Background
Iodine, a trace element found in the soil, is essential for synthesizing thyroid hormones that ensure the proper functioning of the thyroid and assist with cell replication [
1]. Insufficient levels of iodine in the body lead not only to goiter, an enlargement of the thyroid gland, but also to a range of severe physical and cognitive impairments such as mental retardation; cretinism; miscarriage and stillbirth among pregnant women; and growth and developmental abnormalities in infants and children [
2]. According to the World Health Organization (WHO), iodine deficiency is the single greatest preventable causes of mental retardation globally [
3]. Children and adolescents are particularly vulnerable to iodine deficiency disorders (IDDs) [
4] because of puberty-related changes in thyroid function that may increase the need for iodine [
5,
6].
Diets low in iodine are the main cause of IDDs. Iodine is found naturally in soil and water but in many parts of the world, due to a history of heavy rains or glacial melt, soils have been leeched of the mineral [
2,
7]. The primary strategy for reducing the prevalence of goiter and other IDDs has been to increase iodine consumption by iodizing salt [
8]. National salt iodization programs are considered a simple, cost-effective means of preventing IDDs, as salt iodization is relatively easy to implement, and salt is steadily consumed by populations year round; and because countries usually have only a few large salt manufacturers who need to be incorporated into national programs [
7,
9]. Such universal iodization programs have been extremely successful and are considered a global health success story and a model of public/private partnerships for promoting health [
2]. However, iodine deficiency can reappear if salt iodization is interrupted as a result of demobilization of the public health authorities or the lack of interest of the salt industry [
10].
The prevalence of goiter in sub-Saharan Africa has fallen over the past four decades as populations covered by salt iodization programs increased. However, despite this success, goiter and other IDDs are still a significant public health problem among children in Eastern and Southern Africa [
2]. In Ethiopia, as of 2015, the national prevalence of goiter among children aged 6 to 12 was 39.9% (more than 4 million children). According to the World Health Organization/International Council for Control of Iodine Deficiency Disorders/ United Nations Children’s Fund (WHO/ ICCIDD/UNICEF) classification, both goiter prevalence and urinary iodine levels in Ethiopia indicate that the entire country is affected by iodine deficiency [
11] .
One reason for the persistence of IDDs in Ethiopia is the mixed performance of the country’s salt iodization program. Since its launch in the 1980s it has achieved remarkable improvements in iodized salt coverage despite civil conflicts and economic disruptions, which compromised the quality of the program. However, there have been significant challenges in assuring that the level of iodization of salt is sufficient. Studies have found that only a small percentage of households have access to adequately iodized salt in Ethiopia. For example, a study conducted in 2017 reported that although over 89.2% of salt in Ethiopia contains iodine, coverage of adequately iodized salt remains very low (26%) [
12]. This virtual absence of adequately iodized salt has contributed to the endemicity of goiter in Ethiopia.
In addition to the coverage and adequacy of salt iodization, age, socioeconomic status, and a family history of goiter have been shown to be major risk factors for goiter in low-income countries like Ethiopia [
13]. Globally, women have been found to have higher rates of goiter than men [
14]. Some scholars have also suggested that very high levels of consumption of cassava and cruciferous vegetables such as cabbage and kale may be associated with hypothyroidism and thyroid cancer, particularly in areas that are iodine deficient [
15,
16]. Poor salt storage may also contribute significantly to low iodine levels in salt. Recent studies in Ethiopia have found that consuming loose, rather than packaged salt, and storing salt close to open fires, decrease the level of elemental iodine [
17‐
19] in the salt and that these behaviors are common in Ethiopia.
In sum, although there has been significant progress in the reduction of goiter and related IDDs globally, they remain significant burden in Ethiopia due, in part, to poor salt storage practices and a weak universal salt iodization program. There is little consistent data about the prevalence of goiter in Ethiopia, particularly among children; and most publicly available scientific literature and reports on the topic were published before 2016 [
20]. Understanding the extent of goiter and its associated factors is important for designing strategies that can reduce the burden of goiter among children in Ethiopia. This systematic review and meta-analysis, therefore, aims to synthesize recent evidence on the prevalence of goiter among children and its associated factors in Ethiopia.
