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Chronic energy deficiency and the effects of energy supplementation


N.G. NORGAN*

* Department of Human Sciences, University of Technology, Loughborough, Leicestershire, LE11 3TU, U.K.


1. Introduction
2. Definitions and descriptions
3. Approaches to the study of the effects of energy supplementation
4. Supplementation studies
5. Some possible explanations for the small effects
6. Contemporary models
7. Gaps in our knowledge
8. Concluding comments
References



1. Introduction


Chronic energy deficiency is the most widespread nutritional deficiency, it is said to affect half the world's children. There is much concern about the situation and considerable efforts are being made to alleviate this state of affairs. Although nowadays many observers feel that tackling poverty by a redistribution of income and resources is a prerequisite to a reduction in the extent of malnutrition, food distribution programmes may ameliorate the problem. In many countries the bulk of the budgets for child nutrition goes towards nutritional supplementation. The proposition that providing food to the undernourished ipso facto improves nutritional status and well-being has not been seriously questioned until recently. There are now numerous observations and several studies indicating that, for one reason or another, the effects of nutritional supplementation are small and much less than expected. This may be a result of poorly designed and implemented feeding programmes and studies. Alternatively, it may be that our hypotheses and models of the processes involved have been unduly simplistic and inappropriate and we may be missing important effects. We are rarely fortunate to have single causes and effects, so that a combination of these two explanations is possible, indeed probable.

The aims of this paper are:

1. to review the effects of energy supplementations in chronic energy deficiency;

2. to consider why supplementation has such small effects, in particular whether better designed and implemented studies will show greater effects, or whether other outcomes should be investigated;

3. to identify gaps in our knowledge.

As a first step, the variables and components of the processes are described.



2. Definitions and descriptions


2.1. Chronic energy deficiency
2.2. Energy supplementation
2.3. Targets of supplementation
2.4. The effects of supplementation



2.1. Chronic energy deficiency


Chronic energy deficiency (CED) refers to an intake of energy less than the requirement, for a period of several months or years. It is difficult to identify directly, as measurements of energy intakes in free-living individuals and populations are fraught with problems, a predicament exacerbated in the determination of requirements. In the latter case, the practical difficulty of allowing for possible adaptations, behavioural, mechanical, physiological and biochemical, and varying reproductive status render this fundamental nutritional characteristic elusive. As a consequence, CED is usually identified by proxy variables such as deficits in anthropometry, body composition or growth. The fact that these vary according to the intensity and duration of CED would seem an advantage in, for example, identifying those most in need of treatment, but as the range of normality is wide, deviations may occur before being identified as such, or normals may be picked up as deviations. In severe cases of CED, the picture presented leaves no doubt as to the existence of the condition. In milder forms, the proxy variables may be less accurate in identifying the condition, and the sensitivity and specificity of these criteria may leave much to be desired.

2.2. Energy supplementation


Nutritional supplementation is an addition to the diet to make up all or part of a deficiency. It differs from refeeding, where the total provision of foods is undertaken, and from nutritional intervention, where non-nutritional components such as socialisation, health care, etc., are included, intentionally or otherwise.

Supplementation varies according to the type, amount and duration of the supplementation. It is the independent variable, and controlled manipulation gives rise to high internal validity. Supplements may be administered daily at a feeding centre which has to be close to the subjects and requires frequent attendance and high staffing, or distributed weekly and taken home for consumption. This is less efficient in targeting the recipient, as sharing of the supplement may occur. Supplements are invariably based on manufactured, possibly imported, products rather than locally produced or fresh foods, to guarantee homogeneity of composition and adequate supplies.

Some studies have utilised the process of "natural" supplementation, that is the naturally occurring covariation in nutrition and an outcome, as in observations of the previously malnourished. Such retrospective, non-experimental designs have limitations in that conclusions of cause and effect cannot be drawn with confidence.

