The Prevalence, Risk factors and Outcomes of Anaemia in South African Pregnant Women: A Protocol for a Systematic Review and Meta-analysis

The Prevalence, Risk factors and Outcomes of Anaemia in South African Pregnant Women: A Protocol for a Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Protocol The Prevalence, Risk factors and Outcomes of Anaemia in South African Pregnant Women: A Protocol for a Systematic Review and Meta-analysis Vinogrin Dorsamy, Chauntelle Bagwandeen, Jagadesa Moodley This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-16197/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Sep, 2020 Read the published version in Systematic Reviews → Version 2 posted 11 You are reading this latest preprint version Show more versions Abstract Background A significant cause of morbidity and mortality during pregnancy is maternal anaemia. The causes of anaemia and the sequelae are varied, and the prevention and management are public health challenges, especially in resource limited settings and certain geographic locations. South Africa is plagued by a quadruple burden of disease, with high maternal mortality rates affected by hypertensive disorders of pregnancy, HIV, tuberculosis and neglected tropical diseases. This is most prevalent in people of lower socio-economic status. Poor nutrition, chronic infections, lack of access to health care facilities and poor compliance with micronutrient supplementation all contribute to maternal anaemia. The aim of this study is to systematically map the literature to ascertain the pooled prevalence and associated causes of anaemia in the South African pregnant population, which will enable health care workers and other key stakeholders to more pertinently address Sustainable Development Goal 3 focussing on good health and reducing maternal mortality. Methods PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS will be searched, using the keywords ‘anaemia’, ,’haemoglobin’, ‘pregnancy’, ‘South Africa’, to conduct a systematic review and meta-analysis to explore, describe and map literature on the distribution and burden of anaemia in pregnant women in South Africa. The reference list of articles selected for review will be scanned for other articles of interest to our study question. Studies published in any language will be included in this review. As there may be differences in sampled populations in South Africa based on geography and sociodemographic factors, a weighted inverse-variance meta-analysis using a random-effects model will be carried out to generate a pooled prevalence estimate. A Funnel plot and Egger’s regression test will be conducted to assess publication bias. Heterogeneity among studies will be checked using I 2 to determine dispersion and meta-regression analysis will be performed to investigate the source of heterogeneity. The articles obtained by these searches will be analysed for causative factors, severity and outcomes by a parallel and independent review team, using suitable eligibility criteria. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Disagreement will be resolved by independent assessment by a third reviewer. Sub group analysis by region, stage of pregnancy, socio-economic status, severity and cause of anaemia will be conducted if sufficient data is available. Data will be analysed using statistical software, and presented in evidence tables and in meta-analytic forest plots. Discussion This protocol is developed to systematically review the literature on the prevalence and severity of anaemia, risk factors and outcomes in pregnant women in South Africa. Correlation of factors contributing to the development of anaemia and other disorders during pregnancy will facilitate exploration of appropriate medical and behavioural change interventions implemented within other countries or regions that mitigate risk. This study will assist local health systems to inform public health policies and practises for more favourable maternal and fetal outcomes. Sexual & Reproductive Medicine Maternal & Fetal Medicine Anaemia Pregnancy South Africa Background Anaemia, defined as a decrease in red blood cells or haemoglobin, or the reduced capacity of red blood cells to carry oxygen (1) is a common chronic problem in low to middle income countries, such as South Africa. It is a product of socio-economic disparity, affecting mostly the poor and less educated (2). It is most prevalent in the vulnerable: children, adolescents in their growth phase and females of reproductive age(3). The condition is exacerbated by pregnancy, when there is an increased burden to deliver oxygen to the fetus, and can result in intrauterine growth restriction, reduced iron for the baby and increased maternal and perinatal morbidity and mortality (4). Anaemia affects almost 2 billion people worldwide, with iron deficiency anaemia being the commonest cause. As with other low and middle-income countries with similar sociodemographic characteristics, the South African population is more susceptible to anaemia due to the prevalence of chronic nutritional insufficiency and concomitant infective conditions (5). The World Health Organisation (WHO) reports the prevalence of anaemia