4.1 Reporting of the review findings
The protocol for this review is registered at PROSPERO with registration number: CRD42020157886. We will use the Preferred Reporting Items for Systematic review and Meta-analyses (PRISMA-2009) [22] (additional file 3) and (PRISMA-P 2015) [23] (Additional file 1) statements to report the findings. Moreover, we have used the guideline of the Prospero for registration.
4.2 Study design
A systematic review and meta-analysis will be conducted to determine the pooled prevalence of birth asphyxia and its determinants among newborns in Ethiopia.
4.3 Eligibility Criteria
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Participants (P)
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Intervention (I)
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comparison (C)
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Outcomes (O)
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Study type
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Limits
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Inclusion criteria
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Under-five children or children 0-59 months old
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· Risk Factors
OR
· Causes
OR
· Predictors OR
· Determinants
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-Children slept under ITN versus not use ITN
- rural Vs urban
-nutritional status
- male Vs female
-education level of mothers
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· Prevalence OR
· magnitude estimate
AND
· Factors associated with malaria
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Quantitative Studies
· Cohort study
· Case control
· Cross sectional studies
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· English languages
· Not limited by year
· Studies in Ethiopia
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Exclusion criteria
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Children whose age group not well defined
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Studies conducted with:
· Interventional
· case report
· expert opinion
· qualitative methods only
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· Studies conducted in other than Ethiopia
· Studies published with other languages
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4.4 PECO search guide
Population: Under-five children or children 0-59 months old
Exposure: Predictors/determinants of malaria. The determinants are characteristics or exposures that increase the likelihood of malaria among under five children. These may be related to maternal residence, maternal age, educational status, child nutritional status, ITN availability, and distance from malaria breeding sites.
Comparison: The reported reference group for each determinants or associated factors in each study (e.g. malaria in children living in urban area versus children living in rural area, children sleep under ITN versus children not sleeping under ITN beds at night, sex of the children, malnourished child versus well-nourished children, education level of mothers, … etc).
Outcome: We will include studies those assess prevalence of malaria and its determinants among under five children in Ethiopia.
Searching strategy
This meta-analysis will be prepared and presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA, 2009]. We will develop an appropriate and comprehensive search strategy with relevant search terms and pilot test it before the final search. We will search PubMed, MEDLINE, Google Scholar, and Cochrane electronic Databases. We will include articles published from start of indexing until December 30, 2019. We will use Medical Subject Heading (Mesh), keywords, and free text search terms. As the search terms, we will include alternative terms for malaria parasite, and will combine them using Boolean operators. To ensure the comprehensiveness, we will consult an expert librarian. The search strategy for PubMed is supplemented with this protocol (Additional file 2). We will utilize snowballing to screen the references of identified articles for potentially relevant studies. Furthermore, we will contact experts, researchers, and relevant organizations for suggestions on other existing relevant studies. Studies identified by our database searching strategy will be retrieved and managed using Endnote X8 (Thomson Reuters, Philadelphia, PA, USA) software.
Search terms: search (((“under-five children” OR “0-59 months old children” OR infants OR neonates)AND ( malaria OR “plasmodium falciparum” OR “plasmodium vivax” OR “mixed malaria” OR “plasmodium species”) AND (Prevalence OR incidence OR magnitude OR burden) AND (determinants OR “risk Factors” OR predictors OR causes OR associated factors”) AND (Ethiopia OR Ethio OR Etiopia))
4.5 Outcome measurement
This systematic review and meta-analysis will have two main outcomes. The first outcome is estimating the pooled prevalence of malaria among under-five children. Malaria is defined as children with confirmed malaria parasite infection. Pooled prevalence will be calculated by dividing the number of under-five children with malaria to the total number of children who have been included in the study (total sample size) multiplied by 100. The second outcome of the study is to identify maternal and child factors associated with malaria among under-five children. The predictors will be determined in the form of the log odds ratio.
