Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
Published online: October 2, 2014
Assessing the Public Health Impact of Developmental Origins of Health and Disease (DOHaD) Nutrition Interventions Maria Luisa Garmendia a Camila Corvalan a Ricardo Uauy a–c a Institute of Nutrition and Food Technology (INTA), University of Chile, and b Department of Pediatrics School of Medicine, Catholic University, Santiago, Chile; c Public Health Nutrition, London School of Hygiene and Tropical Medicine, University of London, London, UK
Key Words Developmental origins of health and disease · DOHaD · Public health impact assessment · Maternal and infant interventions · Public health · Nutrition
Abstract Investing in the maternal and early-infancy periods (the first 1,000 days, i.e. from –1 to +2 years) is presently acknowledged as a key priority to ensure good nutrition and prevent all forms of malnutrition. The concept is to invest during this period to maximize the human development potential, and the early-life agenda includes prevention of stunting and promotion of optimal brain development as well as ensuring the quality of life of those who survive. Thus, public health assessments of specific interventions need to go beyond the traditional indices of prevention of death and disease. We need to consider including a full range of outcomes such as disability-adjusted life years (DALY) and quality-adjusted life years (QALY) and not only the number of deaths. The longterm outcomes of maternal and infant interventions to prevent obesity and related noncommunicable diseases remain uncertain in terms of their biological impact even under ideal conditions (efficacy); we need interventions with proven effectiveness under real-world conditions (effectiveness).
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0226$39.50/0 E-Mail [email protected] www.karger.com/anm
Conversely, interventions to prevent undernutrition have already been proven effective and are considered cost-effective based on rigorous economic analyses. Continuous evaluation of interventions implemented using the developmental origins of health and disease (DOHaD) model needs to be undertaken, as this will allow progressive improvement and thus maximize the potential impact on the health and well-being of populations. We need to consider the population-attributable risk of obesity and chronic disease and conduct an economic evaluation of the lifelong impact of chronic diseases not only in terms of lives lost but also in relation to lost DALY and QALY. This should help to prioritize preventive actions in line with patterns of disease and disability considering the existing resources and demands. © 2014 S. Karger AG, Basel
Developmental Origins of Health and Disease (DOHaD) Nutrition Interventions
There is now compelling evidence that the first 1,000 days (from –1 to +2 years) [1] provide a critical window to ensure newborn survival and prevent morbidity and to define the long-term susceptibility to nutrition-related chronic diseases. Cardiovascular disease, diabetes, and Prof. Ricardo Uauy Institute of Nutrition and Food Technology (INTA) University of Chile Av. El Libano 5524, Macul, Santiago (Chile) E-Mail ruauy @ inta.cl
Nutrition-infection interactions determine how we grow physically and develop mentally.
Nutrition-physical activity interactions define how we age and die.
100
Adults/elderly • Cardiovascular (CHD, stroke) • Obesity/diabetes/dyslipidemia • Cancer related to diet • Osteoporosis • Aging
Ideal 2000
Survival (%)
75 1930
25
Fig. 1. Impact of events during the early
years. CHD = Coronary heart disease; LBW = low birth weight; IUGR = intrauterine growth restriction.
Physical/mental disability
50
0
Fetus/infants/children • LBW/IUGR • Stunting and wasting • Micronutrient deficiency (vitamin A, I, Fe, Zn) • Infection (HIV/AIDS)
0
20
40
60
80
100
120
Age (years)
cancer are the most common nutrition-related chronic diseases, affecting developing countries and the industrialized world alike. They account for most adult deaths and cases of early disability. The DOHaD paradigm suggests that events such as nutrient deficits or excesses occurring in the so-called ‘sensitive period’ may condition ‘what’ and ‘how’ genes are expressed and thus determine future health and disease risks [2]. Moreover, it is also clear that the early years are a critical period for the development of human capital. Events during this window have an enormous impact on productivity and economic returns not only at an individual level but also for society as a whole (fig. 1). It is well established that the impact of correcting maternal and infant undernutrition via nutrition-specific and nutrition-sensitive interventions is much greater than what can be achieved with adult interventions [3]. For obesity and noncommunicable diseases (NCD), adult interventions have mostly proven futile [4]; thus, targeting pregnant women and infants is likely to be more successful in decreasing the lifetime risk of NCD. More importantly, we have a set of nutrition interventions, such as encouraging physical activity, promoting a healthier diet before and during pregnancy, supporting breast-feeding, and avoiding maternal smoking, that have been proven to be effective and can be implemented in the periconceptional period. Their wide-scale application would prevent undernutrition as
well as obesity, thus promoting lifelong health [5]. In fact, early-life interventions to prevent the consequences of malnutrition and ensure health in general are established as a priority for global health and human development. The prevention of early death is a key component of the millennium development goals to be met by 2015 [6].
