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Infection and catch-up growth
Children and adolescents
Research needs: Infants and children
Research needs: Adults
Working Group: G Clugston,1 KG Dewey,2 C Fjeld,3 J Millward,4 P Reeds,5 NS Scrimshaw,6 K Tontisirin,7 JC Waterlow8 and VR Young9
1Nutrition Unit, WHO, 1211 Geneva 27, Switzerland; 2Department of Nutrition, University of California, Davis, CA 95616-8669, USA; 3Section of Nutritional and Health-Related Environmental Studies, International Atomic Energy Agency, P.O. Box 100,1400 Vienna, Austria; 4Nutritional Science Research Center, School of Biological Sciences, University of Surrey Guildford, Surrey GU2 5XH UK; 5Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street Houston, TX 77030, USA; 6UNU Food and Nutrition Program, Charles Street Station, P.O. Box 500, Boston, MA 02114-0500 USA; 7Institute of Nutrition, Mahidol University, Salaya, Nakhon Pathom 73170, Thailand; 8Centre for Human Nutrition, London School of Hygiene and Tropical Medicine, 2 Taviton Street, London WC1H OBT, UK; 9Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge, MA 02142-1308. USA
requirements, amino acid requirements
1. The estimates of the protein intake of breast-fed infants in Table 1 of the paper by Dewey et al are accepted, noting that these values are 10-26% lower than those in the 1985 report. These estimates assume that at least 46% of the non-protein nitrogen in human milk can be utilized.
2. A survey of the literature suggests that the maintenance requirement is approximately 90 mg N/kg/ day. The value of 120 mg N/kg/day adopted in the 1985 report should be lowered. In accepting the model of the breastfed infant as the basis for estimating the requirements in the first 6 months, it should not be assumed that the mean intake equals the mean requirement. The epidemiological probability approach indicates that at 3-4 months the requirement is less than 170 mg/kg/day, whereas the mean intake is 231 mg/kg/day.
3. The use of a 50% augmentation of the protein needs for growth, adopted in the 1985 report to account for day-to-day intra-individual variability in growth, should be abandoned. To allow for this variation, an adjustment could be added to the coefficient of variability for growth. As suggested in the paper of Dewey et al, the CV for growth ranges from 24 to 46% during the first year.
4. The efficiency of utilization of nitrogen for infant growth can continue to be taken as 70%, as in the 1985 report.
5. The factorial model is considered appropriate for calculating' protein needs during the first year of life. When used to calculate dietary recommendations, differences in the efficiency of utilization of various protein sources in this period must be taken into account. In particular, it is possible that the dietary protein requirements of non-breastfed infants may be higher than those for breastfed infants (regardless of growth rate).
6. The approach to estimating the adequacy of protein intakes based on P/E ratios can be used to derive diets that will provide safe levels of intake when infants are no longer exclusively breastfed.
7. In estimating metabolic needs for amino acids of infants, it should not be assumed that the pattern of amino acids in human milk is the same as the pattern of the requirements. Nonetheless, to provide a generous margin of safety with regard to essential amino acids, the pattern in human milk should be acceptable for estimating dietary allowance in most cases. Thus, the estimates in the 1985 report need not be revised at this time, but the rationale for their adoption should be clarified.
8. More information is needed to determine the appropriate composition of infant formulas. Because of the potential differential rates of utilization of proteins of human milk vs infant formulas, it cannot be assumed that a formula that mimics the amino acid composition of human milk will be optimal for the non-breastfed infant. The definition of optimal should include multiple measures including weight gain, linear growth and other indices. Until more information is available, the present recommendation, derived from the breastfed infant, should not be regarded as indicative of the needs of the infant receiving formula as its only source of milk.
Correspondence to: IDECG
Secretariat, c/o Nestle Foundation, P.O. Box 581,1001 Lausanne, Switzerland.
1. Until more data are available, a reasonable estimate of protein needs following infection is a 20-30% increase in total protein (30-50% in the case of diarrhea) during a recovery period that is two to three times longer than the duration of the illness. In the case of persistent diarrhea with accompanying anorexia, the desired increase may be difficult achieve. When children have diarrhea for 20-30% of their time plus other infections, following the above recommendation will essentially result in a permanent increase in the protein level of the diet provided to them until they reach an age when diarrhea is less prevalent.
2. Requirements for children experiencing catch-up growth should consist of a factor for maintenance and a factor for growth. The latter should be determined for various rates of weight gain, as illustrated in Table 21 of the paper by Dewey et al. The values used for maintenance nitrogen needs and the efficiency of conversion from dietary protein to body protein should be consistent with those chosen for normal infants and children.
3. For stunted children of normal
weight, protein requirement will be determined by their maintenance needs plus rate of
linear growth appropriate for their age and body size. For wasted and stunted children,
protein requirement after normal weight-for-height has been achieved will be determined by
the weight gain expected at an appropriate rate of linear catch-up growth. Estimates are
included in Tables 21 and 22 of the Dewey et al paper. This implies that the P/E
ratio increases with the rate of catch-up weight gain.
