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will not resolve the problem of nutrient deficiencies

for the 624-month age group because young children

eat too little of the fortified staple foods to obtain an

adequate dose of each essential nutrient.

The most promising strategy for this age group is

home fortification of complementary foods (the

foods that are consumed in addition to breast milk,

after ~6 monthsof age).Homefortification (alsocalled

point-of-use fortification and complementary food

supplements) (Nestel et al. 2003) makes it possible to

provide the appropriate amounts of micronutrients

needed by each age subgroup (e.g. 612 months, 1224

months) regardless of how much food they eat and

without the need to make major changes in dietary

practices.Three approaches have been used for homefortification: powders (e.g. Sprinkles), crushable

tablets (e.g. foodlet) and lipid-based [e.g. Nutributter

(Nutriset, Malaunay, France)] or soy-based products.

For governmental and non-governmental organiza-

tions running nutrition programmes or for individual

families, purchasing small quantities of products

needed daily for home fortification is likely to be less

costly per recipient thanpurchasingfortified,commer-

cially processed complementary foods (which are

usually designed to provide a large proportion of the

childs energy needs). Thus, there is greater potential

to reach a large segment of the target population. It

should be noted, however, that in populations with

chronic household food insecurity or where there are

marked seasonal food shortages and high rates of

wasting,a supplement providing additional energy (in

addition to, or instead of,home fortification products)

may be needed during part,or all, of the year.

To date, Sprinkles have been evaluated the most

extensively, primarily as an intervention to treat and

prevent nutritional anaemia. Developed by Stanley

Zlotkin and his research group at the Hospital for

Sick Children in Toronto, Canada, Sprinkles are

single-dose sachets containing micronutrients in a

powdered form, to be sprinkled onto a portion of the

childs food just before it is consumed. The iron in

Sprinkles is ferrous fumarate, which is micro-

encapsulated to prevent the iron from interacting

with food. Other micronutrients, such as zinc, iodine,

copper, folic acid, and vitamins A, C and D, can be

added to the sachet. Crushable or chewable tablets,

such as the milk-based foodlet developed by the

United Nations Childrens Fund for use in the Inter-

national Research on Infant Supplementation (IRIS)

trials (Lock 2003), are multiple micronutrient tablets

that can be easily dissolved in a small amount of

liquid, or crushed and added to complementary foods.

Lipid-based nutrient supplements (LNS) are prod-ucts that provide some energy, predominantly from

fat, in addition to multiple micronutrients. LNS (like

micronutrient powders and tablets) do not contain

water and thus do not support microbial growth, so

they can be safely stored and used in the home even

under poor hygienic conditions (Nestel et al. 2003).

All powdered ingredients are embedded in fat, which

protects vitamins against oxidation and increases the

shelf life of the product. LNS usually have a pleasant

taste, allowing the unpleasant taste of certain micro-

nutrients (such as unencapsulated soluble minerals)

to be disguised. When mixed with complementary

foods, they increase the energy density as well as the

micronutrient content of the home diet. Lastly, soy-

based products for home fortification have been

developed for use in Vietnam (Bruyeron et al. 2007)

and China (Wang et al. 2006). These contain full-fat

soybean flour mixed with micronutrients. They

contain some fat from the soybeans, although not as

much as the LNS products.

The main objective of this review was to evaluate

the efficacy and effectiveness of home fortification of

complementary foods. Because iron and zinc are the

Key messages

Home fortification of complementary foods is highly effective for prevention of iron deficiency and iron-deficiency anaemia.

Products for home fortification of complementary foods that contain both micronutrients and a small amountof energy (mainly from fat and protein) have had positive effects on child growth and development.

Acceptability of home fortification by caregivers and young children is high.

K.G. Dewey etal.284

2009 Blackwell Publishing Ltd Maternal and Child Nutrition (2009), 5, pp. 283321


3/39

most problematic nutrients at this age (Dewey &

Brown 2003), to provide some background, we will

first discuss iron and zinc requirements, and the

amounts of these nutrients needed from complemen-

tary foods.We will then describe the methods for this

systematic review and meta-analysis, and the results

of efficacy and effectiveness trials using home fortifi-

cation with regard to micronutrient status, growth,

morbidity and child development.The remaining sec-

tions will address issues regarding acceptability, ease

of use, safety, cost issues regarding home fortification

programmes and research gaps.

Iron and zinc needs from

complementary foods

Because of the rapid rate of growth during infancy,

iron requirements at 612 months of age are very

high, with recommended intakes set at 9.3 mg day-1

(assuming 10% bioavailability) by the World Health

Organization (WHO) (WHO/FAO, 2004) and

11 mg day-1 by the U.S. Institute of Medicine (2001).

