Economics of preventing premature mortality and impaired cognitive development in children through home-fortification: a health policy perspective.

BACKGROUND: Home-fortification is a new strategy of adding micronutrients including zinc and iron to home-made foods. Zinc supplementation may prevent morbidity and mortality related to diarrheal illnesses, and iron supplementation may improve cognitive development, in children. OBJECTIVES: To project clinical and economic effects of home-fortification in children in an urban slum of Karachi, Pakistan. METHODS: This is a cost benefit analysis of 5,000 simulated male and female infants (6-12 months) assigned to micronutrients or placebo for 4 months and followed for 55 years. We linked the effect of zinc on longitudinal prevalence of diarrhea to mortality, and the effect of iron on hemoglobin to IQ scores and lifetime earnings. Cost estimates were based on volumes of resource utilization from the Pakistan Sprinkles Diarrhea study. Main outcome was incremental benefit defined as the gain in lifetime earnings after accounting for the incremental costs of micronutrients over placebo (societal perspective). RESULTS: Our model projected that the reduction in diarrhea and improvement in hemoglobin concentrations through home-fortification was associated with reduced child mortality, higher IQ scores, and higher earnings. The present value of incremental benefit was $106 (95 percent probability interval = $17 to $193) U.S. dollars, which corresponds to $464.79 ($74.54 to $846.27) international dollars using a purchasing power parity exchange rate. CONCLUSIONS: Home-fortification appears to improve clinical outcomes at a reasonable cost, and may actually be cost beneficial when lifetime earnings are considered.

Is cooking food in iron pots an appropriate solution for the control of anaemia in developing countries? A randomised clinical trial in Benin.

OBJECTIVE: To evaluate the effect of two types of iron pots on haemoglobin (Hb) and serum ferritin (SF) concentrations in young children (6-24 months), adolescent girls (11-15 years) and women of reproductive age (15-44 years), whose households were provided with iron pots for cooking food over a period of 6 months, compared with controls. DESIGN AND METHODS: We randomly assigned 161 households including 339 individuals from the three subgroups to cast iron pots, blue steel pots or oral iron supplements (control). In the control group, children received micronutrient Sprinkles, and adolescent girls and women received iron tablets daily for 6 months. We measured Hb, SF and C-reactive protein concentrations at baseline and 6 months, and compared groups using regression models. RESULTS: Anaemia prevalence (Hb < 110 g l(-1) in infants, Hb < 120 g l(-1) in girls or women) was 47% (cast iron group), 50% (blue steel group) and 50% (control) at baseline. At 6 months, there were no significant differences in Hb concentrations among groups; however, differences in SF concentrations were significant (P < 0.0001)--the control group had higher SF concentrations compared with the groups using iron pots. Also, differences in the prevalence of iron-deficiency anaemia (IDA; anaemia plus SF < 15 microg l(-1)) were almost significant between cast iron and control groups (P = 0.08), and blue steel and control groups (P = 0.05). CONCLUSION: There is no evidence that iron cooking pots are effective against IDA. Further research is warranted to determine whether the iron leached from the pots is bioavailable.

Children with autism: effect of iron supplementation on sleep and ferritin.

To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial.

Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.

Short-term daily or weekly administration of micronutrient Sprinkles has high compliance and does not cause iron overload in Chinese schoolchildren: a cluster-randomised trial.

OBJECTIVES: To examine consumption rates and serum ferritin (SF) concentrations (as a marker of safety) among schoolchildren (3-6 years) provided with daily and weekly micronutrients. DESIGN AND METHODS: Micronutrients were provided for one school term (13 weeks) to a kindergarten in northern China as single-dose Sprinkles sachets containing 30 mg of iron as encapsulated ferrous fumarate, 5 mg zinc gluconate, 50 mg vitamin C, 300 microg vitamin A, 7.5 microg vitamin D3 and 150 microg folic acid. Sixteen classrooms were randomly assigned to: (1) daily supplements for 5 days a week (daily group); (2) weekly supplements (weekly group); or (3) no supplements (control group). Consumption of sachets was monitored for each child and SF concentrations were measured at the end of study. Random effects general linear models and graphs were used to compare the groups. RESULTS: A total of 415 children from 16 classrooms entered the study. At the end of the study, mean consumption rates per child were 86% (daily group; standard deviation (SD) 12%) and 87% (weekly group; SD 16%). Median SF concentrations were 71 microg l(-1) (range 27-292 microg l(-1); daily group), 55 microg l(-1) (range 11-299 microg l(-1); weekly group) and 54 microg l(-1) (range 7-327 microg l(-1); control group); the overall difference was not significant (P=0.06). However, the daily group was significantly different from the control (P=0.02); daily and weekly groups had higher SF at lower percentiles and similar SF at higher percentiles compared with the control group. CONCLUSION: The high consumption rates and appropriate SF concentrations in the supplemented groups suggest that a short-term school programme with Sprinkles is an efficient and safe way to provide micronutrients (including iron).

