Amanda C. Palmer

Vitamin A Fortification of Wheat Flour: Considerations and Current Recommendations:

Background Vitamin A deficiency is a major public health nutrition problem, affecting an estimated 190 million preschool-aged children and 19 million pregnant and lactating women globally, and 83 million adolescents in Southeast Asia alone. Its consequences (disorders) include xerophthalmia (the leading cause of early childhood blindness), increased severity of infection, anemia, and death. Because vitamin A deficiency is largely due to chronic dietary insufficiency of preformed vitamin A and proactive carotenoids, food fortification can offer an effective approach to prevention. Objective To provide guidance on fortifying wheat and maize flour milled in industrial rollers for national fortification programs in countries where vitamin A deficiency is considered a public health problem. Methods Critical review of the literature on the dietary gap in vitamin A intake and levels of wheat flour intake among risk groups as a basis for determining vitamin A fortificant levels. Additional review of efficacy evidence, safety and cost considerations, and country experiences related to wheat-flour fortification with vitamin A. Results Mill-rolled wheat flour is a technically fortifiable, centrally processed food vehicle that, where routinely and adequately consumed by target groups, should be considered a candidate for fortification. Vitamin A can be stable in flour under typical, ambient conditions, with processing losses estimated at approximately 30%, depending on source and premix conditions. Conclusions Factors to guide a decision to fortify flour with vitamin A include the extent of deficiency, availability of other food vehicle options, the centrality of milling, market reach and population intake distributions of the flour products, the dietary vitamin A intake required, and associated costs. Large gaps persist in knowledge of these factors, which are needed to enable evidence-based fortification in most countries, leaving most decisions to fortify guided by assumptions. Where flour can and should be fortified, guidelines are given for providing nearly 25% of the Recommended Dietary Allowance for vitamin A to vulnerable groups consuming varying ranges of flour products. The costs will vary according to the level of fortification.

The use and interpretation of serum retinol distributions in evaluating the public health impact of vitamin A programmes

OBJECTIVE Developing countries have adopted universal, high-potency vitamin A (VA) supplementation and food fortification as major strategies to control deficiency, prevent nutritional blindness and reduce child mortality. Yet questions persist regarding how best to measure impact and when to phase out supplementation. The present paper provides guidance on the use and interpretation of serum retinol (SROL) distributions as indicators of both programme impact and adequate VA intake in a population. DESIGN We reviewed extant data on SROLs response to high-potency VA supplementation and VA-fortified foods in children. RESULTS Supplementation virtually eliminates xerophthalmia and reduces child mortality; however, it shifts the SROL distribution only transiently (<2 months). Regular consumption of VA-fortified foods prevents xerophthalmia, lowers mortality and sustainably improves SROL distributions, from which both compliance and public health impact can be inferred. CONCLUSIONS Given SROLs limited responsiveness to high-potency VA supplementation, target population coverage remains the preferred performance indicator. However, periodic SROL surveys do reflect underlying dietary risk and can guide programming: low or marginal SROL distributions in areas with high supplementation coverage do not signify programme failure, but rather suggest the need to continue supplementation while working to effectively raise dietary VA intakes. We propose that a sustained rise in the SROL distribution, defined as ≤5 % prevalence of SROL < 0·70 μmol/l among vulnerable population groups in at least two consecutive surveys (≥1 year apart), be used as an indicator of stable and adequate dietary VA intake and status in a population, at which point programmes may re-evaluate the need for continued universal supplementation.

Evolution of the Child Health Day Strategy for the Integrated Delivery of Child Health and Nutrition Services

Background In efforts to meet the Millennium Development Goal for mortality among children under 5 years of age, countries require strategies for covering hard-to-reach and older children who are often missed by routine, fixed-site health services. Objective To document the evolution of Child Health Days (CHDs), designed as regular events for the delivery of health and nutrition services to children under the age of five. Methods We extracted information on service delivery strategies and codelivered interventions for the period 1999 to 2010 from global monitoring databases for vitamin A and immunization. Results Our data illustrate a dramatic rise in CHDs over the decade: only two countries held CHDs in 1999; in 2010, 96 CHDs were conducted in 51 countries. Reliance on CHDs has been particularly marked in sub-Saharan Africa, where they are increasingly used to deliver five or more services per event. Whereas early CHDs were largely defined by codelivery of vitamin A, immunizations, and deworming, they have since evolved into diverse packages including services such as water purification tablets and screening for severe malnutrition. Conclusions The scale-up of CHDs is helping countries to achieve high and equitable coverage of essential health and nutrition services. Future research should consider whether the increasingly diverse services delivered via CHDs are guided by epidemiologic considerations, and whether the rising number of codelivered interventions is affecting coverage performance or service quality. Guidance is also needed to ensure that CHDs are implemented as part of systematic efforts to improve health systems.