Assessing the Public Health Impact of DOHaD Nutrition Interventions
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
Health Impacts of DOHaD Nutrition Interventions
From a public health perspective, there are several approaches via which impact evaluations can be carried out. Primarily, we are interested in determining whether a given intervention is able to achieve a biological effect under ‘ideal’ and fully controlled conditions (and thus has a proven efficacy). Conversely, in many cases we are more interested in assessing health impacts under real conditions of delivery and implementation of actions and taking into account the cultural and socioeconomic context of the target population (this is effectiveness). Thus, effectiveness trials are carried out under less controlled conditions than efficacy trials. However, the information they provide is more useful for policy makers because it better represents what would be observed in the general population if this action were implemented at the population level.
227
Table 1. Health impact of early nutrition interventions
Nutrition interventions Women of reproductive age and pregnant women Folic acid supplementation Iron and iron-folate supplementation Maternal multiple micronutrient supplementation Calcium supplementation Iodine through iodization of salt Maternal supplementation with energy and protein Neonates Delayed cord clamping Neonatal vitamin K administration Vitamin A supplementation Kangaroo mother care and promotion of breast-feeding Infants and children Promotion of breast-feeding in infants Promotion of complementary feeding Preventive vitamin A supplementation Iron supplementation Multiple micronutrient supplementation Zinc supplementation
Effect estimates During pregnancy: 79% reduction in the incidence of megaloblastic anemia During pregnancy: 70% reduction in anemia and 19% drop in LBW 11 – 13% reduction in LBW and SGA births 52% reduction in the incidence of preeclampsia 73% reduction in cretinism and 10 – 20% increase in developmental scores in children in iodine-deficient populations 34% reduction in the risk of SGA Significant increase in newborn hemoglobin and higher serum ferritin concentrations at 6 months of age Reduction of clinical bleeding at 1 – 7 days of life Developing countries: 14% reduction in infant mortality at 6 months 27% increase in breast-feeding at 1 – 4 months of age 43% increase in exclusive breast-feeding on day 1, 30% increase up until 1 month, and 90% increase from 1 to 6 months Reduction of the risk of both stunting and underweight 24% reduction in all-cause mortality and 28% reduction in diarrhea-related mortality in children aged 6 – 59 months 49% reduction in the risk of anemia and 76% reduction in iron deficiency Improved linear growth and weight gain Developing countries: 13% reduction in the incidence of diarrhea, 19% reduction in the incidence of pneumonia
Adapted from Bhutta et al. [7]. LBW = Low birth weight; SGA = small for gestational age.
The following early-life nutrition interventions to decrease death and disability related to undernutrition have proven efficacious (in ideal settings) and effective (under real-life conditions): maternal nutritional supplementation (i.e. proteins, folic acid, and iron decrease the risk of newborn adverse outcomes; RR = 0.66 for small for gestational age, 95% CI 0.49–0.89; RR = 0.28 for neural tube defects, 95% CI 0.15–0.52, and RR = 0.81 for low birth weight, 95% CI 0.68–0.97, respectively); promotion of breast-feeding (i.e. 90% increase in exclusive breast-feeding from 1 to 6 months; 95% CI 50–134); appropriate complementary feeding (i.e. decreases the risk of stunting at or before the age of 2 years; RR = 0.68, 95% CI 0.60– 0.76); vitamin A supplementation (i.e. decreases the infant mortality risk at 6 months; RR = 0.86, 95% CI 0.77– 0.97), and zinc supplementation (i.e. results in a 46% decrease in all-cause mortality; 95% CI 12–68) [6, 7] (table 1). On the other hand, the evidence of the impact of maternal and infant interventions on obesity and NCD is more elusive given the expected difficulties in assessing 228
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
outcomes that will occur in the future. Meta-analyses of interventions of diet and exercise during pregnancy have demonstrated that lifestyle interventions can have a positive effect on a variety of maternal outcomes including maternal weight gain (–1.42 kg, 95% CI –0.95 to 1.89 in normal-weight women, and –2.21 kg, 95% CI 2.86–1.59 in obese women), preeclampsia, gestational diabetes, and gestational hypertension [8, 9]. The health impacts of several interventions such as breast-feeding and complementary feeding are still a subject of debate; however, it is likely that ongoing studies will help to clarify these effects in the near future [10, 11].
