Adherence to prenatal iron-folic acid supplementation in low- and middle-income countries (LMIC): A protocol for systematic review and meta-analysis

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Study Justification:
This study aims to conduct a systematic review and meta-analysis on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in low- and middle-income countries (LMIC). The justification for this study is that daily iron-folic acid supplementation has been shown to reduce anemia and improve obstetric outcomes. However, poor adherence to supplementation has been a challenge. By synthesizing contemporary evidence on adherence in LMIC, this study will provide up-to-date knowledge that can be used to optimize maternal and child health outcomes.
Highlights:
– The study will be the first systematic review on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in LMIC.
– The study will use rigorous methods, including the Newcastle-Ottawa Scale and Joanna Briggs Institute critical appraisal checklist, to assess the quality of included studies.
– The study will analyze data using comprehensive meta-analysis software and assess heterogeneity among studies using Cochran’s Q χ2 statistics and Higgins (I2 statistics) method.
– The study will present the results using forest plots and Harvest plots when necessary.
– The study will perform Jackknife sensitivity and subgroup analysis to further explore the data.
– The study will develop a PRECEDE-PROCEED conceptual framework in the context of LMIC to understand the factors influencing adherence.
Recommendations:
Based on the findings of this study, the following recommendations can be made:
1. Improve education and awareness about the importance of prenatal iron-folic acid supplementation among pregnant women in LMIC.
2. Enhance access to and availability of iron-folic acid supplements in LMIC, particularly in remote and underserved areas.
3. Implement strategies to address the side effects of iron-folic acid supplementation and improve acceptability among pregnant women.
4. Strengthen antenatal care services and increase the number of antenatal care visits to ensure regular monitoring and support for adherence.
5. Provide support and involvement from family and relatives to reinforce adherence to prenatal iron-folic acid supplementation.
6. Improve the overall healthcare infrastructure and ensure easy access to antenatal care services in LMIC.
Key Role Players:
1. Researchers: Conduct the systematic review and meta-analysis, analyze the data, and interpret the findings.
2. Clinicians: Implement the recommendations in clinical practice and provide guidance to pregnant women regarding iron-folic acid supplementation.
3. Policymakers: Use the findings to inform policy decisions and allocate resources for improving adherence to prenatal iron-folic acid supplementation.
4. Non-governmental organizations (NGOs): Collaborate with healthcare providers and policymakers to implement interventions aimed at improving adherence.
5. Community health workers: Educate and support pregnant women in adhering to iron-folic acid supplementation.
Cost Items:
1. Research team salaries and stipends
2. Data collection and analysis software
3. Publication and dissemination of findings
4. Training and capacity building for researchers and healthcare providers
5. Development and implementation of educational materials and campaigns
6. Procurement and distribution of iron-folic acid supplements
7. Monitoring and evaluation of adherence programs
8. Infrastructure and equipment for antenatal care services
9. Collaboration and coordination costs with stakeholders and partners

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is strong, but there are some areas for improvement. The protocol outlines a comprehensive search strategy and inclusion criteria, which increases the likelihood of capturing relevant studies. The use of established quality assessment tools also enhances the rigor of the review. However, the abstract does not provide specific details on the number of studies to be included or the expected sample size, which would further strengthen the evidence. Additionally, it would be helpful to include information on the potential limitations of the review and any potential biases that may arise. To improve the evidence, the authors could consider providing more information on the expected timeline for completing the review and any plans for addressing heterogeneity among the included studies.

