The main objective of this study is to determine the pooled prevalence of neonatal septicaemia in the sub Saharan Africa.
What is the pooled proportion of neonates with septicaemia in sub Saharan Africa?
What are the pooled frequency of risk factors of neonatal septicaemia in sub Saharan Africa?
What are the pooled frequency and types of pathogens and antibiogram of neonatal septicaemia in sub Saharan Africa?
What are the pooled outcomes of in-hospital mortality, length of hospital admission and frequency of necrotizing enterocolitis among neonatal with septicaemia in sub Saharan Africa?
What are the cumulative trends of neonatal septicaemia over the years?
This is a protocl for systmatic review and meta-analysis of observational studies conducted in the Sub Saharan Africa. This protocol is design to enable a reliable, transparent and accurate systematic review and meta-analysis. Using this protocol will enable determination of pooled prevalence of neonatal sepsis, pooled prevalence of risk factors, sub-group analysis of pathogens, antibiogram and the pooled prevalence of outcomes of neonatal septicaemia and cumulative trends over the years in the sub Saharan Africa. There is no timeframe or restriction in selecting eligible studies using this protocol.
Observational studies: Cohort studies, case controls, cross-sectional studies, historic cohort studies.
Studies must report the primary outcome: proportion of neonatal septicaemia.
Studies must be retrievable in the English Language.
Studies that report any of the following secondary outcomes, e.g risk factors, outcomes, bacterial isolates and antibiogram, in addition to primary outcome, will be included.
Reviews, editorials, commentaries, methodological articles, letters to editors, case reports
Studies reporting in- vitro and animal studies.
Duplicates/ replicates of studies.
Studies not retrievable in the English Language.
Studies on Surgical patients.
Neonates with multiple congenital malformations.
PICOs: The details for participants, intervention, comparison and outcomes (PICOs) are shown in Table 1.
This review will be reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2015 Statement).15 The Protocol has the PRISMA-P Checklist attached as a supplementary material.
The search will employ sensitive topic-based strategies designed for each database. The search will be carried out in the following databases: PUBMED, EMBASE, CINAHL, RESEARCHGATE, AJOL, GOOGLE SCHOLAR, WEB OF SCIENCE, SCOPUS and COCHRANE LIBRARY. Only observational studies will be included. There is no time frame for selection of studies.
The search strategy includes MESH terms, text words and entry terms. Table 2 shows the search strategies as used in the Pubmed. The same search strategy will be used in other databases with slight modifications.
Data Extraction and Management
a. Data Extraction
Four main tools will be used for data extraction and management: a) EndNote version 9, b) Rayyan QCRI systematic review screening tool and c) Microsoft Excel and d) CMA Version 3 Software
Five levels of data screening will be used for searched studies:
Level 1 would involve screening of identified studies for the study design. Only observational studies, retrievable in the English Language would be selected.
Level 2 will involve screening of selected studies in the titles and abstracts using entry terms, keywords and meSH terms.
At Level 3, selected studies will be further screened for content by reading the full article using the same search strategy.
Level 4 will involve snowballing of literature on references from included studies.
Level 5 will involve grey literature that report primary outcome and or secondary outcomes.
Seven reviewers are involved in this study. A pair of reviewers will independently screen the selected article for eligibility using Rayyan QCRI systematic review screening tool.16 The two reviewers will be blinded from each other using the screening tool. Conflict between the paired reviewer shall be resolved by a third reviewer who would will server as a tie -breaker. The data of all screened studies will be exported into MICROSOFT EXCEL. Snowballing search of relevant studies through the review of the references of selected studies and grey literature will be performed manually.
b. Selection Process:
Agreement between two independent and blinded reviewers who screened titles, abstracts, full texts of eligible observational studies, snowballed articles and grey literature will form the basis for selecting studies for inclusion for systematic review and meta-analysis. Where there are conflicts in decision, this will be resolved by a third reviewer. Authors of eligible studies with any missing data will be contacted via email and telephone.
c. Data Collection Process:
Deduplication of studies will be done using End note version 9.17 Eligible studies will be screened using Rayyan QCRI and exported into Microsoft Excel. All templates for housing extracted data items will be created in Excel.
