The review protocol follows the recommendations of the Briggs Institute Manual of Evidence Synthesis(24). In addition, to ensure transparency and non-duplicity of the publication, as well as to minimize the presence of biases during its execution, this protocol was publicly registered in Prospero database (registration number CRD42020188474).The present study protocol is being reported in accordance with the reporting guidance provided in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement(25).
Review question
What is the prevalence of complex B vitamins deficiency in women at reproductive age in Brazil?
Eligibility criteria
Studies will be selected according to the following criteria:
Population/participants
Women of reproductive age (10 to 49 years of age), including pregnant and lactating mothers. Initially, any study conducted in Brazil aimed identify the deficiency of complex B vitamin will be selected, and their study`s participants will be analyzed. If they includes women at 10 to 49 years, but not only, the authors of study will be contacted to provide the proportion of women in this age group with the outcome. The study will be only eligible if the authors return with the requested information.
Outcome(s)/clinical situation of interest
The outcome of this review is the body deficiency of the Complex B vitamins. The diagnostic of vitamin deficiency should be done by biochemical assessment following the recommended laboratory methods/techniques. The cut-off values for deficiency could vary according to the method/technique used and subsets of the population. Studies in which the deficiency was identified by clinical signals and symptoms will not eligible.
Study design
This systematic review will include cross-sectional studies or cohort. In case of cohort with multiple investigations of our interesting outcome, in global analysis, we will use the rate of the most recent analysis in which it was investigated, but for temporal analysis, all rates investigated in distinct moments of the follow-up will be included. Only fully published studies in the form of a scientific article or academic thesis, dissertation or monograph will be eligible. No published studies or studies without full text access, besides conference proceedings, editorials, case reports, case-control, letters and trials will be not eligible.
Epidemiologic indicator
Studies that provided the prevalence rates of the outcome will be eligible. Original studies that did not present the prevalence rates but described the proportion of eligible women with deficiency of any vitamin from complex B will be eligible if the prevalence may be calculated.
Setting/location
Only studies carried out in Brazil will be eligible. Studies in any setting (primary care, hospital, outpatient, clinic patients) representing the general population or subgroups that reflects populational conditions will be eligible. It will be ineligible: studies carried out only with patients with diseases or any pathological condition (except obesity associated to their comorbidities); situations that affect the digestion, absorption, metabolization rates and daily requirements of the vitamins such as post-bariatric surgery, athletes and vegetarians; and studies on which the vitamins deficiencies are assessed in woman with genetic polymorphisms/variants that affect the body status of the vitamins B complex. However, studies that determine the prevalence of the polymorphism related to and the deficiency rates of the vitamin B, not conditioning one to another, will be eligible.
Information sources and search strategy
The primary source of literature will be a systematic and structured search of the following electronic databases: MEDLINE (PubMed), Embase, Web of Science (main collection), Scopus, SciELO Citation Index (by Web of science), Literatura Latino Americana e do Caribe em Ciências da Saúde - LILACS (by Biblioteca Virtual em Saúde - BIREME) and a Brazilian database of academic thesis and dissertations (Biblioteca Digital Brasileira de teses e dissertações - BDTD). The secondary source of potentially relevant studies will be a consultation to Brazilian researchers in the areas of Health, Medicine, Nutrition, and Public Health allocated in public Universities of the country, by e-mail. The literature searches were designed using search terms underpinning by the inclusion criteria and ensured by MeSH Terms and Emtree terms. The search strategies were created by combining search terms with Boolean operators and using search facilitators (quotation marks, truncation symbol, proximity operators) and were adapted by each database. Before official electronic search, the search strategies were piloted to ensure sufficient specificity and sensitivity. After this step, to improves the specificity we included in the search strategies general terms of exclusion criteria. The search strategies that will be used in the official literature search are presented in supplementary file 1. Additionally, we will perform hand-searching of the reference lists of included studies, relevant reviews, or other relevant documents. No limits of publication date and languages will be defined.
