as sequestering agents in canned products, while NaFeEDTA is a promising iron fortificant. Binding of EDTA with iron is favored in the acid milieu of the stomach, irrespective of whether the EDTA is administered as CaNa2EDTA, Na2EDTA, or NaFeEDTA, but in the more alkaline medium of the duodenum the iron is exchanged, in part, with other metals. The iron released from EDTA is absorbed by the normal physiological mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges with the intrinsic food iron and the EDTA partially protects the iron in this common non-heme iron pool from the effects of inhibitors of iron absorption, such as phytates and polyphenols. When iron is added as NaFeEDTA to an inhibitory meal, it is two to three times better absorbed than is iron added as ferrous sulfate. It also has a similar effect on the intrinsic food iron in the meal. Fortification with NaFeEDTA is most efficacious when administered with cereal- and legume-based diets but offers no advantages over other fortificants when added to meals of high bioavailability. Its potential as a fortificant has been confirmed in five extended fortification trials carried out in developing countries. There is no evidence that NaFeEDTA in the dose range proposed for food fortificants (5 to 10 mg iron daily) will have any direct toxic effects. Na2EDTA and CaNa2EDTA have proved safe over a number of years, while the Joint FAO/WHO Expert Committee on Food Additives concluded in 1999 that NaFeEDTA "could be considered safe when used in supervised fortification programs". Animal and human studies, including the results of two fortification trials, suggest that NaFeEDTA has little or no effect on overall zinc metabolism. Indeed, if anything, it increases zinc and possibly copper absorption. Data on potentially toxic metals, such as lead mercury, aluminum, and manganese, are limited but the evidence that is available is uniformly negative thus far. Further studies in this field are desirable. The long-term potential of NaFeEDTA fortification to cause iron overload is conjectural but the available evidence suggests that homeostatic controls would prevent excess iron accumulation in the normal population. NaFeEDTA, which is pale yellow in color, causes fewer organoleptic changes in a number of stored vehicles, including cereals, than do other soluble iron salts. Other potential vehicles include condiments, several of which have been successfully used in fortification trials. What is currently lacking is a consolidated body of published evidence on the stability of NaFeEDTA during processing, storage, and household cooking in widely consumed food vehicles, coupled with standardized testing of consumer acceptance of each fortified vehicle. While NaFeEDTA seems to be an appropriate fortificant for developing countries, its cost is about six to eight times that of ferrous sulfate in terms of equivalent amounts of iron. Its better absorption (a factor of 2-3) might make it possible to halve the daily fortification level but, it still remains expensive and there is a pressing need for food grade NaFeEDTA at more affordable prices. Another possible option is the use of other salts of EDTA (Na2EDTA or Ca Na2EDTA) together with a soluble source of iron, such as ferrous sulfate. The combination has been shown to be as effective as NaFeEDTA when the EDTA:Fe molar ratio is between 1:2 and 1:1. This approach is, however, only feasible with vehicles that are stored for short periods because of ferrous sulfate's propensity to cause organoleptic changes. The search for an iron source that is more stable but at the same time available to combine with EDTA has been unsuccessful thus far. Target populations for fortification with NaFeEDTA include all those that subsist on cereal- and legume-based diets, with the most appropriate vehicles being cereal products and condiments. The fortification of infant milk and cereal formulas with NaFeEDTA does not seem appropriate, since the amounts of NaFeEDTA required for effective fortification would be close to the acceptable daily intake (ADI) of 2.5 mg EDTA/kg body weight/day.

Clinical and cost effectiveness of a new hepatocellular MRI contrast agent, mangafodipir trisodium, in the preoperative assessment of liver resectability.

