i Introduction What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions Lindsay H. Allen and Stuart R. Gillespie United Nations Administrative Committee on Coordination Sub-Committee on Nutrition (ACC/SCN) in collaboration with the Asian Development Bank (ADB) ii August 2001 Copyright © 2001 Asian Development Bank with the UN ACC Sub-Committee on Nutrition This publication may be reproduced with prior permission from ADB. The designations employed and the presentation of material in this publication do not necessarily imply the expression of any opinion whatsoever on the part of ADB or the ACC/SCN or its UN member agencies concerning the legal status of any country, territory, city or area of its authorities, or concerning the delimitation of its frontiers or boundaries. Suggested citation form for this report: ACC/SCN (2001). What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions, Allen LH and Gillespie SR. ACC/SCN: Geneva in collaboration with the Asian Development Bank, Manila. ISBN 971-561-388-8 Publication Stock No. 070901 Published by the Asian Development Bank, P.O. Box 789, 0980 Manila, Philippines E-mail: adbpub@adb.org; website: http://www.adb.org and ACC/SCN Secretariat, c/o World Health Organization, 20 Avenue Appia, CH 1211 Geneva 27, Switzerland E-mail: accscn@who.int; website: http://acc.unsystem.org/scn/ The Asian Development Bank Nutrition and Development Series This is the first copublication by the ACC/SCN in its Nutrition Policy Series and the Asian Development Bank in its Nutrition and Development Series. The ADB Nutrition and Development Series, begun in 2001, covers the impact of malnutrition in Asia and the Pacific on poverty and depressed human and economic development. The Series stresses three themes: targeting nutrition improvements at poor women and children, with benefits to families, communities, and nations throughout the life cycle; reviewing and applying scientific evidence about nutrition impact for policies, programmes, and developmental assistance that will raise the quality of human resources; and creating opportunities for public, private, and civil sector partnerships that can raise the dietary quality of the poor, and enhance the learning and earning capability of poor children. The Series is intended for ADB member countries, development partners, and scholars interested in applying science and technology to investment decisions. This copublication was prepared under ADB’s RegionalTechnical Assistance 5824—Regional Study of Nutrition Trends, Policies and Strategies in Asia and the Pacific—which was designed and coordinated by Dr. Joseph M. Hunt, ADB’s Senior Health and Nutrition Economist, with the support of William Fraser, Manager of the Education, Health and Population Division (East) of ADB, which sponsored the project. For more information, please contact Dr. Joseph M. Hunt, Series Editor: jhunt@adb.org; phone: (632) 636-6830; fax: (632) 636-2407. Address: Asian Development Bank, 6 ADB Avenue, Mandaluyong City, 0421 Metro Manila, Philippines. iii Introduction FOREWORD � mproving nutrition in developing countries is both humanitarian and an economic imperative. Yet, despite the gains that have been made, the greater progress that is urgently needed has been hampered by the lack of a systematic evaluation of what works and what does not. A major review of this key issue has been long overdue. The monograph therefore fills an important gap by providing an overview on which nutrition interventions improve the nutrition status of women and children, with emphasis on the poor in developing countries. The purpose is to define a core menu of proven investment options supported by sound evidence of efficacy. We expect that this review will be a much-consulted reference to support evidence- based nutrition programming in developing countries. This review takes the perspective of low-income Asia, because the study was commissioned by the Asian Development Bank to inform its policy dialogue with Asian governments. We believe the review will be useful for ADB and all development partners selecting nutrition interventions as stand-alone activities or components in integrated social development projects and programs. Notably, the review draws on global literature and its findings are relevant to all developing countries. The review emphasizes what works and why – for each of the major nutrition problems in Asia: micronutrient deficiencies (vitamin A, iodine and anemia), low birthweight, maternal malnutrition, child growth retardation and arrested cognitive development in early childhood. Supplementation and fortification efficacy and effectiveness trials are reviewed comprehensively. The monograph includes a broader review and impact assessment of food-based approaches to improve maternal and child nutrition. It concludes with recommendations on a core program that passes efficacy and effectiveness tests, and calls for a sensible level of investment in operations research and cost-effectiveness analysis to improve nutrition programming throughout the donor community and national budgets in developing countries. The decision of the United Nations Sub- Committee on Nutrition and ADB to co-publish the monograph recognizes that Asia is the crucible for improving nutrition of children globally, and nutrition programs must be based on what works. We are committed to further dialogue with the nutrition and development communities to increase support for effective nutrition interventions that will support life- long learning and earning opportunities among Asian children. There is probably no more fundamental way to eliminate poverty than to raise the development potential of children. Nutrition is one of the keys to their proper physical and cognitive development. Tadeo Chino Namanga Ngongi President Chair Asian Development Bank United Nations Sub-Committee on Nutrition iv August 2001 v Introduction EXECUTIVE SUMMARY � his review tracks the life cycle impacts of malnutrition in the developing world, highlighting the dynamics of cause and consequence, and then considers what can be done to break the cycle: first from an efficacy perspective, then with regard to large scale effectiveness. The focus is on undernutrition, which may be manifest as stunting, wasting, underweight, foetal growth retardation, low body mass index and various micronutrient deficiencies. The perspective is low income Asia. The review focuses on the five major nutrition problems in Asia and the Pacific region: low birthweight, early childhood growth failure, anaemia, iodine deficiency disorders, and vitamin A deficiency. For each of these, the nature of the problem, its prevalence, distribution, consequences, and causes, are discussed. This is followed by a comprehensive review of existing knowledge of the efficacy of key “nutrition interventions” for preventing or alleviating these conditions. The final two sections review the effectiveness of large scale programmes and the process to be adopted for selecting and prioritizing options. Preventing Low Birthweight Asia has a higher prevalence of low birthweight (LBW) than any other continent, ranging from well over 30% in South Central Asia and Bangladesh to less that 10% in the People’s Republic of China (PRC), the Philippines, Malaysia, and Thailand. LBW is strongly associated with undernutrition of mothers. About 60% of women in South Asia and 40% in Southeast Asia are underweight (<45 kg). LBW is probably the main reason why over 50% of the children in Asia are underweight. It also increases the risk of other health and developmental problems. Interventions to reduce the prevalence of LBW should therefore receive very high priority. Randomized, controlled, efficacy trials to combat LBW have shown the following. Only supplements that provide more energy, rather than more protein, improve birthweight significantly. In populations where protein intake is adequate, high protein supplements (>25% of energy) to pregnant women may even increase neonatal death rates. Maternal supplementation can increase maternal weight gain, infant head circumference and, when there is a serious energy deficit, the length of the newborn infant. The expected benefits from maternal food supplementation in Asia have yet to be determined but are expected to be considerable. For comparison, in The Gambia, locally produced biscuits providing 1,017 kcal and 22 g protein per day from mid- pregnancy, reduced LBW prevalence by 39%, increased birthweight by 136 g and reduced infant mortality by about 40%. Such improvements in pregnancy outcome can be obtained by encouraging undernourished women to consume more of their normal diet, where possible, and providing appropriate energy supplements, ideally formulated from local foods. Where the normal diet is particularly low in protein or in micronutrients, it is important to ensure that these are also provided as supplements. Women with the lowest weights (from conception to early pregnancy) and the lowest energy intakes are the most likely to benefit. Targeting interventions based on maternal body mass index (BMI), skinfold thickness, and height is unlikely to be as useful as targeting based on weight. There are conflicting data on whether supplementation during the second trimester or the third trimester is most effective for improving birthweight. It is clear that supplementation during either of these trimesters can reduce the prevalence of LBW. Young maternal age at conception is an additional risk factor for poor pregnancy outcome. Therefore, it is especially important to target interventions to pregnant women are still growing. Continued supplementation that is given to the mother during her subsequent lactation and next pregnancy may cause an even greater improvement in the birthweight of her next child. Whenever possible, attention should be paid to improving the quality as well as the quantity of food consumed during pregnancy. There is little evidence vi August 2001 that supplementation with individual nutrients (including calcium, folic acid, iron, zinc and vitamin A) can improve birthweight, other than possibly through a reduction in preterm delivery. However, micronutrient supplementation of underprivileged pregnant women is extremely important. It can lead to substantial reductions in maternal anaemia and may also reduce maternal mortality, birth defects and preterm delivery. It improves breastmilk quality and infant nutrient stores. Trials are ongoing to test the efficacy of providing supplements containing balanced amounts of multiple micronutrients. In areas of endemic iodine deficiency, adequate maternal iodine status is critical for the prevention of neonatal deaths, LBW and abnormal cognitive and physical development of the infant. Non-nutrition interventions that can improve pregnancy outcome include reducing energy expenditure in physical work, increasing age at conception, malarial prophylaxis, and cessation of cigarette smoking. Improving Child Growth An estimated 70% of the world’s stunted children live in Asia, and there has been little recent improvement in this situation. South Central Asia has the second highest prevalence of growth stunting in the world (44%) and the prevalence in South-East Asia (33%) is also high. Growth stunting in childhood is a risk factor for increased mortality, poor cognitive and motor development and other impairments in function. It usually persists, causing smaller size and poorer performance in adulthood. Nutrition intervention trials support the following recommendations. Exclusive breastfeeding is strongly recommended for the first six months of life. There is probably no advantage to the infant of introducing complementary foods prior to 6 months, especially where the quantity and quality of such foods is inadequate. Breastfeeding should be continued when other foods are added to the infant’s diet. In general, the quality of complementary foods is poor compared to breastmilk. The energy density of many gruels, soups, broths, and other watery foods fed to infants in developing countries, is often below the recommended 0.6 kcal/g. Energy intake can be increased by reducing where possible, the water added to foods, and by providing additional feedings. At present, there is insufficient evidence to promote the use of amylases