in women of reproductive age women in sub-Saharan Africa to be 57.1% (6), but this varies between regions, with the highest in Central and West Africa(61%) and the lowest level reported in Southern Africa (34%) in 2011. While the authors report a declining trend from 1995–2011, current prevalence data for the region is not available, and data for anaemia in pregnant South African women is outdated. The last census type study was conducted in 2012, and more current studies report on isolated sites only. Food fortification and supplements during gestation are the mainstay of prophylaxis against the sequelae of iron deficiency (7). However, anaemia is also due to other causes. In South Africa, pregnant women face the compound burden of infective causes of anaemia, such as HIV and TB, neglected tropical diseases like hookworm and schistosomiasis, other bacterial infections, as well as nutritional insufficiency and inherited haemoglobinopathies and thalassaemias, which may also exacerbate negative pregnancy outcomes (6). However given that physiological anaemia in pregnancy is associated with protection against fulminant expression of infections such as schistosomiasis and other parasitaemias, non-discriminatory mass treatment with iron supplementation in these cases may contribute adversely to maternal and fetal morbidity and mortality (8). It is therefore important to determine the current burden, causes and consequences of anaemia in pregnant women so as to better guide appropriate treatment protocols which will focus on the specific cause of anaemia, and may differ to current recommendations. Aim and Objectives It is the purpose of this systematic review to establish the present pooled prevalence of anaemia in South African pregnant women. The specific objectives are to Determine the causal or associated factors of anaemia in the pregnant population Describe the type and severity of anaemia Describe the fetal and maternal outcomes associated with anaemia in pregnancy Correlation of factors contributing to the development of anaemia and other disorders during pregnancy will facilitate exploration of medical interventions as well as inform behavioural changes to mitigate current and future risk. Methodology This protocol is written in line with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) guidelines (9). The results will be reported based on the PRISMA 2009 statement, and article screening and selection process will also be demonstrated through a PRISMA-P flow diagram. Eligibility of research question The eligibility of the research question was determined by the Population Exposure Comparator Outcomes (PECO) framework as illustrated in Table 1. All studies reporting on anaemia and reporting on prevalence or haemoglobin concentration during pregnancy in a South African population will be included. There will be no restriction on study design, setting or date of publication. Articles published in any language will be accepted and translated into English using Google Translate if possible. If it is not possible to translate abstracts into English, they will be removed from the study, but listed in an appendix. Identifying relevant studies Search terms used and their synonyms were identified using the Medical Subject Headings (MeSH). The uniterms and Boolean operators in English to be used in the search strategies are (anemia OR anaemia OR haemoglobin OR hemoglobin OR haematocrit OR hematocrit) AND (Pregnancy OR Pregnant women OR Gravidity OR Maternal exposure OR Mother OR Pregnant OR Gravid OR Obstetric OR Antenatal OR Antepartum OR Gestation) AND (South Africa OR Southern Africa or South African or Sub-Saharan Africa). The search strategy will be adapted for the other electronic databases to be searched. The search strategy was piloted in November 2019 to check the appropriateness of selected electronic databases and key words as depicted in Table 2. Study selection The eligibility of retrieved studies will be assessed using the following criteria: Inclusion criteria For studies to be included they should meet the following criteria: Be available in full text Must include pregnant women living in South Africa Must focus on anaemia in pregnancy using the WHO classification of anaemia: <10mg/dL Hb or include such data on pregnant women in studies ascertaining prevalence in various population groups Exclusion criteria Studies will be excluded should they be: Not available in full text Not reporting anaemia or haemoglobin concentrations in pregnancy Full papers not available despite requests to the authors An abstract screening tool, using Google Forms will be developed and distributed to the researchers. Abstract screening, followed by full article screening will be conducted manually, including those articles for which an abstract is not available. A citation manager Zotero v5.0.81 (Zotero.org ) will be used to create a library for this review. The primary investigator will conduct a search using the key fields in the databases created. Eligible studies will be exported to the citation manager, with duplicates removed before abstracts are screened by two independent reviewers. Consensus will be obtained from a third reviewer (JM) in case of disagreement between the reviewers. Full article screening guided by the eligibility criteria will then be carried out independently. A subject librarian will be consulted to optimise the article search procedure to help with retrieving and finding articles to be included in the full-article screening. For those papers that are electronically unavailable, authors will also be contacted directly. The screening results will be reported using a PRISMA-P flowchart (9). Charting of data items As illustrated in Table 3 below, a data charting table will be used to extract background information and process the data items from each study selected. To ensure that all pertinent information regarding the relevant aspects for the study is collected, a data charting form will be developed and piloted, and continually updated. Collating, summarising and reporting the results Risk of bias and quality assessment The quality and risk of bias of selected studies will be performed by both reviewers using the Hoy(10) tool which determines the risk of bias in prevalence studies. The tool uses 10 criteria to assess both internal and external validity of studies based on participant selection criteria as a representation of overall population, how information is collected, and whether parameters used to determine prevalence was consistent in each study amongst participants (10). An overall risk of bias will then be determined based on the individual scores obtained for each of the 10 items and graded according to the number of high risks found: low (≤ 2), moderate (3–4), and high (≥ 5). Where information related to the 10 items is not available, it will be captured as high risk. The quality and scientific evidence of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to assess risk of bias, imprecision, inconsistency and indirectness, as well as publication bias, and placed into one of four categories, ranging from very low (where the true effect is probably markedly different from the estimated effect) to very high (that which was observed is most likely to be true). Randomised controlled trials without limitations will therefore present the most reliable evidence, with observational studies falling into the lowest category, given the potential for confounding. The strength of the recommendations emanating from these studies will be assessed based on the quality of evidence presented. The two authors will independently assess the quality of the studies using the data extraction tool, with consensus on disagreement being achieved with the assistance of a third reviewer. Data Synthesis and Analysis Heterogeneity among studies will be checked using I 2 to determine dispersion. As there may be substantial heterogeneity based on differences in sampled populations in South Africa based on geography and sociodemographic factors, a weighted inverse-variance meta-analysis using a random-effects model will be carried out to generate a pooled prevalence estimate. A Funnel plot and Egger’s regression test will be conducted to assess publication bias. The articles obtained by these searches will be analysed for causative factors and outcomes by a parallel and independent review team, using suitable eligibility criteria. Screening, data extraction, and quality appraisal will be conducted independently by two authors (VD and CB). Disagreement will be resolved by independent assessment by a third reviewer (JM). Sub group analysis by region, stage of pregnancy, socio-economic status, severity and cause of anaemia will be conducted if sufficient data is available. Data will be analysed using STATA v16 (2019, College Station, TX: StataCorp LLC.) and presented in evidence tables and in meta-analytic forest plots. Discussion Thus far very few investigations have focussed on anaemia and concomitant disorders during pregnancy in the Southern African region. Active research in this vulnerable population is urgently required to identify the type and burden of anaemia affecting South African pregnant women and its association with contributing factors such as nutrient deficiency, growth and development of the fetus and neonate, co-morbid diseases such as TB and HIV, hypertensive disorders of pregnancy as well as clinical outcomes and long term sequelae. This protocol has been developed to determine the prevalence, type and causes of anaemia affecting pregnant women in South Africa. The information thus obtained will best inform decision makers in developing health policies and practises most suitable to positively impact on maternal and fetal outcomes. Declarations Amendments This is the first iteration of the protocol. Should it be necessary to amend any part of this protocol, every amendment including the date, the nature of the change and the rationale behind it will be registered independently of the protocol. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study will be included in the published systematic review article and will also be available upon request. The Prisma-P checklist is available in Additional File 1.docx Competing interests The authors declare that they have no competing interests. Funding This protocol for a systematic review forms part of a larger study investigating anaemia and hypertensive disorders of pregnancy in South African women, which is funded by the National Research Foundation (TTK170508230162) in collaboration with the University of KwaZulu-Natal and Medical Research Council of South Africa. The institutions listed have no vested interest in the study and are not involved in the protocol design, analysis plan, data collection and analyses. Further there will be no input from these organisations in the interpretation and publication of the results. Authors’ contributions VD and CB conceptualised the study and prepared the draft protocol under the guidance and supervision of JM. All three authors contributed to the development of the background and planned output of the research as well as the design of the study. Acknowledgements The authors would like to thank Dr Tivani Mashamba-Thomson and Dr Bongani Nkambule for their guidance in the development of this protocol. Author details Vinogrin Dorsamy: Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, South Africa [email protected] Chauntelle Bagwandeen: Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, South Africa [email protected] Jagadesa Moodley: Women’s Health and HIV, School of Clinical Medicine, University of KwaZulu-Natal, South Africa jmog @ukzn.ac.za References Younger P. Stedman’s Medical Dictionary, 28th ed.200734 Stedman’s Medical Dictionary, 28th ed.. Philadelphia, PA: Lippincott Williams and Wilkins 2006. l+2170 pp.+appendices 176 pp. £26.95; $49.95, ISBN: 0 7817 3390 1 Includes CD‐ROM. Ref Rev. 2007 Jan 23;21(1):41–2. Shisana O, South Africa, Department of Health, Human Sciences Research Council, South African Medical Research Council. The South African National Health and Nutrition Examination Survey: SANHANES–1. Cape Town: HSRC Press; 2013. Stevens, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health. 2013 Jul;1(1):e16–25. Hoque M. Risk factors for anaemia in pregnancy in rural KwaZulu-Natal, South Africa : implication for health education and health promotion : original research. 2009 [cited 2015 Nov 14]; Available from: http://reference.sabinet.co.za/document/EJC80328 Mkhize BT, Mabaso M, Mamba T, Napier CE, Mkhize-Kwitshana ZL. The Interaction between HIV and Intestinal Helminth Parasites Coinfection with Nutrition among Adults in KwaZulu-Natal, South Africa. BioMed Res Int. 2017 Mar 22;2017:e9059523. Soares Magalhães RJ, Clements AC. Spatial heterogeneity of haemoglobin concentration in preschool-age children in sub-Saharan Africa. Bull World Health Organ. 2011 Jun 1;89(6):459–68. Cantor AG, Bougatsos C, Dana T, Blazina I, McDonagh M. Routine iron supplementation and screening for iron deficiency anemia in pregnancy: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Apr 21;162(8):566–76. Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW, et al. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ. 2013 Jun 21;346:f3443. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan 1;4(1):1. Hoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol. 2012 Sep;65(9):934–9. Supplementary Files Legend Additional files: Additional file 1.docx Title Prisma P Checklist Description Prisma P checklist in fulfilment of Systematic Reviews protocol Tables Due to technical limitations, Tables 1 - 3 are only available for download from the Supplementary Files section. Supplementary Files addititionalfile1PRISMAPchecklist.docx Table2.docx Table3.docx Table1.docx Cite Share Download PDF Status: Published Journal Publication published 11 Sep, 2020 Read the published version in Systematic Reviews → Version 2 posted Reviewer # 3 agreed at journal 19 Aug, 2020 Review # 3 received at journal 19 Aug, 2020 Review # 1 received at journal 19 Aug, 2020 Editorial decision: Accept 19 Aug, 2020 Review # 2 received at journal 17 Aug, 2020 Reviewer # 2 agreed at journal 13 Aug, 2020 Editor assigned by journal 12 Aug, 2020 Reviewers invited by journal 12 Aug, 2020 Reviewer # 1 agreed at journal 12 Aug, 2020 Submission checks completed at journal 11 Aug, 2020 Editor invited by journal 11 Aug, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-16197","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Protocol","associatedPublications":[],"authors":[{"id":1395191,"identity":"bc52f186-1070-47dc-abec-fc521e35c53e","order_by":0,"name":"Vinogrin Dorsamy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDCCA1Cajb2BmUQtfDwHSNUiJ5FApBa+472PP/zMOZzYJvnG2PDnDgZ5/gb2hx/waZE8c9xMsncbUIt0jnGC5BkGwxkHGJIl8GkxuJHGxsC77bAxG1DLAcM2BsYNQMcS0sL88S9Ii+QZ4wOJbQz2GxgYm38Q0MIgDbRFjk2CxzjhYBtD4gYGZja8tkieOcYmLbstXY6NJ63YsLFNInnGYTY2C3xa+I63MX98u82aR7798GbJn202tv3t7Y9v4NMCBc0wBtBJREZPHXHKRsEoGAWjYGQCAC+ZRNwOyqeTAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0655-697X","institution":"University of KwaZulu-Natal College of Health Sciences","correspondingAuthor":true,"prefix":"","firstName":"Vinogrin","middleName":"","lastName":"Dorsamy","suffix":""},{"id":1395192,"identity":"3ea15ccf-a421-4d89-b1bd-9c42928078ad","order_by":1,"name":"Chauntelle Bagwandeen","email":"","orcid":"","institution":"University of KwaZulu-Natal School of Nursing and Public