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Effect of iron supplements on the occurrence of diarrhoea among children in rural Egypt

Mohammed A. Hussein, Hoda A. Hassan, Azza A. Abdel-Ghaffar, and Soheir Salem

Introduction

Iron deficiency is a major public health problem throughout the world. Surveys have repeatedly confirmed the high prevalence of nutritional anaemia caused by iron deficiency in developing countries [1, 2, 3, 4]. A national nutrition survey in 1978 showed the high prevalence of anaemia in Egypt.

When iron deficiency is widespread and severe, the prevalence of morbidity and the effects on the individual's resistance to infectious diseases are significant [5, 6, 7, 8]. Some of the effects of iron deficiency in a child are decreases in white cell phagocytic function and cell-mediated immunity, which can induce and serve to perpetuate a cycle of worsening malnutrition and infection [9]. Also, decreased gastric juice secretion [10], together with gastric mucosal atrophy, shortened intestinal villus height [11], and reduced activity of intestinal cell enzymes [12] have been documented in iron-deficient individuals.

There have been few epidemiological studies relating the prevalence and the incidence of infections to iron deficiency, and the influence of confounding variables makes those studies that do exist difficult to interpret [13]. The aim of the present study was to investigate the effect of iron supplementation on the number of episodes and course of diarrhoeal attacks.

Materials and methods

This study was part of a comprehensive research project on the functional consequences of iron deficiency. The study included 250 families in a semi-urban area near Cairo. Each family had at least one pre-school-age child (two to six years old) and one school-age child (seven to twelve years old) of either sex. The numbers of children in each age group treated with either iron or a placebo are presented in table 1.

TABLE 1. The number of children in each age group treated with either iron or a placebo

Blood samples were collected before starting supplementation; haemoglobin was determined by the cyanomethaemoglobin method [14] and plasma ferritin was assessed by the radioimmunoassay technique as described by Miles and Cook [15].

On a double-blind basis, irrespective of the haemoglobin level, half of the families received iron supplements for 10 weeks. The pre-school-age and school-age children received 25 and 50 mg daily respectively. Iron was given in the form of ferrous gluconate elixir (CID Pharmaceutical Co., Egypt). The remaining half of the families, including their children, received placebos similar in appearance to the iron for the same period. Those who supplied the iron were college graduates who had been trained for the job and were referred to as "interviewers"; each was assigned to from 10 to 15 families. They administered the iron and placebo elixirs using a calibrated measure during the period between breakfast and lunch to the available family members once a day, six days a week. For the few family members who were not available, the interviewer left doses in suitable containers with instructions that the supplements were to be taken after a meal. Compliance was confirmed on the following day.

The frequency of diarrhoeal disease was determined by visiting the mother or child's guardian daily, six days a week. Information was collected on Saturday for both Friday and Saturday. Ten weeks of baseline observation preceded the ten weeks in which the children received either the iron supplement or a placebo. As suggested by the World Health Organization, the criterion for recording an episode of diarrhoea was the judgement of the mother [16]. The duration of an episode was calculated from the day of onset until the child was free of diarrhoea. Children who did not accept the supplements regularly or who did not participate in the final haematological screening were dropped from the present analysis.

Initial urine and stool examination for parasites were performed in as many subjects as were willing to provide samples (77%). Haematological values before and after intervention were compared using the t-test. Diarrhoeal prevalence before and after the treatments was compared using the paired t-test.

Results

Changes in haematological parameters

Haemoglobin

Anaemia - defined as a haemoglobin concentration of less than 11 g% for pre-school-age children and less than 12 g% for school-age children [16] - occurred in 30.7% of the pre-school children and in 34.1% of the school-age children (table 2).

TABLE 2. The prevalence of anaemia among pre-school-age and school-age children at the beginning of the study

As indicated in table 3, the mean haemoglobin concentration was 11.7 + 1.5 g% and 12.5 + 1.6 g% for preschool children and school-age children respectively before the intervention. The concentrations increased to 12.9 + 1.2 g% and 13.7 + 1.5 g% respectively after the provision of iron supplementation. These increases were highly significant (P<.0001). Significant increases in haemoglobin level were also found in both placebo groups. However, the difference between the mean haemoglobin values of the groups receiving iron treatment or placebo after the intervention was also highly significant (P<.0001).

Plasma farritin

Table 4 shows the mean plasma ferritin levels as an indicator of iron stores before and after the intervention. A significant increase was evident in the two experimental groups, while the two placebo groups showed no change. Before the intervention, the plasma ferritin levels were 22.0 + 19.4 and 25.2 + 21.6 ng/ml respectively for the two experimental groups of children; they increased to 42.0 + 18.9 and 38.2 + 17.5 ng/ml after the intervention (P<.0001). In contrast, the plasma ferritin levels of the placebo groups showed no significant change after the intervention.

