Pediat. Res. 5: 579-585 (1971) Childhood kwashiorkor infants malnutrition intelligence
Relation of Kwashiorkor in Early Childhood and Intelligence at School Age
H. G. BIRCH1281, C. PINEIRO, E. ALCALDE, T. TOCA, AND J. CRAVIOTO
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA, and Department of Nutrition II, Hospital Infantil dc Mexico, Mexico City, Mexico
Extract Measured intelligence at school age was compared in 37 previously severely mal- nourished children and their siblings. The malnourished children all had been hos- pitalized for kwashiorkor (severe infantile malnutrition with edema) when they were between 6 and 30 months of age. The siblings had never experienced a bout of severe malnutrition requiring hospitalization. The sibling controls were all within 3 years of age of the index cases. Full scale WISC IQof the index cases was 68.5 and of the con- trols 81.5. Verbal and performance differences were of similar magnitude and in the same direction. All mean IQ, differences were significant at less than the 5% level of confidence. If an IQ score of below 70 is considered a customary cut-off point for the definition of mental retardation then twice as many of the previously malnourished children as their sibs functioned below this level; 18 malnourished, compared with 9 of the control subjects, had an IQ below 70. Moreover, of those with a low IQ, 10 of the index cases were below 60, contrasted with only 2 of the control subjects. At the other extreme of the distribution, in the conventionally normal range, the re- verse picture obtains; 10 of the control subjects compared with 4 of the index cases had an IQ. of 90 or higher (Table III).
Speculation The long term effect of severe malnutrition in infancy has been suggested but not unequivocally demonstrated in comparative studies of malnourished children with controls drawn from the general population. To demonstrate the relation more con- vincingly it is necessary that children who have experienced such severe malnutrition be compared with their own sibs raised in the same family environment but not ex- periencing the same severity of nutritional insult. If differences in intellectual outcome exist between sib groups at school age the source of these differences may be more clearly related to the antecedent episode of severe malnutrition and hospitalization.
Introduction intelligence. Previous follow-up studies [2, 3, 5, 6, 8,
„ ,, ... r i -i I I • r ,• i, „ «„ 10, 19, 20, 23, 241 have indicated that severe malnutri- Follow-up studies of children, who as infants nave ex- ' J perienced severe malnutrition requiring hospitaliza- tion and hospitalization in early childhood do affect tion, constitute one of the model systems through subsequent intellectual competence, but in each in- which we can assess the degree to which severe malnu- stance research design has limited interpretation. In trition in early life may affect subsequent levels of the main, children have been examined within a short 579 580 BIRCH ET AL. time after recovery and interpretation of an associa- with clear signs of pitting, and when the past dietary tion between reduced level of functioning and anteced- history had identified a greater discrepancy of protein ent malnutrition has been difficult; the possibility ex- than of calorics in the antecedent nutritional circum- ists that the long period of hospitalization necessary in stances. At the lime of admission the children were treating severe malnutrition might itself have contin- between G and 30 months of age. No cases of marasmus ued to exert a depressing effect on mental functioning. were included and the group was relatively homogene- Longer term follow-up studies have in most instances ous both for severity of illness and for type. All chil- not had appropriate control or comparison groups. A dren hail been discharged to the family following nu- unique exception is the study by Champakam, Srikan- tritional rehabilitation. The average time of hospitali- tia, and Gopalan [G], in which the comparison group /Allow was G weeks, with a range of from 1 to 2 months. was matched for age, sex, religion, caste, socioeconomic During the hospital stay children were on metabolic status, family size, birth order, and educational back- wards and were visited by their mothers for a 3- to 4-hr ground of the parents with the index cases. Even in period every other day. The ratio of nursing stalf to that study, however, it was possible that the families of children was high, with one nurse available for every children experiencing kwashiorkor provided less ade- three children. Care in hospital in general was good quate experiential opportunities for intellectual devel- and considerate but no special stimulational proce- opment than did control families