Zinc and Development Zinc has many potentially important biological roles in humans. Among its many functions, zinc is a component of over 100 metalloenzymes and is involved in cell membrane structure, nucleic acid metabolism and gene expression. A lesser known function is induction of the antioxidant metallothionein synthesis, which allows zinc to aid in protection against metal toxicity. Dietary zinc is available from a number of animal sources; especially human milk shellfish and animal meats. Zinc is also available in legumes, nuts and whole grain cereals but it is relatively poorly absorbed from these sources. Absorption occurs by facilitated diffusion throughout the small bowel, followed by transport to the liver through the portal system. Zinc is bound to either albumin or transferrin where it can be stored, actively used in several metabolic pathways or excreted. Most of the excretion takes place in the feces, but there is a small amount excreted in the urine and sweat. Symptoms of mild zinc deficiency may be difficult to characterize, but can include growth retardation, anorexia, loss of taste perception and immune dysfunction 1. Severe zinc deficiency not only depresses growth but also effects skeletal maturation and gonad development causing delayed puberty. Other clinical features include diarrhea, alopecia, skin lesions, increased incidence of infections, delayed wound healing and personality changes. In acrodermatitis enteropathica, a partial block in intestinal absorption of zinc leads to severe zinc deficiency. Zinc and Growth In infants and children, the earliest and most important clinical presentation of zinc deficiency is a decrease in physical growth velocity. Studies have shown that mild zinc deficiency in otherwise healthy children may limit expected growth. It is also known that zinc promotes growth in severely malnourished infants and children. Delayed sexual maturation is also an important feature of zinc deficiency in adolescents and is corrected by zinc repletion together with the resultant catch-up growth. In infants and children with zinc deficiency, growth retardation may also be due to severe anorexia, loss of appetite and reduced food intake. The link between poor growth and zinc status seems to be well established particularly in severe zinc deficiency. There is still some controversy concerning mild zinc deficiency's contribution to poor growth performance 2. Zinc and Development It is well known that zinc is necessary for normal brain growth and function. However, there is no evidence that acquired zinc deficiency is a cause of mental retardation or learning disability, though it may have some bearing on behavioral disorder in infants and children. The relationship of mothers' zinc status to their infants' development was studied by Kirksey et al 3. Zinc intake was assessed during the last six months of pregnancy and the first six months of lactation. Mean gestation was 37.6 weeks ± 1.6 weeks; only one infant was born at less than 35 weeks of gestational age. The Brazelton Neonatal Assessment Scale (BNAS) and the Bayley motor development scale were used to assess development. The BNAS assesses the behavioral organization and development of neonates in an interactive situation with examiners. Neonates who appear more disorganized on this scale are more likely to be rated as difficult to deal with by their caregivers at six months of age. In this study, the BNAS assessment was done between three and five days after birth and the Bayley motor development scale was administered at six months of age. Estimates of dietary zinc intake indicated limited amounts relative to requirements of 2 mg per day. Additionally, diets were from minimally processed cereal grains and therefore were relatively high in fiber and phytate which are recognized as negative factors in zinc bioavailability. Within the BNAS test, there was a positive correlation found between maternal nutrient intakes and the test segment on habutuation. Habituation is a behavioral process describing the ability of infants to inhibit response to a repetitive or familiar stimulus. More rapid habituation is usually interpreted as reflecting more focused attention and more efficient information processing by the neonate. It is thus related to the infant's degree of alertness. Measures of habituation have been used to predict a variety of indexes of cognitive performance in the school years. The neonates' ability to habituate to repeated stimulation correlated with a high maternal intake of animal source iron, available iron, zinc, vitamin B6 and niacin as well as energy and protein intake from animal sources. All of these relationships were significantly correlated to the maternal intake during the second trimester. Low scores for the Bayley motor performance were associated with high maternal intake of plant zinc, fiber and phytate and with low intakes of vitamin C. These results suggest a role for some nutrient interactions. Isolated mild deficits of a single nutrient such as zinc may not be critical for behavioral development. However, if associated with marginal deficits of other micronutrients, the abnormalities may then be amplified. In this study, the poor motor performance of infants was not only related to maternal diets containing low amounts of bioavailable zinc but also to other non-nutritional risk factors associated with socioeconomic status. The risk of delayed motor development was greater for infants who received inadequate micronutrient intakes if they were from families who were at the low end of the socioeconomic status distribution. The influence of zinc on somatic growth and development were studied in very low birth weight (VLBW) infants by Friel et al 4. Fifty-two VLBW infants were randomly assigned to a regular term formula with or without zinc supplement. Neurological development was assessed using the Griffiths Mental Development Scales, an instrument similar to the Bayley Scales of Infant Development. In this test, neurological assessment