The Relationship between Undernutrition and Behavioral Development in Children

A Review of Studies of the Effect of Severe Malnutrition on Mental Development1

SALLY GRANTHAM-McGREGOR2
Tropical Metabolism Research Jamaica, West Indies Unit, University of the West Indies, Mona, Kingston 7,

Diagnosis of severe malnutrition

ABSTRACT This is a review of studies on the relation ship between mental development and severe malnutri tion. School-age children who suffered from early child hood malnutrition have generally been found to have poorer IQ levels, cognitive function, school achievement and greater behavioral problems than matched controls and, to a lesser extent, siblings. The disadvantages last at least until adolescence. There is no consistent evidence of a specific cognitive deficit. The evidence of a causal relationship is strong but not unequivocal because of dif ficulties in interpreting retrospective case control studies. Marked improvements in development can occur after adoption or intervention. Therefore, the outcome depends to a large extent on the quality of the subsequent envi ronment. It is likely that extremely deprived environ ments would exacerbate the effects. There is limited ev idence that other nutritional deficiencies may interact with previous malnutrition in affecting cognition. The mech anism linking malnutrition to poor development is still not established. J. Nutr. 125: 2233S-2238S, 1995. INDEXING KEY WORDS: severe malnutrition IQ development cognition school achievement

Nearly all studies of severe malnutrition have used the Gomez or Wellcome classification to define malnutrition. These do not define a specific disease but rather a varying mixture of clinical signs that may have differing etiolo gies. Furthermore, a variable amount of infection and many other types of deficiencies such as zinc, manganese, copper and iron may be present as well as protein and energy. These may affect growth and behavior differently (Grantham-McGregor 1987). Data on existing deficiencies have rarely been available or examined in studies of the relationship between mental development and severe malnutrition. In spite of a large number of studies, few investigators examined the rela tive contribution of stunting, wasting and edema to men tal development. Therefore, any interpretation of the lit erature is constrained by combining a heterogeneous group of conditions into inappropriate categories.

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Research considerations
Another limitation in the study of the effects of severe malnutrition is that it is not possible to do randomized supplementation trials for obvious ethical reasons. Be cause this is the only truly satisfactory way of demon strating a causal relationship, this puts an onus on the investigator to use well-established epidemiological principles in an attempt to establish a causal relationship.

Prevalence of severe malnutrition

The prevalence of underweight in children (weights below -2 so of the reference) is estimated to have declined globally from 38% in 1980 to 34% in 1990; however, the number of children has actually increased over the same period from 164 to 184 million. Furthermore, the prev alence of malnutrition has not declined in Sub Saharan Africa, where drought and armed conflict has led to severe famine (United Nations Subcommittee on Nutrition 1992). Children in refugee camps and displaced popula tions are also at increased risk of malnutrition (United Nations Subcommittee on Nutrition 1993). The preva lence of severe wasting and edematous malnutrition var ies and is estimated to be as high as 25% in South Asia (United Nations Children's Fund 1993).
0022-3166/95 $3.00 1995 American Institute of Nutrition.

The acute stage of severe malnutrition

Severely malnourished children demonstrate marked behavioral abnormalities in the acute stage. They are more
1Prepared for the International Dietary Energy Consultative Group (IDECG) Task Force workshop on malnutrition and behavior at the University of California, Davis, CA, December 6-10, 1993. This workshop was supported by IDECG, the Nestl Foundation, Kraft Foods and the International Union for Nutritional Science. Guest editor for this supplement publication was Ernesto Polliti, Department of Pediatrics, University of California, Davis, CA 95616. 1To whom correspondence should be addressed: Tropical Me tabolism Research Unit, University of the West Indies, Mona, Kingston 7, Jamaica, West Indies.

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SUPPLEMENT (Cravioto 1977), mothers were observed while their chil dren were having developmental assessments. They were found to be less responsive toward their children, es pecially their successes, than other mothers. They were also less affectionate and spoke less to their children. When answering questions, they were reported to be de fensive and reserved. One study of mothers and children after recovery from severe malnutrition showed that the children tended to stay closer to their mothers (GranthamMcGregor et al. 1989b). Most other studies of maternalchild interaction have involved mild to moderately un dernourished children. The above list is not exhaustive but illustrates the wide-ranging nature of these children's disadvantages. It is also clear that attempts to match for all these disadvantages in case control studies are unlikely to be successful.

