Prevalence of iron deficiency anemia in Brazilian women of childbearing age: a systematic review with meta-analysis

Introduction

The current focus of the “1000-day window of opportunity”, from conception to 2 years of life, has driven nutritional interventions to improve overall health of the maternal-child duo, but it often ignores the preconception period (Dijkhuizen et al., 2019). The high nutritional burden on women was recognized by the United Nations Sustainable Development Goals, aiming to meet the nutritional needs of adolescent girls, as well as pregnant and lactating women, by 2030 (International Food Policy Research Institute, 2016). In order to optimize pregnancy outcomes and avoid harmful effects on the growth, development and health of the fetus and child, it is clear that the nutritional and health status of women of childbearing age should be the starting point. Optimizing the status of micronutrients in this public may be a more effective and preventive strategy than targeted interventions only during pregnancy (World Health Organization, 2009).

Micronutrient deficiencies in women of childbearing age, in addition to harming women’s health, affect pregnancy outcomes, delaying intrauterine growth and child development (Grieger & Clifton, 2014). Women are more vulnerable to micronutrient deficiencies due to their greater biological need and often due to the unequal distribution of food within the same household, by putting their families before their own needs (Darton-Hill, 2012). Among the most common micronutrient deficiencies in women is iron deficiency, which is the decrease in total body iron content (Muthayya et al., 2013). During their childbearing age, women are at increased risk of iron deficiency due to blood loss from menstruation and often have insufficient dietary iron intake to compensate for menstrual losses (Simpson et al., 2011). When the iron deficiency is severe, it may compromise the erythropoiesis process, leading to a decrease in hemoglobin concentration, a situation known as iron deficiency anemia (IDA), which affects a third of women of childbearing age worldwide (Food and Agriculture Organization of The United Nations, 2017). In Brazil, according to the National Survey on Demography and Health of Children and Women (PNDS) carried out in 2006, which was the last survey carried out with the objective of nationally evaluating women of childbearing age, the prevalence of IDA in this group was 29.4% (Brazil, 2009).

In order to tackle IDA, Brazil has several national programs, such as a food fortification program, which enriches wheat and corn flour with iron and folic acid, and was established in 2004 with the aim to decrease IDA (Brazil, 2002). In 2017, the Health Ministry of Brazil updated the fortification requirements, which is now ranges from 4 mg to 9 mg of ferrous sulphate or fumarate per 100 g of flour (Brazil, 2017). A report from 2019 showed that only 61% of the flour samples analyzed showed adequate amounts of iron (Brazil, 2020a). Together with the national fortification program is the National Iron Supplementation Program, established in 2005, which aims to offer iron supplementation to children, pregnant women and women in the post-partum period (Brazil, 2005; Brazil, 2013). Hence, it would be expected that prevalence of IDA in Brazilian women of childbearing age should decrease throughout the years.

Therefore, collecting data on the iron status of Brazilian women of childbearing age is essential for the development of national public policies and for monitoring the effectiveness of existing programs. Thus, we aimed to determine, through a systematic review with meta-analysis, the prevalence of IDA in Brazilian women of childbearing age, and to analyze this prevalence in different contexts.

Materials and Methods

This systematic review with meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Page et al., 2021). A protocol was previously published on the PROSPERO platform (http://www.crd.york.ac.uk/PROSPERO), under the code CRD42020200960.

The protocol of this study was approved by a panel of the National Council for Scientific and Technological Development (CNPq) under the public call number 26/2019. The presentation and defense of the project took place at the ground zero seminar on 04/17/2020. After that, the research was started and the submission to the registry of PROSPERO took place in sequence. Although in the registry of PROSPERO it is stated that on the date of registration we had already carried out the formal screening, this same protocol was already evaluated and authorized by the CNPq.

