Discussion

Brazil is a country of continental dimensions and has faced successive political and economic crises. These facts, in a way, have interfered in the production of information and data related to health conditions of national scope. In the nutritional area, even relatively simple information, such as nutritional status obtained by anthropometry, is scarce in childhood and the last national survey that showed prevalence of malnutrition was conducted in 2008⁽¹⁵⁴⁾. Regarding anaemia, there are virtually no national data that have been obtained by a study designed for this purpose, including representative sampling from all over the country. An attempt to estimate was made in 2006, in Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher (PNDS 2006)⁽¹⁵⁵⁾, in which 3499 blood samples from children under 5 years of age using the dry drop technique were analysed, and Hb values below 11 g/dl were considered as anaemia. However, a number of methodological limitations, including loss of samples and the fact that the dry drop method was not validated for children, led to the results of this study being questioned^{(Reference da Silva Pereira, de Castro and Bezerra156–Reference Vieira and Ferreira158)}. Additionally, these data are currently out dated in about 14 years⁽¹⁵⁵⁾.

For this reason, given the need to know the information about the prevalence of anaemia in the country as a whole and in its regions, in order to structure control measures, some authors have sought to estimate this information based on local studies^{(Reference Jordão, Bernadi and Barros Filho11–Reference Ferreira, Vieira and Livramento13)}. One of the first initiatives in this sense appeared in the literature in 2009, by Jordão et al. ^{(Reference Jordão, Bernadi and Barros Filho11)}, who reviewed fifty-three studies published between 1996 and 2007 and, through meta-analysis, estimated a national prevalence of 53 % of anaemia among children aged between zero and 5 years. Due to the large number of affected children, numerous attempts at fortification were tested in the country, especially studies by the Dutra-de-Oliveira group that sought to fortify drinking water with Fe, considering that to reach all children exposed to anaemia, it would be necessary to fortify food of widespread consumption^{(Reference Nogueira-de-Almeida, De Mello and Ramos114,Reference Dutra-de-Oliveira, Lamounier and Nogueira-de-Almeida159,Reference Dutra-de-Oliveira, Marchini and Lamounier160)} . An aspect that may be relevant for the prevalence has fallen, considering the data from Jordão et al. ^{(Reference Jordão, Bernadi and Barros Filho11)}, and those in the present study refer to the possible impact of government initiatives to combat Fe deficiency. Because of a law published in 2002, from 2004, fortification of wheat and maize flours with Fe and folic acid became mandatory in Brazil^{(Reference Saúde161)} and, in 2005, the Saúde de Ferro programme was implemented, which added initiatives for universal supplementation of children up to 2 years old^{(Reference Básica162)}. These two initiatives may have contributed to the decrease in prevalence observed in these two studies of similar methodology, but covering sequential periods. On the other hand, our meta-analysis showed that, at least between 2007 and 2020, there seems to have been no trend of change in prevalence. The results are found, as can be seen in the graphs referring to the regions, scattered over the years, not seeing a propensity to fall or increase in numbers.

More recently, Iglesias Vásquez et al. ^{(Reference Iglesias Vazquez, Valera and Villalobos12)} found a prevalence of 39·6 % of anaemia among preschool children and schoolchildren in Latin America, reviewing eighteen studies published between 2000 and 2014. And, Ferreira et al. ^{(Reference Ferreira, Vieira and Livramento13)} reviewed thirty-seven studies published between 2007 and 2019 involving 17 741 Brazilian children aged 6–60 months and found, through meta-analysis, a general prevalence of 40·4 % of anaemia. The article by Ferreira et al. ^{(Reference Ferreira, Vieira and Livramento13)} aimed to describe the prevalence of anaemia in different scenarios (health services, populations subject to social inequalities and population-based studies), including thirty-seven studies with children aged 6–60 months. Our analysis included 134 studies, with children from a wider age group and also differed by describing the prevalence according to the regions of the country. These regional inequalities have not been studied in previous meta-analyses^{(Reference Ferreira, Vieira and Livramento13)}.