Economic Impact of DOHaD Nutrition Interventions
Another approach to assess the public health impact of interventions is to consider their economic impact. Economic analyses allow decision makers to prioritize public health activities in the face of limited financial reGarmendia /Corvalan /Uauy
sources. Information for economic assessment can be collected from primary sources (observational studies or randomized controlled trials). However, this information is often needed sooner than it can be obtained from primary studies; this is particularly true when one is interested in assessing long-term outcomes such as mortality or productivity. An alternative solution is to carry out economic impact assessments by combining secondary sources and making projections using realistic assumptions [12]. Economic modeling techniques also allow estimation of a given impact under different projected scenarios. There are several methods of economic analysis that can be used; the choice should be made based on the question to be answered and the available resources (in terms of information and money). Cost analysis refers to any evaluation of costs (direct, indirect, and/or intangible) of a disease without an evaluation of health benefits. This method is frequently used for cost-of-illness studies; it is often used because of its simplicity [13]. On the other hand, a cost-effectiveness analysis refers to the relation between the cost of an intervention and its effectiveness measured in terms of health outcomes (years of healthy life gained or number of premature births averted) compared to an alternative intervention. A cost-utility analysis refers to a specific type of cost-effectiveness analysis in which health outcomes are measured in terms of health utility; this is a more comprehensive approach since it considers qualitative aspects of health. The most common measure used in cost-utility studies is quality-adjusted life years (QALY). QALY combine measures of morbidity and mortality as well as quality-of-life assessment of a disease, including physical function and psychosocial well-being. QALY can be estimated at an individual level but also at an aggregated level using estimated population mean QALY. In the cost-benefit analysis, both the costs and the health outcomes are expressed in monetary units (net benefit), thus allowing decision makers to compare different interventions. However, this requires attributing a given economic value to morbidity, mortality, and quality of life [13]. Interventions that have been proven efficacious and effective in decreasing undernutrition have undergone economic impact assessment to help with their prioritization. Analyses of several of the proposed alternatives have indicated that they are ‘better’ (more cost-effective) than that practices that are presently being used in prenatal care programs (i.e. screening for some diseases and tetanus and malaria prevention) [14]. The World Bank,
in its Scaling Up Nutrition (SUN) report, estimated that micronutrient supplementation and fortification have low unit costs (the cost per child per year is about USD 5), have a high cost-effectiveness [USD 10 per disabilityadjusted life year (DALY) for vitamin A supplementation and USD 73 per DALY for therapeutic zinc supplementation], and a high cost:benefit ratio (i.e. 1:8 for iron fortification of staple foods) [15]. Complementary feeding of children aged 6–23 months is more expensive (i.e. between USD 40 and 80 per child per year), and its effects are more moderate [15]. Similar types of analyses, mostly following cost-effectiveness or cost-utility approaches, have been carried out for several undernutrition-preventive actions. The Economic Commission for Latin America and the Caribbean (ECLAC) has estimated that for the Central American region the economic costs associated with undernutrition represent between 1.7 and 11.4% of the gross domestic product (average 3.8%) [16]. Higher mortality and lower levels of education accounted for 90% of the costs, whereas costs due to morbidity accounted for only 6% and school repetition for 1%; most of the loss was related to a lower productivity of the less-educated adults. In the Copenhagen Consensus of 2012 it was estimated that, for about USD 100 per child, chronic under nutrition could be reduced by 36% in developing countries and that in very poor countries each dollar spent has at least a USD 30 payoff [17]. Economic assessments of obesity and NCD-preventive actions have mainly focused on adult interventions [18, 19]. Maternal and infant actions have been acknowledged as part of the solution but have been excluded from systematic analyses, likely because of the resistance that still exists in some areas to integrate the undernutrition and overnutrition agenda. Nonetheless, in order to move forward, evidence of the economic evaluation of maternal and infant interventions targeted to decreasing obesity and NCD will be needed [12]. An example of what is being done in this field is provided by the assessment of the health economic impact of macrosomia, in which short-term complications for the mother and the child are considered in the context of mothers with excess weight or with gestational diabetes [20]; this model, however, has to be extended to also consider the longterm consequences for both adult health and productivity. Models assessing the economic impact of behavioral interventions such as the promotion of dietary changes or physical activity will face the challenge of having to estimate various scenarios of uptake for the given intervention.
