Effectiveness of a large-scale iron fortified milk distribution program on anemia and iron

deficiency in low-income young children in Mexico

Juan A Rivera, Teresa Shamah, Salvador Villalpando, and Eric Monterrubio

American Journal of Clinical Nutrition 2010; 91: 431-439

OverviewBackground InfoPreliminary StudyFeatured StudySupporting follow up study

Wardlaw, F.M., & Hampl J. S. Iron (Fe). In: Perspectives in Nutrition. 7th ed.

Iron (Fe) Found in every body cell (total 5g)

◦ Increased with dietary intake Heme (40% absorption) Non-heme (2-10% absorption)

◦ Increased with Intestinal absorption

◦ Decreased with sloughing of intestinal cells, blood loss

Wardlaw, G.M., & Hampl J.S. Iron (Fe). In: Perspectives in Nutrition. 7th ed.

Hemoglobin & Myoglobin◦ O2 carrying capacity

Immune function Cognitive development Temp regulation Energy metabolism Work performance

Functions of Iron

Centers for Disease Control

Adult ◦ Women 18 mg/day◦ Men: 8 mg/day

Adolescents◦ Girls: 15 mg/ day◦ Boys: 11 mg/day

Children ◦ 7-10 mg/day

Infants ◦ 11 mg/day

◦ 12 mg/day◦ 17mg/day

RDA’s Average Intake

Centers for Disease Control

Increased Iron Needs Decreased Iron Intake and Absorption

•Rapid growth•Pregnancy•Blood loss

• Heavy menstrual periods

• Frequent blood donation• Some stomach and

intestinal conditions (food sensitivity, hookworms)

•Lack of heme iron sources in the diet (e.g., vegetarian diets) •Low absorption

• Taking antacids beyond the recommended dose or medicine used to treat peptic ulcer disease and acid reflux can reduce the amount of iron absorbed in the stomach.

Increased Iron NeedsPremature Babies Miss the most important final weeks to build Fe

storesInfants Born with Fe stores only last for about 6 moChildren and Adolescence Rapid growth Picky eatersWomen MenstruationPregnancy Increased blood volume and needs Blood loss

Centers for Disease Control

Fe Status Indicators Hb Concentration and Hematocrit

◦ Cheap and easy◦ Used for screening for deficiency◦ Measures amount of functional Fe

Serum Ferritin Concentration◦ Closely related to amount of stored Fe in body◦ More expensive◦ Earliest indicator for depleted Fe stores

Transferrin Saturation◦ Measures vacant Fe binding site◦ Changes with infection, age, and time of day

Am J Clin Nutr. 2010; 91(2) 431-439

Fe Deficiency Most common nutritional deficiency around

the world.

Children under age 5 are one of the most affected age groups◦ Peak prevalence occurs at age 12-23 mo

Affects all socioeconomic status◦ 30% in lowest group◦ 17% in highest

Am J Clin Nutr 2010; 91:431-9

What does this mean?“Anemia and Iron Deficiency

is associated with adverse effects on

neurodevelopment”

Am J of Clin Nutr. 1982; 36 (6) 1162-1169

Bioavailability of iron- and copper supplemented milk for Mexican school children

Experimented with ways to fortify milk with trace minerals

Had to use components that didn’t catalyze off-flavors, peroxidize the lipids, and yet still had good bioavailability Ferrous/ cupric chloride salt Ferric/ cupric Lactobionate chelate

Results: Both showed significant increase in Hb Suggested Milk could be used as a vehicle for Fe or

Cu Supplementation At the time of this study, there were no public

health supplementation programs yet in Mexico

Am J of Clin Nutri. 2010; 91 (2) 431-439.

Milk Subsidized Program“Liconsa” Started in 1944 Distributes whole milk at centers through

out the country Children aged 1-11 years old

◦ 400 mL of milk/ day Other family members living in poverty 2002- started fortifying milk

Am J of Clin Nutr. 2010; 91 (2) 431-439

1999 National Nutrition Survey Found that deficiencies were common o Feo vit Co others

At the time of the study served 5 mil peopleo 4.2 mil aged 1-11 year oldso 650, 000 aged 1 – 2 ½ years

Mexican government decided to provide these nutrients in combination with the whole milk

Am J of Clin Nutr. 2010; 91 (2) 431-439

Effective?1st Step Completed a Randomized Clinical

Trial Results: Fortifying Milk was

effected in improving the Fe status of Toddlers

Am J Clin Nutr. 2010; 91 (2) 431-439

Rationale

Did this apply through a Large-Scale Program?

And does improved Fe Status reduce anemia prevalence?

Am J Clin Nutr. 2010; 91 (2) 431-439.

Design & Subjects

Group-Randomized effectiveness trial in children aged 12-30 months

Participants of the Liconsa Program Selected 12 Milk Distribution

Centers Randomly Assigned:

5 Non-Fortified Milk 7 Fortified Milk

Am J Clin Nutr. 2010; 91 (2) 431-439.

