Effect of zinc supplementation on development and growth of Chilean infants.

OBJECTIVE: To evaluate the effect of zinc supplementation on growth and development during infancy. DESIGN: We randomized 150 term neonates of low socioeconomic status to receive supplemental zinc 5 mg/d (SG) or a lactose placebo (PG); 112 completed a 1-year follow-up. All were breast-fed and given cow milk formula after weaning; solid foods and iron were added at 5 months. Anthropometry measured monthly, psychomotor development (PDI), mental development (MDI), and behavior including motor quality factor were assessed by Bayley Scales at 6 and 12 months. The groups were comparable in maternal characteristics, birth weight, home environment, and mother-infant interaction. RESULTS: No effects of zinc on weight, length, and weight for length at 12 months were found controlling for sex and breast-feeding. The mean PDI (SG: 84.5 +/- 11.5 vs PG: 87.6 +/- 9.9) and MDI (90.9 +/- 10.5 vs 88.9 +/- 9.1) were similar; however, 46 of 52 infants in the PG scored <100 in MDI vs 42 of 57 in the SG (P <.05). A smaller proportion of the SG, 2 of 57, scored low in motor quality factor at 6 months compared with the PG, 8 of 52 (P =.02). The mean at 12 months for the SG was 31.9 +/- 2.8 and for the PG 30.8 +/- 2.9 (P <.05); zinc supplementation entered the multiple regression at 12 months (P =.037). CONCLUSIONS: Zinc supplementation may have a beneficial effect on mental development and motor quality behavior of healthy term infants.

A 14-mo zinc-supplementation trial in apparently healthy Chilean preschool children.

Apparently healthy preschool children (46 boys, 52 girls) aged 27-50 mo from low socioeconomic conditions who attended daycare centers in Santiago participated in a 14-mo long double-blind zinc supplementation trial. Unlike most previous studies, no additional inclusion criteria such as short stature or slow growth rate were considered. Subjects were pair matched according to sex and age and randomly assigned to two experimental groups: the supplemented group, which received 10 mg Zn/d, and the placebo group. Selected anthropometric, clinical, dietary, biochemical, and functional indexes were determined at the beginning of the study and after 6 and 14 mo of intervention. Actual dietary zinc intake was 66% of the recommended dietary allowance. Height gain after 14 mo was on average 0.5 cm higher in the supplemented group (P = 0.10). The response, however, was different between sexes. Boys from the supplemented group gained 0.9 cm more than those in the placebo group (P = 0.045). No effect was seen in girls. Although no significant differences were observed in the rest of the variables studied, trends (0.05 < P < 0.10) in the supplemented group compared with the placebo group for increased midarm muscle area in boys, improved response to tuberculin, and reduced rates of parasite reinfestation were noted. We conclude that in preschool children of low socioeconomic status, zinc is a limiting factor in the expression of growth potential.

Zinc supplementation and growth of infants born small for gestational age.

To analyze the effect of zinc supplementation on postnatal growth of infants born small for gestational age, we selected 68 infants at birth and followed them monthly for 6 months. They were randomly assigned to a supplemented group (group S, n = 35) receiving 3 mg of Zn (acetate) per day, or to a placebo (group P, n = 33), in a double-blind study. Weight increments in group S were significantly higher than those in group P at 2 months (p < 0.003); z scores showed catch-up growth only in group S. Length increments were also greater in group S than in group P, ending at 6 months were 64.9 +/- 1.8 versus 63.4 +/- 3.5 cm (mean +/- SD; p < 0.01); changes in z scores for 6 months were -1.28 to -0.66 in group S and -1.43 to -1.47 in group P (p < 0.001). Weight-for-length improved similarly in both groups (z score, -2.2 to +0.2). The increase in weight-for-age was higher in group S girls (p < 0.034), ending at 6 months with -0.13 +/- 0.59, versus -0.52 +/- 0.62 in group S boys, -1.15 +/- 0.49 in group P girls, and -1.05 +/- 0.80 in group P boys (+/- SD). More infants in group P received cow milk-based formula before 4 months because of inadequate weight increments. An additive effect on weight increase was observed between Zn supplementation (p < 0.02), exclusive breast-feeding after 4 months of age (p < 0.001), and gender (p < 0.02). Plasma and hair Zn values showed a downward trend, less marked in group S than in group P. We conclude that Chilean infants born small for gestational age have better weight and linear growth during the first 6 months of life if they receive Zn supplementation.

