Supplemental Material can be found at:

http://jn.nutrition.org/content/suppl/2010/11/23/jn.110.12371
1.DC1.html

The Journal of Nutrition

Community and International Nutrition

Complementary Foods Fortified with

Micronutrients Prevent Iron Deficiency and
Anemia in Vietnamese infants1,2
Pham Van Phu,4,5 Nguyen Van Hoan,5 Bertrand Salvignol,6 Serge Treche,3 Frank Tammo Wieringa,3
Nguyen Cong Khan,7 Pham Duy Tuong,4 and Jacques Berger3*
3
Institut de Recherche pour le Developpement, UMR 204 (NutriPass), IRD/Montpellier 1/Montpellier 2/SupAgro, BP 64501, 34394
Montpellier, Cedex 5, France; 4Hanoi Medical University, Dong Da, Hanoi, Vietnam; 5Groupe de Recherche et dEchanges
Technologiques, 94736 Nogent-sur-Marne, France; 6World Food Programme, 00148 Rome, Italy; and 7Vietnam Food Administration,
Ba Dinh, Vietnam

Abstract
conducted a randomized controlled trial in 5-mo-old Vietnamese infants (n = 246). Villages (n = 29) were randomly divided
into those receiving instant flour (FF) or a food complement (FC) both fortified with micronutrients or nothing [control (C)].
FF and FC infants received daily for 6 mo at least 2 meals of fortified complementary foods. Micronutrient status was
assessed by measurement of hemoglobin (Hb) and plasma ferritin (PF), transferrin receptor, zinc, and retinol. Final Hb
(mean 6 SD) was higher in the FF (112.5 6 8.0 g/L) and FC (114.0 6 7.0 g/L) groups compared with C (109.0 6 8.0 g/L; P =
0.006). PF (geometric mean [95% CI]) was also higher in FF (19.8 mg/L [17.522.3]) and FC (20.8 mg/L [18.323.6])
compared with C (11.1 mg/L [9.812.5]; P , 0.0001). Anemia prevalence decreased more in the FC group (243.6%)
compared with C (210.3%; P = 0.006). The change in prevalence of PF , 12 mg/L was different in the FF (216.4%) and FC
(26.7%) groups compared with C (+30.4%; P , 0.01). Endpoint prevalence of iron deficiency (ID) and ID anemia (IDA)
were lower in the FF (13.4 and 6.7%, respectively) and FC (15.2 and 3.8%) groups compared with C (57.5 and 37.5%) (P ,
0.0001). Retinol and zinc concentrations did not differ among groups, but endpoint prevalence of zinc deficiency was lower
in FF infants (36.1%) than in C infants (52.9%; P = 0.04). Micronutrient-fortified complementary foods significantly
improved iron status and decreased the prevalence of anemia, ID, and IDA in Vietnamese infants and can be an important
tool to reduce ID in infancy in developing countries. J. Nutr. 140: 22412247, 2010.

Introduction
Stunting and anemia are the most important nutritional problems for Vietnamese infants living in rural areas (1). Growth
faltering starts before 6 mo of age and prevalence of stunting
rises to ~30% at 12 mo and 40% when children are 1520 mo
old. At 6 mo of age, the prevalence of anemia is ~57% (2). Iron
deficiency (ID)8 is one of the most important causes of anemia,
although in some regions in Vietnam, hookworm infection
significantly contributes to the high prevalence of anemia (3).
More recently, other concomitant micronutrient deficiencies
such as zinc, selenium, vitamin A, or vitamin E have been
reported in Vietnamese infants and children (46).
1
Author disclosures: P. V. Phu, N. V. Hoan, B. Salvignol, S. Treche, F. T.
Wieringa, N. C. Khan, P. D. Tuong, and J. Berger, no conflicts of interest.
2
Supplemental Tables 1 and 2 and Supplemental Figure 1 are available with the
online posting of this paper at jn.nutrition.org.
8
Abbreviations used: ARI, acute respiratory infection; C, control; CF, complementary food; FC, food complement; FF, fortified flour; Hb, hemoglobin; ID, iron
deficiency; IDA, iron deficiency anemia; PF, plasma ferritin; TfR, transferrin
receptor.
* To whom correspondence should be addressed. E-mail: [email protected].