to lower the viscosity of cereals. Adding extra energy in the form of oil or sugar can adversely affect the density of protein and micronutrients in the diet. Even where breastmilk intake is relatively low, the amount of protein in complementary foods is usually more than adequate. Therefore, adding protein alone or improving protein quality will not improve growth. Randomized, controlled trials with processed, complementary foods have shown inconsistent impacts on growth. Among nine trials (mostly with infants aged 6 to 12 months), supplements increased weight and length in only three, and weight alone in two more. In the remainder, there was no effect on growth and the expected growth velocity for ages was not attained in any of the studies. The limitations of these trials included: variability in the age at which the intervention started; the composition of the foods and the amounts provided; the extent and replacement of breastmilk; and the baseline nutrition status and morbidity of the infants. Few trials supplied enough micronutrients to permit the children to consume recommended intakes from their diets, plus the supplements. Intervention with food supplements after 12 months is less effective than between 6 and 12 months. However, there is an increased risk of displacement of breastmilk with earlier high intakes of complementary foods, especially before 6 months of age. In most developing countries, and in some groups in developed countries, the micronutrient content of unfortified, complementary foods is inadequate to meet infant requirements. It is particularly difficult for infants to consume enough calcium, iron, and zinc. Moreover, riboflavin, thiamine, vitamin A, and vitamin B6 intakes are often low. Micronutrient fortification of cereal staples is especially important where these are major constituents of complementary foods. Interventions with single micronutrients have shown the following benefits for children with low intakes and deficiencies: vitamin A, prevention of eye lesions, substantial reduction in mortality from measles and diarrhoea, and increased haemoglobin (Hb) synthesis; iron, improved cognitive and motor development of anaemic infants and children; zinc, improved growth of children who are stunted or have low plasma zinc; iodine, reduced infant mortality and prevalence of goitre, and improved motor and mental function; and vitamin B12, improved growth and cognitive function. Multiple micronutrient deficiencies occur simultaneously. Multiple micronutrient supplements improved height velocity in stunted children in Viet Nam, and infants aged <12 months in Mexico, but had no impact on the growth of children in Peru or Guatemala. Additional trials are underway to compare the benefits of multiple micronutrient and single micronutrient supplementation. Novel approaches to providing multiple micronutrients include a fat-based spread, which has improved growth and Hb in stunted children in one trial, and encapsulated “sprinkles”. vii Introduction Micronutrient intake in young children can be increased by higher consumption of animal products. Among 15 complementary feeding trials, in which dry skimmed milk was included as at least one ingredient, growth in length was significantly increased in 12 trials. However, a trial in which dry fish powder was added to fermented maize, showed no benefits. Animal products, such as chicken liver, could be rich micronutrient sources for infants and children, but controlled trials of their efficacy are still lacking. Preventing and Treating Anaemia Asia has the highest prevalence of anaemia in the world. About half of all anaemic women live in the Indian subcontinent: 88% of them develop anaemia during pregnancy. Vast numbers of infants and children are also affected. Low intakes of absorbable iron, as well as malaria and hookworm infections are the main causes of anaemia. Intervention trials have demonstrated the benefits from improving iron status and reducing anaemia. The greatest benefits are realized in the most severely anaemic individuals. Randomized, controlled, clinical trials show that iron supplementation of pregnant women improves Hb and iron status, even in developed countries. Efficacy increases with iron doses of up to 60 mg/d. Where iron supplementation has not been effective this has been due predominantly to programmatic constraints such as lack of available supplements, and poor compliance. No conclusions can be made about the benefits of iron supplementation during pregnancy on maternal or foetal health, function or survival. Most trials have been conducted on relatively small numbers of women in developed countries. Severe anaemia during pregnancy is thought to increase the risk of maternal mortality but there have been no controlled intervention trials on this question. An association between anaemia and preterm delivery has been reported in several large studies but most placebo-controlled trials have been unable to confirm that anaemia causes prematurity. Maternal iron supplementation during pregnancy can improve both maternal and infant iron status for up to about six months postpartum. Daily supplementation during pregnancy is more effective than weekly supplementation for preventing anaemia, especially severe anaemia. The total amount of iron consumed is the most important predictor of the maternal haemoglobin (Hb) response. In malaria-endemic areas, antimalarial prophylaxis combined with iron supplementation is particularly important for preventing maternal anaemia and LBW. LBW infants are born with very low iron stores, and these are depleted by 2 to 3 months postpartum. Because breastmilk cannot meet their iron requirements, they should be supplemented with iron, starting at 2 months of age. Anaemia during infancy can result in long term or permanent impairment of psychomotor function, although more studies are needed. Iron supplementation of anaemic preschool children improves their cognitive and physical development. Improved growth of iron-supplemented preschool children and school children has been observed in some studies but not in others. Anaemia is also associated with lower productivity, even in tasks requiring moderate effort such as factory work and housework. Iron deficiency that has not yet progressed to anaemia may also reduce work capacity. Efficacy trials have shown that iron supplements improve the work performance of anaemic individuals. Except for iron fortification, there have been few attempts to assess the effectiveness of food-based strategies to improve iron status. Increasing intake of vitamin C, through local foods, is probably an inadequate strategy to improve iron status where iron deficiency is prevalent. Targeting animal products to those with the highest iron requirements, and supporting the production of poultry, small livestock and fish, would increase the intake of absorbable iron and other micronutrients. There are strategies available to increase the iron content of plants through genetic enhancement but the efficacy and effectiveness of this approach have not been evaluated. Fortification of foods with iron has produced improvements in iron status in the following countries: Chile, where nationally distributed dry milk, fortified with ferrous sulphate and vitamin C, lowered the prevalence of anaemia in infants from about 27% to close to zero; Ghana, where electrolytic iron, added to a complementary food, reduced anaemia and iron deficiency; India, where double fortification of salt, with iodine and iron, has the potential to prevent both iron and iodine deficiencies and has been effective for improved Hb concentrations; and Venezuela, with fortification of maize and wheat. The search for better fortificants continues. NaFeEDTA has good potential: when added to sugar in a community trial in Guatemala, it increased Hb and ferritin concentrations. Iron added as NaFeEDTA to soy sauce appears to be well absorbed and is being tested in large scale production and fortification trials in the PRC. For children and adolescents, weekly delivery of iron supplements improves iron status almost as well as daily delivery. Delivery of weekly iron, through schools, community-based programmes etc., may be a cheap, effective way to prevent iron deficiency. However, daily supplements are still more effective for pregnant women. Supplements containing multiple viii August 2001 vitamins and minerals could be more effective for improving Hb response than iron alone, because several nutrients are required for Hb synthesis. Multiple micronutrient deficiencies often occur simultaneously and should be prevented and treated. Multiple micronutrient supplements are now being formulated and tested by international organizations. Preventing and Treating Iodine Deficiency Iodine deficiency disorders (IDD) are a serious problem in Asia. Their prevalence in South-East Asia exceeds that in all other regions of the world. The need to eliminate iodine deficiency is very clear, based on its widespread damaging effects and the large numbers of people affected. There are few randomized, placebo- controlled trials of the effects of iodine supplementation. However, the following conclusions are justified. Salt iodization is by far the most important population-based intervention to combat IDD and has been efficacious where iodine concentrations in the salt were at appropriate levels at the time of consumption. Efforts toward establishing and sustaining national salt iodization programmes have accelerated over recent years. Effective partnerships have been forged between UN agencies, national and international NGOs, and the salt industry. Globally, 68% of households in countries with IDD, now consume iodized salt. Iodization rates are 70% in South-East Asia and 76% in the western Pacific; following the World Health Organization (WHO) definitions of these regions. These figures reflect household survey data where available; otherwise production level data are used as a proxy. Cretinism results from maternal iodine deficiency during pregnancy. It can be prevented by supplementing the mother during pregnancy, preferably during the first trimester and no later than the second trimester. Supplementation in late pregnancy, if that is the first time the mother can be reached, may still provide some small benefits for infant function. In one iodine deficient region, iodine supplementation, even in the last half of pregnancy substantially reduced infant mortality and improved birthweight. Iodine deficiency during early life adversely affects learning ability, motivation, school performance and general cognitive function. It is not yet clear whether iodine supplementation, if started during childhood, benefits cognitive function. Neither is it clear whether supplementation improves the growth of children. Giving iodized oil to 6-week old infants caused a 72% reduction in mortality in the first two months. In areas where iodine deficiency is prevalent, it may be useful to administer iodized oil to young infants . Preventing and Treating Vitamin A Deficiency The prevalence of clinical vitamin A deficiency (VAD) is quite low. For the last years in which information is available on children in Asia, it ranged from 0.5% in Sri Lanka to 4.5% in Bangladesh. Other age groups are affected as well, especially pregnant and lactating women. A prevalence of >1% indicates a public health problem. Subclinical VAD is much more common, though the actual prevalence is uncertain owing to a paucity of reliable data at national level. The only national surveys of the prevalence of subclinical VAD in Asia are: 18% for the PRC; 50% for Pakistan; and 10% for the Philippines. These estimates were only for preschool children, and it is highly likely that the prevalence is now less where there have been national supplementation programmes. VAD causes: increased morbidity and mortality of infants, children and pregnant women; poor growth of children; and possibly increased mortality and morbidity of infants infected with HIV. It also contributes to anaemia by interfering with iron transport and utilization for Hb synthesis. The main cause of VAD is low intake of animal products, many of which contain a large amount of retinol. Beta-carotene is the main provitamin A in plants. Although some plants are very