At 1224 months, iron requirements are lower than at

612 months, with the recommended intakes ranging

from 5.8 mg day-1 (WHO/FAO, 2004) to 7 mg day-1

(U.S. Institute of Medicine, 2001). The amount of

iron provided by breast milk is relatively low,

~0.2 mg day-1, which means that the net amount

needed from other sources is ~910 mg day-1 at 68

months and ~57 mg day-1 at 1224 months.Although

some full-term infants have sufficient iron stores at

birth to last until 89 months of age (if they are of

normal birthweight, born to iron-replete mothers and

received the placental transfer of blood via delayed

umbilical cord clamping), most term infants require

an external source of iron at about 6 months (or even

earlier, if they are at high risk of iron deficiency

because of maternal iron deficiency or intrauterinegrowth retardation) (Dewey & Chaparro 2007).

Because the amount of iron needed from comple-

mentary foods is high relative to theusual iron content

of such foods,iron is usually the most limiting nutrient

at this age (Gibson et al. 1998; WHO 1998; Dewey &

Brown 2003). In Bangladesh, for example, iron intake

from complementary foods averaged 0.5 mg day-1 at

68 months and 0.7 mg day-1 at 912 months of age

(Kimmons et al. 2005). After adding the amount pro-

vided by breast milk (0.2 mg day-1), total iron intake

(0.70.9 mg day-1) was only 89% of the amount rec-

ommended by the WHO (9.3 mg day-1). In Malawi,

average iron intake from complementary foods was

1.2 mg day-1 at 68 months, 2.8 mg day-1 at 911

months and 3.5 mg day-1 at 1223 months (Hotz &

Gibson 2001). The estimated bioavailability of iron

was low for all age groups (5.57.4%), with the result

that the percentage of estimated iron needs provided

by complementary foods was only 6% at 68 months,

13% at 911 months and 30% at 1223 months. Only

04% of iron came from meat, poultry or fish. In a

dietary survey of infants 612 months of age in a rural

area in South Africa, 31% consumed iron-fortifiedinfant cereals on the day of the dietary recall, yet

average iron intake was only 2.9 mg day-1 (Faber

2005). Even among those infants who consumed iron-

fortified cereal,average iron intake (5.3 mg day-1) still

fell far short of the recommended intakes because of a

relativelysmallportion size (20 g day-1 drycereal) and

low level of fortification (15 mg Fe per 100 g dry

product). Thus, in most populations in developing

countries, there is a substantial gap between iron

intake and iron requirements.

The recommended intake of zinc is 4.1 mg day-1 at

724 months of age (assuming moderate bioavailabil-

ity) (WHO/FAO, 2004). As is the case for iron, the

amount of zinc provided by breast milk is relatively

low (0.40.6 mg day-1), with the remainder (3.5

3.7 mg day-1) needed from other sources. Thus, the

risk of inadequate dietary intake of zinc is primarily

related to the zinc content of the complementary

foods and the absorption of zinc from these foods.

Animal source foods are rich sources of highly bio-

available zinc. However, these foods are usually

expensive and therefore less accessible to low-income

populations, and are not consumed in vegetarianpopulations. As a result, they are seldom provided to

infants and young children in developing countries in

amounts large enough to meet zinc needs,particularly

from 6 to 12 months of age.Whole grains and legumes

have moderate to high zinc content, but also contain

large quantities of phytate, which forms non-

absorbable complexes with dietary zinc, reducing the

amount of the mineral that is available for intestinal

Home fortification of complementary foods 285



4/39

absorption. Thus, populations with a heavy dietary

reliance on unrefined plant foods, complemented with

only small amounts of zinc-rich animal source foods,

will have lower intakes of bioavailable zinc. This

dietary pattern, coupled with the high zinc require-

ments during early life, places large proportions of

infants and young children in developing countries at

risk of zinc deficiency.

Methods for systematic reviewand meta-analysis

Sources searched and search strategy

The search for relevant publications was performedvia Pubmed with specific key words on 19 July 2007,

and updated on 10 November 2007. All titles and

abstracts were assessed for their relevance to home

fortification. Four separate searches were carried out,

using the key words Sprinkles, foodlets, spreads

AND nutrition AND (children OR infant) (to

capture studies using lipid-based products for home

fortification) and home fortification. Papers written

in English or Chinese were reviewed (based on the

language ability of the reviewers). Two independent

reviewers (K. Dewey and Z. Yang) extracted refer-

ences from the search results based on the following

criteria: (1) randomized clinical trials and programme

evaluations were included to assess both efficacy and

effectiveness; (2) studies were excluded if the fortified

product was used without food (e.g. some of the

foodlet trials). There was no disagreement between

reviewers with regard to the eligibility of studies for

the review.

There were 31 papers found when Sprinkles was

used as the key word. Seven of these were not related

to nutrition, and 12 were related to Sprinkles but

were not reports of randomized trials or programmeevaluations. The remaining 12 papers were used in

this review and meta-analysis. When foodlets was

used as the key word, six papers were found that were

related to the IRIS trials. However, in only one of the

four countries in the IRIS trials, South Africa, was

foodlet mixed with complementary foods. In the other

sites,it was taken between meals after being dissolved

in water. Because this review deals with home fortifi-

cation of complementary foods, only the results from

South Africa will be included. When spreads AND

nutrition AND (children OR infant) was used as the

key word, 20 studies were found, of which 13 were not

related to infant or young children nutrition, and 6

were not reports of randomized trials or programme

evaluations; thus, only 1 paper was selected via this

strategy. There were 33 papers found when the key

word home fortification was used, of which 25 were

review papers or reports of supplementation trials,

and 7 had already been found in the Sprinkles

search; only 1 paper was selected. There were no

papers identified via the computerized search that

had to be excluded because they were not in English

or Chinese.Finally, one additional report was obtained through

personal contacts with other experts. In total, 16

papers were included in the review: 13 reports of effi-

cacy trials, and 3 programme evaluations or effective-

ness trials, for a total of 37 databases (i.e. two group

comparisons) and 6113 children.