4.6 selection of studies
Two authors (AW, and SB) will review the studies, based on inclusion and exclusion criteria. The review will follow three stages. In the first stage, reviewers will assess the titles of the studies identified from the search. In the second stage, abstracts of these selected titles will be included for the final stage of full-text screening. In the third stage, full-text screening, we will screen the full texts selected in the previous stage. If the articles are not open access, we will contact the corresponding author at least for three times. If the authors are not willing to provide the full text, we will exclude that specific article.
In the review, we will only include those studies approved by both authors. The authors will resolve disagreements through discussion or consultation with a third reviewer (KU). We will provide reason for exclusion for all excluded studies. Finally, we will prepare a final list of articles for data extraction
4.7 Data extraction and management
Three authors (AW, SB and MD) will independently extracted all necessary data using a standardized data extraction format, which is adapted from the JBI data extraction format for observational studies [24]. We will pretest the data extraction form on three studies of each type, to ensure that it adequately facilitates the collection of all necessary data required for an effective systematic review and meta-analysis. Discrepancies between data extractors will be discussed to reach consensus. If a consensus cannot be reached, the authors will consult a third reviewer (KU). For each included articles, we will record the first author’s last name, year of publication, the setting where the study was conducted, study design, study period, sample size, the response rate, the population, outcome definition, comparison groups, and the effect estimate.
4.8 Quality assessments
Four authors (AW, SB, KU and MD) will independently conduct quality assessment of included studies, by using the checklist of the JBI appraisal tool for cross-sectional, cohort and case-control studies (Additional file 3). In customising the scale to fit this study, we will took into account the study sampling methods and similarities between the study groups regarding adjustment for confounding factors, the ascertainment of exposure and outcomes, and study design. The abstracting tool will include different questions based on the study designs. The four investigators independently will perform the quality assessment while abstracting the data for the meta-analysis. The quality scores of the four abstractors will be averaged. Finally, the studies with higher scores (>50%) will be included into meta-analysis.
4.9 Data synthesis and analysis
The extracted data will be entered into a Microsoft Excel Database and then imported into STATA version 14.0 (Stata Corp LLC, Texas, USA) software with packages of Meta-analysis for further analysis. The researchers will perform a narrative description of the study population, the studies included, the risk factors identified, and the cause for malaria infection as well as the outcome characteristics. We will use tables and figures to summarize the selected studies and results.
The pooled prevalence of malaria among children under five in Ethiopia will be demonstrated using the random effect model [25]. The Freeman Tuckey variant of the arcsine square root transformation of proportions will be fitted to avoid variance instability when handling proportions close to one [26]. We will assess heterogeneity by using chi-squared test on Cochran’s Q statistic with a 5% level of statistical significance [26] and I2 statistic test [27], assuming that I2 value of 25%, 50%, and 75% being representative of low, moderate, and high heterogeneity, respectively [27]. If the heterogeneity is significant (I2 > 75%), then, we will conduct subgroup analyses and meta-regression to investigate sources of heterogeneity.
Publication bias will be examined by the visual inspection of funnel plots [28] and Egger’s test [29]. A p value < 0.10 will be considered indicative of statistically significant publication bias. Thus, if there is evidence of publication bias, we will use Duval and Tweedie’s trim-and-fill method [30].
For factors associated with malaria among under-five children; two-by-two tables will be constructed (if possible), the odds ratio with 95% confidence interval will be calculated. Then, the statistically significance level will be declared at a p-value less than 0.05. However, if the meta-analysis is not possible, we will conduct narrative synthesis.
4.10 Subgroup and sensitivity analyses
Sub-group analysis will be performed based on study design, sample size, regions or state, year of publication, quality of studies, and study settings of included studies. by years of publication, study setting, study design, and sample size of the studies. Finally, to conduct sensitivity analysis, we will assess the stability or robustness of the pooled estimates to outliers and the impact of individual studies [30].