high in beta-carotene, this is generally less well absorbed by humans than retinol. Beta-carotene from fruits and squashes is substantially better absorbed than that from leaves and vegetables in general. Populations with the highest prevalence of VAD consume low amounts of animal products and fruits rich in beta-carotene. Breastmilk is the main sources of vitamin A for infants. Clinical symptoms of VAD are rare in breastfeeding infants during the first year of life even where the prevalence of VAD is high. Poor maternal vitamin A status, and subsequently low breastmilk retinol content is a risk factor for the earlier onset of VAD in infants, as is early cessation of breastfeeding. Infection with Ascaris lumbricoides lowers serum retinol concentrations. Deworming has improved the values. Poor absorption of vitamin A may also occur in some types of diarrhoea and fever, during which there is also a higher rate of utilization and disposal of the vitamin. In severe protein- energy undernutrition, retinol binding protein synthesis is impaired. Zinc and iron deficiencies also interfere with the utilization and transport of stored retinol. Most countries where VAD is known to be a major public health problem have policies supporting the regular supplementation of children. This is an approach of known large scale effectiveness that can reach the subpopulations affected by and at risk of, VAD. Supplementation of women during pregnancy reduces ix Introduction their higher prevalence of night blindness in areas of endemic VAD. Night blindness carries a higher risk of maternal morbidity and mortality. Maternal mortality from pregnancy-related causes was reduced by 40% with weekly vitamin A supplements and 49% with weekly beta-carotene supplements, in an area of rural Nepal with high VAD. These results need to be confirmed by further studies. High dose vitamin A supplements cannot be given safely to pregnant women. A high dose vitamin A supplement given to infants on the day of birth lowered total mortality during the subsequent 4 months, though a multicentre trial of the efficacy of high-dose vitamin A failed to find an impact on mortality or morbidity during the first year of life. It is likely that the dose given was too low to improve infant vitamin A status for long. Maternal supplementation postpartum can improve both maternal and infant vitamin A status, the latter through higher breastmilk content of the vitamin. Meta-analysis has revealed that high dose vitamin A supplementation reduced mortality from diarrhoea and measles by 23% for infants and for children age 6 months to 5 years. Severe diarrhoea was reduced by low dose vitamin A in one study of severely malnourished children, but the reported benefits of high dose vitamin A on diarrhoea-related outcomes have been variable. Little impact has been found on recovery from acute lower respiratory tract infections. Ongoing research will clarify the benefits of vitamin A supplementation in HIV-infected populations. Evidence to date suggests that supplementation of HIV-positive women may improve pregnancy outcome and that supplementation of infected infants and children can reduce mortality. Food-based strategies have good potential for preventing VAD. Some of food-based interventions have been implemented on a large scale, but few have been evaluated adequately. Significant progress has been made in understanding how to bring about behavioural change in such programmes, and which food-based strategies are likely to be effective for improving vitamin A status. Food-based approaches need to be pursued more vigorously so that they become a larger part of the longer term global strategy for alleviating VAD. However, the recent finding that the bioconversion of provitamin A in dark green leafy vegetables is less than one quarter of that previously thought, has raised doubts about the degree of efficacy of certain diet modification approaches in improving vitamin A status. Breastfeeding promotion, protection, and support remain an essential component of control programmes for young children, as does infectious disease control, not only through immunization, but also via complementary hygiene and sanitation interventions. There is also an urgent need to expand efforts in fortification, where foods reaching the target population groups are processed or where local fortification is feasible. Fortification of oils with vitamin A is mandatory throughout most of South Asia although this is not often enforced. Control approaches, based on improved availability of vitamin A rich foods and possibly genetic modification of staple foods to enhance vitamin A availability, as with iron, have been slower to develop and more difficult to implement, but progress is being made. How Effective are Large Scale Interventions? Most large scale nutrition interventions can potentially affect most of these problems, though there is an extraordinary dearth of well designed evaluations of community-based nutrition interventions. In this section, a series of guidelines is provided for improving the effectiveness, and ultimately the impact, of key nutrition interventions. These derive from lessons learned with past experience in large scale programmatic settings. The key strategies discussed are growth monitoring and promotion, integrated care and nutrition, communications for behavioural change, supplementary feeding for women and young children, school feeding, health-related services, micronutrient supplementation, and food-based strategies. Prioritizing Options Having discussed both the efficacy evidence and the factors conditioning large scale effectiveness of different interventions, this review concludes with a consideration of the process that needs to be initiated for deciding on the type of action or mix of actions that are most appropriate for combating the problem of undernutrition in different situations. The choice will depend on the actual nature and distribution of the malnutrition problem, its causes, and the type of resources that are available. No single intervention or mix of interventions should ever be prescribed in isolation from a participatory process of problem assessment, causal and capacity analysis, and programme design. Cost-benefit and cost-effectiveness analyses may help in deciding priorities. “Key minimum packages” are discussed. As malnutrition usually results from many factors, there are potential synergies between many actions—carried out by multiple actors across sectors—and that the combined effects of such interventions are often not merely additive, but multiplicative. Programme goals should be prioritized with consideration to the level of a country’s development. The review concludes by describing the main elements of successful programme management practices. Community-based nutrition intervention programmes in seven Asian countries are summarized in an Appendix. x August 2001 Lindsay H. Allen, Professor Department of Nutrition University of California, Davis One Shields Avenue Davis, CA 95616-8669 USA EMAIL: lhallen@ucdavis.edu Stuart R. Gillespie, Research Fellow International Food Policy Research Institute, 2033 K Street, Washington, D.C. 20006-1002 USA EMAIL: s.gillespie@cgiar.org AUTHORS xi Introduction ACKNOWLEDGEMENTS � he authors are indebted to the following, all of whom took considerable time to read through earlier drafts and prepare useful comments: Barbara Underwood, National Academy of Sciences, Washington DC, USA, Professor H.P.S. Sachdev of the Maulana Azad Medical College in New Delhi, Sri Irawati Susalit of the Bureau for Health and Community Nutrition, BAPPENAS, Jakarta, Indonesia, Mohammed Mannan, Chairman of the National Nutrition Council in Dhaka, Bangladesh and Joseph Hunt, senior nutrition economist of the Asian Development Bank (ADB) in Manila, who was the ADB task master for the regional study “ADB Regional Technical Assistance Project 5824: Regional Study of Nutrition Trends, Policies and Strategies in Asia and the Pacific”, under which this review was commissioned. Other team members in this process, who have also offered helpful comments and suggestions along the way, include Suresh Babu, Lawrence Haddad, Susan Horton, Venkatesh Mannar and Barry Popkin. We would also like to thank Ginette Mignot of IFPRI for her help in preparing this document, and Roger Pullin in Manila for copy editing. xii August 2001 TABLE OF CONTENTS INTRODUCTION .....................................................................................................................................................................1 Undernutrition Throughout the Life Cycle ................................................................................................................ 1 Research on Interventions to Combat Undernutrition ............................................................................................ 2 Conceptual Framework .................................................................................................................................................. 3 PREVENTING LOW BIRTHWEIGHT ................................................................................................................................ 5 Definitions and Indicators .............................................................................................................................................. 5 Wasting or Stunting in utero .......................................................................................................................................... 6 Prevalence of Intrauterine Growth Retardation (IUGR) ......................................................................................... 6 Consequences of Low Birthweight .............................................................................................................................. 7 Increased Mortality and Morbidity .............................................................................................................................. 7 Greater Risk of Stunting .................................................................................................................................. 7 Poor Neurodevelopmental Outcomes ......................................................................................................... 8 Reduced Strength and Work Capacity ......................................................................................................... 8 Increased Risk of Chronic Disease ................................................................................................................ 8 Causes of Intrauterine Growth Retardation .............................................................................................................. 9 Prenatal Food Supplementation ................................................................................................................................... 9 Beneficial Nutrition Interventions ................................................................................................................. 9 Nonbeneficial Nutrtition Interventions ..................................................................................................... 10 Optimizing Interventions ............................................................................................................................................. 11 Targeting Supplements to Undernourished Women .............................................................................. 11 Best Predictors for Women at Greatest Risk of IUGR ............................................................................ 11 Prepregnancy Weight ................................................................................................................. 11 Attained Maternal Weight at 20, 28 or 36 Weeks of Gestation ..................................................................................................................... 11 Additional, Less Useful Predictors of Women at Greatest .................................................................... 11 Risk of IUGR .................................................................................................................................................... 11 Low Maternal Body Mass Index (BMI) .................................................................................. 