The magnitude and Associated Factors of Pneumonia Among Under-Five Children in Ethiopia: A Systematic Review and Meta-Analysis

Background Currently, Pneumonia is the leading cause of morbidity and mortality among under-five children in developing countries including Ethiopia. Despite, these problems are easily preventable and treatable it contributes to more than 18% of deaths of under-five children every year in Ethiopia. Regardless of these facts, there is a paucity of information regarding the magnitude and its predictors of pneumonia in Ethiopia. Thus, assessing the pooled magnitude of pneumonia and its predictors among under-five children in Ethiopia is the main objective of this review. Methods The international databases such as MEDLINE/PubMed, EMBASE, Google Scholar, Science Direct were scientifically explored. We considered all primary studies reporting the magnitude of pneumonia among under-five children and its predictors in Ethiopia. We retrieved all necessary data by using a standardized data extraction format spreadsheet. STATA 14 statistical software was used to analyze the data and Cochrane Q test statistics and I 2 test was used to assess the heterogeneity between the studies. There was significant heterogeneity between the studies so that a random effect model was employed. Result Recommendations This relatively

In Ethiopia, contradicted and inconsistency studies have been conducted to assess the magnitude and predictors of pneumonia among under-five children. The impact is still higher and with abundant discrepancy and inconstancy across regions related to assessing the magnitude and predictors of pneumonia. Data on the magnitude of pneumonia and their related risk factors are important for planning child health care services but scarce in Ethiopia. Regardless of these facts, in Ethiopia, there is a paucity of information regarding the magnitude and predictors of pneumonia. Thus, assessing the pooled magnitude of pneumonia and its predictors at a country level is essential and will provide an overall figure with better estimation. Therefore, the main objective of this systematic review and meta-analysis was to estimate the pooled magnitude of pneumonia and its predictors in Ethiopia. Findings obtained from this review will contribute to evidence for policymakers and program planners who working at various levels on the area to inform, plan, implement and evaluate health promotion policies and strategies. The study also will provide baseline information for researchers.

Searching strategies and Study design
This review was considered to evaluate the combined magnitude and predictors of pneumonia among under-five children in Ethiopia. In this review, we searched databases without limit to the date of publication and study design. To confirm the scientific accuracy, the Preferred Reporting Items of Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) guideline was used [14]. The international databases include MEDLINE/PubMed, EMBASE, Web of Sciences, Scopus, and Grey literature databases, Google Scholar, Science Direct and Cochrane library were scientifically explored. Also, we assessed reference lists of the articles found through the database search to retrieve additional articles and included the articles relevant to our topic of review. Unpublished studies were retrieved from the official websites of international and local organizations and universities. The search was performed by keywords, medical subject headings (MeSH) terms. We used the search terms independently and/or in combination using "OR", "AND" or "NOT". Keywords/search terms were "magnitude" OR "Epidemiology" AND "Children" AND/OR "Under Five Children" AND/OR "Childhood" AND/OR "factors" AND/OR "associated factors" AND/OR "risk factors" AND/OR "determinants" AND/OR "predictors" AND" Ethiopia". All articles conducted from September 30, 2019, up to November 30, 2019, and all accessible studies up to November 30, 2019, were incorporated in our meta-analysis and systematic review.

Study Identification, Selection and Eligibility Criteria
This meta-analysis and systematic review included the primary studies that assessed the magnitude of pneumonia and predictors among under-five children in Ethiopia.

Inclusion criteria
The magnitude and associated risk factors of pneumonia among under-five children in Ethiopia Study area: Only articles conducted in Ethiopia.

Study design:
All observational studies (cross-sectional, case controls, and cohort) that contain original data reporting the prevalence and associated risk factors of pneumonia among under-five children in Ethiopia were considered.

Language: It included literature published in English.
Population: Studies carried out in Ethiopia among children under five were considered.
Publication condition: A consideration was extended to both published articles and unpublished work in English.

Exclusion criteria:
Research that was unpublished, irretrievable from the internet or failed to receive email replies from the corresponding authors was excluded. Furthermore, research which did not report our results of interest was excluded after a complete review of the texts

Outcome of interest
The main result of this study was to estimate the pooled magnitude and identify pneumonia predictors among children under five in Ethiopia.

Data extraction and synthesis
Data were retrieved by two independent reviewers (YM and FA) by using a standardized data extraction spreadsheet format. The data abstraction format includes the author, the study year, region of study setting (region and rural or urban), study design, sample size, magnitude, and predictor variables. Any disagreements during the extraction process were solved by consensus between the reviewers. If we got incomplete data, we excluded the study after two attempts were made to contact the corresponding author by email. Also, the two authors (YM and FA) performed the quality assessment of studies independently. Any discrepancy was resolved by discussion and agreement.