ID anemia (IDA) has adverse effects on the psycho-motor

development of infants and children (7) and stunting is associated with a higher risk for disease and death (8). Moreover,
stunting is related to impaired physiological, mental, and immunity maturation and it contributes to reduced height in adults, with
a reduction in the capacity for maximal work and in women to a
higher risk of low birth weight infants (9,10). Recent reviews
suggest that iron deficit in early life has persistent negative effects
later in life (11,12) and zinc and multiple micronutrient deficiencies
are associated with a decreased growth rate in children (13,14).
Moreover, iron, zinc, and vitamin A deficiencies are related to
increased susceptibility to and/or severity of infections and impaired
immunity (15).
Adequate feeding practices, including consumption of good
quality and affordable complementary foods, are essential for
infant growth and development. In Vietnam, traditional gruels
are prepared by mothers with rice flour sometimes complemented with leguminous or oil seeds, vegetables, sugar, salt, and
sodium glutamate and are given to infants often before the age
of 4 mo. These gruels have an energy and micronutrient density
too low to appropriately complement breast milk to meet the

2010 American Society for Nutrition.

Manuscript received March 08, 2010. Initial review completed May 31, 2010. Revision accepted September 27, 2010.
First published online October 27, 2010; doi:10.3945/jn.110.123711.

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To investigate whether an intervention including micronutrient-fortified complementary foods can improve iron status, we

nutritional requirements of 6- to 12-mo-old infants and contain

antinutritional components such as anti proteases, phytates, and
lectins (16).
The high prevalence of micronutrient deficiencies, especially
of ID, early in the first year of life warrant early interventions.
Consequently, the National Institute of Nutrition, Vietnam, in
collaboration with the Institute of Research for Development,
France, and the French NGO Groupe de Recherches et
dEchanges Technologiques, developed the Fasevie program to
promote the production by small private or semiprivate
Vietnamese companies of complementary foods in the form of
a ready-for-use, micronutrient-fortified instant flour or as a food
complement containing amylases and micronutrients to be
added to the traditional rice gruels (17). The objective of this
study was to evaluate the efficacy of these 2 types of
micronutrient-fortified complementary foods on the nutritional
status of infants living in rural Vietnam. This manuscript reports
the results on micronutrient status.

Participants and Methods

Sample size. The principal hypothesis was that infants consuming

micronutrient-fortified gruels would have a greater change in hemoglobin (Hb) concentration between baseline and the end of the intervention
than infants in the control group, with an expected difference among
groups of 5 g/L and a SD of 10 g/L, an a of 5%, and a power of 90%. The
calculated sample size was 104 infants/group. This sample size would
also allow detection of a difference in ferritin concentration of 7 mg/L
(with an estimated SD of 14 mg/L). Sample size was increased by 30 to
allow for dropouts. Hence, 134 infants/group at enrollment were required.
Only infants free from chronic or acute illness, severe malnutrition
(weight-for-length or length-for-age Z-scores # 23), or congenital abnormalities were included.
The energy-dense fortified foods were distributed free of charge through
canteens especially set up for the study. No canteen was set up for the C
group that followed traditional feeding practices. Canteens were open daily
from 0600 to 1800 h and parents or caretakers were free to visit anytime
during this period. Gruels were prepared by trained field assistants at the
time parents came into the canteen and were given to infants by the
accompanying person. Parents were asked to come at least 2 times/d and
were free to come as many times as they wanted. Each visit of each infant
was registered. The duration of distribution of energy-dense fortified foods
was 6 mo.
The micronutrient-fortified complementary foods were produced by the
Quang Nam Food and Service Company, Vietnam. The instant flour (FF)
was made with rice (51.3%), soybeans (20.8%), sugar (15.0%), sesame
(5.0%), dry milk (5.0%), iodized salt (0.7%), Ca3(PO4)2 (1.2%), vitaminmineral premix (0.8%), and aromas (0.2%). The FC was made with
soybeans (87.7%), iodized salt (3.1%), Ca3(PO4)2 (6.1%), vitamin-mineral
premix (3.1%), and a-amylases (0.03%). The vitamin-mineral premix was
produced by Roche. The micronutrient compositions of FF and FC are
presented in Supplemental Table 1.
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The study was carried out between December 2001 and November 2003
in Tam Ky district, Quang Nam province in central Vietnam. Twentynine villages were randomly divided into 3 groups to receive: 1) energydense gruels prepared with an instant flour fortified with micronutrients
(FF group, 10 villages); 2) energy-dense gruels prepared with the
micronutrient-fortified food complement (FC group, 10 villages); or 3)
usual gruels [control (C) group, 9 villages). Parents in all groups were
encouraged in addition to feed their children the usual foods.
Participants were 5-mo 6 7-d-old singleton breast-fed infants. At the
time of the study, the recommended age in Vietnam for starting
complementary food was 46 mo of age, in line with WHO guidelines
of the time. Moreover, a survey conducted prior to the current study in
the same area showed that most infants received homemade CF before
the age of 5 mo. The infants were progressively included in the study
when they reached the expected age range.