Discussion
This meta-analysis and systematic review was conducted to estimate the pooled prevalence of goiter among children in Ethiopia. We also assessed factors associated with goiter among children using the available published and unpublished studies.
We found a high prevalence of goiter among children, with an overall pooled prevalence of 40.5% (95% CI: 33.6–47.41). This high prevalence meets WHO’s threshold for endemicity [
3] and implies the presence of moderate to severe iodine deficiency in the country [
53]. Our estimated prevalence is similar to the 39.9% rate (95% CI: 38.6–41.20) found in a nationwide, community-based, cross-sectional study conducted in 2005 [
11] and a systematic review of the literature on progress in eliminating iodine deficiency in Ethiopia which found a 35% child prevalence of goiter [
20]. Additionally, a survey among school children carried out in 2016 found that 48% of school-age children had iodine deficiency [
54]. Assuming that these estimates and ours are accurate, it is striking that the prevalence of goiter has not significantly decreased over time in line with improvements in the distribution of iodized salt in the country.
Low consumption of iodized salt and inadequate levels of iodine in iodized salt may account for these persistently high rates of goiter. A previous Ethiopian study found that one-third of salt samples in the study area were not adequately iodized [
55] and another that a significant proportion (22.2 to 64.6%) of the households in Ethiopia used inadequately iodized salt; well below the WHO recommended level [
56]. In other low- and middle-income countries with more robust salt iodization programs we see dramatically lower prevalence of goiter. For example, in Lesotho where 94.4% of salt samples are iodized, the goiter prevalence in children has been estimated to be 4.9% [
57]. Similarly, in India, a large population-based study found 80% adequate iodized salt coverage [
58] and community-based studies have found goiter prevalence in children ranging from 4.29–13.80% [
58,
59].
Ethiopia’s high prevalence of goiter among children is a significant public health problem. The presence of goiter with iodine deficiency (including mild forms of deficiency) is one of the main causes of delayed mental development among children [
58]. IDDs such as goiter create significant short- and long-term physical, mental and socio-economic harm and their continued presence in Ethiopia underscores the need to reinvigorate the country’s universal salt iodization program [
60]. It is well established that continuous iodized salt supplementation can contribute significantly to the prevention of goiter and cognitive impairment in children [
53,
61,
62].
Providing consistent supplementation will require more training and better equipment for the many small-scale local salt producers in order to improve adequate idolization of salt [
63]. As important as supporting small-scale salt producers will be increasing investment in large, “industrial-scale iodization factories” [
63]. It must also be noted that even in settings with well-functioning universal salt iodization programs infants may not consume enough salt to prevent IDDs, therefore, additional supplementation for pregnant women and infants may be necessary [
10].
We found large regional variation in the prevalence of goiter among children. Regional differences in prevalence may be due to regional differences in soil composition; differences in the consumption of cruciferous vegetables, cassava leaves and wild edible plants that may affect thyroid function; and in differences in the level of bacterial contamination of drinking water. For example, SNNPR, were we saw the highest goiter prevalence (44.22%), has high consumption of wild edible plants and cassava leaves [
64,
65] and many of the SNNPR studies analyzed in this review were conducted in areas where drinking water has significant bacterial contamination [
34], which may significantly increase the risk of goiter [
66]. The second highest prevalence of goiter was reported from Amhara region (41.9% prevalence) which is a mostly highland area with nutrient poor, eroded soils [
67]. In contrast, the Oromia (39.5% prevalence) and Benishangul-Gumuz regions (32.79% prevalence) are lowland forest and farming areas that should have more iodine in the soil [
68,
69]. The observed regional variation in prevalence suggests that when rolling out improved national iodization programs, SNNPR and Amhara may deserve special attention.