apathetic, less active and explore their environment less, both in quantity and complexity, than children who are ill with other diseases. They show less active distress on admission to hospital than other ill children (Geber and Dean 1956, Grantham-McGregor et al. 1990, Williams 1993). They were reported to be irritable when disturbed, although this was not demonstrated systematically (Geber and Dean 1956, Williams 1993). Their behavior improves rapidly with recovery and probably returns to normal ex cept in the quality of explorations (Celedn et al 1980, Grantham-McGregor 1990). Severely malnourished chil dren have attenuated orienting responses to auditory stimuli (Lester 1975). They also have low-amplitude cries that are high pitched, arrhythmical or prolonged (Lester 1976). Similar cries were described in infants suffering from CNS dysfunction. Children's developmental levels are extremely low in the acute stage and generally improve during recovery in all areas of development (Cravioto and Robles 1965, Ge ber and Dean 1956, Grantham-McGregor 1978, Yatkin and McLaren 1970). However, their improvement is no greater than that shown by adequately nourished children who are in hospital because of other illnesses. There is no consistent evidence of a specific deficit. Language scores on developmental tests are poorest in most children in hospital regardless of their nutritional status. There is some evidence that children under 6 mo of age improve less in developmental levels than other chil dren while they are in hospital (Celedn et al. 1980, Cra vioto and Robles 1965). Whether this is due to their re sponse to hospitalization or to malnutrition is not clear.

Case control studies of survivors of early childhood severe malnutrition

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Short-term effects of severe malnutrition

On recovery from the acute stage and immediately af ter, children show poor developmental levels compared with matched controls or siblings (Brockman and Ricciuti 1971, Grantham-McGregor, 1978, McLaren et al. 1973, Pollitt and Granoff 1967).

The environment of severely malnourished children

Before discussing the long-term effects of malnutrition, it is essential to consider the quality of the children's environment. Malnourished children usually come from families who suffer from many disadvantages (GranthamMcGregor 1984). These include poor physical and eco nomic resources, such as overcrowded homes with poor sanitation and water supply, few household possessions and low income. They also tend to have unstable family units, with large numbers of closely spaced children. Pa rental characteristics associated with infant malnutrition include poor health and nutritional status, poor obstetric history, extreme youth or age, low intelligence and ed ucational levels, little media contact, few social contacts, traditional life styles, and low-skilled occupations. The stimulation in the home is poor with few toys or books and little participation by the parents in play activities. Abnormal patterns of maternal-child interaction were also described in some cultures. In the only prospective study of children preceding the onset of malnutrition

Many studies of school-age children who suffered from severe malnutrition in early childhood have been con ducted. They were compared with carefully matched controls and or siblings (Bartel et al. 1978, Birch et al. 1971, Evans et al. 1971, Graham and Adrianzen 1979, Hertzig et al. 1972, Moodie et al. 1980, Nwuga 1977, Pereiraetal. 1979). In most studies that used matched controls, differences favoring the controls were found in tests of IQ, cognitive function or school achievement. Studies involving sib lings had somewhat less consistent findings. Although differences were found in some sibling comparisons (Birch et al. 1971, Hertzig et al. 1972, Nwuga 1977), in others none were found. When the outcome measures are not cognitive function or IQ, differences are less likely (Barteletal. 1978, Graham and Adrianzen 1979, Moodie et al. 1980, Richardson et al. 1973). There is very little information on children after school age (Moodie et al. 1980, Ramalingaswami et al. 1993), and this is insufficient to conclude whether differences remain in adulthood. Characteristics of the acute episode. It is not clear whether age of onset of the severe episode affects the outcome because there is little data from children under 6 mo of age. This is probably because malnutrition in the first few months of life is not common. It is possible that very young children are more vulnerable to nutritional deficits. In a recent study of very short-term supplemen tation of preterm babies after birth, marked and sustained benefits to the children's developmental levels were re ported (Lucas et al, 1990). Over 6 mo of age, there is no consistent evidence of an age effect in the first few years of life. It is unknown whether malnutrition in schoolage children affects their long-term development. There is some evidence that an episode of edema does not increase the risk of poor mental development over and above that associated with the child's weight and height deficit (Hoorweg and Stanfield 1976, GranthamMcGregor 1982, Grantham-McGregor et al. 1989a). The latter two studies provide some evidence that the acute episode in general adds only little to the deficit in mental development.