Assessing the Public Health Impact of DOHaD Nutrition Interventions
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
229
Conclusions
It is clear that investing in the prepregnant mother and the early infant years should be a priority to ensure optimal nutrition. Extending the early-life agenda to include prevention of stunting and altered brain development but also to ensure the long-term health and good quality of life of those who survive is the task in order to maximize human development. In terms of public health assessment of interventions, this implies including a wide range of outcomes such as QALY and DALY and not only mortality in the analysis. In some areas, such as the prevention of obesity and NCD, the evidence of the impact of the interventions is delayed and at best we can have a crude estimate. Moreover, most interventions are still at a stage of documentation of efficacy rather than effectiveness. In the area of undernutrition, impact assessment is more advanced and proven interventions have already undergone economic analyses;
the evidence should now be balanced in a context-specific way to decide which interventions should be prioritized considering the existing resources and demands. Worldwide coverage of maternal and infant programs provides a unique opportunity to extend the DOHaD agenda in an integrated and sustainable manner. Given the cultural diversity of countries, the implementation of maternal and infant policies will have to include evaluation components (from both health and economic aspects) in its design. Adequate policy evaluations will allow the adaption and improvement of ongoing policies to maximize the benefits and decrease the unintended adverse or less desirable consequences of DOHAD interventions.
Disclosure Statement The authors declare that there are no conflicts of interest.
References 1 Victora CG, de Onis M, Hallal PC, Blossner M, Shrimpton R: Worldwide timing of growth faltering: revisiting implications for interventions. Pediatrics 2010;125:e473–e480. 2 Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA: Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res 2007;61:5R–10R. 3 The World Bank. Research at the World Bank: Investing in Early Childhood Development. http://go.worldbank.org/TWVTMQ ZL20 (accessed May 9, 2014). 4 Douketis JD, Macie C, Thabane L, Williamson DF: Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Int J Obes 2005;29:1153–1167. 5 Uauy R, Corvalan C, Casanello P, Kuzanovic J: Intervention strategies for preventing low birthweight in developing countries: importance of considering multiple interactive factors. Nestle Nutr Inst Workshop Ser 2013;74: 31–52. 6 Bhutta ZA, Ahmed T, Black RE, Cousens S, Dewey K, Giugliani E, Haider BA, Kirkwood B, Morris SS, Sachdev HP, Shekar M: What works? Interventions for maternal and child undernutrition and survival. Lancet 2008; 371:417–440. 7 Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Webb P, Lartey A, Black RE, Lancet Nutrition Interventions Review Group, Maternal and Child Nutrition Study
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Group: Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet 2013;382:452–477. Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, Kunz R, Mol BW, Coomarasamy A, Khan KS: Effects of interventions in pregnancy on maternal weight and obstetric outcomes: metaanalysis of randomised evidence. BMJ 2012; 344:e2088. Oteng-Ntim E, Varma R, Croker H, Poston L, Doyle P: Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis. BMC Med 2012; 10: 47. Kelishadi R, Farajian S: The protective effects of breastfeeding on chronic non-communicable diseases in adulthood: a review of evidence. Adv Biomed Res 2014;3:3. Agostoni C, Przyrembel H: The timing of introduction of complementary foods and later health. World Rev Nutr Diet 2013; 108: 63–70. Lenoir-Wijnkoop I, Dapoigny M, Dubois D, van Ganse E, Gutiérrez-Ibarluzea I, Hutton J, Jones P, Mittendorf T, Poley MJ, Salminen S, Nuijten MJ: Nutrition economics – characterising the economic and health impact of nutrition. Br J Nutr 2011; 105: 157–166. Stoto M, Cossler L: Evaluation of public health interventions; in Novick L, Morrow C,