The technology of extrusion cooking used for the FF enables the

inactivation of some of the antinutrient factors and the preparation of
gruels without involving other thermal treatment (17,18). Both extrusion
cooking for the FF and the addition of amylase in the FC increased the
digestibility and the energy and micronutrient density of complementary
foods compared with traditional rice gruels (18).
FF gruels were prepared by simply mixing the instant flour with water
(25 g dry matter for 100 g of gruel). FC gruels were made by adding 25.6 g
of the food complement Favilase to 74.4 g of rice flour and water and
cooking the mixture for at least 10 min. Both gruels had similar nutrient
compositions and an energy density of ~419 kJ/100 g. The composition of
the gruels, as prepared at the canteens during the study, was determined in
47 FF samples and in 48 FC samples and measured at the Institute of
Research for Development laboratory in France (Supplemental Table 2).
The phytate concentrations of the gruels were 0.25 and 0.68 g/100 g dry
matter for the FF and CF groups, respectively.
A total of 426 infants from the selected 29 villages were included in the
study (Supplemental Fig. 1). Three infants were excluded just after baseline,
1 for missing anthropometry data (FF) and 2 with Hb , 70 g/L (1 in the FF
group and 1 in the FC group) who were referred to the health center of the
district for treatment. In total, 377 infants completed the 6-mo intervention
period. The rate of dropouts (n = 46, 11.5%) did not significantly differ
among the 3 groups. The main reasons for dropouts were difficulty in
bringing the infant to the canteen every day (n = 22) or absence of the
infants at the endpoint of the intervention when the second blood sampling
took place (n = 24). Of the 377 infants who completed the study, 349 had
endpoint blood samples, because some parents refused the second blood
sampling at the end of the study.
The nutritional status of infants was assessed before the beginning of
the intervention and again at the end of the 6-mo intervention study,
when the infants were 11 mo old. On the day of blood collection, no
complementary food was given before blood sampling, but infants were
allowed to be breast-fed. Blood samples were collected in 5-mL EDTAcoated vacutainers between 0700 and 0800 h in the Pediatric Department of Quang Nam General Hospital by a trained nurse, and plasma
was separated immediately after blood collection. The Hb concentration
was determined by the cyanomethemoglobin method within 6 h using
Sigma diagnostic kits. A 3-level commercial quality control material
(Dia-HT-1, 2, 3, Diamed) was analyzed together with all samples.
Samples were analyzed in duplicate and the analysis was repeated if the
results differed by .5%. Plasma was collected after centrifugation at
5000 3 g for 10 min at 48C. Five aliquots of each plasma sample were
stored at 708C for later analysis of plasma concentrations of plasma
ferritin (PF), transferrin receptor (TfR), retinol, and zinc. At the end of
the study, plasma samples were transported to the Micronutrient
Department of Research and Application at the National Institute of
Nutrition, Hanoi. PF and TfR were determined using an ELISA
technique (Ramco). Quality control was monitored by analyzing 10% of
the samples in duplicate. Retinol was analyzed by HPLC and zinc was
assessed in duplicate by flame atomic absorption spectrometry using
standards from Wako Puro Chemical Industry LTD, Japan. Hemolyzed
plasma samples were discarded to avoid interference of high zinc content
from RBC. Length (Harpenden infantometer, CMS Weighing Equipment;
precision, 0.1 cm) and weight (SECA-UNICEF, III SE; precision, 10 g) were
measured at baseline and at the end of the intervention.
Anemia was defined as Hb , 110 g/L, the absence of iron stores as PF ,
12 mg/L (19), and tissue ID as TfR . 8.5 mg/L (20). Body iron content was
calculated by the method of Cook et al. (21) using the following formula:
body iron (mg/kg) = 2 [log (TfR:ferritin ratio) 2 2.8229]/0.1207. ID was
defined by PF , 12 mg/L and/or TfR . 8.5 mg/L and IDA by the
concurrence of ID and anemia. Zinc deficiency was defined by a plasma
zinc concentration of ,9.9 mmol/L (22) and vitamin A deficiency by a
concentration of plasma retinol , 0.7 mmol/L (23).
Morbidity was recorded weekly. For FF and FC groups, canteen staff
asked mothers or caretakers about the number of days with diarrhea ($3
liquid stools/d), fever, or cough. In the C group, morbidity records were
performed weekly by trained field workers visiting each household. No
specific treatments were implemented to treat these illnesses.
In the 3 groups, the quantity of experimental gruels as well as
homemade gruels and all other types of complementary foods consumed

