Introduction
Anaemia is a prevalent public health problem in low-income countries. Anaemia has diverse consequences for human health and development. It has been associated with low birth weight, premature birth, and increased child morbidity and mortality as well as with delayed cognitive development, poor physical growth, poor work productivity and low income in adulthood [
1‐
5].
In children < 5 years of age, anaemia is defined as a blood haemoglobin concentration lower than 110 g/l. It affects approximately 43% of preschool-aged (PreSAC) children worldwide [
6,
7]. Among this population group, anaemia is a severe public health problem; the World Health Organization (WHO) reports a prevalence of ≥40% in almost all WHO member states in the African region [
6]. A recent meta-analysis of data on African children reported that the risk of infant mortality decreases by 24% with an increase of 10 g/l in haemoglobin (Hb) concentration [
8]. The youngest age group (< 5 years) had the least favourable changes in anaemia prevalence between 1990 and 2010; indeed, it was the only age group with an increased anaemia prevalence during this period [
9]. In low-income and middle-income countries (LMICs), the immediate causes of anaemia can be grouped into three categories: nutritional deficiencies (iron, vitamins A and B12, riboflavin, folate and other micronutrient deficiencies), inflammation and infections (e.g., soil-transmitted helminth infections, malaria, tuberculosis), and genetic haemoglobin (Hb) disorders (sickle cell disease, thalassaemias, and other disorders) [
4]. Worldwide, it is estimated that the top two specific causes of anaemia in both sexes and all ages from 1990 to 2019 were dietary iron deficiency, as well as hemoglobinopathies and hemolytic anaemias [
10].
Anaemia also has many interrelated distal determinants such as food insecurity, inadequate access to water and sanitation, inadequate maternal and child care, inadequate knowledge of health/nutrition, inadequate education and limited access to health/nutrition services [
4,
11,
12].
In Madagascar, a very low-income country with a gross national annual income per capita of 400 USD, the prevalence of nutritional problems such as anaemia is high. In a recent survey, half of the PreSAC (50.3%) were anaemic [
9,
10], a situation that calls for urgent responses by the government [
13]. There is a lack of study which assess the prevalence of anaemia and associated factors in Madagascar. The availability of local information on prevalence and related risk factors could help decision-makers to improve or strengthen interventions for the control of anaemia. We used data collected in underprivileged areas of Antananarivo during the AFRIBIOTA study to assess factors associated with the occurrence of anaemia. The AFRIBIOTA study is a case–control study that uses a variety of approaches and disciplines to understand the personal and environmental context that leads to and maintains EED and growth delay [
14]. AFRIBIOTA was conducted in Bangui, the capital of the Central African Republic (CAR), and Antananarivo, the capital of Madagascar. This data analysis will be important in designing and targeting approaches to improve the nutritional status of children in these underprivileged areas.
Results
A total of 490 children between 24 and 59 months of age were included in the AFRIBIOTA project; 450 of these children were recruited in the community setting and were eligible for this secondary analysis. Of the 450 eligible children, 25 had errors in anthropometric measurements (discrepancies in the classification of nutritional status between field measurements and those calculated by the software), and 11 did not have data on haemoglobin levels; these children were thus excluded from the data analysis (Fig.
1).
Of the 414 children included in this secondary analysis, 45.7% were male, and the median age was 43.9 months (interquartile range IQR 33.3 to 52.3 months). The main characteristics of the study participants are summarized in Table
1.