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Mays G (eds): Public Health Administration Principles for Population-Based Management. Sudbury, Jones and Bartlett, 2007. Rouse DJ: Potential cost-effectiveness of nutrition interventions to prevent adverse pregnancy outcomes in the developing world. J Nutr 2003;133:1640S–1644S. Horton S, Meera S, McDonald C, Mahal A, Brooks J: Scaling up Nutrition: What Will It Cost? Washington, International Bank for Reconstruction and Development/The World Bank, 2010. United Nations: World economic situation and prospects 2012. New York, United Nations, 2012. Hoddinott J, Alderman H, Behrman JR, Haddad L, Horton S: The economic rationale for investing in stunting reduction. Matern Child Nutr 2013;9(suppl 2):69–82. Cecchini M, Sassi F, Lauer JA, Lee YY, Guajardo-Barron V, Chisholm D: Tackling of unhealthy diets, physical inactivity, and obesity: health effects and cost-effectiveness. Lancet 2010;376:1775–1784. World Health Organization: From burden to ‘best buys’: reducing the economic impact of non-communicable diseases in low- and middle-income countries. Geneva, World Economic Forum, 2011. Lenoir-Wijnkoop I, Nuijten M, van der Beek E, Uauy R: Health economic model for assessing the impact of high birth weight on public health. 8th World Congr Dev Orig Health Dis. Singapore, 2013.
Garmendia /Corvalan /Uauy
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Published online: October 2, 2014
Assessing the Public Health Impact of Developmental Origins of Health and Disease (DOHaD) Nutrition Interventions Maria Luisa Garmendia a Camila Corvalan a Ricardo Uauy a–c a Institute of Nutrition and Food Technology (INTA), University of Chile, and b Department of Pediatrics School of Medicine, Catholic University, Santiago, Chile; c Public Health Nutrition, London School of Hygiene and Tropical Medicine, University of London, London, UK
Key Words Developmental origins of health and disease · DOHaD · Public health impact assessment · Maternal and infant interventions · Public health · Nutrition
Abstract Investing in the maternal and early-infancy periods (the first 1,000 days, i.e. from –1 to +2 years) is presently acknowledged as a key priority to ensure good nutrition and prevent all forms of malnutrition. The concept is to invest during this period to maximize the human development potential, and the early-life agenda includes prevention of stunting and promotion of optimal brain development as well as ensuring the quality of life of those who survive. Thus, public health assessments of specific interventions need to go beyond the traditional indices of prevention of death and disease. We need to consider including a full range of outcomes such as disability-adjusted life years (DALY) and quality-adjusted life years (QALY) and not only the number of deaths. The longterm outcomes of maternal and infant interventions to prevent obesity and related noncommunicable diseases remain uncertain in terms of their biological impact even under ideal conditions (efficacy); we need interventions with proven effectiveness under real-world conditions (effectiveness).
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0226$39.50/0 E-Mail [email protected] www.karger.com/anm
Conversely, interventions to prevent undernutrition have already been proven effective and are considered cost-effective based on rigorous economic analyses. Continuous evaluation of interventions implemented using the developmental origins of health and disease (DOHaD) model needs to be undertaken, as this will allow progressive improvement and thus maximize the potential impact on the health and well-being of populations. We need to consider the population-attributable risk of obesity and chronic disease and conduct an economic evaluation of the lifelong impact of chronic diseases not only in terms of lives lost but also in relation to lost DALY and QALY. This should help to prioritize preventive actions in line with patterns of disease and disability considering the existing resources and demands. © 2014 S. Karger AG, Basel
Developmental Origins of Health and Disease (DOHaD) Nutrition Interventions
There is now compelling evidence that the first 1,000 days (from –1 to +2 years) [1] provide a critical window to ensure newborn survival and prevent morbidity and to define the long-term susceptibility to nutrition-related chronic diseases. Cardiovascular disease, diabetes, and Prof. Ricardo Uauy Institute of Nutrition and Food Technology (INTA) University of Chile Av. El Libano 5524, Macul, Santiago (Chile) E-Mail ruauy @ inta.cl
Nutrition-infection interactions determine how we grow physically and develop mentally.