even when of the dures were applied. same social class [9, 22]. It therefore appeared desirable No detailed data are available with respect to the to compare children who had experienced kwashiorkor quality of the diets received by the children after their with members of their own sibships who had not expe- discharge from the hospital. Although it would be ap- rienced a bout of severe malnutrition in early life since propriate to assume from knowledge of the social cir- such sibs would have been raised within the same fam- cumstances in which the children lived that such diets ily as the index child, and, in this sense, have more were suboptimal, in no cases were any of the children fully shared a common ancestry and microenviron- ever readmitted to any hospital for severe malnutri- ment. tion. At follow-up the children were between 5 and 13 Methods and Procedures years of age. In all cases intellectual evaluation was carried out at least 3 years after discharge from the The index cases were children who had been hospital- hospital. To make follow-up practicable, the cases se- ized and successfully treated for severe malnutrition in lected were restricted to children living in the vicinity the Department of Pediatrics of the Army Central of Mexico City. To obtain the sample the archives of Hospital in Mexico City. To ensure greater homogene- the Department of Pediatrics were searched to produce ity of clinical illness, only children who were diag- a consecutive scries of cases of severe malnutrition at nosed as sulfcring from kwashiorkor were selected for appropriate ages at admission, follow-up, and resi- follow-up study. A child was considered as suffering dence. Fifty-one cases were identified and searched for from kwashiorkor when edema was clinically manifest in the community. Forty-two children were located and 37 of these had a sibling whose age was within 3 Table I. Afjc and sex distribution of index cases and controls at years of the index case anil a family willing to take follow-up examination part in the follow-up. The child chosen as the control Index cases Sib controls was the one in the surviving sibship nearest in age to Age, yr M F Total M V Total the index case and without any prior history of an incident of severe malnutrition. Four of the controls r> •I 1 - d 11 5 1! were within 1 year of age of the index case, 24 within 2 7 :i (i o fi :i Table IV. Full scale IQ by sex in index cases and controls Index cases Control subjects dj («• dl (2)> p d< ;• Males, X = 14 70. 7' ± 14.()8» 82.3' ± 1G.12* 13 20 1.070 2 .252 <0.05 Ar = 21 Females, A' = 23 08 .0 ± 13.83 72.8 ± 10.'J2 22 15 1.057 1.058 N.S. Ar = 10 '//(I) 13 20 df (2) 22 15 1.305 1.211!) d3 0.443 2.134 1' N.S. «U>3 1 Mean. 'Numbers in parentheses are degrees of freedom. * liecausc of significant differences in variance the Fisher-Iiehrens il test was used (Fisher and Yates [13]). by sex (Table IV) it was found that the previously class level of the families studied. No significant sex malnourished boys differed from the control boys sig- difference in test profiles obtained. nificantly, with control subjects having a full scale IQ approximately 12 points higher than patients. Al- Discussion though control girls also had somewhat higher IQ than girls who were previously malnourished the size Our findings indicate that children who have suifcrcd of the difference was insufficient to result in statistical a bout of severe malnutrition (kwashiorkor) requiring significance. This pattern of finding was entirely the hospitalization between the Olh and 30th month of life result of the depressed level of IQ in the girls in the have an IQ at school age which is significantly lower control group. No reasons for this depression could be than those of their siblings who have never experi- found in differing educational experience since there enced such an illness. Mean levels of full scale IQ as were no sex differences in school attendance. A de- well as of verbal and performance IQ were all signifi- pressed level of IQ in girls relative to boys, however, cantly depressed in the index cases. Moreover, a signif- has been repeatedly found in children of school age in icantly greater proportion of the index cases was in the the social groups considered and probably derives defective range of intelligence and fewer in the normal from the far lower value attached to the education of range. An analysis of subtest profiles suggested a rela- girls in this particular subculture. tively uniform depression of competence in the index A fuller appreciation of the differences in measured cases with respect to a variety of cognitive demands. intelligence between the index cases and the control Previous studies [2, 3, 5, (i, 8, 10, 19, 20, 23, 21] have subjects may be obtained