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Prevalence and determinants of anemia among women of reproductive age in developing countries of Asia and Africa: A systematic review protocol


 Background The burden of anemia among women of reproductive age (WRA) is significantly higher in developing countries. Studies have been conducted to estimate the prevalence and magnitude of anemia among women of reproductive age and its associated factors mainly in African and Asian countries. However, findings from the existing literature are not synthesized in a systematic way to make evidence-based decisions. Given the high burden of anemia in Asian and African countries and an enormous amount of literature on the prevalence and determinants of anemia, there is a need to undertake a systematic review on prevalence and determinants of anemia among WRA in developing countries of Asia and Africa. Hence, the objective of this study is to conduct a systematic review on the prevalence and determinants of anemia among WRA in developing countries of Asia and Africa. This synthesis of literature will help to understand the determinants of anemia to design targeted and context-based interventions primarily for WRA. In addition, this systematic review will also assist policymakers, stakeholders and managers to make informed and evidence-based decisions mainly in developing countries of Asia and Africa.Methods The review will focus on assessing the burden of anemia and its determinants in the developing countries of Asia and Africa. PubMed, CINAHL Plus, Science Direct, Medline and Cochrane will be explored using a detailed search strategy. A study will be considered eligible, if it will be a primary epidemiological research conducted through quantitative observational study designs (cross-sectional, case-control or cohort studies) on prevalence and determinants or only determinants of anemia among WRA (15-49 years) in the developing country of Africa or Asia and published in the English language in a peer-reviewed local or international journal from 2000 to 2020.Discussion This systematic review will provide an opportunity to critically appraise and synthesize the findings from individual studies on the prevalence and determinants of anemia to finally generate a summary. These aggregated findings, in turn, can guide practice and inform policymakers to make evidence-based decisions to address the problem of anemia among women of reproductive age. The results of the review will be disseminated through presentations and peer-reviewed publications.