Milk Contents

Distinguished by a ‘color band’ on the package Unknown to researchers,

fieldworkers, personnel and program beneficiaries

Mothers received same instructions to reconstitute

Encouraged to feed 200 ml 2x/day

Am J Clin Nutr. 2010; 91(2) 431-439

Am J Clin Nutr. 2010; 91 (2) 431-439

Collection Methods Weren’t able to get adequate blood

samples for 1/3 of the participants like they had hoped.

Primary Indicators Fe Deficiency- sTfR Primary Indicator for Anemia-Hb

concentration

Am J Clin Nutr. 2010; 91 (2) 431-439.

Definitions

Fe Deficiency: sTfR >3.3 mg/ L

Anemia: Hb <110 g/L

Mild anemia: Hb 100-109.0 g/L

Moderate anemia: Hb 90-99.9 g/L

Am J Clin Nutr. 2010; 91 (2) 431-439.

Data Collection: Baseline, 6mo, 12mo Questionnaire: housing

characteristics, and possession of household goods

Hb concentration C-Reactive Protein Anthropometric Data

Length/ Height and weight

Am J Clin Nutr. 2010; 91 (2) 431-439.

Data Collection: Monthly

Field worker visited home to ensure compliance

Obtained a food frequency questionnaire

Am J Clin Nutr. 2010; 91(2) 431-439.

Statistical Methods Compared the socioeconomic status of

families at baseline between two intervention groups

Adjusted for cluster effects If something was not normally

distributed Looked at Intervention effects for the 6

and 12 mo age groups Plausible confounders: sex, ages,

socioeconomic status, parent’s schooling, daily milk intake, frequency of respiratory and diarrheal infections.

Am J Clin Nutr. 2010; 91 (2) 431-439.

Results

No statistically significant differences between two baseline groups for: Anemia Fe deficiency Milk intake Anthropometric data Socioeconomic status

Am J Clin Nutr. 2010; 91 (2) 431-439.

Results: Effect on Anemia

Lower prevalence and Larger decline in Fortified Milk group

Am J Clin Nutr. 2010; 91 (2) 431-439.

Am J Clin Nutr. 2010; 91 (2) 431-439.

Effect on Iron Status

Fortified Milk group had a statistically significant decline in Iron Deficiency prevalence

Differences between 6 and 12 month measurements for both groups were not statistically significant

Am J Clin Nutr. 2010; 91 (2) 431-439.

Am J Clin Nutr. 2010; 91 (2) 431-439.

Discussion Determined results “biologically

important” “at these early ages, iron repletion's process

and hematopoiesis during a critical time for brain and mental development, which may have long lasting effects on behavior, learning and mental performance”

Decreases mild-moderate anemia by 36% at 6 mo 57% at 12 mo

Reduced indicators of Fe deficiency

Am J Clin Nutr. 2010; 91 (2) 431-439.

Discussion

Used the distribution centers already in place Could have seen a “floor effect”

Am J Clin Nutr. 2010; 91 (2) 431-439.

Limitations Selection bias through changing

indicators once study began Results from iron deficiency should

be interpreted with caution Different subjects in Fortified and Non-

Fortified groups Limited data was published

Am Academy of Pediactrics. 2001; 107(6)1381-1386.

Iron Deficiency and Cognitive Achievement in School- Aged Children and Adolescents in the United States

National Health and Nutrition Examination Survey Cross sectional survey for children 6-16 year

old (n= 5398) Determined Iron Deficiency and Anemia

using serum ferritin and Hb Compared the Fe status to their

standardized test scores

Results

Used Logistic regression to control for Below average scores Other confounding factors

Found: Lower Math scores were associated

with lower than normal Fe status Elevated Risk for lower scores, even

if only Fe deficient

Am Academy of Pediatrics. 2001; 107 (6) 1381-1386.

As working professionals……

Emphasize the importance of Fe at all ages, but especially those with rapid growth Heme vs. Non-Heme

Finding the populations that are known to be at risk for deficiency is important Screen & Intervene

Resources Center for Disease Control. (1998). Morbidity and Mortality Weekly

Report: Recommendations to Prevent and Control Iron Deficiency in the United States. (Vol 47 No RR-3) Atlanta, GA.

Halterman, J. S. et al. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Journal of the American Academy of Pediatrics. 2001; 107 (6) 1381-1386.

Mayo Clinic. Iron Deficiency Anemia. [Accessed 9/1/05] Available from: http://www.mayoclinic.com/health/iron-deficiency-anemia/ds00323.

Rivera, J.A. et al. Effectiveness of a large-scale iron-fortified milk distribution program on anemia and iron deficiency in low income young children in Mexico. Am J Clin Nutr. 2010; 91(2) 431-439.

Wardlaw, G. M., & Hampl J. S. Iron (Fe). In: Perspectives in Nutrition. 7th ed. New York, New York, McGraw Hill. 2007, 428-434.

Rivera, R. et al. Bioavailability of iron- and copper- supplemented milk for Mexican school children. Am J Clin Nutri. 1982; 36 (6). 1162-1169.