The present study, when compared with the three mentioned above^{(Reference Jordão, Bernadi and Barros Filho11–Reference Ferreira, Vieira and Livramento13)}, who evaluated similar age groups, found a lowest prevalence. However, considering that the number of studies included was quite high, it is possible that our data are better able to reflect the real situation. In any case, the figures are extremely high in view of the recognised repercussions of anaemia^{(Reference Lozoff163–Reference Lozoff, Beard and Connor165)} and the situation demonstrated has the potential to compromise the growth and development of about 1/3 of the country’s children.

Fe deficiency has been shown to compromise thyroid function and negatively influence growth^{(Reference Borges, Veiga and Barroso166–Reference Zimmermann169)}. According to Pivina et al., Fe deficiency can cause changes in neurotransmitter homoeostasis, decrease myelin production, impair synaptogenesis and decrease basal ganglia function, negatively affecting cognitive functions and psychomotor development, and is also frequent comorbidity in autism and attention deficit hyperactivity disorder^{(Reference Pivina, Semenova and Doşa170)}. Several studies have proven that Fe deficiency anaemia in childhood due to its negative effects mainly on myelogenesis and synaptogenesis^{(Reference Vallée9)} is associated with changes in development and motor skills and worse cognitive performance in varying degrees (results identified through assessments performed with the Denver II scale), which certainly compromises the learning and, consequently, the permanent intellectual future of these children^{(Reference Lozoff163,Reference Pivina, Semenova and Doşa170–Reference Tam, Keats and Rind173)} . Fe deficiency, interfering in the production and action of cytokines, reducing the phagocytic capacity of neutrophils and macrophages^{(Reference Hassan, Badr and Karam174)} and compromising the production of T lymphocytes, particularly CD4 + Th1 subpopulations^{(Reference Gombart, Pierre and Maggini175)}, has been associated with changes that compromise the proper functioning of both the innate and adaptive immune systems^{(Reference de Pontual176,Reference Martins, Almeida and Lima177)} , increasing susceptibility to infections by intracellular microorganisms. Among the various roles played by Fe in the body should be mentioned the modulating function of the innate immune response^{(Reference Nairz, Dichtl and Schroll178)} which is impaired when the levels of this metal are decreased, predisposing the body to infection^{(Reference Armitage and Moretti179,Reference Jayaweera, Reyes and Joseph180)} .

Historically, Brazil has been unable to effectively reduce its prevalence of Fe deficiency anaemia. Some factors can be listed as possibly responsible for this fact, and one of them dates back to the first year of life, when the use of unmodified cows’ milk is used by 62·4 % of babies aged 0–5 months and 74·6 % of those between 6 and 12 months, when the child is weaned^{(Reference Bortolini, Vitolo and Gubert181)}. Due to the fact that it has little amount of low bioavailability Fe and the chelating potential of milk Ca; and leading to micro haemorrhages in the intestinal mucosa, cows’ milk contributes decisively to the installation and maintenance of Fe deficiency^{(Reference Griebler, Bruckmuller and Kien182,Reference Oliveira and Osorio183)} . Many babies are not able to satisfactorily make up their reserves during the gestational period and even during breast-feeding because the prevalence of anaemia among pregnant and lactating women is also high in the country^{(Reference Bezerra, Leal and Lira184)}. It should also be remembered the low use of fortified foods during the feeding introduction period in Brazilian children^{(Reference Bortolini and Vitolo185)}.