Nutrition-physical activity interactions define how we age and die.
100
Adults/elderly • Cardiovascular (CHD, stroke) • Obesity/diabetes/dyslipidemia • Cancer related to diet • Osteoporosis • Aging
Ideal 2000
Survival (%)
75 1930
25
Fig. 1. Impact of events during the early
years. CHD = Coronary heart disease; LBW = low birth weight; IUGR = intrauterine growth restriction.
Physical/mental disability
50
0
Fetus/infants/children • LBW/IUGR • Stunting and wasting • Micronutrient deficiency (vitamin A, I, Fe, Zn) • Infection (HIV/AIDS)
0
20
40
60
80
100
120
Age (years)
cancer are the most common nutrition-related chronic diseases, affecting developing countries and the industrialized world alike. They account for most adult deaths and cases of early disability. The DOHaD paradigm suggests that events such as nutrient deficits or excesses occurring in the so-called ‘sensitive period’ may condition ‘what’ and ‘how’ genes are expressed and thus determine future health and disease risks [2]. Moreover, it is also clear that the early years are a critical period for the development of human capital. Events during this window have an enormous impact on productivity and economic returns not only at an individual level but also for society as a whole (fig. 1). It is well established that the impact of correcting maternal and infant undernutrition via nutrition-specific and nutrition-sensitive interventions is much greater than what can be achieved with adult interventions [3]. For obesity and noncommunicable diseases (NCD), adult interventions have mostly proven futile [4]; thus, targeting pregnant women and infants is likely to be more successful in decreasing the lifetime risk of NCD. More importantly, we have a set of nutrition interventions, such as encouraging physical activity, promoting a healthier diet before and during pregnancy, supporting breast-feeding, and avoiding maternal smoking, that have been proven to be effective and can be implemented in the periconceptional period. Their wide-scale application would prevent undernutrition as
well as obesity, thus promoting lifelong health [5]. In fact, early-life interventions to prevent the consequences of malnutrition and ensure health in general are established as a priority for global health and human development. The prevention of early death is a key component of the millennium development goals to be met by 2015 [6].
Assessing the Public Health Impact of DOHaD Nutrition Interventions
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
Health Impacts of DOHaD Nutrition Interventions
From a public health perspective, there are several approaches via which impact evaluations can be carried out. Primarily, we are interested in determining whether a given intervention is able to achieve a biological effect under ‘ideal’ and fully controlled conditions (and thus has a proven efficacy). Conversely, in many cases we are more interested in assessing health impacts under real conditions of delivery and implementation of actions and taking into account the cultural and socioeconomic context of the target population (this is effectiveness). Thus, effectiveness trials are carried out under less controlled conditions than efficacy trials. However, the information they provide is more useful for policy makers because it better represents what would be observed in the general population if this action were implemented at the population level.
227
Table 1. Health impact of early nutrition interventions
Nutrition interventions Women of reproductive age and pregnant women Folic acid supplementation Iron and iron-folate supplementation Maternal multiple micronutrient supplementation Calcium supplementation Iodine through iodization of salt Maternal supplementation with energy and protein Neonates Delayed cord clamping Neonatal vitamin K administration Vitamin A supplementation Kangaroo mother care and promotion of breast-feeding Infants and children Promotion of breast-feeding in infants Promotion of complementary feeding Preventive vitamin A supplementation Iron supplementation Multiple micronutrient supplementation Zinc supplementation
Effect estimates During pregnancy: 79% reduction in the incidence of megaloblastic anemia During pregnancy: 70% reduction in anemia and 19% drop in LBW 11 – 13% reduction in LBW and SGA births 52% reduction in the incidence of preeclampsia 73% reduction in cretinism and 10 – 20% increase in developmental scores in children in iodine-deficient populations 34% reduction in the risk of SGA Significant increase in newborn hemoglobin and higher serum ferritin concentrations at 6 months of age Reduction of clinical bleeding at 1 – 7 days of life Developing countries: 14% reduction in infant mortality at 6 months 27% increase in breast-feeding at 1 – 4 months of age 43% increase in exclusive breast-feeding on day 1, 30% increase up until 1 month, and 90% increase from 1 to 6 months Reduction of the risk of both stunting and underweight 24% reduction in all-cause mortality and 28% reduction in diarrhea-related mortality in children aged 6 – 59 months 49% reduction in the risk of anemia and 76% reduction in iron deficiency Improved linear growth and weight gain Developing countries: 13% reduction in the incidence of diarrhea, 19% reduction in the incidence of pneumonia
Adapted from Bhutta et al. [7]. LBW = Low birth weight; SGA = small for gestational age.