1. The factorial model used to calculate protein requirements for children and adolescents should not use estimates of maintenance requirements that are interpolated from the previous 'anchor point' of 120 mg N/kg/day for infants, which is now believed to be too high. The value of l00 mg N/kg/day (at all ages) seems more appropriate based on data from balance studies of children and adolescents cited in the paper of Dewey et al. Nevertheless, this is tentative until the results of a meta-analysis of adult data are available.
2. The 50% augmentation to the protein needs for growth, adopted in the 1985 report to account for day-to-day intra-individual variability in growth, should be abandoned. To allow for this variation, an adjustment could be added to the coefficient of variability for growth.
3. The factorial model incorporating revisions proposed in the paper of Dewey et al should be considered a good approximation of the requirements for preschool children, as it yields estimates that are consistent with short-term balance studies. Limited data on older children and adolescents suggest that the 1985 values are appropriate for that age range. More information is needed to determine whether aspects of the new factorial model for older children and adolescents should be modified.
4. The recommendations of the 1991 FAO/WHO Expert Consultation regarding amino acid requirements of preschool children should be adopted until additional data are available, but further attention needs to be paid to the distinction between requirement and safe levels.
5. Data on the amino acid pattern
required by preschool children have never been published in full and are limited to a
series of studies in a single country. This is an extremely unsatisfactory basis for
determining a dietary recommendation. The group could make no further comment on the
pattern for preschool children presented in the 1985 report and strongly recommends
support for studies using both nitrogen balance and stable isotope techniques, preferably
concurrently, to address this lack of information.
1. An appendix was prepared updating principles and conditions for conducting acceptable nitrogen balance studies.
2. As soon as possible after this workshop, Young and Scrimshaw will make a meta-analysis of all available data on protein requirements of adults, including men and women and the elderly. It must include the conceptual problem of the relationship of energy to protein requirements and the validation of the nitrogen balance results by other methods. While it will be based on the scientific evidence, it will include consideration of the practical implications of alternative assumptions or calculations. It will also consider the level of precision that will be useful.
3. No further comments on the adult protein requirements proposed in the 1985 report will be made until the meta-analysis commissioned at this meeting is available.
4. The values for amino acid requirements in the 1985 report derived from experiments of Rose and collaborators are no longer acceptable or nutritionally relevant because of a series of well identified methodological errors. These include excessive caloric intakes, failure to allow for miscellaneous losses and an overestimate of nitrogen utilization.
5. The pioneer carbon balance
studies of the MIT group are a major step forward and have provided firm evidence for a
requirement for leucine, which is higher than the estimate in the 1985 report. The
available evidence, although far from complete for other key amino acids, particularly
lysine, supports the proposal of higher amino acid requirements for adults. Even though
differences of opinion persist about the general principle on which a requirement pattern
for the other IAAs has been proposed, a large majority of the group accepted as an interim
operational pattern that proposed by Young et al, which is similar to the 1991
FAO/WHO recommendation that the preschool child amino acid pattern be applied to adults.
1. The seven nitrogen balance studies currently available included a total of 104 men and women; all but 14 of these were healthy, well nourished US subjects. The interpretations are mixed, and some but not all of the reports suggest that the 0.8 g of protein per kg per day may not be sufficient for the maintenance of nitrogen balance. Since the deficits are not large and are not consistent, recommendations must be deferred.
2. The meta-analysis of all
available nitrogen balance data on adults to be carried out by Young and Scrimshaw should
include data on the elderly and a comparison of these data with those of younger subjects.
Specific recommendations for the elderly should await the outcome of this review.
1. There is a need for studies of the protein and amino acid requirements of infants and preschool children that include only weight gain and nitrogen balance but also long- and short-term functional outcome measures. Such studies should include observations on full-term, low-birthweight infants and on the relative efficiency of protein utilization in formula fed and breastfed infants.
2. It is essential to determine the degree of intra-individual day-to-day variation in growth rates at different ages and whether the magnitude of short (24-48 h) bursts of linear growth can be influenced by intakes of protein, amino acids and other nutrients.
3. There is a need for better data on the composition of weight gain and on the rate of accretion of fat-free body mass at different ages. With regard to catch-up growth, data are needed on the maximal rate of weight gain that can be achieved without a compromise of body composition.
4. Amino acid requirements at all ages require further investigation. Such studies should include considerations of amino acid use for processes other than protein deposition, and the possibility that amino acids synthesized by colonic bacteria are utilized.
5. More information on the digestibility of protein in diets is needed as it is a major limitation on assessment of diet quality. Studies should include both balance techniques to assess nitrogen and intrinsic labeling to measure amino acid availability.
6. The impact of infection on protein and, in particular, amino acid needs requires further investigation. Information regarding the effect of a low level of infections, as indicated by elevated immune globulins, on amino acid requirements, including the assessment of protein metabolism using stable isotopes, is a particular priority.
7. Better data are required on the
protein and amino acid needs for maintenance, growth and other functions of adolescents.
More studies using stable isotope techniques are urgently needed to determine requirements for essential amino acids in both younger and older adults. These studies should be undertaken in both developing and industrialized countries to assess the effects of different ethnic and dietary factors.
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