Zinc supplementation increases growth velocity of male children and adolescents with short stature.

We assessed the effect of zinc supplementation on growth velocity in 79 children and adolescents (48 males, 38 females) with idiopathic short stature. Their height-for-age was < 5th percentile (NCHS standards) and their weight-for-age was normal. Patients were assigned randomly to a supplemented group (S) to receive Zn 10 mg/day or to a placebo (P) group, according to gender and age, and were followed-up for 12 months using a double-blind design. Weight, height, armspan, length of lower segment and plasma and hair concentrations of Zn were measured at 0, 3, 6 and 12 months. On admission and at 6 months, energy, protein, dietary fiber and zinc intakes were similar for groups S and P; mean zinc intake was < 6.5 mg/day. No differences were found in plasma zinc, hair zinc, weight, armspan or lower segment increments. Pre-adolescent males in group S had a significantly greater increase in stature compared with group P (6.2 +/- 2.1 versus 4.5 +/- 1.2 cm/year p < 0.025); z score improved from -2.42 to -2.24 in group S and from -2.63 to -2.61 in group P. For adolescent males, the difference was also significant (8.3 +/- 1.5 versus 6.2 +/- 2.1 cm/year; p < 0.025). No differences were noted in females. In Chilean male schoolchildren and adolescents with idiopathic short stature, zinc supplementation increases growth velocity over a 12-month period.

Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants.

To evaluate the effect of copper supplementation during recovery from acute diarrhea, we randomly assigned 14 hospitalized infants to receive either 80 micrograms copper sulfate.kg body wt-1.d-1 or a placebo. Metabolic balance and plasma copper and zinc concentrations were measured before randomization (period 1) and 6 d after admission (period 2). Fifteen control subjects were studied after respiratory illness. Fecal copper was not affected by supplementation; fecal zinc during period 2 rose significantly only in the copper-supplemented group. Copper retention was significantly higher in the supplemented infants; plasma concentrations increased for period 2 but were similar to those in the placebo group. Zinc concentrations improved over time in both groups but zinc retention was higher in the placebo group for period 2. A significant interference by copper supplementation on zinc absorption was noted. Copper supplementation during the early phase of recovery from diarrhea is not recommended.

Copper deficiency impairs growth of infants recovering from malnutrition.

To evaluate the effect of copper deficiency on growth in humans we performed a prospective case-control study in 11 infants identified as Cu deficient based on low plasma Cu (less than 70 micrograms/dL [11.0 mumol/L]) and low ceruloplasmin (less than 200 mg/L). Growth was evaluated with anthropometric indices 1 mo before and 1 mo after onset of Cu supplementation of 80 micrograms.kg-1.d-1. Plasma Cu and ceruloplasmin rose significantly after 1 mo of supplementation. Weight-for-age and weight-for-length indices increased significantly after supplementation only in the Cu-deficient group. Daily energy intake was significantly higher in the Cu-deficient group after supplementation than it was in the control group. Daily weight gain after supplementation increased significantly in the Cu-deficient group and the value for daily weight gain after supplementation was significantly higher than that of the control group for the equivalent amount of time. Cu supplementation improves the growth of Cu-deficient infants recovering from malnutrition.