Background: Daily iron-folic acid supplementation reduces anemia and various adverse obstetric outcomes such as preterm delivery, low birthweight, hemorrhage, and perinatal and maternal morbidity and mortality. However, its supplementation has not been successful that attributed to several determinants including poor adherence. Therefore, we aimed to conduct a systematic review and meta-analysis on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in low- and middle-income countries. In addition, we will develop a conceptual framework in the context of low- and middle-income countries (LMIC). Methods/design: We will search PubMed, MEDLINE, EMBASE, EBSCO, Web of Science, SCOPUS, WHO Global Index Medicus, and African Journals Online (AJOL) databases to retrieve relevant literatures. Observational (i.e., case-control, cohort, cross-sectional, survey, and surveillance reports) and quasi-randomized and randomized controlled trial studies conducted in LMIC will be included. The Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) critical appraisal checklist will be used to assess the quality of observational and randomized controlled trial studies respectively. The pooled prevalence and odds ratio of determinants of adherence will be generated using a weighted inverse-variance meta-analysis model. Statistical heterogeneity among studies will be assessed by Cochran’s Q χ 2 statistics and Higgins (I 2 statistics) method. The result will be presented using forest plots and Harvest plots when necessary. Furthermore, we will perform Jackknife sensitivity and subgroup analysis. Data will be analyzed using comprehensive meta-analysis software (version 2). Discussion: Contemporary evidence about the prevalence and determinants of adherence in LMIC will be synthesized to generate up-to-date knowledge. To our knowledge, this is the first systematic review. It would have substantial implications for researchers, clinicians, and policymakers for optimizing maternal and child health outcomes in LMIC. Systematic review registration: The protocol has been registered on International Prospective Register of Systematic Review (PROSPERO), University of York Center for Reviews and Dissemination ( https://www.crd.york.ac.uk/ ), registration number CRD42017080245.

This protocol has been written in accordance with the recommendation of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA-P) 2015 statement [14]. The PRISMA-P Elaboration and Explanation document is also used to develop the protocol [15] (Additional file 1). The protocol has been registered on International Prospective Register of Systematic Review (PROSPERO), University of York Center for Reviews and Dissemination [https://www.crd.york.ac.uk/], registration number CRD42017080245. Preferred Reporting Items for Systematic review (PRISMA-2009) statement will be used to report the findings. Furthermore, PRISMA flow diagram will be used to illustrate study screening and selection process. PubMed, MEDLINE, EMBASE, EBSCO, Web of Science, and SCOPUS databases will be searched to retrieve all available studies. We will also extend our searching to WHO Global Index Medicus and African Journals Online (AJOL). Cross-references of included studies will be hand-searched as well to access additional relevant articles that may have been missed in the search. In addition, we will search existing reviews and perform citing studies/snowballing search in PubMed and SCOPUS databases to screen all studies that cited included studies. Likewise, a search for gray literature will be conducted using Google Scholar and through browsing Hinari (http://www.who.int/hinari/en/), Carolina digital repository (https://cdr.lib.unc.edu/), and SpringerOpen-Open repository (https://www.springeropen.com/get-published/indexing-archiving-and-access-to-data/open-repository). Medical subject headings (Mesh), keywords, and free-text words were identified for selected PECO components. “OR”, “AND”, and “NOT” Boolean operators were used to combine search terms. Moreover, we will contact Cochrane Pregnancy and Childbirth Group, WHO headquarters and regional offices, the nutrition section of the United Nations Children’s Fund (UNICEF), the World Food Program (WFP), and US Agency for International Development (USAID) micronutrient program to identify additional studies [16]. The search strategy for PubMed database has been designed in consultation with medical information specialist and supplemented with this protocol (Additional file 2). The Peer Review of Electronic Search Strategies (PRESS) 2015 guideline statement is followed to prepare the search strategy [17]. The inclusion criteria are (1) observational (i.e., case-control, cohort, cross-sectional, survey, and surveillance reports) and quasi-randomized and randomized controlled trial studies, (2) studies conducted in LMIC, and (3) studies that reported the prevalence and/or least adjusted determinants of adherence. The most up-to-date World Bank country classification, when our review is published, will be used to categorize LMIC [18]. The search will not be restricted to any language and publication year. Qualitative studies that thematically analyzed the determinants of adherence will be included. Studies conducted in study populations other than pregnant women will be excluded. Moreover, case reports and expert opinion will be excluded. We will pilot the eligibility criteria in at least 200 references and double-check if they allow unambiguously included or excluded studies. Covidence web-based software will be used to remove duplicated articles and carry out all of the screening processes. First, articles will be assessed for inclusion through a title and abstract review by two independent reviewers. Disagreement will be solved by consensus; a third reviewer will be invited in case of persistent contradiction. Second, potentially eligible studies will undergo full-text review to determine if they satisfy the criteria set for inclusion. We will do a full-text review in duplicates and clearly document reasons for inclusion and exclusion. Finally, data will be extracted from all articles that meet the inclusion criteria. Data will be extracted using the Joanna Briggs Institute (JBI) data extraction form for experimental/observational studies (Additional file 3) [19]. The data extraction form will be pre-tested with 3–5 eligible studies. Two reviewers will independently extract all relevant information including study setting, sample size, prevalence of adherence to iron-folic acid supplementation, least-adjusted determinants, and source of funding. The prevalence of adherence to iron-folic acid will be extracted only if reported and/or estimated based on experts’ opinion or previously published studies or guidelines. In case of incomplete data, the corresponding author(s) will be contacted to find full information. Disagreement between reviewers will be resolved by consensus. The quality of all included studies will be rigorously assessed by two independent reviewers. The Newcastle-Ottawa Scale (NOS) will be used to assess the quality of cohort and case-control articles [20]. Similarly, cross-sectional studies will be examined using NOS adapted for cross-sectional studies. NOS has a good inter-rater reliability and validity [21]. The NOS criteria and its rating system have been published elsewhere [22]. The Joanna Briggs Institute (JBI) critical appraisal checklist will be used to assess the quality of quasi-randomized controlled trials [23]. Data will be analyzed using comprehensive meta-analysis software (version 2) [24]. Funnel plots and Egger’s regression test will be used to examine the possible risk of publication bias. Heterogeneity among studies will be assessed by Cochran’s Q χ2 statistics and Higgins (I2 statistics) method [25]. I2 describes the percentage of total variations across the studies due to heterogeneity rather than chance. I2 value greater than 80% will be indicative of considerable heterogeneity [26]. In addition, the heterogeneity among studies will be checked manually in terms of study population, geographic distribution, and methods. The pooled prevalence and odds ratio (OR) of determinants of adherence will be generated using a weighted inverse-variance meta-analysis model. If substantial heterogeneity is detected, random-effects model results will be reported. Arcsine transformation will be carried out to minimize the effect of studies with very high or low effect size if normality assumption will be fulfilled [27]. The result will be presented using forest plots [28] and Harvest plots [29] when necessary. Qualitative analysis will be performed to construct a PRECEDE-PROCEED conceptual framework in the context of LMIC [10]. PRECEDE-PROCEED conceptual framework includes four groups of factors: predisposing factors (e.g., age, educational status, income, knowledge on anemia and prevention), enabling factors (e.g., number of iron/folate tablets received, acceptability of iron/folate supplements, sides effects), reinforcing factors (e.g., number of antenatal care visits, use of reminding techniques, support from family and relatives), and environmental factors (e.g., availability of antenatal care, access to antenatal care) [10]. Leave-one-out Jackknife sensitivity analysis will be used to stabilize the variance of studies with very low or very large prevalence estimates [30, 31]. If the point estimate of the new pooled effect size is outside of the 95% confidence interval of the original/previous pooled effect size, it will be concluded that the excluded study has a significant effect on the pooled estimate. Thus, the study should not be included in the final analysis whether the effect of the study is too small or too large. In addition, the random- and fixed-effects model will be compared and decision will be made based on the best fitting model to the data. Subgroup analysis will be carried out based on epidemiological and/or clinical covariates that can impact estimates such as study design, measures of adherence, age of women, residence of women, and geographical distribution. If protocol modifications are required, we will include the detailed description of any changes along with a justification during the publication of the review results.