2.3. Targets of supplementation


Supplementation studies have focused on pregnant and lactating women, and the infant and young child. Occasionally older children and workers have been targeted, and in some cases the whole family may have been recipients. In supplementation programmes, as opposed to research studies, the most needy may have to be identified and targeted. The planning and policy issues of targeting are not considered in this paper.

2.4. The effects of supplementation


The effects of supplementation, the outcome variables, are sought in raised birth weights, improved infant and child growth, and decreased morbidity and mortality. In older children, growth has been the cardinal feature, but considerable attention has been given to whether deficits in behaviour and mental performance are overcome. The importance of activity, play and discretional activities is being recognised and included in studies. The effects on physical work capacity and productivity allow an econometric analysis of supplementation, a point that may impress funding agencies. Evaluation of the effects should be a fundamental part of any supplementation activities.

3. Approaches to the study of the effects of energy supplementation


The simplest model of the effects of energy supplementation is:

Energy supplementation (r) Raised energy intake (r) Raised energy stores

Such a model has been described as a direct intervention model (BEATON, 1982) or a main-effect model (ADAIR and POLLITT, 1985; POLLITT, 1987). Its characteristics are a direct, proportional, linear relationship between the intervention and a specific outcome, with few confounding variables. It portrays supplementation in a dose-response manner with similar responses expected in different populations and is a variant of the clinical trial model.

In CED, the outcome variable would be a reduced incidence in CED or improved nutritional status as shown by the proxy variables of, for example, increase in growth and size in the population. However, already the outcome variables are now less specific and may be influenced by many other environmental factors, such as illness, and poor social and economic circumstances. When the outcome is a functional variable such as work capacity or performance, there are many more stages between supplementation and outcome. With a multistage model, which is also a direct and main-effect model, the effects are expected to be smaller and less specific, and more influenced by intervening and confounding variables. The multistage model has been the common conceptual approach to supplementation effects until recently.

Chronic energy deficiency is characterised by falls in body weight and fatness, falls in resting metabolic rate and habitual physical activity, and in physical working capacity. Such changes were recorded in the classic Minnesota study (KEYS et al., 1950) and are well-recognised outside the laboratory. CED has effects on behaviour and socialisation as well as on energetics, and a single outcome is obviously not representative of all the effects. In addition, some of the changes are interactive. Falls in metabolic rate reduce the extent of depletion of energy stores; reduced size and reduced activity may both influence work capacity. If the effects of supplementation in reversing some or all of the characteristics of CED are to be identified, an appropriate conceptual and methodological approach is required. However, it is the heuristics of models that are important rather than the models themselves. The development and testing of models should provide useful feedback and confirmation to guide research and planning efforts.

4. Supplementation studies


4.1. The INCAP study
4.2. The Gambian studies
4.3. The Bacon Chow Study, Taiwan
4.4. Conclusions



Three typical supplementation studies are described. They are then examined along with other studies such as the Bogota, Colombia study (MORA et al., 1978; 1979; 1981; WABER et al., 1981), the New York study (RUSH, STEIN and SUSSER, 1980) and the USDA Women, Infants and Children (WIC) programme (BERKENFIELD and SCHWARTZ, 1980; HEIMENDINGER et al., 1984; KENNEDY and KOTELCHUCK, 1984; METCOFF et al., 1985) to examine whether the results were affected by inappropriate models, experimental design and execution, and which model best describes the processes and outcomes of supplementation.

A number of reviews and critical appraisals of the various aspects of these supplementation studies have been published recently: AEBI and WHITEHEAD (1980); RUSH et al., (1980); LECHTIG (1981); SUSSER (1981); BEATON (1982); BEATON and GHASSEMI (1982); BROZEK and SCHÜRCH (1984); BARRETT (1984); JOOS and POLLITT (1984); MARTORELL (1984); ADAIR and POLLITT (1985); SCHÜRCH and FAVRE (1986). The effects of supplementation on cognitive performance in children and on body composition, work capacity and productivity are described in the Meeting papers of POLLITT and SPURR respectively.

