ENERGY EXPENDITURE OF CHILDREN WITH KWASHIORKOR

517

ENERGY EXPENDITURE OF CHILDREN WITH KWASHIORKOR

J. G. ABLETT R. A. McCANCE* Medical Research Council Child Nutrition Unit,

Kampala, Uganda The metabolic rates of four normal children and thirteen with moderately severe untreated kwashiorkor were determined while they were asleep in an environment with a dry bulb temperature of 28°C and 55% relative humidity. The metabolic rates of the sick children were subnormal, and rose after a few days or weeks of treatment into the normal range.

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of malnourished children tends to be high or at any rate normal,8-lo and to rise to high levels during recovery. These findings are not really compatible with those on animals, and we have attempted to resolve this discrepancy. McCance 11and Mount et al.3showed that the foodconversion ratios-i.e., the gain of weight per gramme of food consumed-of rats, cockerels, and pigs were normal during rehabilitation after calorie deficiencies, and Waterlow 12 and Rutishauser and McCance 10 showed that this was true after calorie deficiencies and protein deficiencies in children. Ashworth et al. 13 added the point that there was a close association between the intake of energy and the gain of weight. These results are important, for they show that even after a long period of deficiency the ability to utilise the food remains unimpaired. 14

Introduction

AN association between cold and undernutrition goes back almost to prehistory,and subnormal body temperature is now an accepted hazard of infantile malnutrition.2 Moreover, the energy expenditure of calorie-deficient animals, old or young, has frequently been shown to be subnormal, and the evidence for this over a range of environmental temperatures was set out by McCance and Mountand Mount et al.3 Ablett and McCance 4 added further evidence and showed that the energy expenditure of protein-deficient pigs, while also being subnormal, was higher at all the environmental temperatures studied than that of The findings on undercalorie-deficient animals. nourished adults have been similarbut the work on calorie-deficient and protein-deficient children has not been so clear, nor have the effects of recovery. Some have found the energy expenditure of undernourished children to be low,6,7 but against this there is a considerable body of evidence that the energy expenditure *

Present address:

Sidney

Sussex

College, Cambridge.

Patients and Methods Thirteen infants with moderately severe kwashiorkor were selected for this investigation and examined according to the system described by Staff. 15 Their sex, age, weight on admission and after loss of oedema, hxmoglobin, total proteins and albumin in the serum, and other findings are given in the table. Two infants (nos. 11 and 12) died on the third and fourth days after admission, respectively, and before they had lost all their oedema. One of them (no. 11) had a rectal temperature of 38.2°C on admission. In estimating the weights of these two patients after their loss of oedema the weights they would have lost were judged to be close enough to the mean of the others to allow that figure to be used. Whether the results for these two children are included or excluded from the mean, the significance of the difference between the metabolic rates for the patients and the normal infants remains the It

same.

tions,

was

only possible--owing

pressure for

to

eight of the other patients during Four healthy children who were participating in another investigation about normal growth in children from the same social class and district were available as

the metabolic rates of recovery.

SEX, AGE, HEIGHT, WEIGHT, BIOCHEMICAL FINDINGS, AND METABOLIC RATES OF THE PATIENTS ON ADMISSION AND OF NORMAL CHILDREN

*

intercurrent infec-

beds, and other difficulties-to follow

Excluding

no.

13.

518 normal controls. The healthy children were younger than the patients but their weights were about the same, and Talbot’s data show that variations in age from 9 to 36 months make little, if any, difference to the basal metabolicrate.

After admission had been decided upon, which was often not before the late afternoon, the children were given meals of steamed banana and very weak tea until 7 or 8 P.M. This was as a rule much the same food the children had been having at home, and was the usual procedure with all admissions to allow the children time to settle, preliminary examinations to be made, and samples of blood to be taken early on the following morning before starting any dietary treatment. At about 9 P.M. the child and mother were moved from the ward to a warm, darkened room where the metabolic apparatus was housed. The mean dry-bulb temperature in this room was 28°C (range 27-30 °C) and the mean relative humidity was 55% (range 45-60%). The child was covered with a single layer of cotton blanket. These conditions were considered to be within the children’s zone of thermal neutrality, and this was confirmed in one patient by varying the room temperature over the range of 24-31°C. No sedation was given and, with the exception of patient no. 13, measurements were made while the child was sleeping, 3-6 hours after the last meal. The pulse and respiratory rates were measured at intervals while the child was in the warm room, and the metabolic rate was only accepted when they, together with the oxygen consumption and carbon-dioxide excretion, had been reasonably steady over a period of about 30 minutes. After the child had fallen asleep a ventilated plastic hood was carefully placed in position over the head and shoulders. It was usually possible to do this without waking the child, but, if the child was disturbed, a second or even a third attempt after an hour or so was often successful. The children were prepared for the measurements to be made during treatment in exactly the same way as they had been on admission, except that they were given the therapeutic diet and treatment until 7 P.M. The controls were also prepared in just the same way from 7 P.M., but their food beforehand had been breastmilk alone or breast-milk supplemented by steamed banana. The metabolic rate was measured by an open-circuit technique using a Noyens type diaferometer (’MG4 Universal Diaferometer’, Kipp & Zonen, Delft, Holland) for the determination of the oxygen consumption and carbon-dioxide excretion. By this method, room air is drawn through the hood at a known rate and, from measuring the differences in the oxygen and carbon-dioxide contents of the room air and hood outlet air, the oxygen consumption and carbon-dioxide excretion can be estimated. In calculating the metabolic rates, the calorie equivalent of oxygen was adjusted according to the value of the respiratory quotient and, where appropriate, the body-weight after loss of oedema-or an estimate of itwas used. The diet used to treat the sick children was the one described by Dean and Swanne 16 modified for the reasons given by Wharton 11 and with all ancillary detail by Wharton and McCance.18 The total daily calorie intakes during the first few weeks of treatment were usually within the range 130-150 (mean 145) C. per kg.