was measured in a subsample of 144 infants at 6, 7, 8, and 9 mo of age by

weighing all food consumed over a 12-h period. Frequency and duration of
breastfeeding was also assessed. Details on the methodology and results of
this study have been recently published (18). Daily frequency of consumption of the experimental gruels was 2.6 and 2.4 meals/d in the FF and FC
groups, respectively, representing a total of 273 g/d of gruel consumed in
both groups.
Ethical consent. The Scientific Committees of the National Institute of
Nutrition, Hanoi, and the Ministry of Health, Hanoi, reviewed and
approved the study protocol. All parents were informed orally and in
writing about the aims and procedures of the study and written informed
consent was obtained from at least 1 parent before enrollment into the
study. Infants with Hb , 70 g/L at baseline were withdrawn from the study
and referred to the health center for treatment. At the end of the intervention period, all infants still anemic were referred to health centers to
receive iron supplements.

TABLE 1

At recruitment, when the infants were 5 mo old (5 6 7 d), 26.8%

of them had no iron stores (PF , 12 mg/L) and 2.8% had high
TfR values (.8.5 mg/L). Although 67.7% of the infants were
anemic, only 27.6% had ID and 19.5% IDA. Moreover, 79.9% of
the infants had low plasma retinol concentrations and 66% had
low plasma zinc concentrations. Stunting was present in 3% of
infants and ,1% of infants were underweight (only 1 infant was
wasted). There were no significant differences among the 3 groups
for sex distribution (48, 58, and 54% girls, respectively, for FF,
FC, and C), age (5.0 6 0.3, 5.0 6 0.3, and 5.0 6 0.3 mo),
length-for-age Z-scores (20.65 6 0.70, 20.66 6 0.73, and
20.59 6 0.69), weight-for-length Z-scores (+0.56 6 0.90,
+0.45 6 0.78, and +0.61 6 0.83) or for Hb, ferritin, TfR,
retinol, and zinc (Table 1).
The mean values of initial anthropometric and micronutrient
status as well as the prevalence of stunting, wasting, and anemia
of infants who completed the study and infants who dropped out
of the study did not significantly differ (data not shown).
After 6 mo of intervention, Hb was significantly higher in
infants in both intervention groups compared with the C group
(Table 1). Hb increased significantly more in the FC group
compared with the C group. The increase in the FF group was
intermediate and not significantly different from either the FC
and C group. The prevalence of anemia decreased more
significantly in the FC group (243.6%) compared with the C
group (210.3%), whereas the decrease was intermediate in the
FF group (225.7%). Endpoint prevalence of anemia was