The following data items will be extracted from eligible studies and entered into MICROSOFT EXCEL:
1. The last name of the first author and the year of publication
2. The country and region in sub-Saharan Africa
a. Number of neonates with sepsis
5. Number of neonates with confirmed sepsis (bacterial isolate identified by bacterial culture)
6. Number of neonates with probable sepsis (laboratory evidence supports sepsis but no isolate)
7. Number of neonates with presumed or possible sepsis (risk factors for sepsis but no laboratory evidvence)
8. Risk factors for septicaemia
10. Secondary outcomes
a) In-hospital mortality
b) Length of hospital admission
c) Frequency of necrotizing enterocolitis
Data from MICROSOFT EXCEL file will be exported in CMA software for meta- analysis
Data items/Measurable outcomes
The measurable outcomes are
Proportion of neonates with septicaemia in sub Saharan Africa.
The proportion of risk factors in reported neonatal septicaemia in sub Saharan Africa.
The frequency of pathogens and patterns of antibiogram in neonatal septicaemia in sub Saharan Africa.
The frequency of outcomes such as mortality, length of hospital admission and necrotizing entercolitis in neonatal septicaemia in sub Saharan Africa.
The primary effect size is prevalence.
Different primary indexes in individual studies of same design and report outcome will be converted to prevalence in the CMA Software.
Categorical outcomes will be used for subgroup analysis.
Numerical outcomes will be used for meta-regression.
Studies that passed the methodological quality assessment using the NIH quality assessment tool will be extracted. The results will be presented in tabular format.
in addition to a narrative synthesis, the following will be included in the meta-analysis:
The proportion of babies with neonatal septicaemia.
Categorical variables for subgroup analysis
Numerical variables for meta-regression
c. Quantitative analysis
Pooled prevalence of neonatal septicaema, standard error and variance will be calculated with 95% CI. This is the primary measurable outcome.
Sub-group analysis will be performed using categorical data on i) regions in Sub Saharan Africa, ii) types of pathogens, iii) the antibiogram, iv) risk factors and v) the secondary outcomes.
Subgroup analysis will be performed using categorical data such as geographical location, types of bacterial isolates, antibiogram, components of risk factors and outcomes as moderators. Results of subgroup analysis will be presented in forest plots.
Meta-regression will be performed on prevalence of neonatal septicaemia as outcome variable using frequency of risk factors, length of hospital admission, gestational age at birth and mortality as explanatory variables. This will establish a regression model for predicting prevalence of neonatal septicaemia.
A cumulative meta-analysis will performed to check for trend in prevalence of neonatal septicaemia of the years.
Eligible studies will be quantitatively analysed using the Comprehensive Meta-Analysis (CMA) software version 3 (Biostat, USA).18.
Criteria for Quantitative data Synthesis
The pooled prevalence, standard error, variance and 95% confidence interval, and. Heterogeneity will be assessed using the Q statistics and its p-value, tau2 and the Higgins I2. I² values of less than 40% will be considered low heterogeneity while values > 40 but < 75% will be considered moderate and values > 75% are high. A random-effect model will be used for computation in this study. A sensitivity analysis will be performed to check for outlying studies and their effects on pooled prevalence of neonatal septicaemia. Publication bias in the selection of studies will be visually assessed on the funnel plot (trim and fill method) and tested for asymmetry. Other statistical tests such as Egger’s regression intercept, Begg and Mazumdar's rank correlation and Orwin’s fail-safe N will be used where appropriate.
Risk of bias
The risk of bias in the included studies will be accessed for the individual article using the National Institute of Health (NIH) Quality assessment tool for observational cohort and cross-sectional studies. The NIH Quality assessment tool has 10 questions. This will be cross-checked with the Cochrane tool of risk of bias assessment for the strength of the body of evidence; i.e. using specific relevant items from this tool to assess the strength of the body of evidence.. Studies with extreme bias will be subjected to sensitivity testing using the include/exclude function in the CMA Software.
Assessment of Meta-bias
Meta-bias will be assessed as follows:
Method of testing/reporting of neonatal septicaemia at the outcome level.
Reporting of study: Studies that were reported in different units but similar in outcome and design will be converted based on individual case evaluation. This will be evaluated for individual studies by assessing the unit of reporting of studies, for example, whether prevalence with confidence intervals or incidence or proportion will be reported.
Heterogeneity will be assessed at the study level using the Q statistics and its p-value, tau2 and the Higgins I2
Publication bias will be assessed at the study level using the funnel plot (trim and fill method) and test for asymmetry
Sensitivity analysis will assessed at the study level using include and exclude function in the CMA Software