Assessing Child Nutrient Intakes Using a Tablet-Based 24-Hour Recall Tool in Rural Zambia.

Background: Detailed dietary intake data in low-income populations are needed for research and program evaluation. However, collection of such data by paper-based 24-hour recall imposes substantial demands for staff time and expertise, training, materials, and data entry. Objective: To describe our development and use of a tablet-based 24-hour recall tool for conducting dietary intake surveys in remote settings. Methods: We designed a 24-hour recall tool using Open Data Kit software on an Android tablet platform. The tool contains a list of local foods, questions on portion size, cooking method, ingredients, and food source and prompts to guide interviewers. We used this tool to interview caregivers on dietary intakes of children participating in an efficacy trial of provitamin A-biofortified maize conducted in Mkushi, a rural district in central Zambia. Participants were children aged 4 to 8 years not yet enrolled in school (n = 938). Dietary intake data were converted to nutrient intakes using local food composition and recipe tables. Results: We developed a tablet-based 24-hour recall tool and used it to collect dietary data among 928 children. The majority of foods consumed were maize, leafy vegetable, or small fish dishes. Median daily energy intake was 6416 kJ (1469 kcal). Conclusions: Food and nutrient intakes assessed using the tablet-based tool were consistent with those reported in prior research. The tool was easily used by interviewers without prior nutrition training or computing experience. Challenges remain to improve programming, but the tool is an innovation that enables efficient collection of 24-hour recall data in remote settings.

Short-Term Daily Consumption of Provitamin A Carotenoid–Biofortified Maize Has Limited Impact on Breast Milk Retinol Concentrations in Zambian Women Enrolled in a Randomized Controlled Feeding Trial

BACKGROUND Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants. OBJECTIVE We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women. METHODS Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations. RESULTS Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16). CONCLUSIONS Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.

Maternal vitamin A supplementation increases natural antibody concentrations of preadolescent offspring in rural Nepal.

OBJECTIVE B1a lymphocytes-which constitutively produce most natural antibodies (NAb)-arise from an early wave of progenitors unique to fetal life. Vitamin A regulates early lymphopoiesis. In animals, deficiency during this critical period compromises B1 cell populations. The aim of this study was to investigate the effect of maternal supplementation with vitamin A or β-carotene from preconception through lactation on NAb concentrations of offspring. METHODS Participants (N = 290) were born to participants of a cluster-randomized, placebo-controlled trial of weekly maternal vitamin A or β-carotene supplementation (7000 μg retinol equivalents) conducted in Sarlahi, Nepal (1994-1997) and assessed at ages 9 to 13 y (2006-2008). Serum retinol was measured by reversed-phase high-performance liquid chromatography at mid-pregnancy and 3 mo of age. Enzyme-linked immunosorbent assay (ELISA) was used to measure childrens plasma NAb concentrations at 9 to 13 y. RESULTS Unadjusted geometric mean concentrations were 20.08 U/mL (95% confidence interval [CI], 17.82-22.64) in the vitamin A group compared with 17.64 U/mL (95% CI, 15.70-19.81) and 15.96 U/mL (95% CI, 13.43-18.96) in the β-carotene and placebo groups (P = 0.07), respectively. After adjustment, maternal vitamin A supplementation was associated with a 0.39 SD increase in NAb concentrations (P = 0.02). The effect was mediated by infant serum retinol in our statistical models. Although girls had 1.4-fold higher NAb concentrations (P < 0.001), sex did not modify the vitamin A effect. CONCLUSIONS In an undernourished population, maternal vitamin A supplementation enhanced NAb concentrations of preadolescent children. We posit that this was due to a greater allotment of B1a precursors during fetal life and a sustained higher count of NAb-secreting B1a cells.