The protocol you provided is focused on conducting a systematic review and meta-analysis on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in low- and middle-income countries (LMIC). Based on this protocol, here are some potential innovations that could improve access to maternal health:

1. Mobile Health (mHealth) Interventions: Develop and implement mobile phone-based interventions to send reminders and educational messages to pregnant women about the importance of iron-folic acid supplementation. This could help improve adherence rates by providing timely and accessible information.

2. Community Health Worker (CHW) Programs: Strengthen and expand CHW programs in LMIC to provide education and support to pregnant women regarding iron-folic acid supplementation. CHWs can play a crucial role in promoting adherence by conducting home visits, organizing group sessions, and addressing any concerns or misconceptions.

3. Supply Chain Management: Improve the availability and accessibility of iron-folic acid supplements by strengthening supply chain management systems. This could involve optimizing procurement, storage, and distribution processes to ensure a consistent supply of high-quality supplements at health facilities and community settings.

4. Integration of Services: Integrate iron-folic acid supplementation with other maternal health services, such as antenatal care visits and immunization programs. This can help streamline service delivery and ensure that pregnant women receive comprehensive care, including access to iron-folic acid supplements.

5. Behavior Change Communication: Develop targeted behavior change communication campaigns to raise awareness about the benefits of iron-folic acid supplementation and address any cultural or social barriers that may hinder adherence. These campaigns should use culturally appropriate messaging and channels to effectively reach the target population.