by a comparison of their indicated that the level of mental functioning was de- scaled scores on the 11 subtests of the WISC. Figure 1 pressed in children similar to our index cases, at the illustrates the subtest profiles for both groups. In the time of the acute illness and in the period shortly main the profiles parallel one another, with both thereafter. The present data indicate that such effects groups having their lowest scores on the vocabulary are not transient and persist into the school years. test, a finding not unexpected in view of the low social They can, therefore, not be viewed as immediate se- quelae of either serious illness or of hospitalization. It • • CONItOlS 8 is possible that prolonged hospitalization does have » « INDIK CASES persistent effects quite independent of the acute bout of severe malnutrition. This possibility, however, can- not be explored in the existing data but fully warrants an examination in its own right. It would be most useful to examine the effects of long term hospitaliza- tion on children of comparable ages without severe malnutrition, e.g., orthopedic problems. Such chil- SCAl£ SCAlf dren would not exhibit the patterns of apathy, irrita- Fig. 1. WISC subtest profiles for index cases and controls. bility, and environmental unresponsiveness that are so Relation of kwashiorkor and intelligence 583 characteristic of children hospitalized with kwashior- tribute to the depression of intellectual level [17]. This kor and in this sense would not be comparable with factor, too, should result in the minimizing of differ- respect to the interaction of host with environment. ences between controls and cases and provides further Alternatively, it would be valuable to consider the dif- support to the significance of the influence of the acute ferential effects of enriched and nonenriched hospital episode of severe malnutrition on cognitive compe- environments on comparable samples of severely mal- tence. nourished children. Anecdotal data [14] suggest that Our failure to find that either verbal or performance differential patterns of maternal care significantly af- IQ was more significantly affected was not entirely in fect recovery rates at the time of acute illness, and a agreement with the findings of other studies. Barrera- recent as yet unpublished study from Lebanon [26] Moncada [2] found verbal function to be more affected appears to confirm these impressions. than nonverbal aspects of performance. Language The findings are in general agreement with those functions, especially vocabulary, however, arc most reported by liarrera-Moncada [2] and Cabak and Naj- sensitive to differences in general social circumstances. danvic [5]. In these studies, however, the comparison The use of comparison groups from families other groups used as controls were methodologically impre- than the index cases even when controlled for overall cise. Taken as a whole the data of these [5] and the social class would tend to exaggerate differences in present study leave little doubt that children hospital- language competence. In our own group, vocabulary ized for severe malnutrition in early childhood have level was the lowest subtcst score in both cases and levels of intellectual functioning in later years which controls and suggests a general depressing influence of are lower than those of their peers. This finding is in family and social environment. Botha-Antoun, Ba- agreement with that of Champakam et al. [6] in India. bayan, and Harfouchc [3], studying preschool chil- The use of siblings as control subjects has certain dren, also found no difference in the degree to which implications for the interpretation of findings. Such verbal and performance items differed in cases and controls are of course advantageous in that the chil- controls. However, the test which they used, in a strict dren who are compared come from the same families sense, does not permit the reliable separation of verbal and share a common experiential ambience. Demo- and performance demands. graphic data, however, strongly suggest that having a Our findings of sex differences in the degree to child hospitalized for severe malnutrition in fact iden- which cases and controls differed poses a difficult issue tifies a family in which all children arc at risk for for interpretation. It may be argued that a bout of significant subnutrition on a chronic basis. Therefore, severe malnutrition has greater effects on boys than on the cases and controls are similar in sharing a common girls because of genetic differences between the sexes in exposure to subnutrition on a life-long basis and differ their abilities to withstand the negative effects of stress. only in that the cases have a superimposed episode of Such an interpretation, however, is