Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants

Childhood immunization programs may provide infrastructure for delivering vitamin A supplements to infants in developing countries. The effect of giving vitamin A, an immune enhancer, on antibody responses to trivalent oral poliovirus vaccine (TOPV) is unknown. A randomized, double-blind, placebo-controlled clinical trial was conducted to determine the effect of giving vitamin A simultaneously with TOPV on antibody responses to poliovirus. Infants (n = 467) received oral vitamin A, 15 mg retinol equivalent (RE), 7.5 mg RE or placebo with TOPV at 6, 10 and 14 wk of age. Antibody responses to poliovirus types 1, 2 and 3 were measured by a microvirus neutralization assay at enrollment and at 9 mo of age. Seroconversion rates to poliovirus types 1, 2 and 3 ranged from 98 to 100% in the three treatment groups, and there were no differences in mean antibody titers to poliovirus types 1, 2 and 3 among treatment groups. This study demonstrates that oral vitamin A does not affect antibody responses to poliovirus vaccine when integrated with the Expanded Program on Immunization.     

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.     

Redistribution of vitamin A after iron supplementation in Indonesian infants

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.     

Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women

We investigated whether weekly iron supplementation was as effective as the national daily iron supplementation program in Indonesia in improving iron status at near term in pregnancy. In addition, we examined whether weekly vitamin A and iron supplementation was more efficacious than weekly supplementation with iron alone. One group of pregnant women (n = 122)was supplemented weekly with iron (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121) received the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. A third ("daily") group (n = 123), participating in the national iron plus folic acid supplementation program, was also recruited. Data on subjects with complete biochemical data are reported (n = 190). At near term, hemoglobin concentrations increased, whereas serum ferritin concentrations decreased significantly in the weekly vitamin A and iron group, suggesting that vitamin A improved utilization of iron for hematopoiesis. Iron status in the weekly iron group was not different from that of the "daily" group. However, iron status decreased with daily supplementation if <50 iron tablets were ingested. Serum transferrin receptor concentrations increased in all groups (P < 0.01). Serum retinol concentrations were maintained in the weekly vitamin A and iron group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron supplements on a weekly basis can be as effective as ona daily basis if compliance can be ensured. Addition of vitamin A to the supplement improved hemoglobin concentration.     

Integration of vitamin A supplementation with the Expanded Programme on Immunization: lack of impact on morbidity or infant growth

Vitamin A deficiency is associated with increased morbidity and mortality from diarrheal disease, measles, and malaria. It has been proposed that vitamin A supplementation could be linked with childhood immunization programs to improve child health. We conducted a randomized, doubleblind, placebo-controlled clinical trial to evaluate the impact of linking vitamin A supplementation with the Expanded Programme on Immunization on morbidity and child growth. In West Java, Indonesia, 467 six-week-old infants were randomized to receive 7.5 mg retinol equivalent (RE), 15 mg RE, or placebo with childhood immunization contacts at 6, 10, and 14 wks and 9 mo of age. Child growth was assessed through anthropometry, and morbidity histories were obtained. Vitamin A supplementation had no apparent impact upon linear or ponderal growth or infectious disease morbidity in the first 15 mo of age when integrated with the Expanded Programme on Immunization.

Conclusion : Although improving vitamin A nutriture is of general importance in reducing diarrheal and measles morbidity and mortality in developing countries, this clinical trial showed no apparent benefit of vitamin A capsules for infant health when given through childhood immunization programs.     

Vitamin A status and hemoglobin concentrations are improved in Indonesian children with vitamin A and deworming interventions