6. Public-Private Partnerships: Foster collaborations between public and private sectors to improve access to iron-folic acid supplements. This could involve engaging pharmaceutical companies to produce affordable and high-quality supplements, as well as partnering with private healthcare providers to expand the reach of maternal health services.

7. Empowerment and Education: Empower pregnant women through education and involvement in decision-making regarding their own health. Providing comprehensive information about the importance of iron-folic acid supplementation and addressing any concerns or misconceptions can help women make informed choices and improve adherence.

These are just a few potential innovations that could be considered to improve access to maternal health, specifically in relation to adherence to prenatal iron-folic acid supplementation in LMIC. It is important to assess the feasibility, effectiveness, and sustainability of these innovations through further research and pilot programs.
AI Innovations Description
The recommendation described in the protocol is to conduct a systematic review and meta-analysis on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in low- and middle-income countries (LMIC). This recommendation aims to address the issue of poor adherence to iron-folic acid supplementation, which can have negative effects on maternal and child health outcomes.

The protocol outlines the methods and procedures that will be followed in conducting the systematic review and meta-analysis. The researchers will search various databases to retrieve relevant literature, including observational and randomized controlled trial studies conducted in LMIC. The quality of the included studies will be assessed using appropriate tools, such as the Newcastle-Ottawa Scale and Joanna Briggs Institute critical appraisal checklist. Data will be extracted and analyzed using comprehensive meta-analysis software.

The findings of the systematic review and meta-analysis will provide up-to-date knowledge on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in LMIC. This information will be valuable for researchers, clinicians, and policymakers in optimizing maternal and child health outcomes. The protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Overall, this recommendation aims to improve access to maternal health by identifying factors that influence adherence to prenatal iron-folic acid supplementation in LMIC and informing strategies to enhance adherence and improve maternal and child health outcomes.
AI Innovations Methodology
Based on the provided description, the protocol aims to conduct a systematic review and meta-analysis on the prevalence and determinants of adherence to prenatal iron-folic acid supplementation in low- and middle-income countries (LMIC). The goal is to generate up-to-date knowledge that can optimize maternal and child health outcomes in LMIC.

To achieve this, the following methodology will be employed:

1. Literature Search: The researchers will search multiple databases including PubMed, MEDLINE, EMBASE, EBSCO, Web of Science, SCOPUS, WHO Global Index Medicus, and African Journals Online (AJOL) to retrieve relevant studies. They will also search gray literature sources and contact relevant organizations to identify additional studies.

2. Study Selection: The researchers will include observational studies (case-control, cohort, cross-sectional, survey, and surveillance reports) as well as quasi-randomized and randomized controlled trials conducted in LMIC. The inclusion criteria will focus on studies that report the prevalence and/or determinants of adherence to iron-folic acid supplementation during pregnancy.

3. Quality Assessment: The quality of included studies will be assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies, NOS adapted for cross-sectional studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for quasi-randomized controlled trials.

4. Data Extraction: Relevant information including study setting, sample size, prevalence of adherence, determinants, and funding source will be extracted from the included studies. The data extraction form will be pre-tested and two independent reviewers will extract the data.

5. Data Analysis: Comprehensive meta-analysis software will be used to analyze the data. The pooled prevalence and odds ratio of determinants of adherence will be generated using a weighted inverse-variance meta-analysis model. Statistical heterogeneity among studies will be assessed using Cochran’s Q χ2 statistics and Higgins (I2 statistics) method. Funnel plots and Egger’s regression test will be used to examine publication bias.

6. Presentation of Results: The results will be presented using forest plots and Harvest plots when necessary. Qualitative analysis will be performed to construct a PRECEDE-PROCEED conceptual framework in the context of LMIC.

7. Sensitivity and Subgroup Analysis: Jackknife sensitivity analysis will be conducted to assess the impact of individual studies on the pooled estimate. Subgroup analysis will be performed based on relevant covariates such as study design, measures of adherence, age of women, residence of women, and geographical distribution.

8. Protocol Modifications: If necessary, any modifications to the protocol will be clearly described along with a justification when publishing the review results.

By following this methodology, the researchers aim to synthesize contemporary evidence on adherence to prenatal iron-folic acid supplementation in LMIC, which can inform researchers, clinicians, and policymakers in improving maternal and child health outcomes.

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