4.1. The INCAP study


This longitudinal study was designed to observe the effects of chronic malnutrition on physical growth and mental development (LECHTIG et al., 1979; ENGLE et al., 1979). It was conducted in four Spanish-speaking villages in eastern Guatemala. At the time the study began, 15% of infants died before the age of one year. During pregnancy, energy and protein intakes were 6 MJ and 40 g. Mothers were small and light (1.49 m, 49 kg), and weight gain during pregnancy was half that of well-nourished women.

Two types of supplement were provided, atole, a protein-energy supplement, and fresco, which had no protein and one third the energy of atole. Both preparations contained minerals and vitamins in similar amounts. Two villages were randomly assigned to receive atole and two fresco. Supplements were distributed twice daily at a supplementation centre at which attendance was voluntary, so that there was considerable variation in levels of supplementation. Preventive and curative medical care were provided. The target groups were all the mothers and all the children less than seven years. New cohorts of children were included from the start of the study in 1969 until 1973. The study was terminated in 1977.

Birth weights were significantly lower (2997 471 g versus 3114 426 g) in 192 women who had on average a low level of supplementation (180 kJ/d) compared with 165 women with higher levels of supplementation (975 kJ/d). Energy appeared more important than protein and carbohydrate. Although birth weight gains were only 29 g per 42 MJ supplement, the incidence of low birth weight (<2500 g) was halved in the higher level group. Infant mortality fell from 135 to 51/1000.

In 453 0-3-year-old children (MARTORELL, KLEIN and DELGADO, 1980) greater supplement intake was associated with better growth in supine length and weight but not limb circumferences. Skinfold thicknesses decreased with supplementation. At three years, children in the highest supplementation group of more than 800 kJ/d were 1 kg heavier and 4 cm longer than children in a baseline group. The differences equal the pooled SD but were statistically significant nonetheless. Similar differences were observed between atole and fresco villages, but that of height was smaller although still significant.

Behavioural development was tested in over 450 children at 6, 15 and 24 months of age. A Composite Infant Scale, with subscales for mental and motor development, was used. At 6 months of age, children classified as of low (<21 MJ per 3 months), medium (21-42 MJ) and high (>42 MJ) supplement intake showed statistically significant differences only for the mental subscale. At 15 and 24 months, differences were greater and significant for both subscales. Testing continued until 5 years with the INCAP Preschool Battery (ENGLE et al., 1979). A composite score and separate psychological test scores of verbal reasoning, learning and memory, visual analysis and motor skill showed significant difference in the three supplementation groups at 3, 4 and 5 years. More recently, when measured at 6 to 8 years, high-supplementation children showed more interest in and exploration of a novel environment, more involvement in a competitive game, greater persistence on a frustrating task, better motor impulse control and greater initiative across several group tasks than low-supplementation children (BARRETT and RADKE-YARROW, 1985).

4.2. The Gambian studies


In Keneba, in The Gambia, there is marked seasonality in nutritional status of pregnant and lactating women, as indicated by changes in energy intake and body weights. In the wet season, energy intakes are lowest, down to 5.2 MJ/d, and energy expenditure is highest due to the demands of agricultural activities. The amplitude of the weight change is some 4 kg. In the dry season, intakes are higher, 6.2 MJ/d in pregnant women and 7.0 MJ/d in lactating women, but are less than 65% of suggested standards (PRENTICE et al., 1981). During 1980-82, all pregnant women were offered supplements of groundnut-based biscuits and a vitamin-fortified tea drink (PRENTICE et al., 1983). Supplements were available six days a week, consumption was carefully supervised and measured, and home food intakes were assessed. Overall the daily consumption of supplement was 2.8 MJ/d of which 1.0 MJ/d substituted some of the normal diet. Net increases in intake were higher than in most supplementation studies. Compared to baseline measurements of 1978-80, supplementation increased mean birth weight by 100 g, after adjusting for sex, birth order and month of birth, and decreased the incidence of low birth weight from 20 to 6%. However, the effects were mainly restricted to births in the wet season when energy intakes are less adequate (PRENTICE et al., 1981). Birth weights in the months July to January were 224 g higher.