11 Pregnancy Weight Gain ............................................................................................................ 12 Maternal Height ......................................................................................................................... 12 Timing of Supplementation ......................................................................................................................... 12 Duration of Supplementation ..................................................................................................................... 13 Micronutrient Supplementation During Pregnancy ............................................................................................. 13 Supplementation with Single Micronutrients ......................................................................................... 13 Iron ................................................................................................................................................ 13 Folic Acid ..................................................................................................................................... 14 Zinc ................................................................................................................................................ 14 Vitamin A ..................................................................................................................................... 15 Calcium......................................................................................................................................... 15 Iodine ............................................................................................................................................ 15 Supplementation with Multiple Micronutrients .................................................................................... 15 Non-Nutritional Interventions During Pregnancy ................................................................................................ 16 Adolescent Nutrition .................................................................................................................................................... 16 Adolescent Growth ....................................................................................................................................... 16 Adolescent Pregnancy .................................................................................................................................. 16 Adolescent Nutritional Status ..................................................................................................................... 17 Can Adolescents Catch-Up Incomplete Childhood Growth ................................................................ 18 xiii Introduction Intervening in Adolescence ........................................................................................................................................ 19 Improving Dietary Intake ............................................................................................................................ 19 Improving Iron and Folate Status .............................................................................................................. 20 Delaying First Pregnancy ............................................................................................................................ 20 Summary and Conclusions ......................................................................................................................................... 21 IMPROVING CHILD GROWTH ...................................................................................................................................... 23 Growth Patterns of Infants and Children ................................................................................................................ 23 Stunting ........................................................................................................................................................ 24 Underweight ........................................................................................................................................................ 24 Wasting ........................................................................................................................................................ 24 Causes of Poor Growth ................................................................................................................................................ 24 Interactions Between Nutrition and Diseases ........................................................................................................ 26 Consequences of Poor Growth ................................................................................................................................... 26 The Fundamental Importance of Care ..................................................................................................................... 27 Exclusive Breastfeeding ............................................................................................................................................... 28 Complementary Feeding ............................................................................................................................................. 29 Recommendations for Complementary Feeding .................................................................................... 29 Estimating the Amount of Nutrients Needed in Complementary Foods. ........................................ 31 Improving the Nutrient Content of Complementary Foods ............................................................................... 31 Increasing Energy Intake .................................................................... ................................................... 31 Increasing Protein Intake .................................................................... ................................................... 32 Improving the Micronutrient Content (Quality) of Complementary Foods .................................................... 33 Increasing the Consumption of Animal Products ................................................................................................. 33 Improving the Content and Bioavailability of Nutrients in Plant-Based Complementary Foods ......................................................................................................................... 34 Fortification of Complementary Foods with Micronutrients .............................................................................. 34 Efficacy Trials of Complementary Foods ................................................................................................................. 36 Micronutrient Supplementation to Improve Growth ........................................................................................... 36 Iron ........................................................................................................................................................ 36 Zinc ........................................................................................................................................................ 37 Vitamin A ........................................................................................................................................................ 37 Calcium ........................................................................................................................................................ 37 Iodine ........................................................................................................................................................ 38 Multiple Micronutrients ............................................................................................................................... 38 Summary and Conclusions ......................................................................................................................................... 40 PREVENTING AND TREATING ANAEMIA ................................................................................................................ 43 The Prevalence of Anaemia and of Iron Deficiency .............................................................................................. 43 Causes of Anaemia ....................................................................................................................................................... 44 Consequences of Anaemia .......................................................................................................................................... 45 Efficacy of Trials of Iron Supplementation .............................................................................................................. 45 Supplementation in Pregnancy .................................................................................................................. 45 Iron Supplementation of Infants and Preschool Children .................................................................... 46 Iron Supplementation of School Children and Adolescents ................................................................ 48 Frequency, Duration and Prioritization of Iron Supplementation ..................................................... 48 The Role of Other Micronutrients in Anaemia ....................................................................................................... 49 Dietary Interventions to Reduce and Prevent Iron Deficiency ........................................................................... 50 Iron Fortification of Foods .......................................................................................................................................... 51 Efficiency Trials ........................................................................................................................................................ 51 Effectiveness Trials ........................................................................................................................................................ 52 Maize and Wheat Flour Fortification ........................................................................................................ 52 Condiment Fortification ............................................................................................................................... 52 Fortification of Foods for Infants and Children ...................................................................................... 52 Safety of Iron Fortification Programmes . ................................................................................................ 53 xiv August 2001 Complementary Parasite Control Strategies for Prevention of Anaemia ....................................................... 53 Summary and Conclusions .................................................................................................................................................... 53 PREVENTING AND TREATING IODINE DEFICIENCY .......................................................................................... 55 Prevalence of Iodine Deficiency ................................................................................................................................. 55 Causes of Iodine Deficiency ....................................................................................................................................... 55 Consequences of Iodine Deficiency Disorders ....................................................................................................... 56 Cretinism ........................................................................................................................................................ 56 Goitre ........................................................................................................................................................ 56 Impaired Cognitive Function ...................................................................................................................... 56 Increased Perinatal Morbidity and Mortality ......................................................................................... 