difficult to defend acute exacerbation. As a result, growth achievements in view of the significantly lower IQ of control females may be similar in patients and sibs, and developmental over control males. This finding, together with the fact differences minimized. Consequently, the comparison that male and female index cases had comparable of sibs and patients does not provide a full picture of levels of IQ, suggests that females were more signifi- the overall effects of nutritional inadequacy on devel- cantly disadvantaged within the families on a long opment. Rather, it indicates the additional conse- term basis whether or not they have had an acute quence for maldevelopment which may attach to an episode of severe malnutrition and hospitalization. acute episode of severe malnutrition. One would, Such an inference is in accord with the value systems therefore, expect intellectual level in the entire sibship of the social group to which the families belong and in to be depressed, a view supported by our findings. accord with findings on Puerto Rican children in New Therefore, the finding of a difference between children York [1G]. From this point of view the small difference hospitalized in early childhood with a bout of severe between female cases and control subjects can be inter- malnutrition and their siblings is especially convincing preted as an artifact of general social disadvantage for evidence of the negative contribution which an epi- girls in the subculture [21]. sode of kwashiorkor makes to mental development. Interpretation would have been made easier had The use of sibs as controls also means that the children equal sex ratios obtained between sibling and control compared have shared a generally disadvantageous so- groups. It may be argued that since fewer females cial and family environment which in itself can con- were in the control group the IQ level of this group 584 BIRCH ET AL. has been spuriously elevated and that the differences Dobbing and Widdowson [12J on defective myelina- obtained are an artifact of these differences in sex tion without subsequent recovery, of Winick on cell ratio. That this was not the case was indicated by our number [25], of Ambrosius [1] and Brown [4] on brain sex-specific analysis which showed that significant dif- size, of Platt, l'ompiglione, and Stewart [18] on various ferences exist between boys in the index and compari- features of neurointcgrative development, and of son groups. Moreover, it is possible to consider the Chase, Dorsey, and McKhann [7] on enzymatic compe- question differently by a mathematical operation by tence all indicate that severe nutritional insult at a means of which the sex distribution for the control time in life at which the central nervous system is children is equalized with that of the index cases. growing and differentiating most rapidly can perma- When this is done there is a reduction of some 4.5 IQ nently affect structural, biochemical, and functional points for the control group. If one now assumes that integrity. A severe bout of nutritional illness in the the variance remains relatively unaffected and com- ages that we have been considering occurs at a time pares the idealized control group with the index cases when the vulnerability of the nervous system is high. the dilference obtained is still significant at between Our findings of later cognitive dysfunction may well the 0.05 and 0.01 levels of confidence. It was, therefore, reflect a direct consequence of insults sustained by the most unlikely that the findings were the accidental central nervous system. It was also true that the time consequence of the difference in sex ratios between of hospitalization for severe malnutrition coincided cases and sibling control groups. with critical points in the development of behavioral In considering the fact of kwashiorkor in infancy competence which depend for their elaboration on ad- and its association with subsequent intellectual inade- equate environments and experiential opportunities. quacy, it was also necessary to consider the possibility The consequences on cognitive functioning may there- that both the severe malnutrition and the later low fore reflect interference with experience and behavior level of intellectual functioning may have had com- differentiation as well. At the present time we lack mon roots in preexisting central nervous system dam- both the data and the technical abilities required to age. From this point of view, a child may develop distinguish the particular contribution that each of kwasliiorkor because his nervous system was inade- these factors may make to defective cognitive growth. quate from birth and interfered both with his normal It is most probable that primary abnormality in the