An earlier study of similar design on lactating women (PRENTICE et al., 1980) provided a mean net increase of 3 MJ/d over 12 months and resulted in supplemented women being 1-2 kg heavier. However, the pattern of seasonal weight change was maintained, albeit at a lower amplitude. No consistent improvement in breast-milk intake, as evidenced by test-weighings, was found nor were differences in milk energy content apparent.

In a recent smaller study, supplemented pregnant women gained 2 kg more fat than controls from another village (LAWRENCE et al., 1987).

4.3. The Bacon Chow Study, Taiwan


This was a longitudinal double-blind nutrition intervention of rural women at risk nutritionally in an economically depressed area of west-central Taiwan (ADAIR, 1984; ADAIR and POLLITT, 1985). After the birth of a first child, women were randomly assigned to a nutrient-rich dietary supplement group (A) or a placebo group (B) for the lactation period, the gestation period of the subsequent pregnancy and its lactation period. The supplements were handed out twice daily by nurses who monitored intakes. Both groups received a multivitamin and mineral tablet daily and were provided with medical care. The outcome variables assessed included infant birth measurements, postnatal physical growth, motor and mental development, morbidity, and maternal weight and skinfold changes during pregnancy and lactation.

Energy intakes during lactation were significantly different in the two groups (5 and 7.5 MJ/d) but no significant effects were found in maternal weight, weight gain and skinfold thicknesses (ADAIR, 1984). Indeed, few A-B differences in mean values of the outcome variables were found except in some subgroups. Male infants born after a supplemented pregnancy weighed more at birth than brothers born earlier. Sibling correlations were lower in the supplemented group, suggesting that maternal supplementation affected the components of variation in infant anthropometry more than the means (MUELLER and POLLITT, 1982), and that there are differential risk and probability of response in populations (ADAIR and POLLITT, 1985). Important mediators of supplement effects included maternal body size (greater weight gain in mothers with lower weight-for-height), sex of offspring (males being more susceptible to supplementation than females) and season of the year. There were no treatment group differences in mental scores of 8-month-old infants but motor development scores were marginally significantly different. Supplementation had no effect on the Stanford Binet IQ evaluation of 5-year-old children. Thus, supplementation had limited effects on the population as a whole despite the apparent marginal nutritional status.

4.4. Conclusions


These studies and those referred to earlier show only small (100 g) increases in birth weight with supplementation. A more important effect is the reduction in the proportion of low-birth-weight infants. Supplementation appears to have little effect on lactation, and supplements may be better directed to infants than lactating women. In children, mean differences in weight gain are some 0.5-1.0 kg/y (BEATON and GHASSEMI 1982). Significant changes in growth rate measured as height have been demonstrated. These data come from research studies which are likely to be more successful than feeding programmes because of higher levels of commitment. The effects on behavioural development are similarly restricted and, during the first two years, occur primarily in motor items and subscales (Jogs and POLLITT, 1984). In general, although the level of response is conditioned by the relative severity of the CED, deprived children are never brought up to the level of economically and socially advantaged children. The effects of supplementation are disappointing and the fate of most of the supplement is unexplained.

The observed effects do not fit what is expected in the direct intervention main-effect model. The hypothesis that supplementation will increase the intake and improve nutritional status resulting in improved function and performance in growth, behaviour, pregnancy, lactation and work is not borne out. Whether this is a failure of the model or poor experimental design and implementation is considered next.