OBJECTIVE: Anemia is a major public health problem caused by multiple factors. Vitamin A (VA) depletion can affect hemoglobin concentration (Hb). This study investigated the improvement in Hb and VA status in preschool Indonesian children following supplementation with 210 micromol VA and deworming with 400 mg albendazole. SUBJECTS AND DESIGN: Indonesian children (n = 131) infected with Ascaris lumbricoides and/or Trichuris trichiura were enrolled. The children were grouped by length of time since receiving 210 micromol VA through the local health system. Group 1 (VA administered > or = 4 month before baseline) included 51 children with Ascaris and 29 children with Trichuris. Group 2 had received VA < or = 1 month of baseline from the local health post and included 51 children. INTERVENTION AND METHODS: Immediately following baseline Hb and VA status assessment (modified relative dose response (MRDR) test), Group 1 children were given 210 micromol VA and 400 mg albendazole. Group 2 were randomized to be dewormed either 1 week before, at the same time or 1 week after baseline MRDR and Hb measures. Follow-up assessment was 3-4 weeks after baseline. RESULTS: VA status in Group 1 significantly improved in children with either Ascaris (P < 0.0001) or Trichuris (P = 0.028). Although the prevalence of anemia declined, the improvement in Hb was not significant (P = 0.08). In Group 2, improvement in VA status from the VA delivered through the public health system was maintained for more than 1 month. Hb improved (P = 0.0037) and this improvement appeared to be associated with the length of time between deworming and follow-up assessments. CONCLUSION: Public health supplementation programs to improve VA status may also increase Hb concentrations and decrease anemia prevalence, especially when linked to deworming. SPONSORSHIP: These studies were supported by the Thrasher Research Fund, SmithKline Beecham and Hatch-Wisconsin Agricultural Experiment Station number WIS04533.     

Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, Indonesia

OBJECTIVE: High prevalences of vitamin A deficiency and anaemia among adolescents warrant interventions. This study evaluated the effectiveness of school-based supplementation to reduce anaemia and improve vitamin A status. DESIGN: School-based, grade-randomized, intervention. SUBJECTS AND SETTING: In all, 1757 girls and 1859 boys, aged 12-15 y, in 24 Junior High Schools. INTERVENTIONS: Weekly supplementation for 14 weeks with 60 mg iron and 250 microg folate (Fe group; n=978), 10 000 IU vitamin A (VA group; n=970) or both (VAFe group; n=1042) to subjects in 15 schools, compared to subjects in nine other schools not receiving supplements (control; n=626). RESULTS: The baseline anaemia prevalence (Hb <120 g/l) in girls was 20% (prepubertal) and 26% (pubertal), and in boys 24% (pre-pubertal) and 11% (pubertal). Serum retinol concentrations were low (<1.05 micromol/l) in 41% of boys and 45% of girls. The interventions did not increase haemoglobin concentrations. Serum retinol concentration of boys, but not girls, in the VA group increased (0.33 vs 0.07 micromol/l in controls; P<0.01). The risk factors for low serum retinol concentration were lower baseline serum retinol concentration (OR 0.02-0.03) with, for girls, nightblindness at baseline (OR 5.88), and for boys, not receiving vitamin A (OR control: 1.00; VA: 0.37; Fe: 0.77; VAFe: 0.34) and maternal illiteracy (OR mother never attended school 1.00, mother received any formal education 0.17-0.33). CONCLUSIONS: Supplementation with vitamin A increased serum retinol concentration of boys. Iron supplementation did not change Hb. This appeared to be due to poor compliance, and partly related to side effects.     

Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants

Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), and indicators of micronutrient status were analyzed in 418 infants who completed a 6-mo randomized, double-blind, placebo-controlled, supplementation trial with iron, zinc and/or beta-carotene. The acute phase response, defined by raised CRP (plasma concentration >10 mg/L), raised AGP (>1.2 g/L), or both raised CRP and AGP, significantly affected indicators of iron, vitamin A and zinc status, independently of the effects of supplementation. Plasma ferritin concentrations were higher by 15.7 (raised AGP) to 21.2 (raised CRP and AGP) micro g/L in infants with elevated acute phase proteins compared with infants without acute phase response (P < 0.001). In contrast, plasma concentrations of retinol were lower by 0.07 (P < 0.05, raised AGP) to 0.12 (P < 0.01, raised CRP) micro mol/L, and of zinc lower by 1.49 (P < 0.01, raised AGP) to 1.89 (P < 0.05, raised CRP and AGP) micro mol/L. Hemoglobin concentrations and the modified relative dose response were not affected. Consequently, the prevalence of iron deficiency anemia was underestimated in infants with raised acute phase proteins by >15%, whereas the prevalence of vitamin A deficiency was overestimated by >16% compared with infants without acute phase response. Hence, using indicators of micronutrient status without considering the effects of the acute phase response results in a distorted estimate of micronutrient deficiencies, whose extent depends on the prevalence of infection in the population.