Is Iron Deficiency the Cause of Anemia Among Women in Cambodia?

Summary

Globally, the most common cause of anemia is thought to be iron deficiency anemia (IDA). This was assumed to be the major cause of anemia in Cambodia, because Cambodian diets, which consist mainly of rice, lack iron-rich animal food sources. However, our findings from a previous study in Cambodia (a Canadian government funded study investigating multiple interventions to improve food and nutrition security) showed that IDA is almost non-existent and challenges this assumption. In a cross-sectional survey of 450 women from rural Cambodia, only 1.0% had Hb and ferritin levels indicative of IDA (Hb \<120 g/L and ferritin \<15 μg/L). A national survey conducted by UNICEF in 2014 found similarly low rates of IDA (Dr. Arnaud Laillou, UNICEF Cambodia). Further, other micronutrients known to be associated with anemia were also low (\<3%) including folate and vitamins B12 and B6.

In addition, 54% of the Prey Veng women had a genetic Hb disorder (e.g., α-thalassemias), which are inherited diseases that can result in a defective Hb structure and/or impair Hb production, either of which can reduce Hb concentration and increase the risk of anemia. Further, genetic Hb disorders cause ferritin and soluble transferrin receptor (sTfR) concentrations to increase, which reduce the diagnostic sensitivity of these biomarkers to identify IDA.

In 2011, the Cambodian Ministry of Health (MOH) recommended weekly iron and folic acid (IFA) supplementation for all women of reproductive age, consistent with WHO guidelines. However, if iron deficiency is not a major cause of anemia, then at best supplementation is a waste of valuable resources and at worst could cause harm. Further, the justification for provision of multiple micronutrients among this population has not yet been proven, despite the push from some organizations such as the WHO. There is an urgent need to conduct a trial to clarify whether iron or other micronutrient deficiencies are a major cause of anemia in Cambodia.

Research Objectives:

1. To compare Hb concentration (g/L) after 12-weeks of supplementation in women to determine if iron significantly improves Hb concentration, compared to a placebo;
2. To compare Hb concentration (g/L) across the four groups (multiple micronutrients with iron, multiple micronutrients without iron, iron alone, and placebo) after 12-weeks; and
3. To determine which of the hematological indicators (ferritin, sTfR, reticulocyte count and hepcidin) have the strongest diagnostic ability to predict responsiveness to iron therapy after 12-weeks using receiver operating characteristic (ROC) analyses.

Methods: A 2 x 2 factorial randomized controlled trial will be conducted over 12 weeks. A total of \~800 women (18-45 y) with mild or moderate anemia will be recruited and randomized to 1 of 4 groups: multiple micronutrients with iron, multiple micronutrients without iron, iron alone or placebo. Blood will be collected at baseline and at 1 and 12 weeks after the intervention and assessed for Hb, hematological biomarkers, inflammation and genetic Hb disorders. The investigators will use a general linear model to measure differences in Hb concentration across the four groups after the intervention. Receiver operating characteristic curves will be used to determine the diagnostic ability of the multiple hematological indicators to predict responsiveness to iron therapy.

Conditions

• Anemia
• Iron Deficiency
• Hemoglobin Disorder
• Infection
• Inflammation

Interventions

DIETARY_SUPPLEMENT

Multiple micronutrients

12-wk supplementation of vitamin A, B1, B2, B6 ,B12, D, E, niacin, folic acid, zinc, copper, selenium, iodine

DIETARY_SUPPLEMENT

Iron

12-wk supplementation of iron

DIETARY_SUPPLEMENT

Placebo

12-wk supplementation of placebo

Sponsors & Collaborators

• Micronutrient Initiative

  collaborator OTHER

• DSM Nutritional Products, Inc.

  collaborator INDUSTRY

• International Development Research Centre, Canada

  collaborator OTHER_GOV

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Helen Keller International

  collaborator OTHER

• University of British Columbia

  lead OTHER

Principal Investigators

• Kroeun Hou, MPH · Helen Keller International, Cambodia

• Sophonneary Prak, MPH · National Maternal and Child Health Center, Ministry of Health, Cambodia

• Crystal Karakochuk, MSc, PhD(c) · University of British Columbia

• Tim Green, PhD · University of British Columbia

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-07-31

Primary Completion

2016-01-31

Completion

2016-01-31

Countries

• Cambodia

Study Locations