Zinc (Zn) supplementation adversely affects iron status in animal and adult human studies, but few trials have included young infants. The objective of this study was to determine the effects of Zn and multivitamin (MV) supplementation on infant hematologic and iron status.
In a double-blind RCT, Tanzanian infants were randomized to daily, oral Zn, MV, Zn and MV or placebo treatment arms at the age of 6 weeks of life. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12 and 18 months of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 months.
In logistic regression models, Zn treatment was associated with greater odds of ID (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.0–3.3)) and MV treatment was associated with lower odds (OR 0.49 (95% CI 0.3–0.9)). In Cox models, MV was associated with a 28% reduction in risk of severe anemia (hazard ratio (HR)=0.72 (95% CI 0.56–0.94)) and a 26% reduction in the risk of severe microcytic anemia (HR=0.74 (0.56–0.96)) through 18 months. No effects of Zn on risk of anemia were seen. Infants treated with MV alone had higher mean Hb (9.9 g/dl (95% CI 9.7–10.1)) than those given placebo (9.6 g/dl (9.4–9.8)) or Zn alone (9.6 g/dl (9.4–9.7)).
MV treatment improved iron status in infancy, whereas Zn worsened iron status but without an associated increase in risk for anemia. Infants in long-term Zn supplementation programs at risk for ID may benefit from screening and/or the addition of a MV supplement.
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Does zinc with and without iron co-supplementation have effect on motor and mental development of children? A systematic review and meta-analysis
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We are grateful to the field and study staff for their tireless efforts: Esther Kibona (deceased), Frank Killa, Michel Alexander, Phares Zawadi, Susie Welty, Rachel Steinfeld, Anne Marie Darling, James Okuma, Angela Jardin, Elizabeth Long, Jenna Golan and Emily Dantzer. The study was supported by NIH (R01 HD048969; K24DK104676; 2P30 DK040561; K23 AA 020516); Bill and Melinda Gates Foundation (OPP1066203).
All authors have read and approved the submitted version of this manuscript. RCC analyzed the data and wrote the manuscript; KM designed the study, supervised data collection and provided inputs to the manuscript; SA oversaw all laboratory aspects of the study and reviewed the manuscript; JGE performed iron status assays, assisted with results interpretation and reviewed the manuscript; KG assisted with study design, sample management and reviewed the manuscript; RK provided inputs to the study design, oversaw data collection and reviewed the manuscript; EL assisted with statistical analysis and reviewed the manuscript; WF designed the study, provided inputs to the statistical analysis and reviewed the manuscript; CMM oversaw data management, provided inputs to the statistical analysis and reviewed the manuscript; and CD designed the study, oversaw study implementation, contributed to the statistical analysis and provided inputs to the manuscript.
The opinions and statements in this article are those of the authors and may not reflect official UNICEF policies.
Juergen Erhardt is the owner of the company VitMin Lab (Willstaett, Germany), where some of the assays performed in this study were conducted. Roland Kupka is a UNICEF staff member. The remaining authors declare no conflict of interest.
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Carter, R., Kupka, R., Manji, K. et al. Zinc and multivitamin supplementation have contrasting effects on infant iron status: a randomized, double-blind, placebo-controlled clinical trial. Eur J Clin Nutr 72, 130–135 (2018). https://doi.org/10.1038/ejcn.2017.138