Study selection
The results from the literature search will be transferred to Ryyan QCRI, the Systematic Reviews web app (26) for the management of the references. In the app, the repeated references will be identified by one reviewer and only one of its multiple records will remain for the next step. In the phase of study selection, two reviewers will be analyzing the titles, abstracts and full texts for eligibility. They will be blinded and at the conclusion of the process, the judgement of each will be confronted. In case of discrepant judgment about the study eligibility, this study will be analyzed by the reviewers, and a consensus will be reached by discussion. Initially, the titles will be read and if it appears eligible, the abstracts and full texts will be read to confirm eligibility.
Data extraction
Data extraction of the eligible studies will be performed by two reviewers, independently, registering the data in a customized Microsoft Office Excel® sheet, that will be pilot tested prior to initiating the data extraction process. The extracted data by the two reviewers will be confronted and any disagreement resolved by new consultation of the study. In this process, the original authors may be consulted for any additional information not (fully) presented in the publication by e-mail or by Research Gate. The information that will be extracted from the studies are: study identification; year of publication; type of publication; local (city and State) and period in which the study was conducted; study design; population group (pregnant, lactating woman or women not pregnant or lactating) and their characteristics (age range or mean/median, setting of recruitment, proportion of obese or malnourished participants, proportion of chronic diseases; use of medicines and vitamins supplements; and other clinical and demografic characteristics; for pregnant, trimester of the analysis); sampling process; number of participants recruited and analyzed; sample size calculation; vitamins B deficiencies investigated and their diagnostic method; the prevalence data and their 95%ICor the number of cases for prevalence calculation.
Data synthesis
Initially we will perform a narrative description of the summary of results. For the selection process, the results will be presented in accordance with the PRISMA flow diagram. The information extracted about each study (characteristics) and the prevalence rates (and 95% IC) of complex B vitamins deficiencies will be presented in a summary table. The results will be presented separately for pregnant, lactating woman and women not pregnant or no lactating and for each vitamin B assessed.
Meta-analysis will be done using random model and using STATA 16.0 software and the Metaprop and Metapreg packages. Random effects model will be applied to estimate the pooled prevalence, since we will expect heterogeneity among the studies a priori. The proportion (prevalence) of cases will be transformed to logit before combine the data in the metanalytic approach. Statistics for heterogeneity (test Q de Cocran and I²), publication bias (Begg`s test, Egger`s test and Trim & Fill method) if there are ten or more studies in a global meta-analysis, and sensitivity analysis will be also done. For meta-analysis, we entry in the software the prevalence rates and their 95%IC.
For each subpopulation (pregnant, lactating woman and women not pregnant or no lactating) and each vitamin B, if there are two or more studies that fulfilled each subgroup criteria, we intend to stratify the analyzes by:
- Time/Year (temporal analysis), showing the prevalence rates in a timeline graph, and specific for folate, we will stratify in before 2002 and after 2002, because this year it became mandatory to enrich wheat and corn flours with folic acid in the country.
- Age group: 15 to 19 y; 20 to 35 y; >35 y.
- State and Geographic Region of the Brazil: 24 States + Federal District; 5 macro-regions of the country (north, south, southeast; midwest; and northeast).
- For pregnant: trimester of gestation (1st, 2nd or 3th).
- Lactation period: 1st semester; 2nd semester; 2nd year.
- Other that may reduce the possible heterogeneity among the studies and/or modify the prevalence rates. Individual meta-analysis will be done by each subgroup above described, including only studies that attend this subgroup criteria. Meta-regression may be applied to investigate these factors/variables associate with the modification of the prevalence rates.
Risk of bias
The risk of bias will be assessed following the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data (available in https://jbi.global/sites/default/files/2020-08/Checklist_for_Prevalence_Studies.pdf). This tool encompasses nine items about the sampling process, sample size, description of the study subjects, identification / diagnosis of the clinical condition, statistical analysis and response rate. Adequation for each domain / items will be classified as adequate (YES), inappropriate (NO), absence of clear information to judgment (UNCLEAR) or not applicable (N / A). This procedure will be done by two reviewers, independently, and the judgments will be confronted. Eventual disagreements in the risk of bias assessment process will be solved by discussion until consensus. The results of this step will be presented in a table, describing the judgment for each domain assessed and their reason (s).