Micronutrient status of Vietnamese infants at baseline and at the end of the interventions
including either a FF or a FC or following traditional feeding practices (C)1

Hb, g/L
Baseline
Final
Change
PF, mg/L
Baseline
Final
Change
Plasma TfR, mg/L
Baseline
Final
Change
Body iron,4 mg
Baseline
Final
Change
Plasma retinol, mmol/L
Baseline
Final
Change
Plasma zinc, mmol/L
Baseline
Final
Change

FF

FC

P2

157
120
120

106.6 6 8.1
112.5 6 8.0a,#
5.9 6 9.9a

135
106
106

104.8 6 9.6
114.0 6 7.0a,#
9.3 6 12.9a

134
123
123

106.3 6 9.0
109.0 6 8.0b,#
2.6 6 9.9b

NS3
,0.001
,0.001

157
120
120

18.7 (16.321.5)
19.8 (17.522.3)a
22.3 6 27.0a

134
106
105

22.2 (19.125.7)
20.8 (18.323.6)a
29.6 6 26.2ab

133
122
121

20.1 (17.323.4)
11.1 (9.812.5)b,#
214.7 6 24.3b

NS
,0.001
0.009

157
120
120

4.85 6 1.74a
4.46 6 1.70
20.23 6 1.97b

134
106
106

4.69 6 1.64a
4.63 6 1.82
0.03 6 1.99ab

133
123
123

4.12 6 1.65b
4.62 6 2.01#
0.58 6 1.74a

,0.001
NS
0.006

157
120
120

25.0 6 26.2
35.4 6 25.9a,#
9.9 6 30.8a

134
106
105

29.6 6 25.8
35.4 6 21.7a
4.7 6 29.7a

133
122
121

30.9 6 26.0
15.8 6 28.6b,#
215.2 6 25.6b

NS
,0.001
,0.001

157
120
120

0.57 (0.550.59)
0.74 (0.710.78)#
0.18 6 0.23

135
106
106

0.56 (0.540.59)
0.76 (0.730.81)#
0.21 6 0.25

131
123
123

0.56 (0.540.59)
0.72 (0.680.75)#
0.14 6 0.29

NS
NS
NS

157
119
119

9.0 6 3.9
11.3 6 3.3#
2.1 6 5.0

135
105
105

8.8 6 3.9
10.7 6 4.1#
1.8 6 5.2

134
121
121

9.2 6 4.5
10.3 6 3.3#
1.1 6 5.6

NS
NS
NS

Values are mean 6 SD or geometric mean (95% CI). Means in a row with superscripts without a common letter differ, P , 0.05; #different
from baseline, P , 0.05.
2
P-value for the overall difference among groups, controlling for sex, village, and baseline value.
3
NS, P $ 0.05.
4
To convert to mmol, divide mg by 56.
1

Micronutrient-fortified complementary foods in Vietnam

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Statistical analysis. Data were analyzed using SPSS (version 15) on an

intention-to-treat basis. Ferritin and retinol concentrations were not
normally distributed and transformed to logarithms before statistical
analyses. Hb, TfR, zinc, and body iron data are presented as mean and
SD. Data for PF and retinol are given as geometric means and 95% CI.
The differences among groups at each time point were tested using a
linear model correcting for village, sex, and baseline value if indicated.
If the overall difference among groups was significant, groups were
compared using a Bonferroni post hoc test (P , 0.05). Change over
time was tested with a paired samples t test. Comparisons of
prevalence of anemia, ID, and IDA were tested by Pearson x-square
statistics. Change in prevalence from baseline was tested using
McNemars test.