Anemia is a major public health concern among women of reproductive age (WRA) and is associated with high maternal and infant morbidity and mortality (Cappellini & Motta, 2015;Milman, 2011).
Anemia occurs when the number and size of red blood cells or the hemoglobin (Hb) concentration fall below an established cut-off value, consequently impairing the capacity of the blood to transport oxygen to the body (Beutler & Waalen, 2006;Cappellini & Motta, 2015). The World Health Organization (WHO) has defined anemia as Hb levels of <12.0 g/dL among WRA (World Health Organization, 2011). According to the WHO estimates, about half a billion WRA are anemic worldwide, of those around 20.2 million women are severely anemic with a higher burden in low-middle-income countries (World Health Organization, 2015). More specifically, anemia affects nearly two-thirds of WRA in developing countries (Baig-Ansari et al., 2008). Moreover, estimates in high-risk populations in developing countries suggest that total anemia prevalence may be as high as 50% to 80%, with as many as 10% to 20% having moderate to severe anemia (Kassebaum et al., 2014).
South-East Asia carries a high burden of anemia among WRA (41.9%), followed by African and Eastern Mediterranean regions (World Health Organization, 2015). The existing research studies conducted in South-Asian countries depict that two-thirds of WRA suffer from iron deficiency anemia, which is the highest prevalence in the world (Bondevik et al., 2000;Dreyfuss et al., 2000). For example, literature shows that around 75% of women of reproductive age are anemic in rural areas of Pakistan (Baig-Ansari et al., 2008). Furthermore, another study conducted in one of the rural areas of Pakistan reported that 77% of Pakistani women are anemic; of this 20.8 % of the women were found to have mild anemia and 56.5% of the women were suffering from moderate to severe anemia (Parks et al., 2018). Furthermore, a recently conducted national nutritional survey in Pakistan revealed that 41.7% of WRA are anemic, with a slightly higher proportion in rural areas (44.3%) as compared to urban areas (40.2%) (United Nations International Children's Emergency Fund, 2019). Similarly, studies from India show that the prevalence of anemia among WRA ranges from 50% to 90% across different geographic areas of India (Bentley & Griffiths, 2003;Panja et al., 2019;Panyang et al., 2018).
Likewise, community-based cross-sectional studies conducted in Ethiopia depict that 34.5% to 56.8% of the WRA are suffering from anemia across different parts of Ethiopia (Addis Alene & Mohamed Dohe, 2014;Getachew, Yewhalaw, Tafess, Getachew, & Zeynudin, 2012;Haidar, 2010). Similarly, one study from Uganda found that 63.1% of women are anemic, and another study from Bangladesh revealed that more than a third of women are anemic in Bangladesh (Chowdhury et al., 2015).
There is a complex impact of anemia on the health of women and children (Allen, 2000). The consequences of anemia vary according to the type and severity of anemia among both pregnant & non-pregnant women of reproductive age (Kalaivani, 2009;Kozuki, Lee & Katz, 2011). Anemia can lead to multiple adverse consequences among WRA by adversely affecting their quality of life as well as their reproductive capacity, resulting in serious maternal and perinatal outcomes (Ndegwa, 2019;Osungbade & Oladunjoye, 2012). Several studies have shown that anemia among pregnant women can result in poor maternal and fetal outcomes such as intrauterine growth retardation, stillbirths, low-birth-weight, prematurity, intrauterine fetal death, abortion, perinatal mortality, post-partum hemorrhage, and puerperal pyrexia (Beckert, Baer, Anderson, Jelliffe-Pawlowski, & Rogers, 2019;Hare, Freedman, & Mazer, 2013;Kassa, Muche, Berhe, & Fekadu, 2017;Kavle et al., 2008;Tunkyi & Moodley, 2018). For instance, a review of observational studies found a linear association between maternal anemia and maternal mortality, with each 10 g/L increase in maternal hemoglobin associated with a 29% reduction in maternal mortality (Black et al., 2013). Likewise, findings from a systematic review revealed that 25% of low birth weight, 44% of preterm deliveries, and 21% of perinatal mortality are attributable to anemia during pregnancy in low-income countries (Rahman et al., 2016).
Similarly, women with no or primary education are more likely to be anemic as compared to educated women, and also women from low socioeconomic status are more anemic when compared to women from higher socio-economic status in different studies conducted across the world (Irfan, Muhammad, Khan, & Mudassir, 2013;Lover, Hartman, Chia, & Heymann, 2014).
Despite various efforts, anemia has improved minimally (by only 0.2-0.3 percentage points per year) in the past two decades (Mason, Martorell, Saldanha, & Shrimpton, 2013). In addition, multiple interventions have shown to reduce the prevalence of anemia worldwide by 12% between 1992 and 2011, these efforts did not have a similar impact in low and middle-income countries (World Health Organization, 2014). Therefore, more innovative and cause-specific interventions are required to address the increasing burden of anemia in these countries, and to achieve the World Health Assembly target of a 50% reduction of anemia among WRA by 2025 (World Health Organization, 2014).
To design such interventions, it is crucial to understand the determinants or factors of anemia, which have been studied individually by different researchers in their independent studies. Multiple studies have been conducted to estimate the prevalence and magnitude of anemia among women of reproductive age and its associated factors in developing countries (Alflah, Wahdan, Hasab, & Tayel, 2017;Ayoya, Spiekermann-Brouwer, Traoré, Stoltzfus, & Garza, 2006;Baig-Ansari et al., 2008;Bharati, Som, Chakrabarty, Bharati, & Pal, 2008;Kassa, Muche, Berhe, & Fekadu, 2017;Piammongkol, Chongsuvivatwong, Williams, & Pornpatkul, 2006). These independent studies provide a plethora of valuable evidence on the burden and determinants of anemia among WRA mainly in African and Asian countries. However, findings from the existing literature are not synthesized in a systematic way to make evidence-based decisions. Therefore, it is crucial to synthesize the literature on the prevalence of anemia and its determinants in a systematic way to make informed decisions. Thus, the first and foremost step would be to synthesize or aggregate findings from a pool of quantitative studies on the prevalence and determinants of anemia across the range of sociodemographic, biological and nutritional domains. This synthesis of literature will help to understand the determinants of anemia to design targeted and context-based interventions primarily for women of reproductive age residing in developing countries. In addition, this systematic review will also assist policymakers, stakeholders and managers to make informed and evidence-based decisions. This, in turn, will prepare them to design cost-effective and sustainable public health interventions to reduce the high burden of anemia among women of reproductive age mainly in developing countries of Asia and Africa.