The prevalence of goiter among females was roughly 11 percentage points larger than that reported among males. This finding is unsurprising as it is well established in Ethiopian [
20] and global studies [
14] that women have higher rates of goiter than men and that this difference is most pronounced in iodine deficient areas and among younger age groups, particularly among those in late puberty [
5,
6]. These sex differences in goiter prevalence may be due to differences between the sexes in levels of the hormones and sex steroids that affect thyroid function. These differences may be particularly pronounced during puberty and menopause [
5,
70]. Given young women’s relatively higher risk, stand-alone, school- and community-based health education and supplementation programs that target this population may deserve consideration.
Our study also found that the consumption of vegetables and storing salt near to fires modestly increased the odds of goiter among children, and that a family history of goiter had a large estimated positive impact on the odds of having goiter. The consumption of packaged vs. loose salt had no significant association with goiter among children.
The findings on vegetable consumption are somewhat expected as it has long been posited that consumption of goitrogenic foods such as cabbage and cassava increase concentrations of thiocyanate, which might interfere with iodine transport [
71]. Although recent epidemiological and experimental studies provide little evidence for this relationship (and may indeed suggest that thiocyanate improves thyroid function) [
72,
73], animal studies offer some support for the theory that high consumption of goitrogenic foods might lead to hypothyroidism. In animal studies, feeding cassava that metabolized to thiocyanate in the absence of adequate iodine supplementation causes hypo functioning of the thyroid gland [
74]. In recent physiological studies the morphological changes after prolonged consumption of goitrogenic foods were characterized by replacement of colloid containing follicles with cuboidal cells with distinct nucleus that showed hypertrophy and hyperplasia. These morphological changes were also accompanied by inhibition of thyroid peroxidase and 5′ monodeiodinase with simultaneous decrease in serum thyroxine (T4), and triiodothyronine (T3) levels. These anatomical and physiological changes may lead to absolute biochemical hypothyroidism [
73‐
76].
Larger more robust studies of the risks associated with diets that are extremely high in goitrogenic vegetables and assessments of how these risks are balanced with benefits may be warranted. Such studies would require rigorous research designs to control for possible confounding between very high consumption of vegetables such as cassava, which are staples of the poor during times of food insecurity, and factors such as poverty that might also be associated with low-iodine consumption and other micro-nutrient deficiencies that exacerbate IDDs.
We found that the prevalence of goiter was more pronounced among families who stored salt near fires, OR = 1.41, but this estimate was not very precise as our confidence interval ranged from 1.1 (almost no effect on the odds of goiter) to 1.79 (almost double the effect). Other studies have suggested that iodine concentration can be significantly lower when salt was stored near a fireplace before use [
77] due to chemical changes that occur with rapid evaporation [
19,
78]. The consumption of packaged salt had no significant association with goiter prevalence. This finding was somewhat surprising, as, intuitively one would assume that packaged salt would have higher iodine content. However, other factors such as duration of salt storage, and whether salt is covered in storage might also affect iodine content and reduce the importance of packaging. In short, the importance of home storage and packaging practices in preventing goiter is unclear. As a precaution, it may be useful to include instruction on salt storage in nutrition health education until the effects of storage on iodine deficiency outcomes are better established.
The prevalence of goiter was significantly larger among children who had a family history of goiter, OR = 2.38 (95% CI: 1.90–3.99). This finding is expected as family clustering of goiter has been common historically [
79]. A complex, “multifactorial” interaction of genetic and shared environmental factors are thought to a explain higher rates of goiter among people with a family history [
79].
In our study, a risk of bias assessment showed that 13 (68.4%) studies had high quality scores and two (10.5%) had moderate quality scores. Representation and case-definition biases were the most commonly noted. To determine the influence of low methodological quality/high risk of bias on our estimates we estimated pooled prevalence without the low-quality studies. The confidence intervals of our estimates of pooled prevalence with and without these studies overlapped, indicating no significant difference between them. These results suggest that the majority of the primary study authors have met quality standards and lend credibility to our findings.
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