5. Some possible explanations for the small effects


5.1. Are the recipients really malnourished?
5.2. Are the target groups being energy-supplemented?
5.3. Are the target groups appropriate?
5.4. Are the outcome variables appropriate?



5.1. Are the recipients really malnourished?


There are two issues here. The first concerns the validity of energy intake measurements and the second the interpretation of low intakes, low body weight and energy stores.

Considering the expense and effort of supplementation studies, it must be said that a disproportionately small amount of effort seems to have been made to obtain reliable intake data before or during supplementation. Given the intraindividual variation in energy intakes, recall data and weighed intakes over short periods are inadequate. Monitoring of supplement consumption has been satisfactory but the remainder of the intake has not been assessed accurately.

The question of the significance of low intakes and adaptations to these have been considered in detail by James. Low intakes have, over the last 15 years, become acceptable without any real justification for this except that investigators have reported being as careful and as accurate as possible under the field conditions. This has led to a number of hypotheses about adaptations, a term used to mean several different things. Where energy intakes and expenditures have been measured and a discrepancy found, intakes have been regarded as more accurate given the techniques involved (DURNIN, 1984). The new technique of doubly-labelled water is suggesting that, in The Gambia at least, the energy expenditure measurements may be correct, in line as they are with those from indirect calorimetry, and that the error lies in food-intake measurements SINGH et al., in press). This supports the evaluation of our Papua New Guinea data (NORGAN, FERRO-LUZZI and DURNIN, 1974) made earlier by JAMES and SHETTY (1982) and could mean that the need for hypotheses of adaptive processes should be seen in a different perspective. BEATON'S (1984) comment "Either our concepts and understanding are wrong or the data are wrong" remains unanswered.

In the Taiwan and Gambia studies, intake data (5-7 MJ/d) and anthropometric data suggest the subjects were at risk nutritionally. However, reproductive performance was good. In Taiwan, mean birth weights of 3000 g were high for a developing country and only 7% of births weights were below 2500 g. In The Gambia, lactational performance was satisfactory. When performance and functional capacity data conflict with the proxy variables of anthropometry or energy intake (a proxy for energy balance), we ought to accept the former. There must be some doubt as to whether the subjects of many supplementation studies and programmes are as chronically energy deficient as is thought.

5.2. Are the target groups being energy-supplemented?


Supplements are consumed at distribution centres as in the INCAP, Gambia and Taiwan studies or taken home for subsequent consumption as in the Bogota, New York and WIC programme in the USA. Centre-based consumption has obvious advantages in ensuring and measuring supplementation but it does have the disadvantage of being expensive, costly in time with possible low or variable participation. Take-home supplementation is now more common, but direct measurement of the intake of supplement is less frequent, and "leakage" of the supplement away from the intended recipient has been identified in many studies. Supplements may be given to other family members or even sold. BEATON and GHASSEMI (1982) estimate that 30-80% of take-home supplements do not reach the intended child.

A problem with both types of distribution is that substitution of some part of the habitual intake is common and that the net increase in intake may be only 45-70% of the supplement, although values as low as 10% have been reported. While most studies monitor supplement consumption closely, measurements of home intakes have not yet been frequent or accurate enough.

In The Gambia, at least, total intakes come within 10% of those of pregnant women in Cambridge, U.K., but in most studies only a small part of the apparent energy deficit is being met, which in itself may explain some of the poor results obtained.

Characteristically, energy supplementation is not the only intervention taking place. Protein intakes increase by similar or greater degrees than energy, for, when many of the studies were planned and begun, protein supplementation was the goal. Vitamin and mineral supplementation is the rule, and health care, preventive and therapeutic, is made available. Separation of the effects of each of these is rarely possible. Other confounding variables, associated in the same direction as the independent variable with the outcome, may be subtler and unrecognised. In examining the effects of a supplement or a placebo on the behavioural development of children, attendance at a distribution centre itself has a stimulatory effect, and both groups will differ from the normal uninvolved child. Thus, our conceptualisation of the treatment is approximate as supplementation has non-nutritional components.

