Multiple micronutrient supplementation in Tanzanian infants born to HIV-infected mothers: a randomized, double-blind, placebo-controlled clinical trial
ABSTRACT BACKGROUND: Multiple micronutrients (vitamin B complex and vitamins C and E) were effective at reducing infectious disease morbidity, HIV disease progression, and poor pregnancy outcomes in HIV-infected women. OBJECTIVE: The objective was to evaluate whether direct supplementation of these micronutrients to HIV-exposed infants reduces mortality and morbidity. DESIGN: Infants born to HIV-infected women from Dar es Salaam, Tanzania, were randomly assigned to receive daily oral supplementation of multiple multivitamins (vitamin B complex and vitamins C and E) or placebo from age 6 wk for 24 mo. All-cause mortality, hospitalizations, and unscheduled clinic visits were recorded. Morbidities were recorded during monthly follow-up visits. All mothers received multiple micronutrients throughout the study. RESULTS: A total of 1193 infants were randomly assigned to receive micronutrients and 1194 to receive placebo. There were 138 child deaths in the multivitamin group and 124 deaths in the placebo group (HR: 1.13; 95% CI: 0.88, 1.44; P = 0.33). Hospitalizations (RR: 0.83; 95% CI: 0.62, 1.13; P = 0.23), unscheduled clinic visits (RR: 0.97; 95% CI: 0.85, 1.10; P = 0.59), and maternal reports of diarrhea (RR: 0.97; 0.87, 1.10; P = 0.64) were not significantly different between the 2 groups. Fever (P = 0.02) and vomiting (P = 0.007) were significantly lower in the multivitamin group. Among 429 children whose mothers received antiretroviral (ARV) therapy, multivitamin use had no effect on mortality but was associated with a significant reduction in hospitalizations (P = 0.035), episodes of fever (P = 0.005), and episodes of fever and cough (P = 0.019). CONCLUSIONS: In the setting of maternal micronutrient supplementation, supplementation of HIV-exposed infants with vitamin B and vitamins C and E does not reduce mortality. Studies of nutrition supplementation in ARV-exposed infants may be warranted. This trial was registered at clinicaltrials.gov as NCT00197730.
- [Show abstract] [Hide abstract]
ABSTRACT: Vitamin D is a potent immunomodulator, but its impact on morbidity and mortality among infants remains unclear. The objective of the study was to prospectively assess the association of vitamin D status with mortality, morbidity, and growth during the first 2 y of life. A prospective cohort of 253 HIV-infected and 948 HIV-exposed Tanzanian infants enrolled in a randomized trial of multivitamins (not including vitamin D) was studied. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 5-7 wk of age and infants were followed at monthly clinic visits until 24 mo. Physicians performed a clinical exam every 3 mo or when an illness was noted. Serum 25(OH)D concentrations were (means ± SDs) 18.6 ± 10.3 ng/mL and 18.1 ± 9.2 ng/mL for HIV-infected and HIV-exposed infants, respectively. Unexpectedly, serum 25(OH)D concentrations ≥30 ng/mL were significantly associated with higher mortality as compared to the 20-29.9 ng/mL reference for HIV-infected (HR: 2.47; 95% CI: 1.13, 5.44; P = 0.02) and HIV-exposed (HR: 4.00; 95% CI: 1.67, 9.58; P < 0.01) infants after multivariate adjustment. We found no statistically significant association between 25(OH)D concentrations <10 ng/mL and mortality for HIV-infected (HR: 1.43; 95% CI: 0.74, 2.78; P = 0.29) and HIV-exposed (HR: 1.56; 95% CI: 0.60, 4.03; P = 0.36) infants. Among HIV-exposed infants, 25(OH)D concentrations ≥30 ng/mL were significantly associated with clinical [incidence ratio rate (IRR): 1.34; 95% CI: 1.06,1.70; P = 0.02] and confirmed (IRR: 1.71; 95% CI: 1.71; 1.15, 2.54; P < 0.01) malaria diagnoses, whereas concentrations of <10 ng/mL were associated with oral candidiasis (IRR: 1.47; 95% CI: 1.00-2.15; P = 0.046) and wasting (HR: 1.71; 95% CI: 1.20, 2.43; P < 0.01). The observational design of this study does not allow for causal interpretation; however, the results indicate a strong need for additional studies of vitamin D among HIV-infected and -exposed children, particularly in malaria-endemic settings. The parent trial was registered at clinicaltrials.gov as NCT00197730. © 2015 American Society for Nutrition.Journal of Nutrition 01/2015; 145(1):121-7. DOI:10.3945/jn.114.201566 · 4.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Folic acid and iron supplementation has historically been recommended as the preferred anaemia control strategy among preschoolers in sub-Saharan Africa and other resource-poor settings, but home fortification of complementary foods with multiple micronutrient powders (MNPs) can now be considered the preferred approach. The World Health Organization endorses home fortification with MNPs containing at least iron, vitamin A and zinc to control childhood anaemia, and calls for concomitant malaria control strategies in malaria endemic regions. Among other micronutrients, current MNP formulations generally include 88 μg folic acid (corresponding to 100% of the Recommended Nutrient Intake). The risks and benefits of providing supplemental folic acid at these levels are unclear. The limited data available indicate that folate deficiency may not be a major public health problem among children living in sub-Saharan Africa and supplemental folic acid may therefore not have any benefits. Furthermore, supraphysiological, and possibly even physiological, folic acid dosages may favour Plasmodium falciparum growth, inhibit parasite clearance of sulphadoxine-pyrimethamine (SP)-treated malaria and increase subsequent recrudescence. Even though programmatic options to limit prophylactic SP use or to promote the use of insecticide treated bed nets may render the use of folic acid safer, programmatic barriers to these approaches are likely to persist. Research is needed to characterise the prevalence of folate deficiency among young children worldwide and to design safe MNP and other types of fortification approaches in sub-Sahara Africa. In parallel, updated global guidance is needed for MNP programmes in these regions.Maternal and Child Nutrition 11/2013; DOI:10.1111/mcn.12102 · 2.97 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The 2010 Dietary Guidelines Advisory Committee was charged with the task of investigating the effects of multivitamin/mineral supplements on healthy populations and also on those with chronic disease. The evidence from which the committee prepared its conclusions was graded on 5 fundamental criteria: quality, consistency, quantity, clinical impact, and generalizability. The committee concluded that for the general healthy population, evidence was insufficient to make a multivitamin/mineral recommendation. On the other hand, the committee noted the value of some supplemental nutrients for at-risk populations such as iron, folic acid, and vitamin B-12. However, most of the studies referenced for the research used the conventional, all-encompassing, and oversimplified definition of a multivitamin/mineral as being a supplement containing 3 or more vitamins with or without minerals. In the few years since the committee released its 2010 report, several randomized clinical trials showing the benefits of daily multivitamin/mineral supplementation have been completed using supplements containing at least 10 or more vitamins and/or minerals, but there also continues to be some reports that do not find benefit from such supplements. Furthermore, several steps have been taken to advance the science behind these supplements so that consumers, physicians, and government agencies can all have more confidence in understanding the role of supplemental nutrition in the American diet. This review provides new evidence from 2010 onward addressing the committee's primary concerns about multivitamin/mineral research in regard to improving public health. It also includes several recent studies that may be of interest to future committees indicating the potential benefits of these supplements on improving the cognitive performance and mental well-being of healthy populations.Advances in Nutrition 11/2013; 4(6):644-656. DOI:10.3945/an.113.004523 · 4.90 Impact Factor