The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial

Abstract

Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic. In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction ( = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) ( < 0.001) among women who received iron ( = 407) and 1.2 g/L (-0.6, 3.0 g/L) ( = 0.18) among women who received MMNs ( = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively. Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375.

Effect of enhanced homestead food production on anaemia among Cambodian women and children: A cluster randomized controlled trial

“…In the 2014 Cambodia DHS, only 3% of WRA from a nationally representative sample were found to be iron deficient based on inflammation‐adjusted serum ferritin (<15 μg/L), <1% were vitamin A deficient, and approximately 60% of women were found to have a genetic Hb disorder (National Institute of Statistics et al, ; Wieringa et al, ). A subsequent study conducted in Kampong Chhnang province screened 2,846 WRA age for anaemia, of whom 809 were screened as anaemic and enrolled in an iron supplementation trial (Karakochuk et al, ). At baseline, only 19% and 22% of women were iron deficient anaemic, based on inflammation‐adjusted ferritin and sTfR, respectively (Karakochuk et al, ).…”

“…A subsequent study conducted in Kampong Chhnang province screened 2,846 WRA age for anaemia, of whom 809 were screened as anaemic and enrolled in an iron supplementation trial (Karakochuk et al, ). At baseline, only 19% and 22% of women were iron deficient anaemic, based on inflammation‐adjusted ferritin and sTfR, respectively (Karakochuk et al, ). Given the low prevalence of iron and other micronutrient deficiencies associated with anaemia in women and the high prevalence of genetic Hb disorders, we speculate that a nutrition‐sensitive agriculture‐based programme would not be an effective intervention for maternal anaemia reduction in this population.…”

Impact of lunch provision on anthropometry, hemoglobin, and micronutrient status of female Cambodian garment workers: exploratory randomized controlled trial

“…In a recent one-year randomized controlled trial, neither iron ingots added to cooking pots nor daily iron supplements (18 mg/ d) increased Hb concentration in anemic Cambodian women [58]. In comparison, daily high-dose iron supplementation (60 mg/d) for 12 weeks increased Hb in a female study population in Cambodia, while added multiple micronutrients did not confer additional benefits [56].…”

“…In addition, genetic disorders, e.g. Hb E variants and α-thalassemia, are reported to affect > 50% of the Cambodian population, causing lower Hb concentrations regardless of iron stores [16,[54][55][56][57]. In a recent one-year randomized controlled trial, neither iron ingots added to cooking pots nor daily iron supplements (18 mg/ d) increased Hb concentration in anemic Cambodian women [58].…”

Dietary Factors Modulate Iron Uptake in Caco-2 Cells from an Iron Ingot Used as a Home Fortificant to Prevent Iron Deficiency

“…For example, the daily use of micronutrient powders for four months as an in-home fortification strategy has been associated with changes in the gut microbiome profile of weaning infants and an increased abundance of enteropathogens bacteria, which in turn was associated with inflammation [ 26 ]. Likewise, the use of home-fortification strategies should be very tightly controlled in anemic populations where genetic hemoglobin disorders (i.e., mild thalassemia) or inflammation, rather than dietary iron deficiency, are the main causes of anemia, as in such cases it could lead to iron overload [ 27 , 28 , 29 ].…”