Assessing the effects of home fortification

Thepre-specifiedoutcomesof interest included micro-

nutrient status, growth, morbidity and development.

For most outcomes, effect size or relative risk wasused

to quantify theeffect of home fortificationin themeta-

analysis, based on how the results for those outcomes

were reported in the original papers. Effect size allows

oneto calculatethe overall mean impactacross studies

that differ in how the outcome was measured and to

compare results across outcomes. Studies were subdi-

vided into treatment trials and prevention trials, and

analyzed separately. In the treatment trials, the target

population was anaemic at baseline, and a positive

control group (given medicinal iron drops) was used.

By contrast, the prevention trials were generally con-ducted with unselected populations, and the control

group was not given any treatment.

For effect size, we used the formula:

Effect size=

mean for intervention group

mean for control g

rroup

pooled SD for intervention

and control groups

K.G. Dewey etal.286



5/39

Effect size can be interpreted as the per cent of

non-overlap of the intervention groups scores with

those of the control group (Cohen 1988). According

to Cohens (1988) interpretation, an effect size

(Cohens d) of 0.0 indicates that the distribution of

scores for the intervention group overlaps completely

with the distribution of scores for the control group,

and there is 0% non-overlap. An effect size of 0.3

indicates a non-overlap of 21.3% in the two distribu-

tions. Effect size can be categorized as small (~0.2),

medium (~0.5) or large (~0.8).

If data for the change in each outcome between

baseline and final measurements were available, then

they were used to calculate the effect size. If not, the

values at the final assessment were used to calculateeffect size. When the standard deviation (SD) for a

given outcome was not reported in the original paper,

we used the interquartile range (25th and 75th per-

centiles) or range to estimate SD (i.e. for ferritin).

Specifically, we assumed that the variable was nor-

mally distributed and then used the distribution of the

interquartile range (1.35 SD) or the range (a function

of the SD estimated from simulations of the range at

various values ofn) to estimate the SD.

When there were more than three studies in the

meta-analysis, random-effects models were used to

estimate the overall effects. Otherwise, fixed-effects

models were used. Weighted means were estimated

basedon theapplicablemodel.Heterogeneity of effect

size among studies wastested by using chi-square tests,

andpublication bias wasexamined by determining the

correlation between sample size and the absolute

value of the effect size.SAS (release 9.0; SAS Institute

Inc, Cary, NC,USA) was used for all analyses.

Micronutrient status

For micronutrient status, we focused on indicators ofiron, zinc and vitamin A status, because these are the

outcomes that have been assessed most often (very

few studies have included biochemical indices reflect-

ing other micronutrients). To allow for comparisons

across micronutrients, effect size was used to calculate

the effect of home fortification on plasma ferritin,zinc

and retinol concentrations. For haemoglobin (Hb),

effect size was transformed to the mean concentration

in g L-1 based on the pooled SD because mean con-

centration in g L-1 is a widely understood outcome.

Relative risk for anaemia was calculated based on

the percentages with anaemia in the treatment and

control groupsat the end of the intervention period. If

the percentage with anaemia was not reported in the

original paper, then we used the mean and SD for Hb

concentration to estimate the prevalence of anaemia

(Hb < 100 g L-1).

Growth

Effect sizes were calculated for weight-for-age

Z-score (WAZ), length-for-age Z-score (LAZ) and

weight-for-length Z-score (WLZ).When data for thechange in anthropometric outcomes between base-

line and final measurements were available in the

original references, the effect sizes were calculated

based on the change variables. Otherwise, the final

measurements were used to estimate effect size.

Morbidity

Morbidity outcomes were presented in disparate

ways across studies. Diarrhoea, upper respiratory

infection (URI) and fever were the most common

illnesses reported in these studies. There were not

enough data for URI and fever to conduct a meta-

analysis. The prevalence or incidence of diarrhoea

was used to estimate effect size or risk ratio, depend-

ing on the data presented in the original paper.

Child development

There were not enough data for the developmental

variables to conduct a meta-analysis. Results are

simply reported as percentages (Adu-Afarwuah et al.

2007) or means SD (Wang et al. 2006).