The following early-life nutrition interventions to decrease death and disability related to undernutrition have proven efficacious (in ideal settings) and effective (under real-life conditions): maternal nutritional supplementation (i.e. proteins, folic acid, and iron decrease the risk of newborn adverse outcomes; RR = 0.66 for small for gestational age, 95% CI 0.49–0.89; RR = 0.28 for neural tube defects, 95% CI 0.15–0.52, and RR = 0.81 for low birth weight, 95% CI 0.68–0.97, respectively); promotion of breast-feeding (i.e. 90% increase in exclusive breast-feeding from 1 to 6 months; 95% CI 50–134); appropriate complementary feeding (i.e. decreases the risk of stunting at or before the age of 2 years; RR = 0.68, 95% CI 0.60– 0.76); vitamin A supplementation (i.e. decreases the infant mortality risk at 6 months; RR = 0.86, 95% CI 0.77– 0.97), and zinc supplementation (i.e. results in a 46% decrease in all-cause mortality; 95% CI 12–68) [6, 7] (table 1). On the other hand, the evidence of the impact of maternal and infant interventions on obesity and NCD is more elusive given the expected difficulties in assessing 228
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
outcomes that will occur in the future. Meta-analyses of interventions of diet and exercise during pregnancy have demonstrated that lifestyle interventions can have a positive effect on a variety of maternal outcomes including maternal weight gain (–1.42 kg, 95% CI –0.95 to 1.89 in normal-weight women, and –2.21 kg, 95% CI 2.86–1.59 in obese women), preeclampsia, gestational diabetes, and gestational hypertension [8, 9]. The health impacts of several interventions such as breast-feeding and complementary feeding are still a subject of debate; however, it is likely that ongoing studies will help to clarify these effects in the near future [10, 11].
Economic Impact of DOHaD Nutrition Interventions
Another approach to assess the public health impact of interventions is to consider their economic impact. Economic analyses allow decision makers to prioritize public health activities in the face of limited financial reGarmendia /Corvalan /Uauy
sources. Information for economic assessment can be collected from primary sources (observational studies or randomized controlled trials). However, this information is often needed sooner than it can be obtained from primary studies; this is particularly true when one is interested in assessing long-term outcomes such as mortality or productivity. An alternative solution is to carry out economic impact assessments by combining secondary sources and making projections using realistic assumptions [12]. Economic modeling techniques also allow estimation of a given impact under different projected scenarios. There are several methods of economic analysis that can be used; the choice should be made based on the question to be answered and the available resources (in terms of information and money). Cost analysis refers to any evaluation of costs (direct, indirect, and/or intangible) of a disease without an evaluation of health benefits. This method is frequently used for cost-of-illness studies; it is often used because of its simplicity [13]. On the other hand, a cost-effectiveness analysis refers to the relation between the cost of an intervention and its effectiveness measured in terms of health outcomes (years of healthy life gained or number of premature births averted) compared to an alternative intervention. A cost-utility analysis refers to a specific type of cost-effectiveness analysis in which health outcomes are measured in terms of health utility; this is a more comprehensive approach since it considers qualitative aspects of health. The most common measure used in cost-utility studies is quality-adjusted life years (QALY). QALY combine measures of morbidity and mortality as well as quality-of-life assessment of a disease, including physical function and psychosocial well-being. QALY can be estimated at an individual level but also at an aggregated level using estimated population mean QALY. In the cost-benefit analysis, both the costs and the health outcomes are expressed in monetary units (net benefit), thus allowing decision makers to compare different interventions. However, this requires attributing a given economic value to morbidity, mortality, and quality of life [13]. Interventions that have been proven efficacious and effective in decreasing undernutrition have undergone economic impact assessment to help with their prioritization. Analyses of several of the proposed alternatives have indicated that they are ‘better’ (more cost-effective) than that practices that are presently being used in prenatal care programs (i.e. screening for some diseases and tetanus and malaria prevention) [14]. The World Bank,