Another aspect concerns the consumption of Fe of inadequate bioavailability, associated with low-cost foods and low nutritional density, characteristic of the poorest countries, in which good sources of Fe, especially meat and fortified foods, have a higher cost^{(Reference Siqueira, Bezerra and Freitas133)}. Additionally, the diet based on plant protein sources predisposes to the intake of Fe-chelators nutrients, such as phytate, and is usually poor in absorption stimulating nutrients such as vitamin C^{(Reference Gaitán, Olivares and Arredondo186,Reference Mantadakis, Chatzimichael and Zikidou187)} . A recent survey published in 2020 conducted by the Brazilian government showed that food insecurity in the country increased by 33·3 % compared with 2004 and 62·2 % compared with 2013, leading to a significant portion of the population being exposed to inadequate and insufficient micronutrient nutrition⁽¹⁸⁸⁾. The same research showed that in the North and Northeast regions, less than half of the households in these regions had full and regular access to food and that the general sewage network was present only in about half of the households with moderate and severe food insecurity and, in both cases, the existence of a fossa not connected to the health network was quite relevant (43 %)⁽¹⁸⁸⁾; data from the present study found the highest prevalence of anaemia in these two regions. The issue of basic sanitation of very low coverage in the country can also contribute to the difficulty of controlling anaemia, as it provides a greater amount of infectious diseases and intestinal parasitosis^{(Reference Brito, Blanton and Parraga189)}. At the other end of this issue, it is verified that the prevalence of anaemia has shown a slight fall in southeast Brazil in the last 10 years (Fig. 5), which can be explained by the better socio-economic conditions of this region in relation to the others. The Southeast region has the highest Human Development Index⁽¹⁹⁰⁾ and the highest rates of access to basic sanitation in the country⁽¹⁹¹⁾; in addition, with the exception of the South region, the Southeast has the lowest rates of food insecurity in Brazil⁽¹⁸⁸⁾.

Some aspects may have interfered in the results of the present study. There is a tendency for research on a given disease to focus on areas where it is most prevalent. Thus, it is likely that some results, especially those with abnormally high prevalence of anaemia, have been obtained exactly in regions where high results would already be expected. Similarly, areas with more socio-economically privileged populations may have been less investigated than the poorer ones. The data in Figs. 2–6 show that an asymmetric arrangement of the points was observed, demonstrating that this fact must have actually occurred^{(Reference Sterne, Sutton and Ioannidis192)}. For this to be avoided, it would be necessary to study with national sampling, which is not available in Brazil, justifying the search for results that are obtained in another way.

Fig. 4

Forest plot for meta-analysis of the prevalence of anaemia in the Brazilian Northeast region (ordered by year of publication)

Fig. 5

Forest plot for meta-analysis of the prevalence of anaemia in the Brazilian Southeast region (ordered by year of publication)

Fig. 6

Forest plot for meta-analysis of the prevalence of anaemia in the Brazilian South region (ordered by year of publication)

Joint analyses of cross-sectional and longitudinal studies may include bias in the results. However, as shown in Table 1, the impact of the separation of these studies was not relevant for the final results. Similarly, the sample size was also quite different in each of the studies. However, Table 1 shows that the exclusion of studies with low sample size did not alter the prevalence of anaemia in the regions, except in the South region, in which, with drawing studies with sample size smaller than 100, the prevalence increases from 35·4 to 41·3 %. The careful analyses of the individual studies considered showed the existence of outliers, which can be verified in Fig. 7. As can be seen in Table 1, the withdrawal of these surveys practically does not alter the results.

Fig. 7

Contribution of each study to the overall effect size by Baujat plots

Fig. 8

Funnel plot for publication bias analyses considering the 134 studies. The dashed vertical line refers to the position of the pooled prevalence in Brazil

The present study has some limitations. The first, and more importantly, refers to the fact that, considering that local prevalence studies are rarely published in the most important scientific journals, in so that the survey could be made feasible, it was necessary to also seek data in journals of lesser expression. This method may have led to the inclusion of data with a lower degree of reliability, even taking care to include only articles in which quality was verified. Another limitation concerns the fact that almost all studies that seek to determine the prevalence of Fe deficiency anaemia do not include criteria that prove that there is nutritional deficiency. Therefore, the results presented here may include anaemia for causes other than deficiency of Fe food intake. However, knowing that in low- and middle-income countries, the vast majority of cases have nutritional origin and, taking into account that studies with children with an illness condition were not included, this limitation can be considered of little relevant impact. Five studies did not report the Hb cut-off point used to define anaemia, and it was not possible to obtain this information by direct contact with the authors. However, the methodology reported that internationally accepted criteria were used, so that the cut-off points suggested by the WHO were considered to have been used. Finally, it should also be noted that not all studies used the same method of laboratory evaluation, including surveys with different analyses techniques, even with portable methodologies.