Results

TABLE 2

Zinc concentrations also increased in all 3 groups from

beginning to end of the intervention. At the end of the
intervention period, mean zinc concentrations were not significantly different among the 3 groups (Table 1). However, the
prevalence of zinc deficiency decreased significantly in both
intervention groups, whereas it did not change significantly in
the C group and endpoint prevalence was lower in the FF group
compared with C group, with intermediate prevalence in the FC
group (Table 2).
Fever and acute respiratory infections (ARI) were the most
frequent illnesses reported, with 15.7 and 18 d/infant, respectively, over the 6-mo intervention period. Although the overall
number of episodes of diarrhea per infant was small (overall
1.7 d/infant over the 6 mo of intervention), infants in the C
group had more days of diarrhea over the study period
compared with the 2 intervention groups (P , 0.0001) (Table
3). Similar results were found for fever and ARI.

Discussion
The interventions implemented at the community level to
improve the feeding practices of infants, including the regular
consumption of a processed complementary food or a food
complement, both fortified with micronutrients, resulted in a
better iron status and lower prevalence of anemia, ID, and IDA
in infants compared with those following usual feeding practices
in the region. At the end of the intervention, plasma zinc and
retinol did not significantly differ among the 3 groups, but
endpoint prevalence of zinc deficiency was lower in the FF group
compared with the C group.
Micronutrient deficiency was an important health problem in
the infants at the age of 5 mo; s 67% of the infants were anemic,

Prevalence of micronutrient deficiencies in Vietnamese infants at baseline and at the end of the interventions including
either a FF or a FC or following traditional feeding practices (C)1
FF
n

Anemia (Hb ,110 g/L)

Baseline
157
Final
120
Low ferritin (,12 mg/L)
Baseline
157
Final
120
High TfR (.8.5 mg/L)
Baseline
157
Final
120
Low retinol (,0.70 mmol/L)
Baseline
157
Final
120
Low zinc (,9.9 mmol/L)
Baseline
157
Final
119
ID (PF ,12 mg/L or TFR .8.5 mg/L)
Baseline
157
Final
119
IDA
Baseline
157
Final
119

FC

P2

62.4 (54.8, 70.0)

36.7 (28.0, 45.3)a,#

135
106

71.9 (64.2, 79.5)

28.3 (19.7, 36.9)a,#

134
123

66.4 (58.4, 74.4)

56.1(47.3, 64.9)b

NS3
,0.001

30.6 (23.4, 37.8)

14.2 (7.9, 20.4)a,#

134
106

20.9 (13.9, 27.6)

14.2 (7.5, 20.8)a

133
122

27.8 (20.7, 36.0)

58.2 (49.0, 66.5)b,#

NS
,0.001

134
106

2.2 (0.0, 4.7)

1.9 (0.0, 4.5)

133
123

3.2 (0.4, 5.9)

0.8 (0, 2.5)

2.2 (0.0, 4.7)

4.9 (1.1, 8.7)

79.6 (73.3, 85.9)

39.2 (30.4, 47.9)#

135
106

77.4 (69.9, 84.1)

34.9 (25.8, 44.0)#

131
123

83.2 (77.7, 89.6)

45.5 (36.7, 54.3)#

NS
NS

66.2 (59.5, 72.9)

36.1 (27.1, 45.0)a,#

135
105

64.4 (56.9, 71.9)

42.9 (33.3, 52.4)a,b,#

134
121

67.2 (59.5, 74.9)

52.9 (44.3, 61.5)b,#

NS
0.027

32.5 (25.1, 39.8)

13.4 (7.3, 19.6)a,#

134
105

20.9 (14.0, 27.8)

15.2 (8.4, 22.1)a

133
120

28.6 (20.9, 36.3)

57.5 (48.6, 66.4)b,#

NS
,0.001

21.7 (15.2, 28.1)

6.7 (2.2, 11.2)a,#

134
105

17.9 (11.4, 24.4)

3.8 (0.1, 7.4)a,#

133
120

18.8 (12.1, 25.4)