Results

Study selection

At total, 24,624 occurrences were identified in the evaluated databases. Of these, 237 were selected for full-text reading. Finally, 91 studies were included for the qualitative synthesis and 83 for the meta-analysis (Américo & Ferraz, 2011; Araf et al., 2010; Araújo, 2012; Araújo et al., 2013; Arruda, 1990; Arruda, 1997; Bagni, Luiz & Da Veiga, 2013; Batista Filho & Romani, 2002; Bezerra et al., 2018; Borges et al., 2016; Bresan et al., 2018; Bresani et al., 2007; Carvalho et al., 2017; Cavalcanti et al., 2014; Cavalcanti, Diniz & Arruda, 2019; Cintra, 2018; Clemente, 2019; Coelho, 2011; Côrtes, 2006; Da Costa et al., 2013; Da Silva, 2015; Dal Pizzol, Giugliani & Mengue, 2009; Dani et al., 2008; De Camargo et al., 2013; De Carli et al., 2018; De Castro et al., 2019; De França, 2006; De Oliveira, De Barros & Ferreira, 2015; De Sá et al., 2015; De Souza, 2011; Dell Agnolo, 2009; Deméio, Teles-Santos & Dos Santos, 2017; Dos Santos et al., 2020; Dos Santos et al., 2018; Einloft et al., 2010; Fabian et al., 2007; Fávaro, 2011; Ferreira et al., 1998; Ferreira et al., 2007; Ferreira, Moura & Cabral Júnior, 2008; Ferreira, 2016; Frota, 2013; Fujimori, Szarfarc & De Oliveira, 1996; Fujimori et al., 1999; Fujimori et al., 2011; Guerra et al., 1990; Hirata et al., 2017; Instituto Nacional de Alimentação e Nutrição, 1998; Leite, 1998; Lerner, 1994; Lopes et al., 2006; Lucyk, 2006; Machado et al., 2016; Magalhães et al., 2018; Mariath et al., 2006; Marin et al., 2015; Marion, 2013; Marques et al., 2015; Massucheti, 2007; Miranda et al., 2018; Neves, 2018; Niquini et al., 2012; Orellana et al., 2011; Orsolin et al., 2020; Papa et al., 2003; Pereira, 1997; Pereira et al., 2019; Pessoa et al., 2015; Pincelli et al., 2018; Pinho-Pompeu et al., 2017; Quintans, 2011; Renz, 2018; Rezende, 2007; Rocha et al., 2005; Roncada & Szarfarc, 1975; Rondó & Tomkins, 1999; Sales et al., 2021; Santos, 2006; Santos et al., 2009; Santos et al., 2012; Saunders et al., 2016; Sena de Lira, 2009; Silla et al., 2013; Silva, Santos & Oliveira, 2018; Silva et al., 2020; Sinisterra Rodriguez, Szarfarc & Benicio, 1991; Szarfarc, 1974; Szarfarc et al., 1982; Szarfarc, 1985; Tapia et al., 2010; Walter et al., 2021). Details for the selection of studies can be seen in the flowchart in Fig. 1.

Discussion

This is the first systematic review to pool the prevalence of IDA in Brazilian women of childbearing age. IDA is estimated to affect about a third of women of childbearing age in the world (World Health Organization, 2021a). The regions of the globe in which this prevalence is higher are Sub-Saharan Africa, South Asia, the Caribbean and Oceania (Kassebaum et al., 2014). Despite not being part of the regions mentioned, the results of the present study indicate a prevalence of 25% for this condition in Brazil. Such prevalence is considered high, and it was even higher among women in the North and Northeast regions of the country. Furthermore, it is noteworthy that overall, the quality of the included studies was low. To overcome this limitation, we conducted subgroup analyses and meta-regression analysis. Nevertheless, the prevalence of IDA did not show significant differences between studies that used a random sampling approach vs those with non-random sampling.

According to the World Health Organization (WHO), the prevalence of IDA is considered a public health problem when it is above 5%, which gives a degree of significance to the respective severity of this prevalence in the present study (World Health Organization, 2011). Thus, all the grouped prevalence of IDA found in this review fit the classification established by the WHO, ranging from a problem of mild significance (18% of adolescents) to severe (53% of indigenous women). In addition, our findings show a higher prevalence than indicated by the WHO survey for Brazil in 2019 (16.1% for non-pregnant women and 19.1% for pregnant women) (World Health Organization, 2021b, 2021c).

Petry et al. (2016) aimed to carry out, through a systematic review, a survey of the prevalence of IDA in women of childbearing age in countries with low, medium and high human development index. Countries such as Bangladesh (2011/2012), Cameroon (2012), Côte d’Ivoire (2007), Mongolia (2010) and Iraq (2011) showed prevalence (18.5–28.6%) similar to that found in our meta-analysis [115]. We are not aware of a systematic review that has assessed this prevalence in women of childbearing age in Brazil. However, this type of investigation has already been carried out in children under the age of five. Systematic reviews with meta-analyses by Silveira et al. (2021) and Ferreira et al. (2021) show that compared to older studies, the prevalence of IDA in children under five years has been decreasing (Ferreira et al., 2021; Silveira et al., 2021). Reinforcing this, according to the Ministry of Health of Brazil, referring to the National Study on Food and Child Nutrition, the prevalence of anemia in Brazilian children has reduced by half in the last 13 years (Brazil, 2020b). These notes are different from what seems to be happening with women of childbearing age when comparing the studies by the data collection period in this meta-analysis.

