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Overview of long-term nutrition intervention studies in Guatemala, 1968-1989
This is an overview of ten papers published in this issue of the Food and Nutrition Bulletin dealing with two components of a nutrition intervention study: the INCAP longitudinal study, 1969-1977, and the follow-up study, 1988-1989. The latter is a continuation of the former and seeks to test the hypothesis that nutritional improvements in early childhood lead to improved human capital formation in adolescents and young adults. Beneficial outcomes have been found to include greater body size and fat-free mass (particularly in females), improved working capacity in males, and enhanced intellectual performance in bath sexes.
The preceding ten papers review the history, design, and methods of the INCAP longitudinal study on the effects of early nutrition supplementation in child growth and development, describe the villages and their people, present key findings, and review the history, design, and methods of the follow-up study carried out among participants in the longitudinal study. Analysis of the follow-up data continues, but enough results are available to comment on their general nature.
The INCAP longitudinal study
The history and the design of the longitudinal study are reviewed elsewhere in this issue [1, 2]. From a larger set of villages, two large and two small villages were selected and randomly allocated, within category of size, to receive a high-protein, high-energy supplement (atole) or one with no protein and only some energy (fresco). The supplements were provided ad libitum to all residents, but consumption was recorded only for mothers and for children under seven years of age.
Preceded by substantial preparatory work, the study began in 1968 with the selection of the villages and collection of baseline information. Many characteristics, including language and culture, population size and structure, and nutrition and disease patterns, were taken into account in selecting communities that would be as homogeneous as possible . Nonetheless, in-depth analyses carried out later, some based on new information, revealed important differences among the villages. For example, one of the villages (Espíritu Santo, the small fresco village) differed from the rest in terms of geography, ecology, and economy ; and subjects from the atole villages were less educated than those from the fresco villages . The atole villages also had higher mortality rates than the fresco villages before the beginning of the longitudinal study . Nonetheless, children as well as adults in the various villages were similar in their anthropometric characteristics before 1969 .
Technically speaking, the longitudinal study design calls for the village to be the unit of analysis. A drawback of this approach is that it can be followed only for certain outcomes for which baseline data exist (e.g., infant mortality, physical growth). The low power of the village-level design, with only two villages per treatment, makes it unfeasible as the approach to be used routinely. Instead most analyses have used the "subject" as the unit of analysis but adjusted for relevant differences between and within villages, such as in socio-economic status and education. However, such subject-level analysis cannot be said to address causality in the sense that village-level analysis does. Rather, it can be viewed as enhancing plausibility, or the internal consistency of results and hence their persuasiveness . For example, subject-level analyses allow one to explore whether a dose-response relationship exists between the supplement and outcomes of interest. The persuasiveness of the findings is enhanced to the degree that this and other expectations are met. However, factors associated with attendance at the supplementation centre and consumption of the supplement have to be taken into account .
The nature of the intervention
The nature of the intervention that took place can be grouped into its intended and unintended consequences. The major and intended changes in the villages were better medical care and improved nutrition. Medical care included prenatal services, paediatric examinations, and vaccinations, all at no cost to the families. By design, all four villages received the same quality of medical care. The supplementation programme was meant to produce strong nutritional contrasts between the atole and fresco villages. To appreciate why the supplements were formulated as they were , readers must recall that there was a fixation on protein as the main limiting nutrient in the diets of developing countries during the 1960s. Thus, the formulas were chosen so as to cause striking differences between village types in protein intake; the small amount of energy in the fresco was not viewed with concern, and the similar concentrations of vitamins and minerals in the supplements were meant further to isolate protein as the key nutritional difference in intakes between subjects receiving atole and fresco. Implicit in this expectation was the need for the patterns of attendance at the supplementation centres and intake to be similar in the villages. A desired result of similarity in attendance patterns was equivalence in the degree of socialization associated with interpersonal contact at the centres, an aspect of great relevance for the interpretation of supplementation effects on cognitive outcomes. However, the attendance and consumption patterns did not prove to be the same either for mothers  or for children . The volume of fresco consumed by the mothers was about three times greater than that of atole, resulting in nearly equivalent energy supplement intakes by village type. For the children, in the first three years of life, attendance and supplement intake were much lower in the fresco than in the atole villages, so that not only the intakes of protein but also of energy and other nutrients were considerably greater in the atole villages .