Quality Assessment (appraisal) of the individual studies
Duplicate articles were removed manually using Endnote (version X8) after combining the Database search results. To assess the quality of each study, Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) adapted for both cross-sectional and case-control study design was used [15]. The original study was assessed by two reviewers independently and any disagreement between the reviewers was solved by taking the mean score of the two reviewers. Finally, the original studies which score five and above were included in the final review.

Statistical methods and analysis
For farther analysis, we imported the data to STATA version 14.0 statistical software after extracting the data using Microsoft Excel format.
Using the binomial distribution formula, Standard error was calculated for each study. The overall pooled magnitude of pneumonia among under-five children in Ethiopia was calculated using the standard error (SE) from each study. The pooled magnitude of pneumonia with 95% CI was presented using forest plots and Odds ratio (OR) with 95% CI was also presented in forest plot to show the predictors with pneumonia. We identify the heterogeneity between the studies using Cochrane's Q statistics (Chi-square), inverse variance (I 2 ) and p-values [16]. Heterogeneity or variation across studies was assessed using the inverse variance (I 2 ) with Cochran Q statistic at 25%, 50% and 75% was used to declare as low, moderate and high heterogeneity respectively [17].
The statistical output showed that there was significant heterogeneity among the studies (I 2 = 97.9%, P ≤ 0.001) so that we used a random-effects meta-analysis model to estimate the pooled magnitude and predictors of pneumonia among under-five children in Ethiopia. Also, we used a forest plot to detect the presence of heterogeneity. Furthermore, subgroup analysis was conducted by region of the study, study period and sample size, and meta-regression were used to identify the possible source of heterogeneity. The evidence of publication bias was checked using funnel plot symmetry. Besides, the statistical significance of publication bias was assessed using both Egger's and Beggar's test, subsequently, a trim-and-fill analysis was performed, with the pvalue, less than 5% was used to declare the presence of publication bias [18,19].

Selection of studies
A total of 426 studies were identified using electronic searches (through Database searching (n = 422)) and other sources (n =4)) that were conducted from 2014 up to 2019. Of these, 98 studies were excluded due to duplication. From the remaining 328 studies, after reviewing the title and abstract 312 studies were excluded as they were irrelevant for this systematic review and meta-analysis. The remaining 16 full-text articles were assessed for eligibility criteria based on the pre-defined criteria. Among these four articles were further excluded due to they are not in line with the preset criteria. Finally, 12 studies were fulfilled the eligibility criteria and included in this systematic review and meta-analysis (Fig.1).

Characteristics of the studies
In this review, a total of twelve articles met the inclusion criteria. A total of 4598 Study participants included in his systematic review with an estimated sample size a range from 206 to 558 in SNNP [20,21] in individual studies, and all the included studies were published between 2015 and 2019. Both cross-sectional and casecontrol studies were included in the current review.

Magnitude of Pneumonia Among Under Five Children in Ethiopia
The magnitude of Pneumonia Among Under Five Children in Ethiopia from included studies ranged between 4.1% to 39.6% [24,30]. As indicated in the forest plot below, the pooled magnitude of Pneumonia Among Under Five Children from 12 studies in Ethiopia was 20.68% (95% CI: 12.49, 28.88). We identified a high and significant heterogeneity between studies (I 2 = 97.9%%; P ≤ 0.001), indicating great variability in magnitude of pneumonia across studies, random effect analysis model was used to estimate the pooled magnitude of pneumonia among under-five children in Ethiopia (Fig. 2).

Publication bias
Publication bias was observed using both Begg's and egger's test [18,19], the value was found to be significant at a p-value of 0.004 and 0.020 respectively. These tests showed that there was statistical evidence of publication bias at a p-value less than 0.05 and the funnel plot was asymmetry. By considering publication bias trim and fill meta-analysis [31 was done to account for the publication bias. However, based on this analysis, the prevalence of pneumonia among under-five children was 20.68 and no significant change was showed as compared with the main meta-analysis.

Sensitivity and Subgroup analysis
Due to considerable heterogeneity in this review, Subgroup analysis was done to identify the source of heterogeneity based on the region and sample size. Subgroup analysis by region reports the pooled prevalence of pneumonia among under-five children was higher in the Amhara region (27.80 %) followed by Oromia region (22.65 %). Subgroup analysis was also carried out based on the sample size, according to this analysis the prevalence rate of 24.72% and 4.79% were revealed from Sample Size < 384 and Sample Size ≥ 384 respectively ( Table 2). A sensitivity analysis was done to identify outlier studies. According to the analysis, no influential studies were detected so that all of the studies were included in the final analysis (Table 2).

Meta-regression
Besides subgroup analysis and publication bias, univariate and categorical meta-regression analysis was performed undertaken by considering both continuous and categorical data for the included studies to identify sources of for heterogeneity for the pooled prevalence. In meta-regression analysis, Sample size, publication year and study regions were considered for each study. However, there was no statistical significance value from the meta-regression analysis. Hence, the pooled prevalence of pneumonia among under-five children was not associated with sample size, publication year and study region ( Table 3).

