Hemoglobin Response to 12 Weeks of Iron Supplementation is Substantially Lower among Non‐Pregnant Cambodian Women with Genetic Hemoglobin Disorders
Authors: Karakochuk Crystal D , Barker Mikaela K , Barr Susan I , Vercauteren Suzanne M , Devlin Angela M , Whitfield Kyly C , Hou Kroeun , Harding Kim B , De Regil Luz M , Kraemer Klaus , Green Tim J 
Published: November 2023

ObjectiveWe measured the effect of 12 wk of oral iron (Fe) with or without multiple micronutrients (MMN) on hemoglobin (Hb) response (Hb increase of ≥10 g/L) among Cambodian women of reproductive age screened as anemic.MethodsIn this 2×2 factorial double‐blind randomized controlled supplementation trial, 2,846 non‐pregnant women (18–45 y) were convenience sampled from 26 rural villages in Kampong Chhnang province, Cambodia. Those (n=809) with Hb ≤117 g/L (capillary blood, HemoCue® 301) were randomized to 12 wk of daily oral Fe (60 mg elemental), MMN (14 nutrients excluding Fe), Fe+MMN, or placebo capsules.ResultsBaseline anemia prevalence (Hb <120 g/L) was 58% (n=468/808) based on a Sysmex hematology analyzer (venous blood collected 1 wk post HemoCue® screening). Baseline iron deficiency was 25% and 22% based on serum soluble transferrin receptor (>8.3 mg/L) and inflammation‐adjusted ferritin (<15 μg/L), respectively. Overall, 74% of women (n=596/808) had a genetic Hb disorder (primarily, Hb E variants and α‐thalassemia). Of all women who received Fe (with or without MMN), 25% (n=95/383) responded with an Hb increase ≥10 g/L at 12 wk; among women confirmed anemic using the Sysmex analyzer, 37% (n=85/232) responded. Among women with depleted iron stores at baseline (ferritin <15 μg/L) who received Fe (with or without MMN), 67% (n=57/85) had an Hb response ≥10 g/L at 12 wk. The proportion of women with an Hb increase ≥10 g/L at 12 wk was substantially lower among women with a genetic Hb disorder who received Fe (with or without MMN) (18%, n=53/287), as compared to women with no Hb disorder who received Fe (with or without MMN) (44%, n=42/96). There were no significant differences in the proportions of Hb responders and non‐responders in the MMN and placebo groups, by baseline iron status (iron‐depleted or replete) or by the presence/absence of a genetic Hb disorder.ConclusionThe proportion of anemia amenable to iron supplementation among our surveyed population of women (~37%) is at the low end of the 95% CI of the estimate for Southeast Asia (45% [95% CI: 35%, 53%]) as reported in the 2011 WHO Global Prevalence of Anemia Report. The proportion of Hb responders among women with a genetic Hb disorder was substantially lower than among women without an Hb disorder (less than half; 18% vs. 44%, respectively), demonstrating that women with an Hb disorder were much less likely to derive benefit from Fe supplementation. We conclude that it is crucial to understand the multifactorial causes of anemia in each country‐specific setting or population (e.g., the prevalence of Hb disorders) in order to design and implement effective anemia reduction strategies and programs.Support or Funding InformationFunding was provided by the Micronutrient Initiative, Sight and Life, and the Canadian Institutes of Health Research (CIHR). C.D.K. received a CIHR Vanier Scholarship, a CIHR Michael Smith Foreign Study Supplement, and a Doctoral Research Award from the International Development Research Centre.