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Galler and colleagues (1987a) compared the mental development of school-age children who had suffered from kwashiorkor with those diagnosed as marasmic and found no difference. However, the definition of maras mus was weight-for-age below 75% of the reference val ues that includes heavier children than that defined by the Wellcome classification. In addition, the independent effects of height-for-age, weight-for-height and edema were not considered. It is, therefore, difficult to interpret the findings. Cognitive deficits and motor skills. In spite of the large numbers of studies, few examined a comprehensive range of cognitive functions. Most investigators looked at global IQ measures. The finding that reasoning and perceptual-spatial functions are affected is reasonably consistent (Champakam et al. 1968, Hoorweg and Stanfield 1976, Nwuga 1977). However, the data are insuf ficient to identify specific deficits in cognitive function with confidence, although they may be present. Motor skills were generally found to be affected (Cravioto and Arrieta 1986, Galler et al. 1987b, Hoorweg and Stanfield 1976), although not always (Bartel et al. 1978), and the children were described as clumsy (Richardson et al. 1972). Intersensory integration (Cravioto and Ar rieta 1986, Champakam et al. 1968, Pereira et al. 1979) and the acquisition of Piagetian milestones (Galler and Ramsey 1987) are delayed in younger children. These tests do not discriminate between groups in older children because they tend to score at the ceiling of the tests (Srikantia 1979). Behavior. Formerly severely malnourished children were reported to have more behavior problems than comparison groups. Most studies used mothers' or teach ers' reports and only a few studies used direct observa tions. Children were observed to play with toys for shorter periods and stay closer to their mothers (Grantham-McGregor et al. 1989b) and to be more unrespon sive when given a task (Cravioto and Arrieta 1986). Teachers reported that formerly malnourished children make poorer relationships with their peers and teachers, have poorer attention and are more distractible than their classmates (Galler et al. 1983b, Richardson et al. 1972, Richardson et al. 1975). In addition, they were sometimes reported to have less emotional control (Galler et al. 1983b) and be less active and more obedient (Hoorweg 1976). It is likely that the different cultures will modify the behavior of children differently and may explain some of the inconsistencies between the findings from different studies. School performance. Previously malnourished chil dren were often found to have poorer school grades than matched controls (Galler et al. 1990, Richardson et al. 1973). This is so in spite of the children being matched for their school class with the controls. However, in sev eral studies no difference was found between formerly malnourished children and their siblings (Graham and Adrianzen 1979, Moodie et al. 1980, Richardson et al. 1973), albeit in one study a difference was found (Pereira et al. 1979). It may be that family attitudes to education, poor attendance and late enrollment swamp any addi tional intellectual disadvantage the malnourished group may suffer.

Interpretation

of findings

The constraints of case control studies are well rec ognized. There is only one study that demonstrated that the children's developmental levels were the same as those of the comparison group, preceding the episode of mal nutrition (Cravioto and Arrieta 1986). Also, only one study controlled for the effect of hospitalization (Grantham-McGregor et al. 1978). Most importantly, it is un likely that the groups were matched for all the sociocultural factors which may affect mental development (Richardson 1974). These factors would tend to exagger ate the effects of malnutrition. On the other hand, when siblings were used for the control group, they were often chronically undernourished themselves. This would have reduced any difference attributed to undernutrition to that due to the acute episode alone. Considering all the studies, the finding that previously malnourished children show a deficit in tests of cognitive function or intelligence if they return to poor environ ments, is reasonably consistent. There is some suggestion that the acute episode, per se, may not be as important as the underlying chronic undernutrition, and this may explain the more inconsistent findings from the studies in which siblings were used. The strength of the effect was generally found to be considerable; also there are several plausible biological mechanisms that could explain how malnutrition may affect mental development (see below). Further, one can not ignore the data from recent supplementation studies (discussed by others) that show that even lesser degrees of undernutrition affect children's cognitive function, at least concurrently. Using epidemiological principles (Hill 1965), it is therefore reasonable to attribute a causal relationship to early childhood malnutrition and poor performance on cognitive tests in later childhood. Further case control studies of survivors of severe malnutrition are unlikely to assist in determining whether the relationship between poor mental development and severe malnutrition is causal or not.

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Children's response to an improved environment

Children's development improves in the acute stage of malnutrition if they participate in a stimulation pro gram. However, the benefits are transient (Cravioto and Arrieta 1979, McLaren et al. 1973). There is limited ev idence that a longer program of stimulation, which in volves the families, produces benefits that last at least to adolescence (Grantham-McGregor et al. 1994). Surpris ingly, there is no study of the effects of providing stim ulation with good nutrition and health care on a longterm basis. Studies of severely malnourished children who are adopted by more affluent families indicate that intelli gence improves markedly when health care, nutrition and stimulation are provided continually (Colombo et al. 1992, Winick et al. 1975). In one study (My Lien et al. 1977), children who were adopted at an older age had lower IQ levels than those adopted younger. However, this latter study was confounded by institutionalization

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SUPPLEMENT than those who received more supplementation. The re sponse to Stressors in recovered severely malnourished children has not been examined. However, in experiments with rehabilitated malnourished rats, Levitsky and Barnes (1970) showed that the rats had abnormal responses to several different types of Stressors.

in that all the children had been in an orphanage in early life. It was also confounded by the time since adoption, which was shorter for the older adopted children. It is therefore uncertain whether complete recovery is possi ble, and if there is an age at which recovery is less likely to occur.

Malnutrition in an extremely deprived environment

It is likely that where the environmental conditions are extremely poor, the effects of severe malnutrition would be much greater. For example, in several countries at present famine and food shortage are accompanied by armed conflict, family disruption, reduced schooling op portunities and lack of play opportunities. In these sit uations, the prognosis for the children's future devel opment is extremely grave. There are little data on this and an urgent need for information.