consists of five subscales of development including locomotor, personal/social, hearing and speech, eye/hand coordination and general performance skills. Significant differences in locomotor development between the two groups were found at three, six, nine and twelve months. These results suggested a developmental advantage for infants receiving supplemental zinc. Krebs et al 5studied the growth pattern of healthy term infants exclusively breast fed for five months or more and its relationship to zinc intake. Throughout the first seven months of life, mean energy intake of these infants were lower relative to current recommendations. As zinc intake from human milk decreases steadily during this time frame, zinc intake of breast fed infants is found to be adequate only throughout the first five months of exclusive breast feeding. Subsequently, zinc intake is marginal and introduction of weaning foods is necessary to supplement potential mild deficiency. Unfortunately, the authors did not study development in these normal, healthy infants. The association of zinc deficiency or insufficiency with poor development is further strengthened by results from a recent study from New Delhi. Sazawal et al 6studied the effect of zinc supplementation on observed activity in low socioeconomic Indian pre-school children. A cohort of 93 children presenting to the local dispensary with mild diarrhea were selected for an ongoing, double-blind, randomized trial of zinc supplementation. After an initial assessment, children received a multivitamin preparation containing vitamins A, B1, B2, B6, D3, E and niacinamide. In addition, the experimental group received zinc gluconate (10 mg of elemental zinc) in the vitamin preparation. Of the 93 children selected, 48 received zinc and 45 did not. the children were then observed from the date of enrollment and up until six months thereafter. Trained field workers visited the children every fifth or sixth day. A selected sample of all children enrolled in the main study were chosen for development assessment. . Seventy-one percent of the children received the supplementation preparation for more than four months, 26% had received it for two to four months and 3 % for less than two months. Children were assessed at 12-23 months and the activity recorded was classified under an activity rating scale ranging from stationary to fast movement. The children were observed on two separate days a number of times each day. A percentage of time spent in each of the activities was calculated for each child. The percentage of total time observed at each activity level was then multiplied by a factor representing energy expenditure and the products of all recorded activities were then summed up. Children who were in the zinc supplemented group spent, on average, 72% more time in performing activities in the high movement group compared to control group children. The activity rating was 12% higher by the children's activity rating scale and 8.3% higher by the energy expenditure score. These differences were significantly higher even after controlling for confounding variables. The effect of zinc supplementation on activity was greater in males. It was postulated that perhaps boys needed higher zinc requirements for infant growth than girls. Further evidence that zinc influences child development is provided by a study on the effects of zinc supplementation on activity patterns of rural Guatemalan infants. As part of a larger randomized controlled trial on the effects of zinc supplementation in six to nine month old infants in rural Guatemala, Bentley et al 7recorded motor activities at the time of supplementation (up to seven months) and after seven months of supplementation. Infant activity was assessed by serial sampling of observed positions and activities during a twelve hour observation period. The observations were made at baseline, three months, seven months, and seven months after the end of supplementation. During the supplementation period, no differences were observed between the supplemented and non-supplemented groups. However, seven months after the end of the trial period, the zinc supplemented infants were sitting up more frequently and were playing more often than the unsupplemented infants. They were also crying and/ or whining less often than those receiving the placebo. Confounding variables such as infant age, motor development, sex, maternal education, socioeconomic status and nutritonal status were controlled for and had no influence on the results. Conclusion These studies suggest that a number of infants and children may be at risk of developing subtle developmental delay if they do not receive sufficient zinc in the first few years of life. Although most of the studies were done in low socioeconomic groups, results apply to North American infants and children. The influence of zinc on development in very low birth weight infants has been demonstrated in a group of Canadian infants. In this group, it appears that supplementation with zinc may offer a developmental advantage 8. Similarly, in exclusively breast fed infants, addition of zinc after five months of exclusive breast feeding through beikost might be advisable. Foods rich in zinc include animal meats, shellfish, milk and milk products, whole wheat bread, cereals such as Rice Krispies and Shredded Wheat, eggs and potatoes. Finally, in infants and children with repeated episodes of diarrhea and a risk of increased zinc losses, mild zinc deficiency may develop thus influencing cognitive and locomotor development and eventually influencing school performance in the later years. Before we conclude that a significant number of infants and children in North America would benefit from zinc supplementation (together with other multivitamines) to enhance the potential positive influence of zinc on somatic growth and development in intellectual performance, more research in our patient population is needed. References
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