37.5 (28.8, 46.2)b,#

NS
,0.001

Values are mean percentage (95% CI). Means in a row with superscripts without a common letter differ, P , 0.05; #different from baseline, P , 0.05.
P-value represents Pearsons x-square.
3
NS, P $ 0.05.
1
2

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NS
NS

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significantly lower in the FF and FC groups compared with the C

group (Table 2).
At the end of the intervention, PF had significantly decreased
in the control group, whereas PF had not changed significantly in
the 2 other groups (Table 1). Endpoint PF was significantly
higher in the FF group and in the FC group compared with the
control group and did not significantly differ between the FF and
FC groups. The change in prevalence of infants with no iron
stores was significantly different in both the FF and FC groups
compared with the C group; the prevalence decreased by 16.4
and 6.7% in the FF and FC groups, respectively, but increased by
30.4% in the C group. At the end of the intervention, the
prevalence of low PF concentrations was significantly higher in
the C group compared with the 2 other groups (Table 2).
Endpoint mean TfR did not differ among the groups at the
end of the intervention period. However, changes were significantly different between the FF and C groups; TfR significantly
decreased in the FF group, whereas it increased in the C group
(Table 1). Changes were intermediate in the FC group and not
significantly different from the 2 other groups. The prevalence of
ID and IDA was significantly lower at the end of intervention in
the FF and the FC groups compared with the C group (Table 2;
Fig. 1). Body iron concentration (data not shown) and total
content (Table 1) were significantly higher at the end of the study
period in both the FF and FC groups compared with the C group.
Total body iron decreased significantly in the C group during the
study period but increased in the FF and FC groups.
Retinol concentrations increased and the prevalence of low
plasma retinol decreased in all the groups from the beginning to
the end of the intervention. At the end of the intervention, the
mean retinol concentration and the prevalence of low plasma
retinol were not significantly different among the 3 groups
(Table 1).

FIGURE 1 Prevalence of anemia, ID, and IDA in

246 Vietnamese infants at baseline and at the end
of the 6-mo FF, FC, or C intervention period. At
baseline and endpoint and for each category, labeled
means without a common letter differ, P , 0.05.

this latter group. The poor sensitivity and specificity of plasma

zinc concentrations to changes in dietary zinc could have also
limited the impact of the interventions.
Similarly, the phytic acid:iron molar ratio was higher in the
FC gruel (1.7:1) than the recommended ratio of 1:1 (31). The
ratio of 0.95:1 in the complementary food, which also contained
ascorbic acid that contributes to decrease the inhibitory effect of
phytates on iron absorption, would explain why its effect on
iron status was as good as the FC despite lower iron content.
The goal of these interventions was to ensure that all infants
received at least 2 meals/d of adequately and safely prepared
experimental gruels. Several elements of the intervention may
explain the positive impact on the micronutrient status of infants.
However, we think that the regular consumption of gruels
fortified with ferrous fumarate and other micronutrients was the
main cause of improvement of anemia and iron status in the
infants. Indeed, the experimental gruels were consumed mainly

TABLE 3

Incidence of morbidity in Vietnamese infants over the

6-mo intervention period including a FF or a FC or
following traditional feeding practices (C)1

n
Diarrhea
Total episodes, n
Total days, n
Days/infant, n
Fever
Total episodes, n
Total days, n
Days/infant, n
ARI
Total episodes, n
Total days, n
Days/infant, n

FF

FC

157

135

134

P2

62
110
0.7 6 1.7a

12
21
0.2 6 0.6a

156
581
4.3 6 7.2b

,0.0001

733
1911
12.2 6 9.2a

611
1779
13.2 6 0.6a

859
2999
22.4 6 15.3b

,0.0001

733
2398
15.3 6 13.4a

626
2254
16.7 6 11.8a

763
3036
22.7 6 17.4b

,0.0001

Values are n or means 6 SD. Means in a row without a common letter differ, P ,
0.05.
2
P-value for the overall difference among groups, controlling for sex, village, and
baseline value.
1

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28% were iron deficient, 80% were vitamin A deficient, and

