Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children’s physical growth and risk of infection: study design and rationale for a randomized controlled trial

Abstract

Background: Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10-14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea.Methods: The present study is a community-based, randomized controlled trial in the Lao People's Democratic Republic (PDR). Three thousand, four hundred children 6-23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA.

Hemoglobins F, A2, and E levels in Laotian children aged 6‐23 months with Hb E disorders: Effect of age, sex, and thalassemia types

“…The study procedures are described in detail elsewhere. 13 Briefly, children were considered eligible if they were 6-23 months of age, and their families accepted weekly home visits, planned to remain within the study area for the duration of the study and signed the informed consent document. Children were ineligible if they met one of the following criteria: severe anemia (Hb < 70 g/L), weight-for-length z-score <−3 standard deviation, 14 This add-on study was approved by the Ethics Committees of Khon Kaen University (HE592006).…”

Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial

“…The overall study design, data collection methods, and effect of the intervention on primary outcomes have been reported in detail elsewhere. 27,28 In brief, the study was conducted among 3,407 infants in rural villages of Khammouane Province, central Lao PDR, from September 2015 to April 2017. Children were eligible to participate in the study if they were 6-23 months of age at enrollment, and their family planned to reside in the study catchment area for the duration of the study and was willing to accept weekly home visits.…”

“…7,21,30 The biochemistry subgroup of the parent trial (n = 140 per group) was a convenience sample based on logistical feasibility (i.e., all children enrolled from September to December 2015 in the two health districts closest to the study office were included in the subgroup until the sample size was met because of daily requirements for transportation of blood samples to Thailand). 27 Samples for the present analyses were randomly selected from this subgroup, provided they met the following criteria: plasma samples available from baseline and endline collections and data available for C-reactive protein (CRP), α-1-acid glycoprotein (AGP), and hair cortisol concentrations. Fecal markers of intestinal inflammation (myeloperoxidase, neopterin, and calprotectin) were assessed in a separate subsample of study participants, enrolled from February to August 2016 because of the timing and allocation of research funding, and are thus not included in the present analyses.…”

“…Fecal markers of intestinal inflammation (myeloperoxidase, neopterin, and calprotectin) were assessed in a separate subsample of study participants, enrolled from February to August 2016 because of the timing and allocation of research funding, and are thus not included in the present analyses. 27 Randomization and intervention products. Eligible study participants were individually randomized to one of four intervention groups and assigned to receive the following: 1) daily PZ supplement tablets, containing 7 mg zinc and placebo tablets for diarrhea (PZ group); 2) daily preventive MNP supplements, containing 10 mg zinc, 6 mg iron, and 13 other micronutrients, and placebo tablets for diarrhea (MNP group); 3) daily placebo preventive supplements and therapeutic zinc tablets, containing 20 mg zinc for 10 days for diarrhea treatment (TZ group); and 4) daily placebo preventive powder and placebo tablets for diarrhea (control group).…”

“…31 The tested MNP formulation contained a higher amount of zinc (10 mg zinc as zinc gluconate) and a lower amount of iron (6 mg iron as ferrous fumarate) than standard MNP formulations to address the concerns of a lack of impact on zinc status and zinc-related functional outcomes and potential adverse effects of MNP containing higher doses of iron on diarrhea. 27 In addition, the MNP contained 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg thiamin, 0.5 mg riboflavin, 6 mg niacin, 0.5 mg vitamin B-6, 0.9 μg vitamin B-12, and 150 μg folic acid. The preventive and therapeutic zinc tablets, and the placebo tablets, were dispersible and produced by Nutriset SAS (Malaunay, France).…”