Table 1
Characteristics of the study participants (n = 414)
Sex | | | | 0.215 |
Female | 49 (21.8%) | 176 (78.2%) | 225 | |
Male | 52 (27.5%) | 137 (72.5%) | 189 | |
Age (months) | | | | < 0.001 |
Median (IQR) | 36 [29.5–45.1] | 46.4 [36.6–53.2] | 43.9 [33.3–52.3] | |
Stunting | | | | 0.006 |
Yes | 58 (31.0%) | 129 (69.0%) | 187 | |
No | 43 (19.0%) | 184 (81.0%) | 227 | |
History of acute malnutrition | | | | 0.069 |
Yes | 5 (50.0%) | 5 (50.0%) | 10 | |
No | 96 (23.7%) | 308 (76.3%) | 404 | |
Clogged nose | | | | 0.595 |
Yes | 56 (25.7%) | 162 (74.3%) | 218 | |
No | 45 (23.0%) | 151 (77.0%) | 196 | |
Runny nose | | | | 1 |
Yes | 64 (24.4%) | 198 (75.6%) | 262 | |
No | 37 (24.3%) | 115 (75.7%) | 152 | |
Dental caries | | | | 0.097 |
Yes | 31 (19.6%) | 127 (80.4%) | 158 | |
No | 70 (27.3%) | 186 (72.7%) | 256 | |
Dermatitis | | | | 0.940 |
Yes | 7 (27.0%) | 19 (73.0%) | 26 | |
No | 94 (24.2%) | 294 (75.8%) | | |
Cough | | | | 1 |
Yes | 37 (24.5%) | 114 (75.5%) | 151 | |
No | 64 (24.3%) | 199 (75.8%) | 263 | |
Dietary diversity score | | | | 1 |
Low | 37 (24.7%) | 113 (75.3%) | 150 | |
Adequate | 64 (19.5%) | 200 (80.5%) | 264 | |
Weaning age | | | | 0.856 |
≤ 12 mo | 8 (19.5%) | 33 (80.5%) | 41 | |
12–24 mo | 19 (23.2%) | 63 (76.8%) | 82 | |
≥ 24 mo | 60 (23.4%) | 196 (76.6%) | 256 | |
Missing data | 14 | 21 | 35 | |
Age at the introduction of first food | | | | 0.733 |
< 6 mo | 32 (23.0%) | 107 (77.0%) | 139 | |
≥ 6 mo | 68 (25.1%) | 203 (74.9%) | 271 | |
Missing data | 1 | 3 | 4 | |
Mother’s nutritional status | | | | 0.740 |
Not underweight | 85 (32.5%) | 258 (67.5%) | 261 | |
Underweight | 14 (24.5%) | 43 (75.5%) | 75 | |
Missing data | 2 | 12 | 14 | |
Intestinal carriage of at least one parasite | | | | 0.795 |
Yes | 85 (23.5%) | 274 (76.5%) | 359 | |
No | 13 (26.5%) | 36 (73.5%) | 49 | |
Presence of Entamoeba histolytica | | | | 0.080 |
No | 68 (21.4%) | 249 (78.5%) | 317 | |
Yes | 20 (32.8%) | 41 (67.2%) | 61 | |
Missing data | 13 | 23 | 36 | |
Faecal anti-trypsin | | | | 0.960 |
Normal | 72 (24.0%) | 227 (76.0%) | 299 | |
Elevated | 17 (23.0%) | 57 (77.0%) | 74 | |
Missing data | 12 | 29 | 41 | |
Faecal calprotectin | | | | 0.001 |
Normal | 43 (23.7%) | 196 (76.3%) | 239 | |
Too high | 45 (33.8%) | 88 (66.2%) | 133 | |
Missing data | 13 | 29 | 42 | |
Blood level of citrulline | | | | 0.284 |
Too low | 1 (20.0%) | 4 (80.0%) | 5 | |
Normal | 96 (25.0%) | 288 (75.0%) | 384 | |
Too high | 0 (0.0%) | 8 (100%) | 8 | |
Missing data | 4 | 13 | 17 | |
Iron deficiency | | | | < 0.001 |
Yes | 52 (58.4%) | 37 (41.6%) | 89 | |
No | 48 (14.9%) | 275 (85.1%) | 323 | |
Missing data | 1 | 1 | 2 | |
Household socioeconomic level | | | | 0.506 |
Low | 72 (26.2%) | 203 (73.8%) | 275 | |
Middle | 26 (21.0%) | 98 (79.0%) | 124 | |
High | 3 (20.0%) | 12 (80.0%) | 15 | |
Thirty-four percent of the included children (34%) had an age of introduction of the first food before the sixth month, 10.8% had a weaning age of 12 months or less, and 21.6% were weaned between 12 and 24 months of age. Our data showed that 2.4% of the children had had a previous episode of malnutrition and that 45.2% were currently stunted. The proportion of children with low dietary diversity scores was 36.2%. At the time of inclusion, 63.3% of the children had a runny nose, 38.2% had dental caries, and 36.5% had a cough. Fourteen percent (14%) of the children’s mothers were considered underweight (BMI < 18.5 kg/m2). Approximately 66.4% of the children came from households with low socioeconomic scores.