65% were zinc deficient, findings consistent with the most recent
national surveys (1,2). Because no acute phase response indicators such as CRP or AGP were measured in this study, the
prevalence of ID may have been underestimated (24) and the
prevalence of zinc (25) and vitamin A deficiencies (24) slightly
overestimated. Using suggested cutoffs for ferritin concentrations of 20 or 30 mg/L in populations where infections and
inflammation are prevalent (26) would indicate low iron stores
in 48.3 and 66.5% of the infants, respectively.
In the C group, ferritin and total body iron decreased
significantly, whereas Hb increased slightly. This would reflect
a shift in iron from body reserves to erythrocytes (27) to
compensate for insufficient iron absorption. This could have
been favored by the half-yearly vitamin A capsule campaign,
because vitamin A is known to mobilize iron from stores for
erythropoiesis (28). In both experimental groups, Hb and total
body iron increased significantly, whereas ferritin did not change
significantly. Iron supplied by the fortified complementary foods
was used to increase Hb synthesis and to maintain adequate iron
stores. This confirms that increasing iron intake and absorption
from food is essential from 6 mo of age to protect infants from
ID. Indeed, usual feeding practices did not allow the infants to
maintain adequate iron stores and the prevalence of infants with
no iron stores doubled from 28 to 58% in the C group.
We cannot exclude the possibility that the prevalence of
subclinical infection at the time of the endpoint blood collection
was not the same in each group. Indeed, the incidence of ARI
and diarrhea was higher in the C group over the intervention
period. However, because inflammation leads to an underestimation of the prevalence of ID, the observed difference among
the C group and the 2 intervention groups is likely to be an
underestimation of the true difference.
The prevalence of zinc deficiency decreased significantly and
was lower at the end of the intervention only in the FF group
compared with the C group, indicating improved zinc status in
the infants in this group. The high iron:zinc ratio of 11:3 in the 2
fortified complementary foods, as well as phytates, may have
limited zinc absorption (29), which starts to decline at phytic
acid:zinc molar ratios above the range of 610 (30). In the FC,
this ratio was 8.9:1 and in FF the ratio was 4.0:1, which may
explain the reduction of the prevalence of zinc deficiency only in

2246

Phu et al.

deficiencies in infancy and early childhood in many developing

countries.
Acknowledgments
We thank Prof. Ha Huy Khoi, director of the National Institute
of Nutrition at the beginning of the Fasevie program, for his
support and help to the Fasevie program and this study. J.B.,
B.S., and S.T., with contributions from P.V.P. and N.C.K.,
designed research; P.V.P., N.V.H., J.B., B.S., and P.D.T.
conducted research; J.B. and F.W. performed statistical analysis;
J.B., F.W., and P.V.P. wrote the paper; and J.B., F.W., and P.V.P.
had primary responsibility for final content. All authors read
and approved the final manuscript.

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in place of homemade gruels, did not affect the total duration

and frequency of breastfeeding, (18) and allowed higher
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The daily micronutrient intakes in infants in the FF and FC
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received gruels at home. This has probably contributed to
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intervention groups could have decreased the incidence and
duration of diarrheal diseases. The higher incidence of ARI in
the C group would suggest that some of the micronutrients
supplied in complementary foods, such as vitamin A or zinc,
played a positive role, as previously reported (36). Except for the
delivery of free gruels to the experimental groups, all other
elements of the interventions were similar: all parents in the
3 groups were informed before the study about appropriate
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Only a few studies have evaluated the impact of complementary foods fortified with iron and sometimes other micronutrients on iron status of infants and were recently reviewed
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of 1317% in the prevalence of anemia. In some studies, ferritin
was also measured, showing that in most cases, the impact was
greater on the prevalence of ID than on IDA. A recent
randomized control trial carried out in South Africa examined
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anemia and micronutrient status of infants aged 612 mo
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respectively, and the proportion of anemic infants significantly
decreased. However, the consumption of fortified porridge for
6 mo had no consistent effect on plasma retinol concentrations
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complementary food and the FC, respectively. Reductions in the
prevalence of anemia and ID in our study were also consistent.
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