5. Effect of protein and energy on growth of children with primary malnutrition

Virtually all children with severe protein-energy malnutrition (PEM) have deficits in both total body fat and total body protein. Nutritional rehabilitation aims to replace these deficits as rapidly as possible. Historically, the emphasis in treatment was placed on high protein intakes, but it was later recognized that calories and not protein were often the limiting factor in the rate of weight gain during recovery (DEAN and SKINNER, 1957). The efficacy of high-energy feeding to achieve rapid weight gain during recovery from PEM is well documented (WATERLOW, 1961; JACKSON and WOOTTON, 1990). What is less certain is the relationship between the high energy intake and the composition of the tissue being laid down during rapid catch-up growth in the child recovering from PEM.

The increase in body weight during recovery from PEM may be regarded as equal to the increment in lean tissue plus the increment in fat tissue. The former consists of the increase in muscle mass plus the increase in non-muscle lean tissue. This latter increase is small compared to the increase in muscle mass, and the weight gained during recovery may be equated to the increase in fat tissue plus the increase in muscle tissue (JACKSON et al., 1977).

Fat has an energy content of 9.4 kcal/g and protein 5.7 kcal/g. Assuming that fat tissue has 15% as water, the stored energy of tissue fat is 8 kcal/g. Similarly, since lean tissue has an average protein content of 20%, it has an energy storage value of 1.2 kcal/g. A hypothetical line can be constructed using the axes, cost of growth, and increase in muscle mass expressed as a percentage of the increase in body weight.

Thus, if all the tissue laid down were fat tissue, and none of the increase in body weight were due to new muscle tissue, the cost of growth would be 8 kcal/g. Conversely, if all the new tissue gained were lean, the cost of growth would be 1.2 kcal/g (JACKSON et al., ROBERTS and YOUNG, 1988).

Muscle tissue is reduced by up to 70% in children with severe PEM; it provides the largest store of potentially available protein in the body. During recovery from malnutrition there is a significant: increase in muscle mass. This increase is proportionately greater than the increase in body weight and may differ according to the initial degree of stunting or wasting (REEDS et al., 1978). The evidence suggests that both hypertrophy and hyperplasia must take place, but the extent to which each process contributes to the muscle repletion has not been clarified.

Malnourished infants during the period of rapid catch-up growth are able to accept higher energy intakes when fed high energy density diets (ASHWORTH, 1976). It is not clear how the effect of the energy density of the feed affects the control of intake, nor is it clear if this effect is independent of the protein content of the diet. There is good evidence of spontaneous regulation of energy intake from the first week of life in full-term infants (FOMON, 1967). Both AGA and SGA infants consume a greater volume of a low energy density regimen than high energy density regimen. During the first 4 to 6 weeks of life, the reduction in intake after a high-energy feed is not sufficient to compensate fully for the difference in energy content; thus, higher energy intake results when a high energy density formula is given than when a low-energy feed is provided. After 6 to 8 weeks, normal infants are able to compensate, and there is no difference in energy intakes on feeds of different energy densities. We have observed that while most malnourished infants decrease their energy intake after normal weight-for-length is achieved, some maintain a high energy intake beyond the repletion phase. That is, they exceed normal weight-for-length by increasing adipose tissue mass (CHAVEZ et al., 1980). Thus, the set point for appetite regulation during recovery from malnutrition may be affected by conditions related to the infant or to the diet (Figures 1 and 2).

Energy and protein metabolism are closely interrelated (MUNRO, 1964). Several short-term studies have shown that the protein intake required for nitrogen equilibrium decreases with increasing energy intake. This occurs not only when the initial energy intake level is deficient but also when intake exceeds requirements. On the other hand, a reduction of protein intake while energy intake remains constant can reduce the rate of growth in terms of weight and height, even when nitrogen balance is not negative. The mechanisms producing these effects are not clear. It is also known that with an energy intake that is borderline or inadequate, an increase in protein intake can result in improved weight gain. Energy requirements for maintenance of weight and normal body composition may be less when dietary protein is adequate. Except for post-prandial thermogenesis, protein intake does not have a specific effect on energy requirements (BROOKE and ALVEAR, 1982).

Figure 1. Longitudinal follow-up of a group of 90 infants admitted under 6 months of age with marasmic protein-energy malnutrition to the CONIN Nutrition Recovery Center Program in Chile.

Anthropometry is expressed as mean values % of WHO median standard. After 2 months of age, catch-up weight was mainly fat, as evidenced by weight-for-length and triceps fat-fold gains (CHAVEZ et al., 1980).

Amino acid intake is the primary determinant of nitrogen retention when energy intake is fixed and adequate; conversely, an increased amino acid supply will be useless if energy is limiting (WATERLOW, 1986). Rapid rates of growth and of protein turnover require a generous energy supply. The energy cost of growth in infants with average composition of the tissue laid down has been estimated to be 5 kcal/g (FAO/WHO/UNU, 1985), of which about half can be accounted for by the energy content of the fat and protein that are deposited.

The requirements for catch-up growth can be estimated based on the available evidence. First, relatively more protein is needed for weight gain (assuming normal, balanced tissue gain) than for maintenance; therefore the P/E ratio in the diet needs to be higher than normal. Second, catch-up growth requires an increased intake of both energy and protein but the increase is several-fold greater for protein than for energy (WATERLOW, 1961).