In the studies considered here, duration of supplementation does not seem to have been a direct factor limiting the effects and magnitude of the outcome. The type of supplement, whether based on local foods or manufactured products, does not seem to affect uptake of the supplement although it may influence its fate. BEATON and GHASSEMI (1982) report that premixed infant formulae are less shared in the family than ingredients of a mix of local foods. The success in achieving a large net increase in intake in The Gambia has been attributed to a palatable supplement made available at a convenient time, early in the morning.

5.3. Are the target groups appropriate?


This question refers to two issues, the representativeness of the target group and their suitability in terms of their capacity to change nutritional status.

Supplementation studies require adequate control groups and random assignment of subjects to target and control groups. Under these circumstances, the individual differences in outcome can be ascribed more confidently to the manipulated independent variable, than to confounding factors. Random assignment has been a feature of most research studies (Bogota, New York, Taiwan). In the INCAP study, villages were randomly assigned to treatments. The retrospective comparison of different groups with and without supplementation, as in The Gambia, is less satisfactory because of possible secular trend effects such as those seen in the Taiwan study (ADAIR and POLLITT, 1985). Concurrent measurement of control and target group is recommended.

Varying participation may qualify the effects of randomisation. Weight gain is often proportional to degree of participation and non-attenders differ from regular attenders. In the early years of the INCAP study, less than two-thirds of the births were weighed although in this case no bias was introduced, as in 1970-73, when coverage was 92%, no differences were found compared to earlier figures. In the Taiwan study, non-attenders were followed up in their homes to avoid this effect and to raise levels of supplementation.

Are the target groups able to respond to supplementation? Given that malnutrition exists in the community the choice of pregnant and lactating women, infants and children and workers seems appropriate, but children under two years are underrepresented in supplementation studies (BEATON and GHASSEMI, 1982). Infants will and should be encouraged to breast-feed but the late introduction of solid foods may be responsible for much of the increase in malnutrition that begins at this age, and more work on this group is required. Results from the Bogota study have been interpreted to suggest that prenatal supplementation may be less useful than later supplementation (JOOS and POLLITT, 1984). Similarly, direct supplementation of children may be more cost-effective than supplementing lactating women.

5.4. Are the outcome variables appropriate?


Anthropometry of mothers, infants and children has occupied a central place in assessing the outcome of supplementation. Weight and fat gain or loss have been taken to indicate nutritional adequacy in growth, pregnancy and lactation and in the performance of work. Anthropometric variables can be measured objectively with sufficiently high precision and measures of central tendency and dispersion calculated. However, anthropometric variables are proxy variables for CED and nutritional status. An abnormal or impaired state is best represented by a change in function or capacity. As yet, few of these are sufficiently specific to energy nutrition, or not enough is known about the intervening and confounding factors to warrant introduction at this stage.

The ability of Gambian women with low body weight and apparent low energy intake to lactate as efficiently as women of higher weights, energy intakes and energy stores is an example of a function being a more appropriate outcome variable than anthropometry. Changes in anthropometric measures are slow to develop, and other outcome variables may change first. Improvements in social responsiveness may precede increases in weight in supplemented children (BARRETT, 1984).

An overemphasis on anthropometric outcomes has contributed to the longevity of the direct main-effect model and led to a misinterpretation of some other effects of supplementation. For instance, the sharing of supplements is a feature of most studies, particularly take-home distribution studies. With outcome variables such as anthropometry or a functional capacity, sharing represents an inefficiency of supplementation.

Beaton has argued convincingly that leakage, that is, sharing plus substitution of the normal intake, can still confer positive benefits on the intended recipient. If the supplement is consumed by others, more home food is available for the recipient and others in the family have benefited (BEATON, 1982; BEATON and GHASSEMI, 1982). Even if the supplement is sold, the income benefits the family, including the intended recipient. Supplementation can thus have multiple effects, many of which are indirect and have not been considered previously and which may be more important than the small changes in anthropometric variables.