Research Question
Given the high burden of anemia in Asian and African countries and an enormous amount of literature on the prevalence and determinants of anemia, there is a need to undertake a systematic review on the topic of prevalence and determinants of anemia among women of reproductive age in developing countries of Asia and Africa. Hence, my objective is to conduct a systematic review on the prevalence and determinants of anemia among women of reproductive age in developing countries of Asia and Africa. The specific research question for this review is: What is the prevalence and determinants of anemia among women of reproductive age in developing countries of Asia and Africa?

Material And Method
The protocol has been designed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P) checklist (Moher et al., 2015) ( Figure 1).
The review will focus on assessing the burden of anemia and its determinants in the developing countries of Asia and Africa. Additionally, this review will provide a high level of evidence on the prevalence and determinants of anemia. This, in turn, will help to make judgments about the evidence and inform recommendations to address the high burden of anemia among women of resource-poor settings.

Eligibility Criteria
We will undertake a systematic review on the prevalence and determinants of anemia among women of reproductive age (WRA) in Asian and African developing countries. The criteria to define a developing country are based on the World Bank's 2018-guidelines of country classification. Overall, the eligibility criteria are grouped into nine categories including population, intervention, outcome, and settings, etc. (Table 1). More specifically, a study will be considered eligible for inclusion, if it is primary epidemiological research conducted through quantitative observational study designs (crosssectional, case-control or cohort studies) on prevalence and determinants or only determinants of anemia among WRA (15-49 years) in the developing country of Africa or Asia and published in the English language in a peer-reviewed local or international journal from 2000 to 2020. An inclusion/exclusion screening form is given in Table 2.

Information sources and search strategy
An electronic systematic literature search will be carried out to measure the prevalence and determinants of the anemia among WRA in developing countries of Asia and Africa. Although there are a large number of databases to search articles on the given research topic, we will search five large electronic databases including PubMed, CINAHL Plus, Science Direct, Medline and Cochrane for the current systematic review. These databases will be explored using a detailed search strategy including search terms or combinations. In addition, within these databases, we will approach Moreover, the reference list of included records will also be appraised to identify relevant articles.
The databases will be searched by two researchers independently. The search strategy will be piloted to ensure sufficient specificity and sensitivity. More specifically, articles will be searched using the combination of search terms set out for the defined research question. The preliminary search strategy is illustrated in Table 3. These search items are grouped according to PICOS criteria: 1) Population (WRA), 2) Intervention /Exposure (determinants), 3) Comparison group (non-anemic women), 4) Outcome (anemia), and 5) Settings (developing countries of Asia and Africa). We have identified four major concepts (anemia, WRA, determinants, and developing countries) and their synonyms such as low hemoglobin/hematocrit level (anemia), married women/married pregnant women/ married non-pregnant women (WRA), factors/predictors/co-variates/causes (determinants) and low-middle income countries/low-income countries/less developed countries (developing countries). In addition, we will also consider using different spellings of major concepts such as anemia vs anaemia and hemoglobin vs haemoglobin, etc. to capture relevant articles. This will be followed by combining the major concepts using combinations (AND, OR) germane to the research question. Moreover, we will use truncation (*) to identify more research articles with the same root word. Additionally, indexed keywords in the Medical Subject Headings (MeSH) will be used to ensure uniform search terms.
As an example, to capture the relevant article in a given database following simple search term can be used using major concepts and combinations:

Example 2: (women of reproductive age* OR pregnant* OR married* OR non-pregnant* OR 'married pregnant woman' OR 'married non-pregnant woman') AND (determinants OR factors OR causes OR predictors) AND (anemia* OR iron deficiency anemia*) AND (Developing African countries OR low and middle-income Asian countries) (Table 3).
We will also apply search limits or filters on publication year (2000-2020), language (English), age group (15-49 years), gender (females) and type of studies (quantitative observational) to include eligible articles in the search. Moreover, to make my search efficient, we will use pre-defined filters (developed by few researchers using possible synonyms regarding some major concepts) on the major concepts such as population or region. Examples of such filters relevant to my topics are given in Table 4.

