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*
Clinical Sciences Division, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka 1000, Bangladesh;
Center for Community Health, University of Southern Mississippi, Hattiesburg, MS 39406-5122; and
**
Society for Applied Research, Calcutta 700054, India
2To whom correspondence and reprint requests should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • iron • growth • weight • height • children
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). In Bangladesh, the prevalence of iron
deficiency anemia is very high (Husain and Ali 1998
).
There is substantial evidence that anemia in children is associated
with decreased physical (Rao et al. 1980
) and mental
development (Webb and Oski 1973
), impaired immune
function and reduced capacity of leucocytes to kill microorganisms
(Chandra 1983
, Pearson and Pitcock 1976
, Stockman 1981
). The adverse effects of
iron deficiency anemia on physical and mental development and
immunocompetence have prompted programs of mass supplementation
(Scrimshaw 1991
) and food fortification with iron
(Dallman 1990
). However, there is conflicting evidence
concerning the beneficial effect of iron supplementation on growth in
children. Some studies have shown improved development (Angeles et al. 1993
, Aukett et al. 1986
), whereas others
have not (Lozoff et al. 1982
). In a review, Allen (1994)
cited some studies that both found and did not find a
growth response to iron supplementation. Rosado et al. (1997)
found no effect of iron on either morbidty or growth. A
recent study demonstrated an adverse effect of iron supplementation on
weight gain of iron-replete young children (Idjradinata et al. 1994
). In this study, we examined the effect of
long-term oral iron supplementation on growth in malnourished
Bangladeshi children. |
SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Children aged 6–71 mo were included in the study after informed
consent was obtained from their parents. Children with any congenital
abnormality, metabolic disorder or any clinical sign of anemia were
excluded. The study site was a poor periurban community ~10 km
northeast of Dhaka, Bangladesh (Mitra et al. 1997
). The
inhabitants of this community are of low socioeconomic status, and the
heads of most of the households are rickshaw-pullers, day laborers
or fishermen. The ICDDR, B: Centre for Health and Population Research
maintains a clinic in this community where treatment of common
illnesses is provided free of cost once a week. The most frequent
illnesses are common cold, fever, pneumonia, diarrhea and skin
infections. The study was approved by the Ethical Review Committee of
the ICDDR, B.
Study design.
This was a double-blind, randomized controlled trial. The households were randomly assigned to either the intervention or comparison group. All of the eligible children of the households were included in the study; they were given either iron (25 g/L ferrous gluconate; 3 g/L elemental iron) plus vitamins A [80,000 retinol equivalents (RE)/L], D (2 mg cholecalciferol/L) and C (10 g/L) (intervention group) or only vitamins A, D and C (comparison group). The randomization list was prepared by a person not directly involved in the study. The supplementations were prepared as syrups with similar color and were dispensed in identical bottles serially numbered according to randomization list.
Supplementation procedures.
Mothers were instructed to administer one teaspoon (5 mL) of syrup
containing 125 mg of ferrous gluconate (15 mg elemental iron) plus
vitamins or only vitamins daily for 12 mo after the child had been fed.
The dose of iron was based on the WHO/UNICEF/UNU recommendation
(WHO/UNICEF/UNU 1994
). Compliance with the
supplementation was monitored by community health workers who visited
assigned houses daily and recorded the amount of syrup taken by
measuring the amount left over from the amount provided.
Measures of weight and length (standing height in children >24 mo old)
were taken once a month, and morbidity was recorded on alternate days.
Body weight was measured using a balance (Seca, Germany) with a
precision of 20 g, and length was measured using a locally
constructed length board with a precision of 0.1 cm. The effect of iron
supplementation on morbidity was reported earlier (Mitra et al. 1997
).
Statistical analysis.
Data were analyzed using SPSS for windows (version 6.1.2, SPSS, Chicago, IL). Proportions were compared by chi-square tests. The difference between means was tested by using Student's t test for normally distributed data and by the Mann-Whitney test in the case of skewed data. An ANOVA was performed to control for potential confounders such as sex and age and to test for interaction effects by age, sex and initial body size. Statistical significance of difference was set at a probability level of 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). The reason for dropout was out migration, and there was one
death due to drowning.