Efficacy and effectiveness results

Table 1 lists the studies included in this review. There

were 5 treatment trials, all using Sprinkles, and 11

prevention trials, of which 8 used Sprinkles as one of

the interventions, 2 used crushable tablets, and 3 used

lipid-based or soy-based products (one of the preven-




6/39

Table1.Summaryofhomefortificationinterventionsandoutcomesmeasured

Author

Typeo

f

stu

dy

Levelo

f

evidence

Site

Natureo

fintervention

Contro

lgroup

Con

tinuousoutcomes

Categorica

loutcom

es

Preventiontr

ials

Adu-A

farwuah

etal.(2007)

Efficacy

1++

Ghana

Childrenrece

ive

dad

ded

micronutr

ientsthrough

home

fort

ificationw

ith

Sprin

kles,

Nut

rita

bsor

Nutr

ibutter;N

utr

ibutter

grouprece

ivedextraenergy

through

fortifi

edfat-

based

pro

duct

.

Duration:6months

Non-i

ntervention

groupat

12months

Ferritin

,TfR

,Hb

,Zn

,Weight,

Lengt

h,W

AZ

,LAZ

,WLZ

Low

ferr

itin

,highTfR

,

anaem

ia,u

nderw

eight,

stunting,wasting

,diarr

hea

,

cough

,URI,fever

,wal

king

indepen

dentlyat

12months,

malar

ia

Christo

fides

etal.(2005)

Efficacy

1-

Canada

Childrenrece

ive

dSprin

kles

addedtocomp

lementary

foo

ds

dai

ly.Du

ration:

6months

Place

bo

Ferritin

,TfR

,Hb

,weight,

le

ngt

h,W

AZ

,LAZ

,WLZ

HighTfR

,diarr

hea,vom

iting,

dar

kstoo

ls

Giovann

ini

etal.(2006)

Efficacy

1++

Cam

bo

dia

Childrenrece

ive

dad

ded

micronutr

ientsthrough

home

fort

ificationw

ith

Sprin

kles.

Duration:1

2m

onths

Place

bo

Ferritin

,Hb,WAZ

,LAZ

,

W

LZ

,plasma

fattyac

ids

Low

ferr

itin

,anaem

ia,

morb

idity,gastro

intest

inal

discom

fort

Kuusipalo

etal.(2006)

Efficacy

1+

Malaw

i

Childrenrece

ive

d

micronutr

ientsan

denergy

through

fortifi

edfat-

based

pro

duct

.

Duration:1

2w

eeks

Place

bo

Hb,

weight,

lengt

h,W

AZ

,

LAZ

,WLZ

Menon

etal.(2007)

Programme

evaluat

ion

1+

Haiti

Childrenrece

iving

foo

d

assistance

(for

tifiedw

heat

soy

blen

d)weregiven

Sprin

kles.

Duration:2months

Fort

ifiedw

heatsoy

blen

dw

ithout

Sprin

kles

Hb

Anaem

ia

Shar

ieff

etal.(2006c)

Efficacy

1+

China

Childrenwereg

iven

Sprin

kles

dai

lyorweek

ly.

Duration:1

3w

eeks

Non-i

ntervention

group

Ferritin

,Hb

Low

ferr

itin

K.G. Dewey etal.288



7/39

Shar

ieff

etal.(2006a)

Efficacy

1+

Pak

istan

Infantsrece

ived

Sprin

kles

addedtocomp

lementary

foo

ds

dai

ly.

Duration:2months

Place

bo

Ferritin

,Hb,diarr

hea

(longitu

dinalpreva

lence

),

Fever

(days/ch

ild)

Low

ferr

itin

,anaem

ia

Smuts

etal.(2005)

Efficacy

1++

South

Africa

Childrenrece

ive

dad

ded

micronutr

ientsthrough

home

fort

ificationw

ith

Foodlet.

Duration:6months

Place

bo

Ferritin

,Hb,Zn

,VitA

,

w

eight,

lengt

h,W

AZ

,

LAZ

,WLZ

Low

ferr

itin

,lowz

inc,

low

vitam

inA

,anaem

ia,

un

derweight,stu

nting,

wasting,

diarr

hea,

ARI,fever

Zlotk

inetal.

(2003a)

Efficacy

1+

Ghana

Childrenrece

ive

dSprin

kles

conta

ining

Fe

(microencapsu

late

dFe

fumarate)alone,

Fe+

vitam

inA

or

Fe

drops.

Duration:6months

Place

bo

Ferritin

,Hb,vitam

inA

Malar

ia,a

naem

ia

Wangetal.

(2006)

Programme

evaluat

ion

2++

China

Infants

412monthso

fage

weregivencomp

lementary

foo

ds

fort

ified

withMMN

orcomp

lemen

tary

foo

ds

alone

Dai

ly.

Duration:1

220months

Comp

lementary

foo

dsaloneor

non-i

ntervention

group

Hb,

weight,

lengt

h,W

AZ

,

LAZ

,WLZ

,development

quotient

Anaem

ia,u

nderwe

ight,

stunting

Worl

dVision

Mongo

lia,

2005

Programme

evaluat

ion

2+

Mongo

lia

Children

635m

onthso

fage

rece

ived

Sprin

klesw

ithFe

andvitam

inD

.Other

componentso

fthe

NutritionProg

ram

inclu

ded

thepromotion

of

breastfee

ding

and

consumptiono

fnutr

ient

(Fe)rich

foods,an

d

increasingnutrition

know

ledgean

dcapac

ity

in

hea

lthfaci

litie

san

d

commun

ities.