Demonstrating zinc and iron bioavailability from intrinsically labeled microencapsulated ferrous fumarate and zinc gluconate Sprinkles in young children.

Nutrient-nutrient interactions are an important consideration for any multiple-micronutrient formulation, including Sprinkles, a home-fortification strategy to control anemia. The objectives of this randomized controlled trial were as follows: 1) to compare the absorption of zinc at 2 doses given as Sprinkles; and 2) to examine the effect of zinc and ascorbic acid (AA) on iron absorption from Sprinkles. Seventy-five children aged 12-24 mo were randomly assigned to the following groups: 1) 5 mg of labeled zinc (67Zn) with 50 mg AA (LoZn group); b) 10 mg of labeled zinc (67Zn) with 50 mg AA (HiZn group); or 3) 5 mg zinc with no AA (control). All groups contained 30 mg of labeled iron (57Fe). Intravenous infusions labeled with 70Zn (LoZn and HiZn groups) and 58Fe (control) were administered. Blood was drawn at baseline, 48 h and 14 d later. The percentage of zinc absorbed did not differ between LoZn (geometric mean = 6.4%; min-max: 1.7-14.6) and HiZn (geometric mean = 7.5%; min-max: 3.3-18.0) groups. However, total zinc absorbed was significantly different between the LoZn (geometric mean = 0.31 mg; min-max: 0.08-0.73) and HiZn (geometric mean = 0.82 mg; min-max: 0.33-1.82) groups (P = 0.0004). Geometric mean percentage iron absorption values did not differ between the LoZn (5.9%; min-max: 0.8-21) and HiZn (4.4%; min-max: 0.6-12.3) groups and between the LoZn and control groups (5.0%; min-max: 1.4-24). We conclude that zinc in the form of Sprinkles has a low bioavailability, yet provides adequate amounts of absorbed zinc in young children, and that there is no effect of zinc or AA on iron absorption from the given formulations of Sprinkles.

Physiologic mechanisms can predict hematologic responses to iron supplements in growing children: a computer simulation model.

BACKGROUND: Iron deficiency is the most common preventable nutrition problem in developing countries. Several randomized clinical trials (RCTs) have been conducted to determine the effectiveness of various iron dosing schemes in multiple settings. OBJECTIVE: The objective was to determine whether enough is known about iron metabolism to predict hemoglobin and serum ferritin (SF) concentrations with a computer model and whether the model could be used as a substitute for new RCTs. DESIGN: Guided by the physiology of iron absorption and regulation, we used data from RCTs that tested iron Sprinkles to develop a computer model. Of 2 RCTs in Ghana, we used 1 to compute the amount of iron absorbed from a given dose in anemic and nonanemic children and the other to compute the resulting change in hemoglobin concentrations. We used this model to predict hemoglobin and SF concentrations in a new RCT in China and compared model-predicted values with actual values by using summary statistics (means and medians) and quantile-quantile plots. RESULTS: The model-predicted hemoglobin means were within +/-2 g/L, and SF medians were within +/-3 microg/L of the corresponding means and medians of the actual values. On quantile-quantile plots, the predicted hemoglobin quantiles were within +/-5 g/L, and SF quantiles were within +/-10 microg/L of the corresponding quantiles of the actual values. CONCLUSION: Our model of iron metabolism can accurately predict hemoglobin and SF concentrations after iron supplementation with Sprinkles in children; the model can thus obviate the need for repeating RCTs in multiple settings.