56 Iodine Efficacy Trials .................................................................................................................................................... 57 Effects on Goitre Reduction ......................................................................................................................... 57 Effects on Pregnancy Outcome ................................................................................................................... 57 Effects on Infant Mortality ........................................................................................................................... 58 Effects on Child Growth............................................................................................................................... 58 Potential for Iodine Toxicity ........................................................................................................................ 59 Summary and Conclusions ......................................................................................................................................... 59 PREVENTING AND TREATING VITAMIN A DEFICIENCY (VAD) ..................................................................... 61 Prevalence of Vitamin A Deficiency .......................................................................................................................... 61 Consequences of Vitamin A Deficiency .................................................................................................................... 61 Efficacy Trials to Improve Vitamin A Status ........................................................................................................... 62 Effect on Pregnancy Outcome ..................................................................................................................... 62 Impact on Morbidity and Mortality of Infants and Children .............................................................. 63 Prevention of Childhood Illness ................................................................................................................. 63 Benefits of Providing Vitamin A to Infants in the Expanded Programme in Immunization ....................... 63 Improved Growth .......................................................................................................................................... 64 Impact on HIV Infection .............................................................................................................................. 64 The Efficacy of Food-Based Strategies to Improve Vitamin A Status ................................................................ 64 Summary and Conclusions ......................................................................................................................................... 66 EFFECTIVENESS OF LARGE SCALE INTERVENTIONS ......................................................................................... 69 Growth Monitoring and Promotion .......................................................................................................................... 70 Integrated Care and Nutrition Interventions ......................................................................................................... 70 Communications for Behavioral Change ................................................................................................................ 75 Specific Nutrition-Related Recommendations ........................................................................................ 77 Supplementary Feeding of Young Children and Women .................................................................................... 78 School Feeding ............................................................................................................................................... 80 Health-Related Services ............................................................................................................................... 81 Complementarities Between Health and Service Delivery and Community Nutrition .......................................................................................................................... 83 Effectiveness of Supplementation for the Control of Iron and Vitamin A Deficiency .................................................................................................................................................... 83 Iron ........................................................................................................................................................ 83 Vitamin A ........................................................................................................................................................ 84 Food-Based Strategies for Control of Iron and Vitamin A Deficiency ............................................................... 85 Control of Iodine Deficiency Disorders ................................................................................................................... 85 PRIORITIZING OPTIONS .................................................................................................................................................. 89 Benefit-Cost and Cost-Effectiveness Analyses ........................................................................................................ 90 Determining Unit Costs of Intervention ................................................................................................... 90 Cost-Effectiveness .......................................................................................................................................... 91 Key “Minimum Packages” ........................................................................................................................................... 92 Programme Management Principles ......................................................................................................................... 92 xv Introduction Contextual Success Factors ........................................................................................................................... 93 Programme Success Factors ......................................................................................................................... 93 Role of Programmes in National Nutrition Improvement .................................................................................. 94 REFERENCES .......................................................................................................................................................................... 95 APPENDIX 1 PROFILES OF SOME COMMUNITY-BASED NUTRITION INTERVENTIONS IN ASIAN COUNTRIES, FROM THE ASIAN DEVELOPMENT BANK REGIONAL TECHNICAL ASSISTANCE (RETA) PROJECT 5671 ON “INVESTING IN CHILD NUTRITION IN ASIA” AND OTHER RELEVANT PROJECTS AND STUDIES Bangladesh ..................................................................................................................................................... 117 Cambodia ....................................................................................................................................................... 118 People’s Republic of China ......................................................................................................................... 119 India ...................................................................................................................................................... 120 Pakistan ...................................................................................................................................................... 121 Sri Lanka ...................................................................................................................................................... 122 Viet Nam ...................................................................................................................................................... 123 List of Tables TABLE 1: Incidence (%) of low birthweight (LBW) and LBW with intrauterine growth retardation (IUGR-LBW) in some Asian countries ........................................................................................................................................................... 6 TABLE 2: Estimated incidence (%) and expected numbers of low birthweight (LBW) and LBW with intrauterine growth retarded (IUGR-LBW) infants in developing countries in 2000 ....................................................................................... 7 TABLE 3: Prevalence (%) of stunting and underweight in preschool children and corresponding gross national product (GNP) per capita in the Asia-Pacific region ....................................................................................................................... 25 TABLE 4: Estimated daily amounts of nutrients needed from complementary foods, by age of infants, and usual breastmilk intake in developing countries ........................................................................................................................ 30 TABLE 5: Desirable nutrient density of complementary foods (per 100 kcal) by age of infants, and usual breastmilk intake in developing countries ............................................................................................................................................. 31 TABLE 6: Intervention trials with complementary foods ....................................................................................................... 35 TABLE 7: Interventions with multiple micronutrients ........................................................................................................... 39 TABLE 8: Haemoglobin (Hb) limits used to define anaemia based on WHO/UNICEF/UNU (1996) recommendations ................................................................................................... 43 TABLE 9: Indicators for prevalence of iodine deficiency disorders (IDD) as public health problems ........................ 55 TABLE 10: Prevalence of clinical vitamin A deficiency (VAD) in Asian countries ............................................................... 61 xvi August 2001 TABLE 11: Guide for assessing the quality of implementation of a growth promotion programme ............................. 72 TABLE 12: Costs and effects of micronutrient interventions ................................................................................................... 91 List of Figures FIGURE 1: Undernutrition throughout the life cycle .................................................................................................... 2 FIGURE 2: Causes of undernutrition in society ............................................................................................................. 3 FIGURE 3: The inadequate dietary intake-disease cycle ........................................................................................... 26 FIGURE 4: Development quotients of stunted children with various treatments, compared to those for nonstunted children and controls .............................................................................................................. 28 FIGURE 5: The “Triple A” Process ................................................................................................................................. 89 List of Boxes BOX 1: Example of a Job Description for a Community Growth Promoter ................................................... 71 BOX 2: The Hearth Model ......................................................................................................................................... 76 BOX 3: Common Causes of Failure in Scaling-Up Supplementary Feeding Programmes ......................... 78 BOX 4: Integrated Management of Childhood Illness (IMCI) Evaluation ...................................................... 82 BOX 5: Strategy for Control of Iodine Deficiency Disorders (IDD) in Nepal ................................................ 