in its Scaling Up Nutrition (SUN) report, estimated that micronutrient supplementation and fortification have low unit costs (the cost per child per year is about USD 5), have a high cost-effectiveness [USD 10 per disabilityadjusted life year (DALY) for vitamin A supplementation and USD 73 per DALY for therapeutic zinc supplementation], and a high cost:benefit ratio (i.e. 1:8 for iron fortification of staple foods) [15]. Complementary feeding of children aged 6–23 months is more expensive (i.e. between USD 40 and 80 per child per year), and its effects are more moderate [15]. Similar types of analyses, mostly following cost-effectiveness or cost-utility approaches, have been carried out for several undernutrition-preventive actions. The Economic Commission for Latin America and the Caribbean (ECLAC) has estimated that for the Central American region the economic costs associated with undernutrition represent between 1.7 and 11.4% of the gross domestic product (average 3.8%) [16]. Higher mortality and lower levels of education accounted for 90% of the costs, whereas costs due to morbidity accounted for only 6% and school repetition for 1%; most of the loss was related to a lower productivity of the less-educated adults. In the Copenhagen Consensus of 2012 it was estimated that, for about USD 100 per child, chronic under nutrition could be reduced by 36% in developing countries and that in very poor countries each dollar spent has at least a USD 30 payoff [17]. Economic assessments of obesity and NCD-preventive actions have mainly focused on adult interventions [18, 19]. Maternal and infant actions have been acknowledged as part of the solution but have been excluded from systematic analyses, likely because of the resistance that still exists in some areas to integrate the undernutrition and overnutrition agenda. Nonetheless, in order to move forward, evidence of the economic evaluation of maternal and infant interventions targeted to decreasing obesity and NCD will be needed [12]. An example of what is being done in this field is provided by the assessment of the health economic impact of macrosomia, in which short-term complications for the mother and the child are considered in the context of mothers with excess weight or with gestational diabetes [20]; this model, however, has to be extended to also consider the longterm consequences for both adult health and productivity. Models assessing the economic impact of behavioral interventions such as the promotion of dietary changes or physical activity will face the challenge of having to estimate various scenarios of uptake for the given intervention.
Assessing the Public Health Impact of DOHaD Nutrition Interventions
Ann Nutr Metab 2014;64:226–230 DOI: 10.1159/000365024
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Conclusions
It is clear that investing in the prepregnant mother and the early infant years should be a priority to ensure optimal nutrition. Extending the early-life agenda to include prevention of stunting and altered brain development but also to ensure the long-term health and good quality of life of those who survive is the task in order to maximize human development. In terms of public health assessment of interventions, this implies including a wide range of outcomes such as QALY and DALY and not only mortality in the analysis. In some areas, such as the prevention of obesity and NCD, the evidence of the impact of the interventions is delayed and at best we can have a crude estimate. Moreover, most interventions are still at a stage of documentation of efficacy rather than effectiveness. In the area of undernutrition, impact assessment is more advanced and proven interventions have already undergone economic analyses;
the evidence should now be balanced in a context-specific way to decide which interventions should be prioritized considering the existing resources and demands. Worldwide coverage of maternal and infant programs provides a unique opportunity to extend the DOHaD agenda in an integrated and sustainable manner. Given the cultural diversity of countries, the implementation of maternal and infant policies will have to include evaluation components (from both health and economic aspects) in its design. Adequate policy evaluations will allow the adaption and improvement of ongoing policies to maximize the benefits and decrease the unintended adverse or less desirable consequences of DOHAD interventions.
Disclosure Statement The authors declare that there are no conflicts of interest.
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