BACKGROUND: Improved preoperative assessment of focal liver disease and tumors could have a potentially significant impact on their treatment. Mangafodipir trisodium (Teslascan; Nycomed Amersham Imaging, Little Chalfont, UK) is a new hepatocellular contrast agent for use with state-of-the-art MR imaging that, in early reports, is accurate in detection and characterization of liver lesions. METHODS: Records and diagnostic images of all patients undergoing enhanced Teslascan MRI (T-MRI) at our institution were reviewed. We assessed the relative sensitivities of contrast-enhanced CT scan (CECT) and T-MRI in detecting lesions, as well as the impact of T-MRI in the decision to operate or not on patients. In those patients taken to surgery, the correlation between T-MRI and intraoperative palpation and intraoperative ultrasound (IOUS) was determined. RESULTS: Fifty-four patients were noted on CECT to have focal liver lesions and subsequently underwent imaging with T-MRI. The T-MRI correlated with CT findings in 22 patients (41%), upstaged the liver disease in 26, and demonstrated fewer lesions in 6. Only 43 patients were considered operative candidates and T-MRI influenced the operative decision in 32 patients (74%), dissuading operative intervention in 14. In the 25 patients without clear preoperative evidence of unresectability who were taken to the operating room, T-MRI correlated with findings of intraoperative palpation in 19 (76%). In the 20 patients who underwent IOUS, T-MRI correlated with IOUS in 14 patients (70%). IOUS detected an additional nine lesions, all of which were <1 cm. Seventeen patients underwent resection and/or ablation of their liver lesions. Compared with pathology, sensitivities of CECT, T-MRI, and intraoperative evaluation were 61%, 83%, and 93%, respectively. T-MRI failed to predict hepatic-specific unresectability in only one of eight patients, the other seven having extrahepatic disease. CONCLUSIONS: These findings suggest that T-MRI is more sensitive than CECT in the preoperative predicting of the resectability of hepatic lesions. Despite T-MRI accurately correlating with intraoperative surgical findings, IOUS should be performed on all patients prior to a final decision to resect or ablate a focal liver lesion.

A comparative study of smear layer removal using different salts of EDTA.

Three solutions of EDTA--a 15% concentration of the alkaline salt, a 15% concentration of the acid salt, and a 25% concentration of the alkaline salt--were evaluated for smear layer removal in root canal systems. All solutions were adjusted to pH 7.1 using either NaOH or HCl. When the EDTA solutions were alternately used for root canal irrigation with 5.25% NaOCl, they completely removed the smear layer in the middle and coronal thirds of canal preparations, but were less effective in the apical third. None of the EDTA solutions by themselves were effective at completely removing the smear layer at any level. The alkaline tetrasodium salt, pH adjusted with HCl, is more cost effective and performed equally as well as the more commonly used disodium salt.

Management of childhood lead poisoning: clinical impact and cost-effectiveness.

OBJECTIVES: No consensus exists regarding the preferred treatment of childhood lead poisoning. The authors used decision analysis to compare the clinical impacts and cost-effectiveness of four management strategies for childhood lead poisoning, and to investigate how effective chelation therapy must be in reducing neuropsychologic sequelae to warrant its use. METHODS: The model was based on a 2-year-old child with moderate lead poisoning [blood lead level 1.21 to 1.88 mumol/L (25 to 39 micrograms/dL)]. The following strategies were compared: 1) no treatment; 2) EDTA provocation testing, followed by chelation if testing is positive (PROV); 3) penicillamine chelation with crossover to EDTA provocation testing if toxicity occurs (PCA); 4) EDTA provocation testing with crossover to penicillamine chelation if testing is negative (EDTA). RESULTS: The EDTA and PCA strategies prevented 22.5% of the cases of reading disability and resulted in an increase of 1.02 quality-adjusted life years compared with no treatment. When the costs of outpatient EDTA testing and chelation are considered, the EDTA strategy is more cost-effective than the PCA strategy; when inpatient costs are considered, the PCA strategy becomes more cost-effective. When costs of remedial education are considered, all strategies are cost-saving compared with no treatment if chelation reduces the risk of lead-induced reading disability by more than 20%. CONCLUSIONS: Treatment strategies for childhood lead poisoning vary in clinical impact, cost, and cost-effectiveness. Chelation of the 1.4% of United States preschoolers whose blood lead levels are 2.21 mumol/L (25 micrograms/dL) or higher could prevent more than 45,000 cases of reading disability, and save more than $900 million per year in overall costs when the costs of remedial education are considered.