86 xvii Introduction ACC/SCN Administrative Committee on Coordination (of the United Nations)/Sub-Committee on Nutrition ADB Asian Development Bank AGW Anganwadi worker (India) AKU Aga Khan University ANC Antenatal care ANM Auxiliary Nurse Midwife (India) ARI Acute respiratory infection AusAID Australian International Development Agency BHA Butylated hydroxyanisole, an antioxidant used to prevent lipid oxidation BINP Bangladesh Integrated Nutrition Project BFHI Baby-Friendly Hospital Initiative (People’s Republic of China and Pakistan) BMI Body mass index measured as weight (in kg) divided by height (in m) squared. CASD Community Action for Social Development (Cambodia) CBC Communications for behavioural change CBNC Community-based nutrition component (Bangladesh) CDD Control of diarrhoeal disease CF Conceptual Framework CIDA Canadian International Development Agency CNC Community Nutrition Center (Bangladesh) CNO Community Nutrition Organizer (Bangladesh) CNP Community Nutrition Promoter (Bangladesh) CNW Community Nutrition Worker (India) CPCC National Programme of PEM Control for Vietnamese Children CRSP Collaborative Research Support Programme DALYs Disability-adjusted life years DPT Diphtheria-polio-tetanus immunization LIST OF ABBREVIATIONS DSD District Secretary’s Division (Sri Lanka) ELC Early Childhood Learning Centre EPI Expanded Programme on Immunization EU European Union Fe Iron FNB Food and Nutrition Board FWA Family Welfare Assistant (Bangladesh) GM Growth monitoring GNP Gross National Product HANDS Health and Nutrition Development Society (Pakistan) HA Height-for-age Hh Household Hb Haemoglobin HKI Helen Keller International ICCIDD International Coordinating Committee on Iodine Deficiency Disorders ICDS Integrated Child Development Services (India) ICRW International Center for Research on Women ICMR Indian Council for Medical Research IDECG International Dietary Energy Consultative Group IDA Iron deficiency anaemia IDD Iodine deficiency disorders IEC Information-education- communication IFPRI International Food Policy Research Institute IMCI Integrated Management of Child Illness INACG International Nutritional Anaemia Consultative Group INCAP Instituto de Nutricion de Centro America y Panama IQ Intelligence quotient IRDP Integrated Rural Development Programme (India) IU International Units IUGR Intrauterine growth retardation IUGR-LBW Refers to infant’s born at term (>37 weeks) with LBW (see below) xviii August 2001 JRY Food-for-work scheme (India) JFT Janasaviya Trust Fund (Sri Lanka) LA Length-for-age LBW Low birthweight LHW Lady Health Worker (Pakistan) LMP Last menstrual period MCH Mother and child health MICS Multiple Indicator Cluster Survey (UNICEF/Cambodia) MIS Management information system MOH Ministry of Health (Pakistan) MOHFW Ministry of Health and Family Welfare (Bangladesh) NAS National Academy of Sciences (USA) NCHS National Center for Health Statistics NDTF National Development Trust Fund (Sri Lanka) NERP Nutritional Education and Rehabilitation Programme (Viet Nam) NFA National Food Authority (Philippines) NGOs Nongovernmental organizations NIDs National Immunization Days NIDDEP National Iodine Deficiency Disorders Elimination Programme (People’s Republic of China) NNMB National Nutrition Monitoring Bureau NMMP National Mid-Day Meals Programme (India) NNNCP National Nutritional Anaemia Control Programme (India) NNPA National Nutrition Plan of Action (Cambodia) NRC National Research Council (USA) NREP National Rural Employment Programme (India) ORT Oral rehydration therapy PAHO Pan-American Health Organization PAR Population-attributable risk PDS Public Distribution System (India) PEM Protein-energy malnutrition PHM Public Health Midwife (Sri Lanka) PI Ponderal index PNIP Participatory Nutrition Improvement Project (Sri Lanka) PRB Population Reference Bureau RE Retinol Equivalent RETA Regional Technical Assistance RR Relative ratio SGA Small-for-gestational-age T3 Triiodothyronine T4 Thyroxine TB Tuberculosis TBA Traditional birth attendant (Pakistan) TGR Total goitre rate TINP Tamil Nadu Integrated Nutrition Project TPDS Targeted Public Distribution System (India) TSH Thyroid stimulating hormone UNICEF United Nations Children’s Fund UNU United Nations University USAID United States Agency for International Development USI Universal salt iodization VAC Vitamin A capsule VAD Vitamin A deficiency VDC Village Development Committee (Cambodia) VAP Village Action Plan WA Weight-for-age WH Weight-for-height WHO World Health Organization WL Weight-for-length xix Introduction Anganwadi Courtyard in Hindi. Anganwadi workers are community-based workers in Integrated Child Development Services (ICDS) in India Bayley score Performance on the Bayley tests of motor and mental development Bitot’s spots Lesions of the conjunctiva that occur in vitamin A deficiency Body mass index A measure of adult nutritional status, essentially thinness; defined as bodyweight in kilograms divided by height in metres squared (kg/m2) Dais Midwives (Pakistan) Development quotient The conversion of raw scores of development to standardized scores; e.g. for motor or mental development. Eclampsia Maternal convulsions in late pregnancy; one symptom of pregnancy-induced hypertension. Electrolytic iron Iron produced by electrolysis; used for fortification Elemental iron A generic term for iron powders produced by various processes (e.g. H- reduced, electrolytic, carbonyl, atomized) and used as food fortificants. Grama Niladhari Administrative unit (Sri Lanka) Height-for-age An indicator of the degree of stunting of a child (see below), defined as his/ her height in relation to the median height of a reference population of that age. Intrauterine growth retardation Birthweight below a given low percentile limit for gestational age (e.g., birthweight less than 10th percentile for gestational age); typically reflects inadequate supply of nutrients and oxygen to the foetus. Jaggery Raw sugar Low birthweight Weighing less than 2,500 grams at birth. Megaloblastic anaemia An anaemia characterized by the presence of large, nucleated red blood cells, as occurs in severe folate or vitamin B12 deficiency. Odds ratio The ratio of the odds of a condition or disease in an exposed population to the odds of the same condition or disease in a nonexposed population. Phytates Phytic acid combined with minerals. These constitute 1-2% of the weight of whole grain cereals, nuts, seeds and legumes, and impair mineral absorption from these foods. Population-attributable risk In an exposed population of those who have a condition or disease, the proportion for whom this is attributed to being in the exposed (vs. nonexposed) group. Ponderal index Weight/length3; an indicator of wasting in young infants. Pre-eclampsia Development, during pregnancy, of hypertension with proteinuria and/or oedema. Prelacteal feeding The potentially harmful practice of delaying breastfeeding, and feeding the newborn such foods as milk, honey, or sugar water. These prelacteal feeds are unnecessary and can introduce infection in the baby. They also interfere with the physiology of lactation and delay establishment of breastmilk. Primagravidae Women who are in their first pregnancy. Raven’s progressive matrices A non-verbal IQ score that is allegedly free from culture bias. Relative risk The ratio of the probability of a condition or disease in an exposed population to the probability of the same condition or disease in a nonexposed population. Samurdhi A poverty alleviation programme in Sri Lanka Small-for-gestational-age At or below the 10th percentile of a birthweight-for-gestational-age curve GLOSSARY xx August 2001 Stunting The anthropometric index ‘height-for-age’ reflects linear growth achieved pre- and postnatally, with deficits indicating longterm, cumulative effects of inadequacies of nutrition and/or health. Shortness in height refers to a child who exhibits low height-for-age that may reflect either normal variation in growth or a deficit in growth. Stunting refers only to shortness that is a deficit, or linear growth that has failed to reach genetic potential as a result, most proximally, of the interaction between poor diet and disease. Stunting is defined as low height-for-age; i.e., below 2 standard deviations (or 2 Z-scores) of the median value of the National Center for Health Statistics/World Health Organization International Growth Reference for length- or height-for-age Teratogenic Causing abnormal foetal development, such as birth defects. Thalassaemia minor Thalassaemias are inherited disorders in which haemoglobin synthesis is impaired. Thalassaemia minor is the heterozygous form and is usually asymptomatic, with a mild hypochromic, macrocytic anaemia. Thana Administrative district in Bangladesh (see “union”) Thriposha Supplementary feeding programme in Sri Lanka Total goitre rate The prevalence of goitre (enlargement of the thyroid gland) in a specific population group, usually expressed as a percentage. Goitre reflects significant iodine deficiency in the population. Underweight The anthropometric index ‘weight-for-age’ represents body mass relative to age. Weight-for-age is influenced by the height of the child and his or her weight and is thus a composite of stunting and wasting (which makes its interpretation difficult). In the absence of wasting, both weight-for-age and height–for-age reflect the long term nutrition and health experience of the individual or population. General lightness in weight refers to a child having a low weight-for-age. Lightness may represent either normal variation or a deficit. Underweight specifically refers to lightness that is a deficit and is defined as low weight-for-age, i.e.; below 2 standard deviations (or 2 Z-scores) of the median value of the National Center for Health Statistics/World Health Organization International Growth Reference for weight-for-age. Undernutrition A condition in which the body contains lower than normal amounts of one or more nutrients. Union Administrative unit (Bangladesh) Wasting A recent and severe process that has produced a substantial weight loss, usually as a consequence of acute starvation and/or severe disease. Chronic dietary deficit or disease can also lead to wasting. The anthropometric index ‘weight-for-height’ reflects body weight relative to height. Thinness refers to low weight-for-height and may indicate normal variation or a deficit in weight. Wasting refers to thinness that is a deficit, defined as low weight-for-height, i.e., below 2 standard deviations (or 2 Z-scores) of the median value of the National Center for Health Statistics/World Health Organization International Growth Reference for weight-for-height. The statistically expected prevalence of wasting (as with underweight and stunting) is between 2-3%, given the normal distribution of wasting rates. Weight-for-age An indicator of the degree of underweight of a child (see above), defined as his/her weight in relation to the median weight of a reference population of that age. Weight-for-height An indicator of the degree of wasting of a child (see above), defined as his/ her weight in relation to the median height of a reference population of that age. Z-score The deviation of an individual’s value from the median value of a reference population, divided by the standard deviation of the reference population. 