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7/29/2019 Sytematic Review and Meta-Analysis
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7/29/2019 Sytematic Review and Meta-Analysis
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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
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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
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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
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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-
Home fortification of complementary foods 287
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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
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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
Home fortification of complementary foods 289
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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
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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.
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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
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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.
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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
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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