As for the country’s internal differences, according to data from the National Health Survey conducted between 2013 and 2014 with women aged over 18 years, the macro-regions of Brazil that had the lowest prevalence of iron deficiency anemia were the southern regions (9.0%) and Midwest (7.9%) (Machado et al., 2019). In our study with women of childbearing age, the lowest prevalence was found in the South (20%) and Southeast (21%) regions. However, in relation to the highest prevalence, both the National Health Survey (2013–2014) and our analyzes highlight the North (14.6% vs 30%, respectively) and Northeast (15.7% vs 30%, respectively) regions (Machado et al., 2019).

Such differences between the macro-regions within Brazil can be explained by the evident social inequality and distinct development between the macro-geographic regions, making the South-Southeast two regions with greater development, providing a better quality of life, and the opposite generates higher prevalence in the North-Northeast regions (Ferreira Filho & Horridge, 2006). The root of this inequality among Brazilian macro-regions is complex and involves several factors. Briefly, the South and Southeast regions of Brazil have historically received more incentives from Brazilian governments, especially regarding industrialization and allocation of foreigner’s investments, which contributed to the social development of these regions. On the other hand, the North and Northeast region did not go through an industrialization process and remained with economic activities with lower aggregated value (Monteiro-Neto, 2014).

Paying attention to risk factors for IDA implies improving the quality of life of women of childbearing age, since this nutritional deficiency has already been shown to be associated with cognitive impairment and neuropsychiatric disorders increasingly common in children and adolescents, such as autism and anxiety disorder (Islam et al., 2018). In adolescence, it has an impact on physical and mental development, such as cognitive impairment, impairment of the proper functioning of the respiratory system, causing fatigue, fatigue and weakness, which can be considered a trigger for weight gain due to the lack of willingness to performing physical exercise (Garzon et al., 2020; World Health Organization, 2001). Furthermore, pregnant women who start this physiological period with IDA have higher risks of maternal and perinatal death, premature birth, low birth weight and infant morbidity (Batista Filho, De Souza & Bresani, 2008; Lício, Fávaro & Chaves, 2016), in addition to impacts during pregnancy itself, such as emotional instability, pre-eclampsia, cardiovascular and immune function changes, and lower physical and mental performance (Garzon et al., 2020).

Given the relevance of this public health problem to the lives of individuals, the Brazilian government implemented in 2005 the National Iron Supplementation Program, which consists of: prophylactic iron supplementation for specific population groups (for all children aged 0–6 months age, pregnant women starting prenatal care until the third month postpartum); fortification of food for children with powdered micronutrients; promotion of adequate and healthy diet to increase consumption of iron-rich foods; and the mandatory fortification of corn and wheat flour with iron and folic acid (Brazil, 2013). The studies conducted by Araújo et al. (2013) and Fujimori et al. (2011) indirectly showed that such flour fortification was able to reduce the prevalence of iron deficiency anemia in pregnant women (Araújo et al., 2013; Fujimori et al., 2011). However, we have not identified any studies that have evaluated this strategy in another population group for the interest of this systematic review.

This systematic review has some limitations that may influence our conclusions. First, we highlight the wide variation between the sizes and quality of the included studies, which possibly contributed to the finding of the high heterogeneity identified in the meta-analyses, as well as the very low quality of evidence. Still, we tried to explore via subgroup and meta-regression analysis the impact of the study quality in our results. In addition, the discrepancy in the number of studies between Brazilian macro-geographic regions is highlighted, which can make the comparison between them uneven. We also highlight the small number of studies aiming at evaluating indigenous populations, which may have made the pooled prevalence of this sample unrealistic in our analysis. Finally, we highlight the need for further studies to update the assessment of the prevalence of IDA in women of childbearing age, since few studies were conducted after 2015 and it was difficult to conduct a time-series comparison to highlight possible temporal changes in the prevalence of this nutritional deficiency.

Conclusions

IDA in women of childbearing age remains a public health problem in Brazil, and the population in the North and Northeast of the country need greater care for the prevention and treatment of this condition. Thus, greater efforts by the Brazilian government are needed to strengthen and better supervise the national programs of iron supplementation and fortification.

Supplemental Information