To conclude this section, there have been many problems in the identification of the undernourished, the degree of supplementation, the randomness of treatment groups and the choice of outcome variables such that these have made some contribution to the observed small effects of supplementation. The possibility of multiple effects and other evidence considered in the next section suggest that our conceptualisation of the processes and effects of supplementation should be modified.

6. Contemporary models


The beneficial effects of leakage of supplement have been proposed as evidence for a multiple effect model. In both take-home and centre-based supplementation there is often a mismatch between the energy ingested and an anthropometric outcome. Birth weight gains in the INCAP study were 7 g per 10 MJ, and in the Gambian study weight change accounted for only 7% of the supplement. Considerable amounts of energy are missing. BEATON and GHASSEMI (1982) state that only 15% of the energy distributed to children is utilised in growth processes. They have attempted to account for the missing energy of supplementation in children. The best results are a weight gain of about 1 kg/y requiring about 600 kJ/d. The extra intakes are some 120800 kJ/d. Increased body size of 1 kg in a 12-kg child would raise maintenance energy requirements by about 8% or an average of 170 kJ/d at the midpoint of the year. This leaves a large apparent disparity between net intake and the improved growth.

An explanation for missing energy may be that supplementation leads to "de-adaptation", e.g., that basal metabolic rates are increased over and above the size effect, and that physical activity increases. In pregnant Gambian women, LAWRENCE et al., (1984) found the net extra energy cost of tissue maintenance to be 4 MJ. However in women supplemented with amounts sufficient to raise birth weight 190 g but not body weights this increased to 55 MJ. These workers report a 5% higher energy cost of activity in supplemented women, an amount comparable with the extra thermic effect of the ingested supplement (LAWRENCE et al., 1985). It is widely believed by the Gambian villagers that supplemented lactating women have more energy for farming activities (PRENTICE et al., 1980). These observations await verification as REINA, SPURR and BARAC-NIETO (1987) report in their abstract to the Meeting no effect of supplementation on activity energy expenditure in Colombian boys and girls. CHÁVEZ and MARTÍNEZ (1982) have reported differences in behavioural measurements of activity in infants and young children.

Individual differences in responsiveness to supplementation are another argument for refinement of models and hypotheses. The sex of the offspring determines the extent of the response to supplementation. In the Bogota and Taiwan studies, males showed a greater response, probably as a result of their greater vulnerability to environmental conditions. The effects of malnutrition on subsequent mental development vary according to whether the child is brought up in a developed, western country or in environmentally impoverished conditions. The results from the INCAP, Bogota, Taiwan and New York studies, which might be ranked in that order in terms of degree of deprivation, suggest the magnitude of the effects of supplementation (but not the level of significance) depends on the degree of total environmental deprivation. Further factors affecting responsiveness, such as maternal attitude, attendance, distance from distribution centre, etc., illustrate the nature and multiplicity of confounding factors and the need for more detailed models and considerations.

The importance of the environmental context cannot be overemphasised. It will influence the nature and severity of CED, the types of local supplements available, who is affected and what the effects are. The environment determines the disease pattern, the responses to infection and the level of health. The proxy variables of CED and the outcome variables are equally affected by physical, biological, social and cultural environmental challenges. The signs of CED and changes in outcome may be non-nutritional in origin. This mix makes for very complex situations and it is unlikely that there is one direct linear pathway linking supplementation to all the outcomes. Our models should allow for multiple outcomes and non-linear indirect pathways. These are featured in some contemporary descriptions of the relationship of nutrition to growth and performance (BEATON and GHASSEMI 1982; ADAIR and POLLITT, 1985). Our studies should change from bivariate to multivariate designs, from studies of outcome variables to studies of the processes occurring, if we are to better understand the complex processes of human reactions.


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