A Quarter of a Century of Progress to Prevent Vitamin A Deficiency Through Supplementation

A quarter of century has passed since FRI published its first comprehensive review on vitamin A deficiency (VAD) and its prevention. At the time, the major impetus to prevent VAD was to reduce xerophthalmia in preschool children. Today, we have a broader understanding of the public health implications of VAD, with disorders including xerophthalmia, mortality, severe infection, and anemia in preschool children and pregnant women. While deficiency affects most developing countries, nearly half of all deficient children and women live in Southern Asia. Prevention has made substantial strides. High potency vitamin A supplementation (with 200,000 IU) remains a prophylactic mainstay, delivered through fixed facilities, enhanced outreach activities, and national child health day campaigns twice annually. Surprisingly, the costs of semi-annual delivery of vitamin A have changed little over the years, with new cost estimates remaining comparable to earlier figures of US ∼

A Changing Landscape for Vitamin A Programs Implications for Optimal Intervention Packages, Program Monitoring, and Safety

0.50 per child per year. Emerging is the potential to reduce infant mortality by ∼20% in Southern Asia by giving a single, oral, 50,000 IU dose of vitamin A to newborns. While ∼500 million vitamin A capsules are routinely distributed worldwide each year to achieve effective control, progress has been slower with efforts to improve diet on a purposeful global public health scale. Future advances through effective dietary diversification and various means of food fortification will be required before periodic supplementation can be phased down as a major population strategy for controlling vitamin A deficiency.

Current Capabilities and Limitations of Stable Isotope Techniques and Applied Mathematical Equations in Determining Whole-Body Vitamin A Status.

Background: Vitamin A deficiency (VAD) remains a widespread public health problem in the developing world, despite changes in under-5 mortality rates, morbidity patterns, and intervention options. Objective: This article considers the implications of a changing epidemiologic and programmatic landscape for vitamin A (VA) programs. Methods: We review progress to prevent VAD and its health consequences, assess gaps in VA status and intervention coverage data, and assess data needed to guide decisions regarding the optimal mix, targeting, and dose of VA interventions to maximize benefit and minimize risk. Results: Vitamin A supplementation programs have contributed to the reduction in under-5 mortality rates, but alone, do not address the underlying problem of inadequate dietary VA intakes and VAD among preschool-aged children in the developing world. A combination of VA interventions (eg, supplementation, fortified foods, multiple micronutrient powders, and lipid-based nutrient supplements) will be required to achieve VA adequacy in most settings. Current efforts to measure the coverage of multiple VA interventions, as well as whether and how much VA children are receiving, are few and fragmented. Conclusions: Where intervention overlap exists, further effort is needed to monitor VA intakes, ensuring that targeted groups are consuming adequate amounts but not exceeding the tolerable upper intake level. Vitamin A status data will also be critical for navigating the changing landscape of VA programs. Data from these monitoring efforts will help to guide decisions on the optimal mix, targeting, and exposure to VA interventions to maximize public health benefit while minimizing any potential risk.

Should universal distribution of high dose vitamin A to children cease

Background: Retinol isotope dilution (RID) methodology provides a quantitative estimate of total body vitamin A (VA) stores and is the best method currently available for assessing VA status in adults and children. The methodology has also been used to test the efficacy of VA interventions in a number of low-income countries. Infections, micronutrient deficiencies (eg, iron and zinc), liver disease, physiological age, pregnancy, and lactation are known or hypothesized to influence the accuracy of estimating total body VA stores using the isotope dilution technique. Objective: Our objectives were to review the strengths and limitations of RID methods, to discuss what is known about the impact of various factors on results, and to summarize contributions of model-based compartmental analysis to assessing VA status. Methods: Relevant published literature is reviewed and discussed. Results: Various equations and compartmental modeling have been used to estimate the total body VA stores using stable isotopes, including a newer 3-day equation that provides an estimate of total body VA stores in healthy adults. At present, there is insufficient information on absorption of the isotope tracer, and there is a need to further investigate how various factors impact the application of RID techniques in field studies. Conclusions: Isotope dilution methodology can provide useful estimates of total body VA stores in apparently healthy populations under controlled study conditions. However, more research is needed to determine whether the method is suitable for use in settings where there is a high prevalence of infection, iron deficiency, and/or liver disease.