Duration:averageo

f

13months

Pre-

and

post-i

ntervention

Anaem

ia,u

nderwe

ight,

stunting,wasting




8/39

Table1.Continued

Author

Type

of

study

Levelo

f

evidence

Site

Natureo

fintervention

Contro

lgroup

Continuousoutcomes

Categorica

loutcom

es

Sprin

klestreatmenttr

ials

Christo

fidesetal.(2006)

Efficacy

1+

Ghana

Anaem

icchil

drenrece

ived

ironthroug

hhome

fort

ification

withdifferent

doseso

fSp

rin

klesor

iron

drops.

Duration:8

wee

ks

Iron

drops

Ferr

itin

,Hb,diarr

hea

(e

piso

des

/child)

IDA

,teethstaining

,dar

k

stoo

ls,e

aseo

fus

e

Hirveetal.(2007)

Efficacy

1+

India

Anaem

icchil

drenweregiven

ironthroug

hhome

fort

ification

withdifferent

doseso

fSp

rin

klesor

iron

drops.

Duration:8

wee

ks

Iron

drops

Ferr

itin

,Hb,diarr

hea

,

vo

miting,cough

,fever

,co

ld

(e

piso

des

/child)

Anaem

ia,t

eethsta

ining,

dar

k

stoo

ls

Hyderetal.(2007)

Efficacy

1+

Banglades

h

Anaem

icchil

drenrece

ived

ironthroug

hhome

fort

ification

withSprin

kles

dai

lyorweek

ly.

Duration:8

wee

ks

Sprin

kles

dai

ly

Ferr

itin

,Hb,TfR

Low

ferr

itin

,highT

fR,

anaem

ia,d

arkstoo

ls,l

oose

stoo

ls,e

aseo

fus

e

Zlotk

inetal.(2003b)

Efficacy

1++

Ghana

Ironor

iron+zincwasgivento

anaem

icch

ildrenthrough

home

fortifi

cationw

ith

Sprin

klesdai

ly.

Duration:2

months

Sprin

kles

ironon

ly

Ferr

itin

,zinc,

Hb

,WAZ

,LAZ

,

W

LZ

Low

ferr

itin

,anaem

ia,l

owzinc

Zlotk

inetal.(2001)

Efficacy

1++

Ghana

Anaem

icchil

drenweretreate

d

withSprink

lesor

iron

drops

dai

ly.

Duration:2

months

Iron

drops

Ferr

itin

,Hb

Anaem

ia,d

iarr

hea,m

alar

ia

1++:ran

dom

izedcontro

lledtr

ialsw

ithvery

lowrisko

fbias;

1+:ran

dom

izedcontrolle

dtr

ialsw

ithlowrisko

fbias;

1-:ran

dom

izedcontro

lledtr

ialsw

ithhighrisko

fbias;

2++,n

on-r

ando

mizedtr

ials

withlowrisko

fcon

foun

ding;

2+:non-r

andom

izedtr

ialsw

ithmo

deraterisko

fconfo

un

ding.

K.G. Dewey etal.290



9/39

tion trials used all 3 approaches). Of the prevention

studies, eight were efficacy trials and three were pro-

gramme evaluations.

Description of individual studies

Studies with micronutrient powders

Research to evaluate the impact of home fortification

began with treatment trials using Sprinkles. The first

two studies targeted anaemic children 618 months of

age in Ghana. In the first study (Zlotkin et al. 2001),

557 anaemic children were randomly assigned to

receive Sprinkles with 80 mg Fe plus 50 mg of ascor-

bic acid per day, or 40 mg day-1

of ferrous sulfatedrops (in three separate doses) for 2 months. Adher-

ence, defined as receiving the supplements 4 day

week-1, was high in both groups (83% for Sprinkles,

92% for drops). At the end of treatment, median fer-

ritin concentration was significantly higher in the

drops group (107 vs. 71 ug L-1 in the Sprinkles group),

but mean Hb values were similar and anaemia was

successfully treated in a similar percentage of chil-

dren in the two groups (56 vs. 58%). In the second

trial (Zlotkin et al. 2003b), 304 anaemic children were

randomly assigned to receive Sprinkles with the same

amounts of iron and ascorbic acid as in the first trial,

with or without 10 mg of zinc (as zinc gluconate).

Overall, 82% of children received Sprinkles at least

5 day week-1.At the end of treatment,median ferritin

concentration did not differ significantly between

groups, but fewer children in the iron + zinc group

had low values (16 vs. 24%). However, the iron + zinc

group had significantly lower mean Hb and percent-

age of recovery from anaemia (63 vs. 75%). Both

groups had a significant decrease in plasma zinc con-

centration during the 2-month treatment period, and

there was no significant difference in growth status atthe end of the study.The authors concluded that both

versions of Sprinkles were successful in treating

anaemia, but the addition of 10 mg of zinc did not

improve zinc status or promote catch-up growth. The

authors subsequently evaluated the effect of two

doses of zinc on the absorption of 30 mg iron from

Sprinkles in the same rural Ghanaian population

using staple isotope methods (Zlotkin et al. 2006).