The extent of dietary improvement caused by the supplementation programme is shown in figures 1 (see FIG. 1. Energy intake of children 15-36 months old from home diet and supplement) and 2 (see FIG 2. Protein intake of children IS-36 months old from home diet and supplement) for energy and protein respectively . From 15 to 36 months, the differences in total energy intakes between the atole and fresco villages were about 90-100 calories. The total energy intakes in the atole villages were 11%12% greater than in the fresco villages. This is net of the small replacement effect caused by the supplements. These differences in total energy intake are not large. Most feeding programmes aimed at young children are designed to provide more than 100 calories a day (that they often fail to achieve this is another matter) . The supplementation programme had a much greater relative impact on protein intake: intakes in the atole villages were almost 9 g, or 40%, greater than in the fresco villages. There were also large differences for vitamins and minerals. Thus, in contrasting total intakes, differences are evident for energy, protein, and other nutrients. There is no theoretical reason to suppose, just because the percentage increase in total intake is less for one nutrient than for another (e.g., energy versus protein), that one difference is more important than the other. The importance depends on what is limiting in the diet.
The results on the effects of the nutrition intervention in children are best viewed as providing information on the value of improving food consumption in general rather than that of any particular nutrient. For the women in the study, however, the energy rather than the protein or other nutrients in the supplement best explains the relationship between intake during pregnancy and the improvements in birth weight . The analyses to support this claim are made possible by the overlapping ranges in supplement energy intakes during pregnancy in the atole and fresco villages.
The unintended effects of the design are potentially many. The continued presence of a team of outsiders in small, traditional villages over eight years must have had a significant effect on attitudes and even practices in health, nutrition, and child rearing, among other areas. These effects are probably very important but remain unmeasurable. Because the data collection activities were similar in all four villages and because the INCAP personnel were routinely rotated among all the villages, it is reasonably certain that the effects, whatever their nature, were similar in the atole and fresco villages.
Effects in early childhood
The nutrition intervention benefited the children in many ways. Supplementation during pregnancy improved birth weights: the risk of delivering a low-birth-weight baby was half as great for women who ingested more than 20,000 kcal from the supplements during pregnancy as for those who ingested less than that . Infant mortality rates were markedly reduced: in 1969-1977 they declined by 66% in the atole villages from the 19491968 rates, compared with 24% in the fresco villages and 19% in non-intervened (i.e., control) villages . Whereas the number of days children were ill with diarrhoea was not reduced by the intervention , atole did protect against the negative effects of diarrhoea on growth . Atole also promoted speedy recovery from wasting  Although the effects of atole on growth in children were important , they were confined to the first three years of life . Specifically, atole intake was not related to growth from three to seven years of age. Another improvement associated with the intervention was enhanced motor development . Finally, atole had only a minor effect on mental development, certainly much less than anticipated .
The results of the impact of the nutrition intervention on physical growth in three-year-olds may be seen in figures 3 (see FIG. 3. Changes over time in percentages of three-year-olds with severe growth failure (length 3 SD or more below the reference median), by supplement type, sexes combined) and 4 (See FIG. 4. Changes over time in percentages of three-year-olds with severe growth failure, by supplement type and sex), which show, by supplement type and calendar time, the percentages of children who were severely stunted, defined as being shorter than three standard deviations (SD) below the NCHS mean.' When the study began in 1969, the prevalence of severe stunting was extremely high, around 45%, but was similar in the atole and fresco villages. Over the course of the study, the figure was reduced by half in the atole villages but stayed about the same in the fresco villages.
A logistic regression model was used to test the time trends shown in figure 4. The model that best fit the data included severe stunting as the dependent variable (1 = severely stunted, 0 = others) and the following independent variables: treatment, sex, year, and the interaction terms treatment * sex, treatment * year, and sex * year (table 1). The analysis indicates that the atole villages had less severe stunting than the fresco villages; the significant interaction terms reveal a significant decline in the atole villages, most pronounced in girls.
TABLE 1. Logistic regression results of trends in severe stuntinga by treatment type, sex, and year (model X2 = 49.96, df = 6)
|Treatment * sex||-0.811||0.299||-2.713||<.01|
|Treatment * year||-0.175||0.062||-2.837||<.005|
|Sex * year||-0.070||0.062||-1.134||NS|
a. Defined as being shorter than 3 SD below the NCHS median (see text).
b. Atole = 1, fresco = 0.
c. Male = 1, female = 0.
d. The year is expressed continuously as one of five values: 69, 70.5, 72.5, 74.5, and 76.5. The values are the average for each category.
The important improvement occurred in the absence of changes in diarrhoeal diseases . Had both infection and diet been altered, the expected effect no doubt would have been greater. It is of interest that growth rates from five years of age to adulthood in the study population were not very different from those observed in well-to-do populations . Certainly, later childhood and adolescence cannot be said to be stages in life when marked growth failure occurs. Rather, the first three years are when growth retardation in Guatemala is intense and when nutrition interventions can have the greatest impact on growth.
The follow-up study
There have been some nutrition follow-up studies conducted in developing countries, but they have focused on specific groups, such as survivors of severe malnutrition; to the best of our knowledge, apart from the INCAP study reported on here, no long-term follow-up studies of nutrition interventions have ever been carried out. Another distinguishing feature of the present study is its comprehensiveness : no other study of any kind in developing countries has included such a range of measures of human function.