1 Introduction INTRODUCTION his review tracks the life cycle impacts of undernutrition in the developing world, especially in the low income countries of the Asia-Pacific region. After highlighting the dynamics of cause and consequence, it considers interventions: first from an efficacy perspective, then with regard to large scale effectiveness. Another paper1 focuses on the problem of overnutrition. These papers were prepared under the Asian Development Bank (ADB) – International Food Research Institute (IFPRI) Regional Technical Assistance Project RETA 5824 on Nutrition Trends, Policies and Strategies in Asia and the Pacific. Undernutrition may be indicated by foetal growth retardation, low body mass index (BMI), stunting, wasting, underweight, anaemia, and micronutrient deficiencies. Five major nutrition problems in developing countries, with a special emphasis on Asia, are reviewed here: low birthweight (LBW); early childhood growth failure; anaemia; iodine deficiency disorders ( IDD); and vitamin A deficiency ( VAD). For each of these, the nature of the problem, its prevalence, distribution, consequences and causes, are discussed; followed by a review of the efficacy of key nutrition interventions. The effectiveness of large scale programmes is then reviewed, and the process for selecting and prioritizing options discussed. A nutrition intervention is defined here as one that has the prevention or reduction of undernutrition as at least one of its primary objectives. Such interventions are usually intended to have an impact on the main immediate causes of undernutrition, namely, inadequate dietary intake, poor caring practices, and disease. These determinants are strongly interrelated in a synergistic cycle (Figure 1). The interventions reviewed here are primarily community-based, although they may or may not be community-driven. They include: breastfeeding promotion; growth monitoring and promotion; communication for behavioural change (CBC), including improved complementary feeding, supplementary feeding, and micronutrient supplementation. Nutrition interventions through health services are also reviewed � briefly. Fortification of essential foods, an approach to micronutrient deficiency, and approaches to improve household food security are also discussed in separate papers2, 3. Maternal and child care in the region have also been reviewed4 and only highlights are reiterated here. The starting point of this review is a description of the nutrition situation in developing countries, especially in Asia. It concludes with a series of guidelines for maximizing the effectiveness of large scale interventions. Specific issues of coverage, targeting, intensity, programme design, implementation, management, monitoring, evaluation and institutional capacity development are not covered, as these have been dealt with elsewhere5, 6, 7. Undernutrition Throughout the Life Cycle Undernutrition often starts in utero and may extend throughout the life cycle. It also spans generations. Undernutrition occurs during pregnancy, childhood, and adolescence, and has a cumulative negative impact on the birthweight of future babies. A baby who has suffered intrauterine growth retardation (IUGR) as a foetus is effectively born malnourished, and has a much higher risk of dying in infancy. Survivors are unlikely to catch up significantly on this lost growth and are more likely to experience developmental deficits. Moreover, the consequences of being born malnourished extend into adulthood. Strong epidemiological evidence suggests a link between maternal and early childhood undernutrition and increased adult risk of various chronic diseases. During infancy and early childhood, frequent or prolonged infections and inadequate intakes of nutrients (particularly energy, iron, protein, vitamin A, and zinc) may add to the contribution of IUGR to preschool underweight and stunting. Underlying such immediate causes will be inadequacies in one or more of the three main preconditions for good nutrition: food, care and health. Most growth failure occurs from 2 September 2001 WOMAN Malnourished Inadequate food, health, & care Reduced capacity to care for baby Higher mortality rate Impaired mental development PREGNANCY Low weight gain ELDERLY Malnourished ADOLESCENT Stunted CHILD Stunted BABY Low Birthweight Increased risk of adult chronic disease Inadequate food, health & care Reduced mental capacity Reduced mental capacity Inadequate food, health, & care Inadequate food, health, & care Higher maternal mortality Inadequate foetal nutrition Inadequate catch-up growth Untimely/inadeqate weaning Frequent infections before birth until two to three years of age. A child who is stunted at five years of age is likely to remain stunted throughout life. Apart from the indirect effects on the mother, micronutrient deficiencies during pregnancy have serious implications for the developing foetus. Iodine deficiency disorders may cause foetal brain damage or stillbirth. Folate deficiency may result in neural tube or other birth defects and preterm delivery, and both iron deficiency anaemia and vitamin A deficiency may have significant implications for the future infant’s morbidity and mortality risk, vision and cognitive development. In adolescence, a second period of rapid growth may serve as a window of opportunity, albeit limited, for compensating for growth failure in early childhood. However, even if the child catches up some lost growth, the effects of early childhood undernutrition on cognitive development and behaviour may not be fully redressed. A stunted girl is likely to become a stunted adolescent and later a stunted woman. Apart from direct effects on her health and productivity, adult stunting and underweight increase the chance that her children will be born with LBW. And so the cycle turns. Research on Interventions to Combat Undernutrition The research process through which interventions are designed to combat undernutrition is a dynamic and iterative step-by-step process as follows: i. describe the problem; ii. identify risk factors; iii. explore the context and identify the determinants; iv. select or formulate possible interventions; v. test interventions in carefully controlled double-blind efficacy trials; vi. formulate public nutrition interventions; vii. assess the efficacy of public nutrition interventions (e.g., through community-based trials); viii. assess the effectiveness of public nutrition interventions (e.g., at the national level); and ix. monitor the adequacy and impact of large scale, public nutrition interventions. ������� � ��� ���� ������� ������ �������� ��� ���� �� ���� ������� � ���������� ���� ����� � ������� �� ���� ��� ���� ���� ��� ����� ���� � !�� "����# $�%� ��� �%������� ������� ������� ������������������������ ���� ����� 3 Introduction Not all of these steps are needed in every case, but it is important to realize that there is a big difference between steps vii and viii. Efficacy refers to the impact of an intervention under ideal conditions, when the components of the intervention (e.g., food supplements) are delivered directly to all individuals in the target group (i.e., 100% coverage). This is more likely to occur in research with a high level of supervision over delivery of the programme and the careful measurement of outcomes. Such trials demonstrate potential; i.e., what can optimally be achieved. Any new approach to controlling a particular nutrition problem should be subjected initially to efficacy trials, to determine whether a biological impact is actually possible in ideal conditions (step v). Only then should the ensuing steps be taken to introduce the intervention as part of a large scale programme. Effectiveness refers to the impact of an intervention under real world conditions, when programmes are scaled up to reach large populations. Small scale efficacy does not easily translate into large scale effectiveness and impact. Conceptual Framework The life cycle depicted in Figure 1 shows how various nutrition problems, causes, and consequences change and interact over time. To understand better what causes such problems, it is necessary to consider systematically the causes of undernutrition at different levels in society. The widely used food-care-health conceptual framework (Figure 2) illustrates these causes, and their interactions, at three levels: immediate, underlying, and basic. The synergistic interaction between the two immediate causes (inadequate dietary intake and disease) fuels a vicious cycle that accounts for much of the high morbidity and mortality in developing countries. Three groups of underlying factors contribute to inadequate dietary intake and infectious disease: household food insecurity, inadequate maternal and child care, and poor health services in an unhealthy environment. These underlying causes are, in turn, underpinned by basic causes that relate to the amount, control, and use of various resources8. �������� ���� ��������� ������������������ �� ������� &� �'! �())�� ����� �� � ��� � �� ��� �� ���� � � ���� � � � ��� �� � � � � � � ��� � � � � � � � � � � � ���� � � � � � ��� *��+� &� �'!� Inadequate dietary intake Malnutrition and death Inadequate education Political and ideological superstructure Formal and non-formal institutions Insufficient health services and unhealthy environment Inadequate acess to food Inadequate care for mothers and children Economic structure Potential resources Disease 4 September 2001 This framework is used as an organizing principle for discussions of aetiology and approaches to remedial action. Nutrition-relevant interventions are also designed to impact at the underlying level to combat inadequacies in one or more of the main preconditions (food, care, and health) usually at the household and/or community levels. Poverty is both a fundamental cause and an outcome of undernutrition. Economic losses from undernutrition include, as percentages of total losses from all causes: foregone human productivity, 10-15%; foregone GDP, 5-10%; and losses in children’s disability-adjusted life years (DALYs), 20-25%9. Not only is economic growth foregone, but it is foregone for the poor, who need it the most. Nutrition-fuelled economic growth promises to reduce income inequality. Moreover, improved nutrition is a particularly powerful antipoverty intervention because it can be achieved at low cost and it has a lifelong impact. In terms of a propoor, economic growth strategy that is sustainable, investment in nutrition is one of the best options. 5 Preventing Low Birthweight PREVENTING LOW BIRTHWEIGHT � he prevalence of low birthweight (LBW) is higher in Asia than elsewhere10, predominantly because of undernutrition of the mother before pregnancy, exacerbated by undernutrition during pregnancy. About 60% of women in South Asia and 40% in South-East Asia are underweight (<45 kg), 40% of them are thin, with body mass index (BMI) <18.5, and more than 15% are stunted (<145 cm)11. Being of low weight at birth has a profoundly adverse effect on the health and development of the neonate. It is a risk factor for stunting, which starts in utero and becomes worse if the diet or health status is inadequate during postnatal development. LBW is probably the main reason why over 50% of the children in South Asia are underweight12. The adverse consequences of LBW continue to be manifested during childhood, and are passed on to the next generation when women, who have been chronically undernourished in their past, become pregnant. LBW and subsequent stunting are caused by undernutrition and other health problems, rather than by racial or ethnic differences. Improvements in maternal nutrition and health can increase birthweight, survival and growth of the child, and subsequent size and function (including health, productivity and mental performance) in adult life. Drawing on much recent work13, the prevalence, consequences and causes of LBW, and the efficacy of nutrition interventions aimed at preventing LBW are reviewed here. The main focus is on interventions during pregnancy, but approaches to improving adolescent nutrition status are also reviewed. Micronutrient interventions are evaluated from the perspective of their effect on birthweight, rather than on micronutrient deficiency, which is addressed later. Recommendations are made about the nature, timing and targeting of nutrition interventions to improve pregnancy outcome. Many non-nutrition or indirect interventions, such as immunization and sanitation, have significant nutrition effects9 but these are beyond the scope of this review. Definitions and Indicators Numerous terms have been used to describe infants who are born smaller than is desirable. Many of these are confusing, overlapping, and of limited practical value in developing countries. The focus here is on the most practical and commonly applied terms. LBW is defined as weighing less than 2,500 g at birth. It is one of the most common statistics because it requires a single measurement, weight at birth, and no information about gestational age. There are two main causes of LBW: being born small for gestational age, or being born prematurely. In developing countries, the majority of LBW infants are small but are not born prematurely. Nevertheless, 6.7% of LBW infants are born preterm in developing countries14. To deal with the influence of prematurity, a World Health Organization (WHO) Expert Committee proposed the term “IUGR-LBW” (“Intrauterine Growth Retardation – Low Birthweight”)15, 16. This refers to infants born at term (>37 weeks of gestation) with LBW (<2,500 g). It replaces the older term “small- for-gestational-age” (SGA). It is often difficult or impossible to assess gestational age accurately. For example, using ultrasound rather than the reported date of the last menstrual period (LMP) lowers the estimated prevalence of SGA by about 30 to 50% in developed countries17, 18. In Asia, LBW (including preterm infants) estimates are only slightly higher than IUGR-LBW estimates (Table 1). This means that, for practical purposes, LBW is a valid indicator of the prevalence of IUGR. A regression equation, developed using data from 60 countries where both LBW and gestational age data were recorded10, can be used to convert LBW to IUGR-LBW. An important caveat is that both the LBW and IUGR- LBW definitions exclude infants who weigh more than 2,500 g at birth, but less than the 3,300-3,500 g birthweight of well nourished infants in developing countries. Many of these “smaller than normal” infants are likely to have been IUGR and will probably suffer adverse functional consequences of their suboptimal weight. The IUGR-LBW category also 6 September 2001 Country, location Year LBW (%) IUGR-LBW (%) People’s Republic of China, 6 subdistricts of Shanghai 1981-1982 4.2 3.4 India, Pune 1990 28.2 24.8 Indonesia, Bogor area 1983 10.5 8.0 Myanmar, rural and urban 1981-1982 17.8 12.7 Nepal, rural 1990 14.3 11.8 Nepal, urban 1990 22.3 18.2 Sri Lanka, rural 1990 18.4 15.8 Thailand, rural and urban 1979-80 9.6 6.9 Viet Nam, Hanoi + 1 rural district 1982-1984 5.2 4.2 �������� �� � ��������������������������������� ����������� �������� �������������� ���� � �� !