They found that 10 mg of zinc reduced iron absorp-

tion, whereas 5 mg of zinc did not.

After confirming that Sprinkles were effective for

treating anaemia, the same research team then evalu-

ated whether continued use of Sprinkles for another 6

months after recovery would prevent recurrence of

anaemia (Zlotkin et al. 2003a). The 437 successfully

treated, previously anaemic children in trial 1 were

randomly assigned at 820 months to receive

Sprinkles with iron (40 mg), iron + vitamin A (600 ug

retinol equivalents), ferrous sulfate drops (12.5 mg

Fe day-1) or placebo Sprinkles. The children were

evaluated after 6 months of supplementation and

again at 12 months after supplementation ended.

In all groups, more than 80% of children receivedSprinkles or drops at least 4 day week-1. There were

no significant changes in mean Hb, ferritin or serum

retinol values from baseline to the end of the sup-

plementation period in any of the four groups. The

proportion remaining non-anaemic 12 months post-

supplementation was similar among groups (77%).

The authors concluded that in children previously

treated for anaemia, further supplementation was not

needed, perhaps because iron needs decrease with

age while iron intake increases, and the iron reserves

following initial supplementation were adequate to

prevent recurrence of iron deficiency.

The next question addressed was the minimum

dose of iron needed from Sprinkles (Christofides et al.

2006). In this trial, 133 anaemic children 618 months

of age in Ghana were randomized to one of five

groups: Sprinkles with 12.5, 20 or 30 mg Fe as ferrous

fumarate, Sprinkles with 20 mg Fe as ferric pyrophos-

phate, or ferrous sulfate drops providing 12.5 mg

Fe day-1. Adherence was 84% in the Sprinkles groups

compared with 69% for the drops. After the 2-month

treatment period, serum ferritin and Hb increased in

all five groups, and there were no significant differ-ences in final values among groups.The percentage of

children with iron-deficiency anaemia at the end of

treatment was 49% and did not differ among groups.

The authors concluded that a dose of 12.5 mg of iron

per day as ferrous fumarate in Sprinkles is sufficient

to improve iron status within 2 months.

Six efficacy trials with Sprinkles have been con-

ducted outside of Ghana. In Bangladesh (Hyder et al.




10/39

2007), 136 anaemic (Hb < 110 g L-1) children were

randomly assigned to receive daily Sprinkles with

12.5 mg Fe, or weekly Sprinkles with 30 mg Fe and

placebo sachets on the remaining 6 days/week. After

the 2-month intervention, anaemia decreased by 54%

in the daily group and 53% in the weekly group, but

those receiving daily Sprinkles had a greater increase

in serum ferritin. Hb response among children with

initial Hb < 100 g L-1 was also greater in those receiv-

ingdailySprinkles.The conclusion wasthatdailyuse of

Sprinkles was somewhat more effective than weekly.

To assess acceptability of Sprinkles for use in

Aboriginal Canadian communities, 102 non-anaemic

children 418 months of age in three such communi-

ties were randomly assigned to receive eitherSprinkles with 30 mg Fe day-1 or placebo Sprinkles

for 6 months (Christofides et al. 2005). Of the 62 sub-

jects who completed the study, adherence was 61%

for Sprinkles and 59% for placebo. There were no

significant differences in serum ferritin, Hb concen-

tration or anaemia prevalence between groups,

although there was a slight shift towards higher Hb

values in the Sprinkles group.There was a marginally

significant difference in serum transferrin receptor

concentration, indicative of lower iron status in the

placebo group.Although adherence was not as high as

in previous studies, the authors reasoned that taking

Sprinkles at least 50% of the time would still be effi-

cacious in preventing iron-deficiency anaemia. The

lack of impact on Hb in this study was probably as a

result of the relatively small sample size and low

prevalence of iron deficiency in this population.

Sharieffet al. (2006a) conducted a randomized trial

in Pakistan in which 75 children 612 months of age

who had a history of diarrhoea in the previous 2 weeks

were randomly assigned to receive either(1)Sprinkles

containing 30 mg Fe, 5 mg zinc, 50 mg vitamin C,

300 ug vitamin A, 7.5 ug vitamin D and 150 ug folicacid; (2) the same Sprinkles but with heat-inactivated

lactic acid bacteria (LAB); or (3) placebo Sprinkles.

Duration of treatment was 2 months. Supplements

were consumed an average of 60% of study days in all

three groups. The effects on serum ferritin and Hb

were not significant (mean Hb at the end of the

study was 103 g L-1 for Sprinkles, 102 g L-1 for

Sprinkles + LAB, and 99 g L-1 for placebo). However,

the longitudinal prevalence of diarrhoea (the number

of days that the child had diarrhoea divided by the

total number of days of observation) was significantly

lower in children receiving Sprinkles (15%) than in

those receiving Sprinkles + LAB (26%) or placebo

(26%). Similarly, the mean number of febrile days was

lower in the Sprinkles group (1.2 days) than in the

Sprinkles + LAB (5.9 days) or placebo (3.2 days)

groups. The authors concluded that provision of

Sprinkles with multiple micronutrients reduces diar-

rhoea andfever, butcontrary to expectations, addition

of heat-inactivated LAB negates these effects.