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). The other baseline characteristics did not differ between the
two groups. The weight and height gains did not differ between the two
groups after adjusting for age (Table 3, ANOVA) and they did not differ between groups as a function of
initial size (Table 4, ANOVA). There was also no difference in weight and height gains
in the two groups when boys and girls were analyzed separately. Among
boys, the weight gain over the 12-mo period was 1.44 ± 0.59 kg
(n = 40) in the intervention group and 1.36 ± 0.46 kg (n = 55) in the comparison group (P
= 0.45). The height gain was 6.01 ± 1.41 cm/y (n
= 40) and 6.08 ± 1.38 cm/y (n = 55) in the
intervention and comparison groups, respectively (P = 0.79). Among girls, the weight gain was 1.30 ± 0.68 kg/y
(n = 67) in the intervention group and 1.42 ± 0.61 kg/y (n = 61) in the comparison group
(P = 0.30). The height gain was 6.01 ± 1.53 cm/y
(n = 67) and 6.23 ± 1.8 cm/y (n = 61) in the two groups, respectively (P = 0.41). There
were no interactions among treatment group and age, sex and initial
size on weight or height gain.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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,
Rosado et al. 1997
). Other studies, however, found a
positive effect of iron on growth in children (Angeles et al. 1993
, Aukett et al. 1986
). The beneficial effect
of iron supplementation in these studies was observed mainly in anemic
or iron-deficient children (Angeles et al. 1993
,
Chwang et al. 1988
, Lawless et al. 1994
).
We did not measure the iron or hematological status in our children.
However, the majority of our children were malnourished (median
weight/age Z-score <-2.0), and it is probable that they had some
degree of iron deficiency. In an earlier study, Florentino and Guirriec (1984)
reported that the percentage of anemic children
in Bangladesh was 74–82% (0–4 y: 82%, preschool: 74%). A recent
study also reported a high prevalence of anemia (Husain and Ali 1998
), i.e., 66.5% in male and 71.3% in female children <5 y
old. The stratified analysis also showed that the weight and height
increments were not different between the intervention and comparison
groups based on the initial size of the children.
The effect of iron supplement on weight and height gain in earlier
studies was explained by a reduction in morbidity and improvements in
appetite and food intake (Lawless et al. 1994
). We do
not have data on the dietary intake of these children. However, as
reported earlier, morbidity in this cohort of children was similar in
the intervention and comparison groups except in infants <12 mo old
who had more dysenteric illnesses in the iron-treated group
(Mitra et al. 1997
). Failure of the iron supplementation
to reduce morbidity possibly explains the lack of a positive effect of
iron supplementation in increasing growth in these children.
In developing countries in which hookworm is heavily endemic, deworming
programs have been shown to improve iron status (Stoltzfus et al. 1998
) and growth (Stoltzfus et al. 1997
).
Hall et al. (1992)
reported that the prevalence of
Ascaris lumbricoides is very high (89%) in Bangladesh. The
lack of improvement of growth with iron supplementation could be due to
a high worm load. However, because this was a randomized trial, the
negative effect of worm infestation would be similar between the two
groups. A recent study (Palupi et al. 1997
) showed that
antihelminthic treatment did not have an additional effect to iron in
improving the hemoglobin status of preschool children.
Another potential explanation for the lack of effect of long-term
iron supplementation could be another micronutrient deficiency such as
that of zinc. An association between zinc deficiency and growth
impairment has been well documented (Hambidge et al. 1972
). In addition, a population in which protein energy
malnutrition is highly prevalent is likely to suffer from micronutrient
deficiencies especially zinc (Walravens et al. 1983
) and
vitamin A (Fawzi et al. 1997
). The presence of these
micronutrient deficiencies could have limited the growth response to
iron. This is one of the limitations of single micronutrient
supplementation. However, because this was a randomized trial, the
deficiency of other micronutrients would have occurred equally in the
two groups.
Idjradinata et al. (1994)
reported that iron
supplementation reduced weight gain in iron-sufficient children,
Whereas height increments were similar in iron-treated and
comparison groups. On the other hand, beneficial effects of iron
supplementation on growth velocity were observed in children with iron
deficiency (Angeles et al. 1993
, Aukett et al. 1986
). The adverse effect of iron on weight gain in children
with adequate iron status has raised concerns among public health
researchers about supplementing iron to children. Iron supplementation
did not decrease the weight and height velocities in the children of
this study. However, we do not know the iron status of our subjects. It
is very important to examine the effect of iron supplementation on
growth velocity in both iron-deficient and iron-sufficient
children. Further studies to examine the adverse effect of iron
supplementation on growth in nonanemic and anemic children are
therefore warranted.
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FOOTNOTES |
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Manuscript received October 16, 1998. Initial review completed November 25, 1998. Revision accepted February 22, 1999.
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REFERENCES |
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