Fig. I-Effect of

treatment on the metabolic rates during sleep of seven infants with kwashiorkor (*-*) and of four normal controls (X).

thirteen patients are shown in fig. 1 and of one of them (no. 13) in fig. 2. Twelve of the thirteen patients had subnormal metabolic rates on admission and the other patient had a metabolic rate which was in the lower part of the normal range. During recovery, the metabolic rates of the eight infants studied increased to normal values after a few days or weeks of treatment. In the one patient with a metabolic rate within the normal range on admission, the rate was just above or in the upper part of the normal range during recovery. The four normal children had metabolic rates close to 19 and well a normal standard modified from Talbot within ±15% of it. The difference between the mean metabolic rates of the patients on admission (71 C. per kg.4 per 24 hours) and of the four normal infants (95 C. per kg.3/4 per 24 hours) is significant (P<0-005). Patient 13 was much older than the others, and his measurements have been excluded from the calculation of the means. In other respects the clinical findings on this patient were characteristic: his home surround-

Results

The metabolic rates of the thirteen infants with kwashiorkor on admission and those of the four normal infants are given in the table. Changes in the metabolic _rate during the treatment and recovery of seven of the

Fig.

2-Effect of treatment complicated by measles weight and resting metabolic rate of patient 13.

on

the

519

ings had been bad and he had been treated for kwashiorkor at a dispensary in the country about 2 years before. The basal metabolic rate for a child of this age should be within the range 76-102 C. per kg.3/4 per 24 hours, so that the B.M.R. of patient 13 was about 60% of the normal mean on admission. It rose by the 5th day of treatment into the range normal for his age, and remained there for 10 days. His weight during the Further progress was same period went up 2-5 kg. he was very ill, which measles, during complicated by ate little, and lost weight, but he was discharged doing well about a fortnight later. Details of this patient are shown separately in fig. 2. Discussion

The general findings reported here are consistent with the work on animals and adult human beings. The findings are similar to those obtained on proteindeficient pigs4 and do not conflict with the work in Uganda on food-conversion ratios in malnourished infants 10 or with the work on animals.33 Our results show that the B.M.R. is low in untreated kwashiorkor, and the evidence suggests that the change in energy expenditure associated with protein and calorie deficiencies in children resemble those reported for animals and adult human beings. The cause of the low B.M.R.s has not yet been elucidated.55 The metabolic pathways may be changed,2Oand the turnover-rate of the proteins in some organs may be low,21.22while the absence of all the normal metabolism of growth must certainly be a contributory cause. The high or normal results reported by some workers (and discussed by Rutishauser and McCance 10) may be explained by one or more of the following considerations :

(1) The children were studied, not on admission but after a few days to a fortnight or more of treatment, by which time their metabolic rates might well have been

high. (2) They were studied too soon after a substantial therapeutic meal. Ashworth 9 showed that the metabolic rate in malnourished infants was raised by approximately 30% and 10% 1 and 3 hours, respectively, after a meal. Krieger 23 also described this effect. If food-conversion ratios are normal in infants recovering from malnutrition, the raised heat production can only be attributed to the specific dynamic action of the meal 24 or to growth occurring in augmented spurts soon after meals, as suggested by Ashworth9 and Krieger. 23 (3) Body fat is often considerably reduced in malnourished infants, and hence metabolic rates expressed in terms of body-weight (C. per kg.) would be misleadingly high, since the oxygen consumed by fatty tissue is low. The additional fat in the adult human female, for example, will explain why the B.M.R.S of normal women tend to be lower than those of men.25 Distortion to the high side due to lack of fat might be considerable in a severely wasted child, but the presence of oedema would tend to offset the effect. For this reason Monckeberg et al. 26expressed their results on the basis of height, and Varga 7 has discussed this