Study selection
Citation management system (Endnote software) will be used to manage the records exported from all the electronic databases (Yali, 2004). In the first step, all the studies will be screened by study titles using the Endnote software. The shortlisted studies will then be screened by study abstracts. Lastly, the full text of selected studies will be retrieved and screened against the eligibility criteria. In order to ensure the reliability of screening articles among the two reviewers, a pre-defined screening form will be developed and pilot testing will be conducted as per the eligibility criteria. Both reviewers will describe outcome measures after reviewing the studies to verify the relevance of the articles. Strong justifications for excluding studies will be provided by each reviewer. Any disagreement between the two reviewers will be resolved by a third reviewer in a consensus meeting. The third reviewer will be consulted to make the final decision about whether the study meets the eligibility criteria for inclusion. The PRISMA flow diagram will be used to report the study selection process.

Data collection process
A customized data extraction sheet will be filled by two independent reviewers (SA, SAA) for the eligible studies. Data extraction tables of both reviewers will be matched to ensure that all key findings are included in the systematic review. A third evaluator will be involved (JS), if discordant information is observed during the data extraction process. The data extraction sheet will be pilot tested before initiating the data extraction process. Alongside, existing studies on this research area have been reviewed to determine items of the data extraction form. The items included in the preliminary data extraction form include the title of the article, author, publication date, country of study, date of extraction, reviewer name, purpose/aim of the study, study type, study population, prevalence and determinants of anemia and study limitations. The summary of included studies on the prevalence and determinants of anemia among WRA will also be provided in the main results paper.

Quality assessment of eligible studies
Both reviewers (SA, SAA) will independently assess the quality of each study using the different Newcastle-Ottawa Scales for cross-sectional and cohort studies (Lo, Mertz, & Loeb, 2014) . This scale is used to assess the quality of descriptive and analytical studies by assessing potential sources of bias in the selection, comparability of participants and the assessment of study outcome. Based on this scale, the maximum score for selection is 4 points, while it is 2 points for comparability and maximum score for the outcome is 3 points making a total score of 9. Each eligible study will be scored against 9 maximum points and study with higher scores will depict high quality.

Synthesis of included studies
First, the findings of the review will be synthesized narratively. Initially, we will perform a descriptive analysis of all the final included studies to record their main characteristics such as study title, authors, publication year, study aim, study methods, sampling strategy, characteristics of study participants, prevalence and determinants of anemia. Then, a narrative synthesis will be carried in which final studies will be grouped under the main heading of four major determinants such as sociodemographic determinants, dietary, reproductive and biological determinants. Firstly, the two independent reviewers (SA, SAA) will read each included study several times to extract data and group-related results. Later, the reviewers will record analytical interpretations of findings to capture emerging themes. Finally, the reviewers will highlight potential determinants of anemia among women of reproductive age in developing countries of Asia and Africa.

Discussion
A more comprehensive understanding of the prevalence and determinants of anemia is required to improve the health of women especially in developing countries of Asia and Africa. The protocol will lead to a systematic review which synthesizes evidence on the prevalence and determinants of anemia in urban and rural communities of developing countries in Asia and Africa. Systematic review findings will be made publicly available. This systematic review will provide an opportunity to critically appraise and synthesize the findings from individual studies on the prevalence and determinants of anemia to finally generate a summary. These aggregated findings, in turn, can guide practice and inform policymakers to make evidence-based decisions to address the problem of anemia among women of reproductive age. The results of the review will be disseminated through presentations and peer-reviewed publications.

Availability of data and materials
Materials described in this paper pertain to the study protocol only and there are no raw data reported. The datasets will be collected and analyzed and can be made available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Authors' contributions
The study was conceptualized by SA & SAA. SA prepared the first draft of the manuscript and SAA provided her input to improve the manuscript after editing. All authors have contributed to this manuscript, and reviewed and approved the final version of the paper. Zhang, S. M., Willett, W. C., Selhub, J., Hunter, D. J., Giovannucci, E. L., Holmes, M. D., . . . Hankinson, S. E. (2003)    Flow chart summarizing the identification and selection of papers for systematic review