The follow-up study permits us to ask whether the benefits found in early childhood persist into adulthood. A novel contribution is that it allows examination of functional effects that can only be measured later in life, in effect extending the horizon for evaluating nutrition interventions. Its central hypothesis was that better nutrition during early childhood leads to adults with a greater potential for leading healthy, productive lives.
Most of the subjects were adolescents when the data were collected in 1988. The issue of when best to carry out the study was debated intensely among the research members, and, although it was agreed that it would be better to measure the subjects as adults, it was felt that the opportunity to carry out the study might not exist later. It was also recognized that much would be learned about adolescence per se by going ahead with the study; this was seen as a significant contribution, since much less is known from nutrition studies in developing countries about adolescents than about young children.
The use of the word "potential" in the hypothesis was deliberate. It was realized that productivity in an economic sense could not be assessed adequately in a young population. Such assessment could only come later when the subjects formed independent households and settled into their occupations. Similarly, other functions, such as parenting, could be measured only when they formed families.
Overview of key results
Data were collected on many functional domains , but only three are emphasized in this brief overview: body size and composition, work capacity, and intellectual performance. All three areas are important, and improvements in one or all would be seen as contributing to human capital formation.
Three aspects stand out with regard to the body size and composition results. First, the adolescents who were exposed to atole during the first three years of life were taller and had greater fat-free mass (FFM) than those who received fresco. However, some attenuation of the effects was observed at the age of three years; that is, a small degree of catch-up was seen in the fresco villages. It is interesting that the anthropometric effects were greatest in females. Of the subjects older than 16 years who were exposed to the supplements from birth to three years of age, 49% of the fresco women had very short stature compared with 34% of the atole women (see FIG. 5. Prevalence of very short stature (<149 cm) in women 16 years old or over who were exposed to supplement from birth to three years of age (X2 = 3.70, p » .06)). (Little or no growth in height occurs after 16 years . Similar findings are obtained when the analysis is restricted to women older then 18: fresco, 12/27, or 44%; atole, 9/32, or 28%.) Differences in FFM also stand out: The females from the atole villages had 2.1 kg more FFM than those from the fresco villages. These differences are equivalent to an effect size of about 0.5that is, equal to a shift of 0.5 SD; an effect of this magnitude can be called medium, using Cohen's labels .
Work capacity improved in subjects exposed to the supplements in their first three years of life, but only in males. Atole males had maximum oxygen consumptions (VO2 max) 0.3 litre per minute greater than those of fresco males. The difference is equivalent to about 0.7 SD, approaching what can be called a large effect size . Another interesting finding is that the larger working capacity of the atole males could not be explained by differences in FFM (i.e., VO2 max/kg FFM was still greater in the atole villages). The nature of these qualitative tissue differences between the atole and the fresco subjects is unclear.
A feature of all analyses carried out to date with respect to measures of intellectual performance is that they have controlled for schooling variables, because the villages differed in patterns of school attendance since before the study began [2, 3]. One of the fascinating discoveries is that intellectual performance was more affected in adolescence among subjects exposed to the supplements during gestation and the first two years of life than in those exposed later in life. (The behavioural analyses have focused on a different sample than the biological analyses exposure during gestation and the first two years of life versus exposure during the first three years of life respectivelybecause of different perceptions about vulnerability in each area and the fact that effects of atole on growth were seen only in children under three years of age .) The atole-fresco differences in children were less than 0.2 SD, compared with around 0.6 SD in adolescents, using a summary variable of intellectual performance (i.e., a factor score that combines literacy, numeracy, general knowledge, Raven's progressive matrices, reading, and vocabulary). The effects in children can be described as small and those in adolescents as medium to large. There are also strong indications that the effects in adolescents occurred only in those cohorts exposed to supplementation during gestation and the first two years of life. Examination of the subcomponents making up the summary variable shows that effects were found in four of six tests. Effects were seen in bath males and females.
Potential significance of the results
The greater body size and increased FFM in females would be expected to affect reproductive fitness positively . Short stature is a risk factor for cephalopelvic disproportion, delivery complications and maternal obstetric mortality; a height under the cut-off point of 149 cm (4 feet 11 inches) is often used as a criterion of obstetric risk in women . Also, greater FFM has been found to lead to higher birth weights.
The improved working capacity in men might result in increased productivity in those engaged in hard physical labour. The literature clearly supports this expectation .
Finally, sharp minds are valued by all societies and by parents everywhere in recognition that improvements in intellectual performance are bound to improve the capacity of individuals to function in a variety of settings. One suggestion is that such improvements might lead to better employment opportunities and greater earnings. Another is that better intellectually endowed adults will be better parents by virtue of being better providers, as well as by being more able to meet the developmental needs of their children.
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