approach. The best reference standard against which to express the metabolic rates of malnourished infants has often been discussed, but there still does not seem to be a final answer. If results are to be expressed on some basis relating to weight, 4 seems to be about the best general exponent for B.M.R. studies. 27 Monckeberg

al.26 preferred to use height, which in normal infants is highly correlated with the B.M.R.; these workers showed that the metabolic rate was low in malnourished infants if height was used but normal, or The even a high normal, if weight was substituted. effect of expressing the present results in terms of height would be to increase the difference between the patients and normal infants. We thank Mrs. Alma Whitelaw for her help and Prof. B. Laurence, Dr. Latimer Musoke, and Dr. P. de Buse for their interest and help. Requests for reprints should be addressed to R. A. McC. et

REFERENCES 1. 2. 3. 4. 5.

6. 7. 8. 9. 10.

McCance, R. A., Mount, L. E. Br. J. Nutr. 1960, 14, 509. Brenton, D. P., Brown, R. E., Wharton, B. A. Lancet, 1967, i, 410. Mount, L. E., Lister, D., McCance, R. A. Br. J. Nutr. 1963, 17, 407. Ablett, J. G., McCance, R. A. ibid. 1969, 23, 265. Keys, A., Brozek, J., Henschel, A., Mickelsen, O., Tayler, H. L. The Biology of Human Starvation. Minneapolis, 1950. Kerpel-Fronius, E. Mod. Probl. Pediat. 1957, 2, 146. Varga, F. Pediatrics, Springfield, 1959, 23, 1085. Montgomery, R. D. J. clin. Invest. 1962, 41, 1653. Ashworth, A. Nature, 1969, 223, 407. Rutishauser, I. H. E., McCance, R. A. Archs Dis. Childh. 1968, 43, 252.

McCance, R. A. Br. J. Nutr. 1960, 14, 59. Waterlow, J. C. J. trop. Pediat. 1961, 7, 16. Ashworth, A., Bell, R., James, W. P. T., Waterlow, J. C. Lancet, 1968, ii, 600. 14. Ashworth, A. Br. J. Nutr. 1969, 23, 835. 15. Staff, T. H. E. E. Afr. med. J. 1968, 45, 399. 16. Dean, R. F. A., Swanne, J. J. trop. Pediat. 1963, 8, 97. 17. Wharton, B. A. in Glaxo Conference on Calorie Deficiencies and Protein Deficiencies (edited by R. A. McCance and E. M. Widdowson); p. 147. London, 1968. 18. Wharton, B. A., McCance, R. A. in Current Pediatric Therapy (edited by S. S. Gellis and B. M. Kagan); vol. III, p. 7. Philadelphia, 1968. 19. Talbot, F. B. Am. J. Dis. Child. 1938, 55, 455. 20. Waterlow, J. C. Lancet, 1968, ii, 1091. 21. Cohen, S., Hansen, J. D. L. Clin. Sci. 1962, 23, 351. 22. Hoffenberg, R., Black, E., Brock, J. F. J. clin. Invest. 1966, 45, 143. 23. Krieger, I. Pediatrics, Springfield, 1966, 38, 63. 24. Salter, J. M. in Physiological Basis of Medical Practice (edited by C. H. Best and N. B. Taylor); p. 1291. Edinburgh, 1966. 25. Durnin, J. V. G. A., Passmore, R. Energy, Work and Leisure. London, 1967. 26. Mönckeberg, F., Beas, F., Horwitz, I., Dabancens, A., Gonzalez, M. Pediatrics, Springfield, 1964, 33, 554. 27. Kleiber, M. in Proceedings of the 3rd Symposium on Energy Metabolism (edited by K. L. Blaxter); p. 427. New York, 1965.

11. 12. 13.

COUNTER-CURRENT IMMUNOELECTROPHORESIS IN THE DIAGNOSIS OF MENINGOCOCCAL INFECTIONS B. M. GREENWOOD H. C. WHITTLE OLIVERA DOMINIC-RAJKOVIC

Departments of Medicine, Pœdiatrics, and Bacteriology, Ahmadu Bello University, Zaria, Nigeria Sum ary

fluid (C.S.F.) and sera tested for the presence of meningo-

Cerebrospinal were

coccal antigen by immunoelectrophoresis. Antigen was demonstrated in the C.S.F. in 47 of 68 suspected cases of meningococcal meningitis, whilst meningococci were demonstrated by gram stain and culture in 45 of the same samples. Group-typing was readily achieved by immunoelectrophoresis. The technique was easy and cheap and gave a rapid answer. Meningococcal antigen was readily eluted from filter-paper strips impregnated with C.S.F. and stored at room