Parasitic infestation

Ascaris was the most prevalent parasite among children of both groups, affecting 26.4% of pre-school children and 22.7% of school-age children (table 5). Schistosoma mansoni affected 6.7% and 3.6% of the these groups respectively, while Schistosoma haematobium and pinworm were uncommon. There was only one case of positive hookworm infestation.

Diarrhoeal attacks

Table 6 shows the number of episodes of diarrhoea and the average duration of episodes for those who received iron treatment and those who received placebos. For the two- to six-year-olds, there was a significant drop in the mean number of episodes per individual per month, from 0.38 before iron supplementation to 0.25 after supplementation (P<.05). Also, there was a non-significant decrease in the average duration, from 1.0 to 0.7 day per month. On the other hand, for the placebo group aged two to six, there was a significant increase in the number of episodes and a non-significant increase in the duration.

In the school-age children a non-significant drop in the average number of episodes per individual per month occurred, from 0.32 before iron supplementation to 0.23 after supplementation (P<.05). Also, the average duration dropped from 0.85 to 0.52 day per month. Among those who received the placebo in the school-age group, the increases in the average number of episodes per individual per month and the average duration were not significant.

Discussion

The haematological response to iron supplementation is the most reliable means of determining iron deficiency. In the present study, the iron-supplemented groups had a highly significant increase in plasma haemoglobin and ferritin. There were lesser, but significant, increases in haemoglobin in children who received placebo treatment, which may have been due to seasonal changes in their diets. However, the change in the iron status of the placebo groups was not sufficient to improve iron stores, as judged by the lack of increase in their plasma ferritin levels. Similar changes attributed to seasonal factors have been reported for Guatemalan children [17, 18].

TABLE 3. Mean haemoglobin concentration before and after intervention among pre-school-age and school-age children

TABLE 4. Mean plasma ferritin levels before and after intervention

TABLE 5. Prevalence of parasitic infestation Parasites (% infestation)

TABLE 6. Mean number of episodes and duration of diarrhoeal attacks per individual per month

*Significant difference between means before and after intervention (P<.05).

It was anticipated that pathological blood losses associated with hookworm disease and schistosomiasis [19] might be a factor in the occurrence of anaemia in this population. However, the prevalence and severity of these parasitic infections were not sufficient to produce detectable effects on haematological status. It is assumed, therefore, that the high prevalence of iron deficiency is primarily due to the poor availability of iron in the diet.

The ability of neutrophils and macrophages to kill ingested bacteria and fungi is impaired in iron-deficient children [20, 21]. This impairment is presumably due to the reduced activity of the intracellular-iron-dependent enzymes necessary for the respiratory burst that kills ingested bacteria [22, 23]. Iron deficiency also alters the proportion and function of various T-cell subsets with marked depletion of lymphocytes [24, 25]. In electron microscope studies, over 40% of the lymphocytes from iron-deficient patients were found to have abnormalities in their mitochondria [11, 26]. These biochemical and functional changes are reversed by iron therapy.

Higher prevalences of diarrhoeal and respiratory diseases have been reported in iron-deficient rubber tappers in Indonesia [27] and children in Alaska [28]. In the Indonesian study and other reports [29, 30], these diseases decreased with iron supplementation. The findings of this study of a decrease in morbidity from diarrhoeal disease with improved iron status are consistent with the above observations and have important public health implications for iron-deficient populations.

Gross et al. [24] and Keusch et al. [25] reported that iron deficiency altered the proportion and function of various T-cell subsets with marked depletion of Iymphocytes. In election microscope studies, 40% of the Iymphocytes from iron-deficient patients were found to have abnormal changes in their mitochondria [11, 26]. The ability of neutrophils and macrophages to kill ingested bacteria and fungi was reduced in iron-deficient children [20, 21].

In rats, an increase in morbidity and mortality with experimental salmonella infection in iron-deprived animals was associated with a decrease in myeloperoxidase-containing cells in the gastrointestinal mucosa [22]. However, a totally iron-free diet inhibited the infection by depriving the bacteria of iron for replication [22]. In human subjects with severe iron deficiency, massive therapeutic doses of iron can exacerbate infections by providing iron for replication of the infectious agent before it can contribute to recovery of impaired immunity. However, the levels provided through supplementation or fortification allow recovery of the immune system without being sufficient to stimulate the replication of infectious agents.

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