The fact that undernutrition reduces the rate of growth must have been known for thousands of years, but malnutrition does more than this. By limiting the supply of nutrients for growth, it accentuates the development of those tissues which, at the time in question, have greater structural and perhaps metabolic stability than the rest (McCANCE, 1962). WIDDOWSON and McCANCE (1975) have described that there is a critical point in development when the size of an animal determines its appetite thereafter, and hence its rate of growth and dimensions at maturity. A small size at this critical time brought about by undernutrition is not followed by catch-up growth, however liberal the diet. A full diet produces catch-up growth only if the undernutrition, whatever its cause, has occurred after this critical period is over. Feeding can only restore a young animal to its percentile channel of growth and its ability to do this after long periods of undernutrition becomes progressively limited by the animal's chronological age. There is a time after which catch-up growth becomes impossible (WIDDOWSON and McCANCE, 1975).

Figure 2. Longitudinal follow-up of a group of 90 infants admitted under 6 months of age with marasmic protein-energy malnutrition to the CONIN Nutrition Recovery Center Program in Chile.

After 2 months of age, energy intake (solid circles) decreased as weight gain (open circles) slowed down (CHAVEZ et al., 1980).

ASHWORTH (1969) has described catch-up growth in malnourished infants of mean age 16.5 months, whose growth rates were fifteen times faster than those of normal children of similar ages and five times as fast as that of normal children of similar height or weight. Rapid growth was associated with high food intake (165 kcal and 3.8 g protein/kg body weight/d). This phenomenon occurred while infants were depleted and stopped upon reaching their expected weight-for-height (ASHWORTH, 1969). Children fed ad libitum a diet with 17% protein calories are able to regulate energy intake according to the demands of their body mass. If the P/E: ratio is lowered to 11%, they are able to consume 20% extra energy in an attempt to meet the level of protein necessary to reach maximal growth capacity determined by weight deficit (Rio et al., 1979).

Figure 3. Longitudinal follow-up of a group of 90 infants under 6 months of age with marasmic protein-energy malnutrition admitted to the CONIN Nutrition Recovery Center Program in Chile; weight-for-length is expressed as percent of WHO standard.

Infants with high (> than median) energy intakes (open circles) during recovery had similar gain in weight-for-length than those with low (£ than median) energy intakes during the first 2 months. At this time the group with high energy intake exhibited gain-for-weight above the expected for given length. Intake data for the group as a whole corresponds to solid circles in Figure 3 (CHAVEZ et al., 1980).

Long-term observations of children severely malnourished in early life suggested permanent reductions in body length (STOCK and SMYTHE, 1967; GRAHAM, 1968). Other observations indicate that, if these children have the benefit of a dramatic improvement in their environment, they are able to exhibit catch-up growth (GRAHAM and ADRIANZEN, 1972; SCHUMACHER, PAWSON and KRETCHMER, 1987). In general, younger children tended to gain more length during recovery. This suggests that there is an influence of biological age on the capacity for catch-up growth (WALKER and GOLDEN, 1988).

Figure 4. Longitudinal follow-up of a group of male infants admitted uncle 6 months of age with marasmic protein-energy malnutrition to the CONIN Nutrition Recovery Center Program in Chile, followed throughout childhood (solid triangles); a group matched by socioeconomic and ethnic background without antecedents of malnutrition in early life is depicted in closed circles. Growth curves correspond to WHO standard (ALVEAR, VIAL and ARTAZA, 1991).

We have demonstrated that 180-220 kcal and 3.5 g protein/kg/d support a weight gain of 10-15 g/kg/d in infants under 2 years of age being treated for PEM. These infants have been followed for up to 15 years after discharge. A subgroup of infants gained weight beyond the median expected weight-for-length by the time of discharge, namely 110% of the WHO standard (Figure 3). On the first year follow-up, this group showed faster linear growth velocity than infants discharged with normal weight-for-length, but subsequently their growth velocity slowed down. Long-term follow-up of this cohort through adolescence demonstrated that they were shorter at 14 years of age than the group discharged with normal weight-for-length relationship (ALVEAR, VIAL and ARTAZA, 1991) (Figure 4). We have also described a relationship between arm fat area, length-for-age, bone age and weight-for-age suggesting that the extra amount of fat gained during early treatment accelerated bone age maturation. Thus, although faster growth was achieved in the short term, stunting in the long term was worse (ALVEAR et al., 1986).

The energy cost of repleting tissue deficit ranges from 4 to 5 kcal/g weight gain (KERR et al., 1973). The impressive gains in weight made by recovering malnourished infants are largely fat, and reconstruction of lean body mass does not occur equally at all rates of weight gain. Protein status may be maintained if protein in the diet is quantitatively and qualitatively sufficient.

If protein intake is low or of poor quality, the development of obesity may be accompanied by a simultaneous deterioration of lean body composition (MacLEAN and GRAHAM, 1980). If protein intake is increased to 4-5 g/kg/d and energy raised to 170 kcal/kg/d, it is possible to obtain a weight gain of 11.8 g/kg/d, shortening the time of treatment without increasing the fat percent of total weight gained (FJELD, SCHOELLER and BROWN, 1989a). These authors have also reported, using doubly-labelled water to assess energy expenditure, that metabolizable energy needs for growth during recovery from PEM can be predicted based on initial metabolic mass, rate of weight gain, and composition of the weight gain (FJELD, SCHOELLER and BROWN, 1989b). Several studies in animals and humans including infants suggest that, on an isoenergetic basis, carbohydrate is more effective than fat in supporting protein retention (NOSE et al., 1987). Recent studies suggest that N urea utilization in malnourished children is also enhanced by carbohydrate feeding (JACKSON, 1989).