Predictors of pneumonia among under-five children
In this review, a total of 12 studies were included for analysis of predictors of pneumonia among under-five children. We identified six main associated factors with the pooled odds ratio ranging from 2.45 to 4.11. These predictors were Vaccination, Place of food cooking, VitA  (Table 4).

Discussion
Currently, pneumonia among under-five children is a driving cause of morbidity and mortality in middle and lowincome countries including Ethiopia. Assessing prevalence and its risk factors of pneumonia are essential for proper planning of child health care services, for proper management and prevention strategy. In this metaanalysis, we systematically reviewed studies assessing pneumonia and associated factors among under-five children in Ethiopia. As far as our knowledge, there is no previous review of the issue. Thus, this systematic review and meta-analysis aimed to estimate the pooled prevalence of pneumonia and its predictors in Ethiopia. The pooled Prevalence of Pneumonia Among Under Five Children from 12 included studies in Ethiopia was 20.68% (95% CI: 12.49, 28.88), (I 2 = 97.9%%; P ≤ 0.001). This finding is lower than another studies done in Austria (4.1%) [31], in Mali (6.7%) [32], in Kenya (6.9%) [33]. In contrast to this, our finding is higher than the studies done in Bangladesh (21.3% ) [34], in Nigeria (31.6%) [35] , in Uganda (53.7% ) [36]. This discrepancy may be due to socio-economic and socio-demographic vitiations, the difference in the study setting, seasonal variation, inaccessibility and provision of Vitamin A supplementation and immunization, lack of confirmatory laboratories and imaging investigations. This review showed that children from the household who used charcoal and main house for a place of cooking were more than two times more likely to develop pneumonia than those who did not use it. This finding was supported by other studies [22,37,38]. The possible explanations could be high indoor air pollution may adversely affect host defenses of the respiratory tract against pathogens. This finding also supported by the UNICEF report confirmed that exposing children to household air pollution like solid fuels during cooking food in the main house double their risk of pneumonia [39]. Children who were not ever supplemented with Vitamin A were almost three times more likely to develop pneumonia as compared to children who got Vitamin A supplementation. This finding is in agreement with that of a study done in Rwanda [40]. This may due to the fact that the role of vitamin A is essential in the growth and development of respiratory epithelial cells and lung tissue [41]. Our study finding indicated that unvaccinated children were 2.45 times more vulnerable to develop pneumonia as compared to children who fully vaccinated which were supported by the study undertaken in India [42]. This could be justified that vaccinations and immunizations prevent children from developing infections that can lead to pneumonia as a complication [43]. Also, the odds of pneumonia among under-five children who had not got exclusive breastfeeding were 2.46 times higher risk to develop pneumonia as compared to children who had got exclusive breastfeeding during the first six 6 months. This result is in agreement with the UNICEF report [39]. This review revealed that children who had MUAC less than 11.5 cm were three times more likely to develop pneumonia than children who had MUAC greater than or equal to 11.5. It supported by a study conducted in India [44]. This might have explained that undernutrition which weakens the child's overall immune system and undernourished children have weakened respiratory muscles, which inhibits them from adequately clearing secretions found in their respiratory tract makes the child vulnerable to pneumonia [39]. According to this review, Children who had a history of respiratory tract infection were 4.11 times more likely to develop pneumonia compared to those who had no respiratory tract infection which was supported by the studies done in Kenya and Netherlands [45,46].

Strengths and limitations
Primarily, this systematic review and meta-analysis used internationally accepted tools for a critical appraisal system for quality assessment of individual studies. It included both published and unpublished articles.

Conclusion And Recommendation
This review showed that the prevalence rate of pneumonia was relatively high in Ethiopia compared to other studies' reports from developing countries. Vitamin A supplementation, vaccination status, malnutrition, history of child respiratory tract infection, place of food cooking and breastfeeding status during 6 months were independent potential predictors of under-five pneumonia. Hence, appropriate intervention on potential determinates such as health education on exclusive breastfeeding and nutrition, place of food cooking, increase immunization and Vitamin A supplementation and early control of respiratory tract infection was recommended to prevent those risk factors.

Availability of data and material
The datasets analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests
We have confirmed that we have no competing interests.

Funding
No funding was obtained for this study.
Authors' contributions YM and FA: developed the study design and protocol, literature review, selection of studies, quality assessment, data extraction, statistical analysis, interpretation of the data and developing the initial drafts of the manuscript and prepared the final draft of the manuscript. Both authors read and approved the final manuscript Acknowledgments we gratefully thank the primary authors of the included studies.

Authors information
1 Department of Biomedical Sciences School of Medicine, Debre Markos University, Debre Markos, Ethiopia.

Supplementary Files
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