The mechanisms
The abnormal behavior seen in the acute episode is transient and improves rapidly. This almost certainly has a metabolic basis, although it is uncertain which nutrients are responsible. The mechanism causing more permanent behavioral changes is more difficult to determine. It is possible that if the nutrient deficiencies continue for a long time and the children's behavior remains abnormal, that they will acquire skills only slowly and this will gradually lead to a cognitive deficit. It was hypothesized that reduced activity levels were critical in producing poor development. However, in a recent review we could find little data to support this hypothesis (Grantham-McGregor et al. 1990). The quality of the child's exploration is more likely to play a role. Meeks Gardner and colleagues (1993) showed that stunted children explored their environment with less enthusiasm and happiness and were more apathetic than nonstunted children. This behavior predicted future change in development. In most follow-up studies, severely malnourished children returned to poor environments where the stan dards of nutrition remained questionable. The behavioral abnormalities described in some of the studies (e.g., Galler et al. 1983a, Richardson et al. 1972) may be partly ex plained by continuing poor nutrition. This could impede the children making a full recovery. It may be pertinent that Grantham-McGregor and col leagues (1989b) showed that previously malnourished children played less with a toy than control children. However, a second group of malnourished children who had participated in a stimulation program showed no such problem. The program did not include nutritional sup plementation, which raises the questions as to whether the unexploring behavior that is characteristic of mal nourished children may be partly explained by unstimulating home environments. It is also possible that irreversible changes occur in the brain and these produce behavioral changes. The marked improvements shown by an extremely short-term period of supplementation in preterm babies (Lucas et al. 1990) suggests that this is a factor at least at this early stage of development. Electrophysicological abnormalities were found in children several months after recovery from severe mal nutrition (Barnet et al. 1978). Other evidence of changes to the brain comes mainly from animal research and will be discussed by others. The evidence that severe malnutrition in early child hood can lead to poor cognitive function, intelligence and behavior problems in later childhood if the children re turn to poor environments is strong but not unequivocal. Marked improvements in development can occur with vastly enriched environments, which include good health, nutrition and stimulation. Analogously, it is highly likely

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Malnutrition independent circumstances

of poor social

When malnutrition occurs secondary to other diseases in children in developed countries, it is less likely to be associated with poverty, although poor parenting may lead to more severe or prolonged episodes in some cir cumstances (Rush 1984). Several studies of secondary malnutrition were conducted; however, the samples tended to be small (Valman 1974), and the malnutrition often was not severe (Ellis and Hill 1975) or prolonged. There is some evidence of a small effect (Carmona da Mota et al. 1990, Kleinetal. 1975, Lloyd-Still et al. 1974) in children, but no evidence that this persists to adulthood (Berglund and Rabo 1973, Lloyd-Still et al. 1974). The smaller effects of malnutrition found in these studies compared with those found in studies in developing countries may be explained by the good nutrition and stimulation the children experience subsequent to the episode of malnutrition. Further, the good quality of the environment may afford some protection in the acute stage. This protective effect of stimulation was found in animal research.

Interactions between severe malnutrition and other nutritional deficiencies

It was shown that the cognitive functions of school children who survived severe malnutrition in early child hood were detrimentally affected by short-term food de privation, whereas adequately nourished children were not (Simeon and Grantham-McGregor 1989). We recently showed that underweight schoolchildren's cognitive function improved when they were given breakfast, whereas that of better nourished children did not (Chan dler et al. 1993). It is possible that similar interactions may occur with other nutrient deficiencies or infections and previous malnutrition. However, this was rarely ex amined. It is also possible that previously malnourished children who received little nutritional supplementation coped less well with frustrating or competitive situations

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that extremely deprived environments will exacerbate the effects of malnutrition. Therefore, the outcome depends to a large extent on the quality of the subsequent envi ronment. Malnutrition interacts with short-term food deprivation in its effect on children's cognitive function. It is likely that other nutrient deficiencies or infections will also interact with previous malnutrition in their ef fect on cognition. Several questions remain unanswered because of in sufficient data. These are as follows: 1. Whether the effects of severe malnutrition last until adulthood 2. Whether specific cognitive functions are affected 3. Whether malnutrition in the first few months of life has a greater effect from that occurring later, and whether malnutrition in older children has an effect 4. Whether complete recovery can occur with enriched environments 5. The nature of the precise mechanism of how mal nutrition causes a behavioral deficit, and which nu trients are involved 6. Whether malnutrition interacts with other nutrient deficiencies in their effect on cognitive function 7. Whether previously malnourished children's re sponses to different Stressors is abnormal Future research will be facilitated by reliance on a more satisfactory definition of protein-energy malnutrition a definition that is urgently needed.

LITERATURE

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