PIP: To evaluate the effect of copper deficiency on growth in humans a prospective case-control study was performed in Chile on a group of 11 infants identified as Cu deficient based on low plasma Cu (70 mcg/dL (11.0 mcmol/L) and low ceruloplasmin (200 mg/L). Growth was evaluated with anthropometric indices 1 month before and 1 month after onset of Cu supplementation of 80 mcg x 1/kg x 1/d. Plasma Cu and ceruloplasmin rose significantly after 1 month of supplementation. Weight-for-age and weight-for-length indices increased significantly after supplementation only in the Cu-deficient group. Daily energy intake was significantly higher in the Cu-deficient group after supplementation than it was in the control group. Daily weight gain after supplementation increased significantly in the Cu-deficient group and the value for daily weight gain after supplementation was significantly higher than that of the control group for the equivalent amount of time. Cu supplementation improves the growth of Cu-deficient infants recovering from malnutrition.

Controlled trial of zinc supplementation during recovery from malnutrition: effects on growth and immune function.

To evaluate the effect of zinc on growth and immune function, 32 marasmic infants were selected on admission to the nutrition recovery center; 16 received 2 mg/kg daily of elemental zinc supplement as acetate and the remaining received a placebo. Immunity was assessed by skin-test response, T-cell blastic proliferation immunoglobulins, and infectious morbidity. Weight-for-length gain for initial 60 days in Zn-supplemented group was 9% of standard vs 3% for placebo (p less than 0.05). Energy intake was similar in both groups. Incidence of infections, especially pyoderma, was significantly higher in placebo group: 10 of 16 vs 3 of 16 in the supplemented group (p less than 0.025). Plasma Zn was correlated with number of febrile days in the prospective month (r = -0.66, p less than 0.05). The percent anergic infants decreased and serum IgA increased significantly only in Zn-supplemented group. Zinc supplementation has significant effects on weight gain and host defense mechanisms despite normal plasma levels. Zinc supplementation is recommended for optimal recovery from marasmus.

Red cell superoxide dismutase activity as an index of human copper nutrition.

Red cell superoxide dismutase (SOD) activity was evaluated as a biochemical index of copper nutrition in a double-blind study of 17 infants recovering from malnutrition and receiving marginal copper intakes. Children were paired on admission by sex, birth weight, nutritional status and antecedents of diarrhea and breast feeding. Nine served as controls receiving a copper sulfate supplement (80 micrograms/kg daily for 120 d; eight received a placebo and were supplemented only if plasma copper levels dropped below 90 micrograms/dl or on d 90 for at least 30 d. After copper supplementation there was a significant rise (paired t-test; P less than 0.05) in plasma copper (96 vs. 165 micrograms/dl); ceruloplasmin (33 vs. 50 mg/dl) and SOD (1073 vs. 1371 U/g Hb). After supplementation these values were similar to those of the controls. SOD was correlated with plasma copper (r = 0.78; P less than 0.001) and not with weight-for-age or weight-for-length. Addition of copper in vitro did not modify the SOD activity. Red cell SOD is a good marker of copper nutrition in humans and correlates well with plasma copper.

Controlled trial of copper supplementation during the recovery from marasmus.

To evaluate copper nutritional status and the effect of a Cu supplement during recuperation, 27 marasmic infants were selected on admission to the nutrition recovery center at the Instituto de Nutrición y Tecnología de los Alimentos. Thirteen infants received 80 micrograms/kg/day of copper supplement as sulphate and the remaining a placebo. They were paired by birth weight, age, and sex. Anthropometric indices, complete blood count, ceruloplasmin, and Cu were measured on admission and at monthly intervals. Superoxide dismutase activity was measured in hypocupremic infants and was found to be low. The mean +/- SE Cu levels on admission were 127 +/- 10 micrograms/dl for the supplemented group and 137 +/- 10 micrograms/dl for the control. We found an increase in plasma Cu to 159 and 162 micrograms/dl on days 30 and 60 in the supplement group, and a significant decrease after day 30 in the placebo group. The ceruloplasmin levels followed this trend. Hypocupremia was found in 30% of the placebo group and none in the supplement group. The placebo group had a significantly higher prevalence of severe lower respiratory infections. It is concluded that a significant proportion of marasmic infants fed a milk-based diet present, during recovery, biochemical evidence of Cu deficiency. Supplementation with Cu is suggested.