Among the participants who provided stool samples (n = 408/414), the proportion of children infected with at least one of the investigated parasites was 88%. The most commonly identified parasites were Trichuris trichura (67.4%) and Ascaris lumbricoides (53.7%).
Thirty-six percent (36%) of the children had elevated stool calprotectin levels, 96.7% had normal citrulline values, and 21.6% showed iron deficiency.
The proportion of children with anaemia was 24.4, and 9.4% of the participants had iron deficiency-related anaemia.
The results of the logistic regression analysis are presented in Table
2. They show that child age, faecal calprotectin level and iron status are independently associated with the occurrence of anaemia. We found that older children were less likely to have anaemia than younger children (OR
a: 0.95; 95% CI: 0.93–0.98). Children with high levels of faecal calprotectin and iron deficiency were more likely to show anaemia than those with normal faecal calprotectin levels and those with no iron deficiency; the adjusted odds ratios were 2.5 (1.42–4.41) and 6.14 (3.39–11.13), respectively. We found an interaction between age and iron deficiency, the association between iron deficiency and the occurrence of anaemia differs according to age. Irrespective of age, the presence of iron deficiency is associated with a high risk of anaemia, with a higher risk in the older age groups (for children < 43.8 months, the OR was 6.07 [2.58–14.26], for those ≥43.8 months, the OR was 8.7 [4.0–19.0]).
Table 2
Logistic regression analysis between the characteristics of children and the occurrence of anaemia among children 24–59 months of age
Agea (in months) | 37.2 [29.7–45.1] | 46.5 [36.3–53.8] | 0.94 (0.92–0.96) | 0.95 (0.93–0.98) | < 0.001 |
Faecal calprotectin level |
Normal | 38 (16.8%) | 187 (83.2%) | 1 | 1 | |
Too high | 43 (34.7%) | 81 (65.3%) | 2.33 (1.43–3.8) | 2.5 (1.42–4.41) | 0.002 |
Iron deficiency |
No | 40 (14.5%) | 236 (85.5%) | 1 | 1 | |
Yes | 41 (56.1%) | 32 (43.9%) | 8.05 (4.78–13.56) | 6.14 (3.39–11.13) | < 0.001 |
Presence of Entamoeba histolytica |
No | 63 (21.5%) | 229 (78.5%) | 1 | | |
Yes | 18 (31.6%) | 39 (68.4%) | 1.79 (0.98–3.25) | | |
Dental caries |
Yes | 52 (24.7%) | 158 (75.2%) | 0.65 (0.4–1.05) | | |
No | 29 (20.9%) | 110 (79.1%) | 1 | | |
History of acute malnutrition |
Yes | 5 (50.0%) | 5 (50.0%) | 3.21 (0.91–11.32) | | |
No | 76 (22.4) | 263 (77.6%) | 1 | | |
Stunting |
Yes | 44 (29.1%) | 107 (70.9%) | 1.92 (1.22–3.03) | | |
No | 37 (18.7%) | 161 (81.3%) | 1 | | |
AgeaIron deficiency | | | | 1.07 (1.01–1.013) | 0.026 |
Discussion
Our study conducted in children 24–59 months of age living in poor neighbourhoods of the city of Antananarivo aimed to assess factors associated with anaemia. Approximately one quarter (24.4%) of the children were anaemic. Older age was a protective factor, whereas iron deficiency and gut inflammation (high faecal calprotectin levels) were risk factors for anaemia.
Consistent with previous data, our results suggest that older children were less likely to be anaemic than younger children [
24‐
26]. A higher prevalence of anaemia in younger children could be caused by failure to meet the particularly high demand for iron during this period of rapid growth; this might result in nutritional gaps that increase the risk of iron deficiency and anaemia [
11].