Giovannini et al. (2006) conducted a double-blind,

placebo-controlled trial using Sprinkles among 204

infants in Cambodia.At 6 months of age, infants wererandomly assigned to receive either (1) Sprinkles with

12.5 mg Fe, plus zinc (5 mg),vitamins C, A and D, and

folic acid [multiple micronutrients (MMN)]; (2)

Sprinkleswith iron andfolicacid (FFA);or (3)placebo

Sprinklesfor a periodof 12 months.Infantswith severe

anaemia (Hb < 70 g L-1) at baseline were excluded,

but 13% of infants were iron deficient (ferritin


11/39

sachets also included 30 mg ascorbic acid, 300 mcg

Retinol Equivalents (RE) vitamin A, 160 mcg folic

acid and 5 mg zinc. In total,432 children 618 months

of age with baseline Hb between 70 and 100 g L-1

were enrolled, and 381 completed the 2-month treat-

ment period. There were no significant differences

between groups in Hb or ferritin at the end of the

study. Compliance was lower and side effects were

significantly more common in the group receiving

iron drops than in the Sprinkles groups. As in the

earlier study in Ghana (Christofides et al. 2006), the

authors concluded that a dose of 12.5 mg of iron per

day as ferrous fumarate in Sprinkles is as efficacious

as higher doses of iron in Sprinkles or iron drops.

Only one study has directly compared the efficacyof Sprinkles with that of other forms of home fortifi-

cation of complementary foods. Adu-Afarwuah et al.

(2007, 2008) randomly assigned 313 infants in Ghana

to receive either Sprinkles, a crushable tablet or an

LNS product (called Nutributter) containing 6, 16

and 19 vitamins and minerals, respectively, daily from

6 to 12 months of age.All products included iron, zinc,

vitamins A and C, and folic acid. Infants (n = 96) not

randomly selected for the intervention were assessed

at 12 months only. All three supplements were well

accepted, with no significant difference among groups

in the percentage of days that supplements were con-

sumed (mean 87%). At 12 months, there were no

significant differences among the three intervention

groups in mean Hb, ferritin or transferrin receptor

concentrations. The crushable tablet and Nutributter

groups, but not the Sprinkles group, had significantly

greater mean Hb than the non-intervention control

group.All three intervention groups had significantly

lower mean transferrin receptor and greater ferritin

concentrations than the non-intervention control

group. Between 6 and 12 months, the percentage of

infants with anaemia (Hb < 100 g L-1

) decreased sig-nificantly (by 1112 percentage points) in all three

intervention groups, from 23 to 30% at 6 months to

1018% at 12 months, whereas the prevalence of

anaemia at 12 months was 32% in the non-

intervention control group. There was a significant

positive effect of Nutributter on weight and length

gain, but no effect on growth with the Sprinkles or

crushable tablets.All three supplements had a benefi-

cial effect on the percentage of infants who were able

to walk independently at 12 months of age, with the

greatest impact seen in the Nutributter group.

Effectiveness of Sprinkles on a large scale has been

evaluated as part of a comprehensive nutrition pro-

gramme implemented in Mongolia by World Vision

and the government of Mongolia (World Vision

Mongolia, 2005). Following baseline surveys in two

different programming areas, a multi-pronged pro-

gramme was designed to reduce the high prevalence

of both anaemia and rickets.The programme included

distribution of Sprinkles (40 mg Fe, 10 mg zinc,

400 IU vitamin D, 600 IU vitamin A, 50 mg vitamin C

and 150 ug folic acid) free of charge to more than

14 000 children 636 months of age. Other pro-gramme components included provision of iron syrup

to anaemic children 3659 months of age, iron/folate

tablets to pregnant and lactating women, monthly

community-nutrition workshops and social marketing

using multimedia campaigns. A follow-up survey was

conducted ~2 years after programme implementa-

tion. Ninety per cent of eligible children in the inter-

vention areas received Sprinkles for a mean duration

of 13 months. The prevalence of anaemia in children

636 months of age decreased from 55% at baseline

to 33% at follow-up. Some of this reduction could

have been a result of the other programme compo-

nents, such as prenatal iron supplementation and

encouraging consumption of iron-rich foods such as

meat. However, the evaluation study indicated that

the frequency of use of Sprinkles was related to the

prevalence of anaemia: at the time of the final survey,

93% of children 636 months of age who used

Sprinkles did so at least three times per week,and this

group had a lower prevalence of anaemia (31%) than

those who used Sprinkles less often (52%).