feeding and with his stimulating value to his family. nervous system anil defective experience are both mak- In such a case, both the kwashiorkor and the later ing independent and interactive contributions. Inde- intellectual level could be viewed as deriving from pendently of the particular underlying process, how- primary organismic inadequacy. While only an anter- ever, the data leave little doubt that severe malnutri- ospective study of infants at risk can answer the ques- tion with hospitalization has a long term persistent tion fully, the data of the present study provided no clfect on measured intelligence. support for the hypothesis. Parental recall as well as In view of the suggestion first made by Cravioto and hospital case records did not suggest that the index Robles [10], that the younger the child is at the time children prior to their illness had differed from their of hospitalization for severe malnutrition the less com- siblings in any of the significant features of develop- plete his behavioral recovery, as well as in view of the ment or physical attributes. Rather, it appeared that findings of Winick [25] and Davison and Dobbing [11] in most cases relatively "normal" development in an that the nervous system is at greater structural risk for environment producing marginal status had occurred permanent damage in the younger malnourished in- until it was interrupted either by infectious illness, by fant, it would have been desirable to compare and altered maternal health, or by changing family circum- contrast our index cases in terms of age at the time of stances which contributed to the exacerbation of nutri- hospitalization. The numbers available for each semes- tional inadequacy and to the development of kwa- ter of age, however, were loo small to make serious shiorkor. analysis possible. Other research in progress, we hope, The depression of intellect in children hospitalized can provide some answers to this aspect of the ques- for severe malnutrition between (i and 30 months of tion. age must be viewed against the growing body of data References tmtl Xole.s on the particular vulnerability of the central nervous 1. AMIIKOSIUS, I). K.: El coinportatniinto del peso de algnnns system to nutritional insult at critical periods of devel- oiganos en ninos con desnntrition dc trrcer grado. liol. Mcil. opment. The data of Davison and Dobbing [11] and llosp. Infant. Mcx., IS: 17 (l'JGl). Relation of kwashiorkor and intelligence 585 BARRERA-MONCADA, G.: Eslndios Sobre Altcraciones del 1G. LESSER, G. S., FIFER, G., AND CLARK, D. II.: Mental abilities of Crccimicnto y Del Dcsarrollo l'sicologico del Sindrome Pluri- children from different social-class and cultural groups. catcncial (Kwashiorkor). (Editora Grafos, Caracas, 1903). Monogr. Soc. Res. Child Develop., 30: 4 (19G5). 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B., AND SMYTHE, P. M.: The effect of undernutri- 10. CRAVIOTO, J., AND ROULES, 15.: Evolution of adaptive and tion during infancy on subsequent brain growth and intel- motor behavior during rehabilitation from kwashiorkor. lectual development. S. Afr. Med. J., 41: 1027 (1967). Amcr. J. Orthopsychiat., 35: 449 (19G5). 25. WINICK, M.: Nutrition and cell growth. Nutr. Rev., 26: 195 11. DAVISON, A. N., AND DOHIIING, J.: Myelination as a vulnerable (1968). period in brain development. Brit. Med. Bull., 22: 40 (19GG). 26. YATKIN, V. S., MCLAREN, D. S., ABU-KHADRA, S., AND IIARB, 12. DOBBING, J., AND WIDDOWSON, E. M.: The effect of undernu- S.: Unpublished data. trition and subsequent rehabilitation on myelination of rat 27. Supported in part by the Association for the Aid of Crippled brain as measured by its composition. Brain, SS: 357 (19G5). Children, The National Association for Retarded Children, 13 FISHER, R. A., AND YATES, F.: Statistical Tables for Biological, the Nutrition Foundation, the Milbank Memorial Fund, the Agricultural and Medical Research, cd. 6. (Hafner Publishing Company, New York, 19G3). William Waterman Fund for the Combat of Dietary Diseases, and National Institute of Child Health and Human Develop- 14 GEBER, M., AND DEAN, R.: The psychological changes ac- ment Grant no. HD 00719. companying kwashiorkor. Courr. Norm., 6: 3 (195G). 15 KENNEDY, W. A., VAN E RIET, V., AND WHITE, J. C: A norma- 28. Requests for reprints should be addressed to: H. G. BIRCH, tive sample of intelligence and achievement of Negro ele- Department of Pediatrics, Albert Einstein College of Medi- mentary school children in the southeastern United States. cine, 1300 Morris Park Avenue, Bronx, N. Y. 10461 (USA). Monogr. Soc. Res. Child Develop., 2S: 6, serial 90 (1903). 29. Accepted for publication December 16, 1970. Copyright © 1971 International Pediatric Research Foundation, Inc. Prinltd in U.S.A.