������ �"�#���"�� ���� ����" ������� �� � � � ��� � ���� ������������������ ����� �� �������������� �� ������������� �������� ��� ��!�"� ����� �� ��� �� ������ � ������ ��#� ����� � � � � � � ���� � � � ��� �� � ���� � � ����$%���$&��$# excludes preterm infants who were IUGR. For these reasons, the IUGR-LBW category substantially underestimates the true magnitude of intrauterine growth retardation. Defining IUGR as a birthweight below the 10th percentile of the international ‘birthweight for gestational age’ curve16, has given, on average, incidences that are 14.5% higher than when the IUGR-LBW definition is used10. Wasting or Stunting in utero The foetus undergoes its maximum increase in length at 20-30 weeks of gestation, and in weight during the third trimester19. Therefore, the timing of undernutrition in utero has different effects on weight and length. Stunted (also called symmetrically or proportionately growth-retarded) infants have a normal ponderal index (PI) (defined as weight/length3) but their weight, length, head and abdominal circumferences are below the 10th percentile of reference values. Wasted (asymmetrically or disproportionately growth retarded) infants have a relatively normal length and head circumference, but their body weights and PIs are low due to a lack of fat, and sometimes of lean tissue. Wasting is thought to result from undernutrition that occurs late in pregnancy, when fat deposition is most rapid. Only 1% of foetal body weight is fat at 26 weeks compared to 12% at 38 weeks. However, stunting may reflect undernutrition throughout pregnancy14. The postnatal development and function of wasted newborns is distinctly different from those who are stunted. Prevalence of Intrauterine Growth Retardation (IUGR) In developing countries, IUGR has been estimated to affect between 14 and 20 million infants per year10, or as many as 30 million11. Fourteen million is equivalent to 11% of all births in developing countries10. The higher estimates may be closer to reality because most birthweight data are obtained from clinics and, in developing countries, babies born at home are more likely to have LBW. Nevertheless, these estimates provide a useful basis from which to target attention and to allocate resources. Rates of IUGR-LBW can be categorized as percentages of all births, as follows: low (<5%), moderate (5-10%), high (10-15%) and very high (>15%). For LBW and IUGR-LBW respectively, the highest incidences are found in South Central Asia (28%, 33%). The average prevalence is 11% of births in all developing countries, and about 21% in South- East Asia10 (Table 2). At the national level, the highest incidences for LBW and IUGR-LBW respectively are: Bangladesh (50%, 39%), India (28%, 21%) and Pakistan (25%, 18%). For other Asian countries, the corresponding data are: Sri Lanka (19%, 13%); Cambodia (18%, 12%); Viet Nam and the Philippines (11%, 6%); Indonesia and Malaysia (8%, 4%); Thailand (8%, 3%), and the People’s Republic of China (PRC) (6%, 2%)10. 7 Preventing Low Birthweight ������$� �"��#��� � � �� � ��� ����� ��%&���� � �#���"���� ���������������� ������� ���� ������ �������� �������������� � �� �� !������ �� �"�� � �'���&� ����� ����"�� �$((( LBW IUGR-LBW Incidence (%) Expected No. Incidence (%) Expected No. (<2,500 g) b (thousands) c (<2,500 g; ³ 37 weeks) (thousands)c Africa a n.a. n.a. n.a. n.a. Eastern n.a. n.a. n.a. n.a. Middle 21.3 853 14.9 597 Northern n.a. n.a. n.a. n.a. Southern n.a. n.a. n.a. n.a. Western 17.2 1,451 11.4 962 Asia d 18.0 13,774 12.3 9,344 Eastern c 5.8 1,250 1.9 409 South Central 28.3 10,917 20.9 8,062 South Eastern 10.3 1,190 5.6 647 Western 8.3 417 4.5 226 Oceania e 15.0 29.2 9.8 19 Melanesia 15.4 29 9.9 19 Micronesia n.a. n.a. n.a. n.a. Polynesia 4.0 0.2 0.2 0.03 All developing countries 16.4 17,436 11.0 11,677 ��'"���� ������������� ��(�� ���� �����!�� �"������ �"��)� �� �*�� ��� (� ������� ���� ����� ����������#�� � ����� �� ������� ������� �� � ��������� ��� �������� ��� ��!�"� ����� �� ��� �� ������ � � ������ ��# ���� � � � � � � ���� � � � ��� �� � ���� � � ����$%���$&��$# ��'����� � ���( ��"������%+++�����(��� �����"��)*��������,��� �-������ ���-��������#�*�!�.��/��)� �� �*�� ���# �01��� ��� �����# ��01��� ���2������ �� �� �*�!�3����� # �#�#�4��������� ��(���(��������"�������� ����� � ���( ��"��!���5��+6# Consequences of Low Birthweight Increased Mortality and Morbidity Whether a newborn infant is stunted or wasted has an important influence on its future development. For example, stunted infants have a higher neonatal mortality than those who are wasted, and also contribute most to poor child survival and development. Wasted infants demonstrate more postpartum weight catch-up20, 21, whereas stunted infants tend not to catch up to the reference growth norms. Infants who weigh 2,000-2,499 g at birth have a four-fold higher risk of neonatal death than those who weigh 2,500-2,999 g, and a ten-fold higher risk than those weighing 3,000 - 3,499 g22. The more severe the growth restriction within the LBW category, the higher the risk of death. For example, weighing more than 2,500 g but less than 3,000 g at birth, also carries a greater risk for neonatal mortality and morbidity. This is especially true for infants with a low PI23. For a given birthweight, being born small because of preterm delivery is a stronger risk factor for perinatal mortality than if the smallness is due to growth restriction22. Being born preterm, as well as having LBW carries the strongest risk of mortality10. IUGR and LBW infants are more susceptible to hypoglycaemia and to birth asphyxia. In a substantial number of studies they suffered more diarrhoea and pneumonia for a few months after birth22, explaining in part why LBW is also a risk factor for postneonatal death. In the few studies from which data are available during the first weeks of life, wasted, LBW newborns experienced more morbidity21, 23, 24 whereas stunted newborns were more likely to die during this time25, 26. This may reflect the greater capacity for the LBW infant to catch up in weight and immune function. The impaired immunocompetence of stunted infants is more likely to persist. In a retrospective study in The Gambia27, being born during and up to two months after the so-called “hungry season” was a strong predictor of mortality after age 15 years. Being born in the hungry season was also associated with about a four-fold greater risk of dying between the ages of 15 and 45 years, and a ten-fold greater risk of 8 September 2001 dying between the ages of 35 and 45 years. The deaths were mostly related to infections, or to childbirth in women, and were probably caused by the effects of undernutrition in utero on development of the immune system. Greater Risk of Stunting Weight at birth is a strong predictor for size in later life because most IUGR infants do not catch-up to normal size during childhood. In Asian countries, such as Bangladesh, the PRC, India, Pakistan, the Philippines and Sri Lanka, the incidence of LBW predicts the prevalence of underweight during preschool and subsequent years5. A review of 12 studies that provided data on the subsequent growth of IUGR infants (preterm infants excluded) revealed that they underwent partial catch- up growth during their first two years of life28. After age 2 years, there was little further catch-up and the IUGR infants remained stunted during the rest of their childhood, adolescence and adult life. At 17 to 19 years of age, males and females who were born IUGR-LBW were about 5 cm shorter and weighed 5 kg less than those who were not born IUGR-LBW. Importantly, the magnitude of these differences is similar in developed and developing countries. This suggests that, as a general rule, later undernutrition does not magnify the impact of IUGR. Controlling for maternal height did reduce the influence of birthweight on size at 17- 19 years, but birthweight remained a significant predictor. Low maternal height is in itself a reflection of prior undernutrition. Menarche and maturation are probably not delayed by being born IUGR29. From a Guatemala longitudinal study28, data are available on a subset of children followed from birth to adolescence. Although the length Z-scores of the IUGR infants tended to catch up somewhat by 3 years of age, the absolute increments in length were the same for children born IUGR, both with birthweights 2,500 – 3,000 g and 3,000 – 3,500 g. In other words, IUGR children actually grew the same amount during the first 3 years of life as those with a heavier birthweight. The apparent catch-up in Z-scores is an artefact, due to the splayed distribution of these scores: smaller children improved their Z-scores more per unit growth28. The above-mentioned studies illustrate that the size and nutritional status of pregnant women are more important than postnatal factors as determinants of the growth of their children in later life. Poor Neurodevelopmental Outcomes LBW infants are more likely to experience developmental deficits. Undernutrition that affects head circumference before 26 weeks of pregnancy has a greater impact on neurologic function than does undernutrition later in pregnancy30. The adverse effects of early childhood undernutrition on behaviour and cognitive development may not be fully redressed, even with better diet and care later. In the USA, from a collaborative study on births between 1959 and 1965, the mean IQ scores at four years of age for each birthweight group were: 737-2,000 g, 94; 2,000-2,500 g, 101; and 2,500-3,000 g, 103. A study of the association between IUGR and cognitive development and behaviour in the first six years of life31 concluded that deficits in performance of the IUGR group began to appear between 1 and 2 years of age. These deficits were larger in high risk subgroups; e.g., those who were born smallest, or when IUGR occurred early in pregnancy. The size of the difference was less at 4 to 7 years of age. However, it is unclear whether IUGR followed by good postnatal nutrition has a measurable effect on cognitive or behavioural development in adolescence, because of dilution by many socio- environmental influences on development32. Reduced Strength and Work Capacity In the Guatemala longitudinal study28, males and females at an average of 15 years of age, who were born IUGR, performed significantly more poorly on tests of strength, compared to those born weighing at least 2,500 g28, 33. Specifically, they could apply approximately 2 to 3 kg less force to a hand grip dynamometer. The lower work capacity of adults who were IUGR babies is m