Search

Author(s): Wessells, K Ryan; Arnold, Charles D; Stewart, Christine P; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Becquey, Elodie; Brown, Kenneth H; Byrd, Kendra A; Campbell, Rebecca K; Christian, Parul; Fernald, Lia CH; Fan, Yue-Mei; Galasso, Emanuela; Hess, Sonja Y; Huybregts, Lieven; Jorgensen, Josh M; Kiprotich, Marion; Kortekangas, Emma; Lartey, Anna; Le Port, Agnes; Leroy, Jef L; Lin, Audrie; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Mutasa, Kuda; Naser, Abu Mohd; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Rahman, Mahbubur; Schulze, Kerry; Smith, Laura E; Weber, Ann M; Zongrone, Amanda; Dewey, Kathryn G | Abstract: ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsProvision of SQ-LNS decreased the prevalence of anemia (Hb l 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin l 12 µg/L) by 56% and iron deficiency anemia (IDA; Hb l 110 g/L and plasma ferritin l 12 µg/L) by 64%. We observed positive effects of SQ-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for g 12 months and provided 9 mg/d vs. l 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma RBP and a 56% reduction in vitamin A deficiency (RBP l 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Author(s): Byrd, Kendra A; Williams, Thomas N; Lin, Audrie; Pickering, Amy J; Arnold, Benjamin F; Arnold, Charles D; Kiprotich, Marion; Dentz, Holly N; Njenga, Sammy M; Rao, Gouthami; Colford, John M; Null, Clair; Stewart, Christine P | Abstract: BackgroundThe relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized.ObjectiveWe investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya.MethodsWe quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype.ResultsIn this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (Pnln0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (βn=n0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (βn=n0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [βn=n0.94 (95% CI: 0.68, 1.20) and βn=n0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (βn=n0.45; 95% CI: -0.10, 1.00).ConclusionHepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.