An effectiveness study with Sprinkles has also been

conductedin Haiti,where children 620 monthsof agewho were receiving take-home rations of fortified

wheat soy blend as part of a maternal and child health

and nutrition programme were randomized to receive

or notreceive 30 sachets of Sprinkles (12.5 mg Fe, plus

zinc,vitaminA,folicacid andvitamin C)permonthfor

2 months (Menon et al. 2007). The prevalence of

anaemia dropped by 45% in the intervention group,

whereas it increased by 22% in the control group.




12/39

Changes in Hb were largest in the youngest children

(69 months) and in those who were anaemic at

baseline.

Studies with crushable tablets

The efficacy of crushable multiple-micronutrient

tablets, called foodlets, was evaluated in four coun-

tries involved in the IRIS trials.However, in only one

of the four countries, South Africa, was the foodlet

mixed with complementary foods. In the other sites, it

was taken between meals after being dissolved in

water. Because this paper deals with complementary

feeding interventions, only the results from South

Africa will be discussed (Smuts et al. 2005).The IRIS

study design involved four intervention groups:(1) daily multiple micronutrients (DMMs); (2) daily

placebo; (3) weekly multiple micronutrients (WMM)

plus placebo on the other 6 days/week; and (4) daily

iron (DI). In SouthAfrica, 265 infants 612 months of

age from a rural area in Natal Province were random-

ized to these four groups and followed for 6 months.

Compliance was estimated to be >90%. At baseline,

40% of infants had Hb < 110 g L-1. At the end of the

study, serum ferritin was significantly higher in the

DMM and DI groups compared with placebo. Hb

increased by 6.3 g L-1 in the DMM group, 2.5 g L-1 in

the DI group, and 2.5 g L-1 in the WMM group, com-

pared with a decrease of 0.6 g L-1 in the placebo

group. The difference in Hb concentration compared

with placebo was significant only in the DMM group.

The authors concluded that DMMs were more effec-

tive than DIs or WMMs for improving anaemia, as

well as iron, zinc, riboflavin and tocopherol status.

As described above, Adu-Afarwuah et al. (2007,

2008) compared the efficacy of crushable tablets with

that of Sprinkles and Nutributter. Crushable tablets

and Sprinkles had very similar effects on iron status,

anaemia, growth and motor development.

Studies with lipid-based or soy-based nutrient

supplements

Fortified lipid-based products have been successfully

used for rehabilitation of malnourished children

(Diop el et al. 2003; Maleta et al. 2004; Manary et al.

2004; Ciliberto et al. 2005; Ndekha et al. 2005; Patel

et al. 2005), but only two studies have assessed their

use for home fortification of complementary foods

(Kuusipalo et al. 2006; Adu-Afarwuah et al. 2007,

2008). These studies have used products containing

peanutpasteand soyor milk,plusadditional vegetable

oil, andwere consumed in quantities ranging from 5 to

75 g day-1. The products can be consumed directly

without any further preparation but can also be mixed

with other home-prepared complementary foods.

Depending on the amount consumed, this category of

complementary food supplements can also be consid-

ered as a type of ready-to-use food. In Malawi, Kuusi-

palo et al. (2006) conducted a pilot study to determine

the appropriate dose and composition of the product

to be used in subsequent trials.Malnourished children

617 months of age (n = 126) were randomly assignedto receive 0, 5, 25, 50 or 75 g day-1 of LNS (with either

milk or soy as the main protein source) for 3 months.

Mean Hb increased by 917 g L-1 in all of the groups

receiving LNS compared with almost no change

(+1 g L-1) in the control group. Growth outcomes did

not differ significantly among groups (likely because

of low statistical power) but tended to be higher in

the groups receiving 50 g day-1 of LNS.

In China, soy-based nutrient supplements for home

fortification of complementary foodshave been devel-

oped and evaluated (Wang et al. 2006,2007).The daily

dose of 10 g of the product contains 44 kcal, 6 mg iron,

4.1 mg zinc, 385 mg calcium, 0.2 mg vitamin B2 and

280 IU vitamin D. Infants 412 months of age

(n = 1500) were given the fortified or control product

with the same amount of energy for 1220 months.

Mean Hb increased by 3 g L-1 for infants receiving the

fortified product at 24 months of age compared with

the control group. LAZ decreased in both groups,

but the fortified product group had less of a decrease

than the control group (effect size of~0.17). Cognitive

and motor development at 24 months were signifi-

cantly higher in the fortified product group than in thecontrol group.

Pooled effects on micronutrient status

Effects on iron status and anaemia

Table 2 shows the effects of home fortification on

iron status and anaemia. Of the five Sprinkles treat-

ment trials (Table 2a), only three studies included a

K.G. Dewey etal.294



13/39

Table2a.ImpactofSprinklesinter

ventionsonanaemiaandironstatus(treatmenttrials)

Author

Site

Targetgroup

Stu

dygroups

n

Fe

dose

Mean

(SD)

Hb(gL-

1)

Anaem

ia

(%)

Med

ian

(min

,max

)

Ferritin

(mcg

L-

1)

ID(%)

Mean

TfR

(mg

L-

1)

High

TfR(%)

Efficacytr

ials

Christo

fidesetal.(2006)

Ghana

618months

Hb

sytematic review and meta-analysis

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