We found that children with high levels of faecal calprotectin were more likely to suffer from anaemia. Faecal calprotectin is a biomarker of gut inflammation [
27]. Calprotectin is a cytoplasmic calcium-binding protein that is found in neutrophils, monocytes and early-stage macrophages. Measurement of calprotectin levels in stool is currently used to diagnose inflammatory bowel diseases, but it has also been used to evaluate the possible presence of other disease states that present with an inflammatory component [
28], such as
Schistosoma mansoni infection [
29] and colorectal inflammation [
30]. As in our study, an association between anaemia and inflammation was found in preschool children who participated in the BRINDA study [
25]; that study reported that inflammation was associated with anaemia in the groups with high and very high infection burdens but not in the groups with low or moderate infection burdens. These findings are consistent with our results, as our study was conducted in disadvantaged neighbourhoods in which many children had a high infection burden, illustrated by the fact that almost all of the children included in our study (88%) were infected by at least one intestinal parasite. However, we failed to find an association between the presence of intestinal parasites and the occurrence of anaemia. Despite the fact that intestinal parasitic carriage was not significantly associated with anaemia, we detected at least one intestinal parasite in 86.7% of anaemic patients. Therefore, efforts to protect children living in these underprivileged neighbourhoods from infection by these parasites are urgently needed.
In our study, iron deficiency increased the risk of developing anaemia. This is consistent with the fact that iron is needed for erythropoiesis and that failure to meet the body’s demand for iron can lead to iron-restricted erythropoiesis. Inadequate iron supply can result from either nutritional iron deficiency or iron restriction during infection and inflammation [
31]. Iron deficiency has long been assumed to contribute to approximately 50% of anaemia cases globally [
32]; however, a study conducted across a range of countries with varying rankings on the Human Development Index showed that only approximately one quarter of anaemia cases were associated with iron deficiency, while the rest had other aetiologies. We found that in underprivileged neighbourhoods of Antananarivo, iron deficiency and gut inflammation were associated with the occurrence of anaemia. These results suggest that local inflammation may cause gastrointestinal malabsorption of iron [
33] and subsequently lead to anaemia.
We found a proportion of 24.4% of children with anaemia, a value that is 50% lower than the national prevalence of the disease. This difference might be explained by the particular characteristics of the study population, as we assessed a group of children who lived in an underprivileged area and were specifically selected according to their nutritional status. There might thus be a bias in our study compared to the estimate of anaemia prevalence nationwide, which was determined using a representative sample. Our study was conducted in an underprivileged area in which many nutritional interventions (distribution of meals and flour, sensitization, and other interventions) are conducted, and this could have led to an improvement in the children’s diets that influenced their Hb levels.
Our findings have implications for strengthening the existing public health and nutrition efforts in Madagascar intended to benefit children living in underprivileged urban areas. Under the third nutrition plan for 2017 to 2021 (
Plan National d’Action pour la Nutrition PNAN III 2017–2021) [
34], numerous interventions to improve maternal and child nutrition have been planned; they include activities that will reduce the prevalence of anaemia and micronutrient deficiency (mainly iron) in children under five, such as iron supplementation, deworming, malaria prevention during pregnancy and promotion of home food fortification (provision of multiple micronutrient powders (MNPs)). According to our results, the current strategies should be combined with the prevention and treatment of infectious diseases that might lead to inflammation, such as parasitic infections, which are very common in our population study. This could be accomplished by promotion of WASH activities, deworming, and other interventions. These combined strategies will address all the factors associated with anaemia and will optimize iron intervention efforts, as iron deficiency is known to be multifactorial.
Our study has several limitations. The study population is not representative of the entire population of Antananarivo, the capital city; however, the results do illustrate the anaemia situation in underprivileged areas of Antananarivo, which represents approximately 20% of the total population of the city. Some data, such as disease history and history of acute malnutrition, might have introduced recall bias; thus, we limited our survey of disease history to inquiring about serious illnesses that required hospitalization (for diarrhoea or respiratory disease) in the year prior to the study. Nevertheless, the findings of this study will enable public health decision-makers to improve their policy actions to fight anaemia. Such policy actions should be focused on decreasing the burden of infectious diseases and on improving young children’s dietary quality and micronutrient intake.
Acknowledgements
We are grateful to the administrative and health authorities in the Commune Urbaine d’Antananarivo, the community health workers in the Fokontany, the National Office of Nutrition, The Regional Office of Nutrition of Analamanga, the Department of Nutrition of the Ministry of Public Health, the staff of the Centre de Santé Maternelle et Infantile de Tsaralalana, the Centre Hospitalier Universitaire Mère Enfant de Tsaralalana, the Service de Chirurgie Pédiatrique du CHUJRA Ampefiloha, and the DLIS (Direction de Lutte contre les IST/SIDA), and the parents of the participants for their help and collaboration.
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