Economic gains of a home fortification program: evaluation of "Sprinkles" from the provider's perspective.

INTRODUCTION: This paper models the effects of a home-fortification program (using Sprinkles which contain zinc and iron and other micronutrients), in Pakistan, a country with high levels of infant mortality, anemia, and diarrhea. It uses the results of randomized trials of the effect of Sprinkles on anemia and on longitudinal prevalence of diarrhea. METHODS: Based on previous literature, the effect of Sprinkles on intermediate outcomes (diarrhea and anemia) is linked to longer-term outcomes (infant and young child mortality, and cognitive achievement and hence adult wages). Three different measures of cost effectiveness are presented: the cost per death averted (effect via zinc supplementation on reduction of longitudinal prevalence of diarrhea); the cost per 'disability adjusted life year' (DALY) saved (same modality); and the gain in earnings due to higher cognitive functioning for each dollar spent (effect via iron supplementation on reduced anemia). RESULTS: We estimated that the cost per death averted is dollars406 (dollars273-dollars3248), the cost per DALY saved is dollars12.2 (dollars8-dollars97) and the present value of the gain in earnings is dollars37 (dollars18-dollars51) for each dollar spent on the Sprinkles program. These estimates were developed for a low-income country (GDP per capita = dollars417) with a high infant mortality rate (IMR = 83/1000), high prevalence of anemia (93%), and high mean longitudinal prevalence of diarrhea (17%). DISCUSSION: These outcomes are particularly favourable in Pakistan. The outcomes are more favourable when used with children 6-12 months. Further longer-run field trials of Sprinkles with larger populations would be helpful.

Acceptability of micronutrient sprinkles: a new food-based approach for delivering iron to First Nations and Inuit children in Northern Canada.

Iron deficiency anemia (IDA) is a significant public health problem among Canadian Aboriginal children. The objectives of this study were to determine the acceptability and safety of microencapsulated-iron sprinkles, a new powdered form of iron packaged in a single-serving sachet for prevention of IDA. A total of 102 non-anemic children aged 4 to 18 months from three communities were randomized to receive sprinkles containing 30 mg Fe/day (NR = 49) or placebo (NR = 53) for six months. To assess acceptability, adherence and side effects were monitored bi-weekly. To assess safety, serum ferritin (SF) concentration and anthropometry were measured at baseline and end. Mean adherence was 59.6 +/- 27.7 percent. There were no differences in adherence, SF, anthropometric status or side effects between groups. Although there were no differences in hemoglobin (Hb) concentration and anemia prevalence from baseline to end and between groups, the Hb curve shifted to the right (increased) for the sprinkles group and to the left (decreased) for the placebo group. Sprinkles may provide a safe and acceptable option to the current standard of care (i.e. ferrous sulphate drops) for the provision of iron in Canadian Aboriginal populations.

Controlling iron deficiency anemia through the use of home-fortified complementary foods.

Iron deficiency anemia (IDA) is more common in South Asian countries including India, Bangladesh and Pakistan than anywhere else in the world. During infancy and early childhood, IDA is associated with impaired psycho-motor development and cognitive function that may be irreversible. As a consequence, there is a growing awareness that IDA is one of many factors impeding socio-economic prosperity of developing nations. The combination of unacceptably high prevalence rates and inadequate preventative programs highlights the need for new effective sustainable strategies to control IDA. The burden of iron deficiency can be reduced by taking a more holistic approach that would include promotion of healthy weaning practices and use of appropriate complementary foods, together with improving the nutritional value of such foods. There is an increasing body of peer-reviewed literature to support the contention that "micronutrient Sprinkles" is an effective strategy to improve the nutritional value of home-prepared complementary foods and thus to reduce the burden of iron deficiency among children. By combining data from recently conducted randomised control trials, Sprinkles were shown to be as efficacious as iron drops for treating childhood anemia. The iron in Sprinkles is well absorbed, and Sprinkles are easy to use and well accepted by young children and their caregivers. Integrated into existing public health programs, Sprinkles has the potential to improve the effectiveness of such programs.