Health","correspondingAuthor":false,"prefix":"","firstName":"Chauntelle","middleName":"","lastName":"Bagwandeen","suffix":""},{"id":1395193,"identity":"b17b83c1-7faf-410a-9367-0cd4d943f5df","order_by":2,"name":"Jagadesa Moodley","email":"","orcid":"","institution":"University of KwaZulu-Natal School of Clinical Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jagadesa","middleName":"","lastName":"Moodley","suffix":""}],"badges":[],"createdAt":"2020-03-02 15:22:19","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-16197/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-16197/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13643-020-01460-0","type":"published","date":"2020-09-11T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":13574938,"identity":"bd01c0d0-a70e-4cfd-bb67-33dc6f809e6b","added_by":"auto","created_at":"2021-09-17 04:01:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":304746,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-16197/v2/8d12a9a8-188b-4da4-a6c6-3f986d351eb4.pdf"},{"id":1943233,"identity":"fa42338c-fec4-4046-a339-9a387e5370bf","added_by":"auto","created_at":"2020-08-15 22:51:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":30206,"visible":true,"origin":"","legend":"","description":"","filename":"addititionalfile1PRISMAPchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-16197/v2/addititionalfile1PRISMAPchecklist.docx"},{"id":1943235,"identity":"e59a5f15-cdc9-40f9-9119-cb5467b81ec3","added_by":"auto","created_at":"2020-08-15 22:51:25","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12232,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-16197/v2/Table2.docx"},{"id":1943234,"identity":"1a907458-7ed8-4c7c-9496-f9a7961d2a70","added_by":"auto","created_at":"2020-08-15 22:51:25","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":12790,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-16197/v2/Table3.docx"},{"id":1943236,"identity":"442435b5-1599-4b4f-a7da-646264524cee","added_by":"auto","created_at":"2020-08-15 22:51:25","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":12755,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-16197/v2/Table1.docx"}],"financialInterests":"","formattedTitle":"The Prevalence, Risk factors and Outcomes of Anaemia in South African Pregnant Women: A Protocol for a Systematic Review and Meta-analysis","fulltext":[{"header":"Background","content":"\n\u003cp\u003eAnaemia, defined as a decrease in red blood cells or haemoglobin, or the reduced capacity of red blood cells to carry oxygen (1) is a common chronic problem in low to middle income countries, such as South Africa. It is a product of socio-economic disparity, affecting mostly the poor and less educated (2). It is most prevalent in the vulnerable: children, adolescents in their growth phase and females of reproductive age(3). The condition is exacerbated by pregnancy, when there is an increased burden to deliver oxygen to the fetus, and can result in intrauterine growth restriction, reduced iron for the baby and increased maternal and perinatal morbidity and mortality (4).\u003c/p\u003e\n\u003cp\u003eAnaemia affects almost 2 billion people worldwide, with iron deficiency anaemia being the commonest cause. As with other low and middle-income countries with similar sociodemographic characteristics, the South African population is more susceptible to anaemia due to the prevalence of chronic nutritional insufficiency and concomitant infective conditions (5). The World Health Organisation (WHO) reports the prevalence of anaemia in women of reproductive age women in sub-Saharan Africa to be 57.1% (6), but this varies between regions, with the highest in Central and West Africa(61%) and the lowest level reported in Southern Africa (34%) in 2011. While the authors report a declining trend from 1995–2011, current prevalence data for the region is not available, and data for anaemia in pregnant South African women is outdated. The last census type study was conducted in 2012, and more current studies report on isolated sites only.\u003c/p\u003e\n\u003cp\u003eFood fortification and supplements during gestation are the mainstay of prophylaxis against the sequelae of iron deficiency (7). However, anaemia is also due to other causes. In South Africa, pregnant women face the compound burden of infective causes of anaemia, such as HIV and TB, neglected tropical diseases like hookworm and schistosomiasis, other bacterial infections, as well as nutritional insufficiency and inherited haemoglobinopathies and thalassaemias, which may also exacerbate negative pregnancy outcomes (6).\u003c/p\u003e\n\u003cp\u003eHowever given that physiological anaemia in pregnancy is associated with protection against fulminant expression of infections such as schistosomiasis and other parasitaemias, non-discriminatory mass treatment with iron supplementation in these cases may contribute adversely to maternal and fetal morbidity and mortality (8).\u003c/p\u003e\n\u003cp\u003eIt is therefore important to determine the current burden, causes and consequences of anaemia in pregnant women so as to better guide appropriate treatment protocols which will focus on the specific cause of anaemia, and may differ to current recommendations.\u003c/p\u003e\n\u003ch3\u003eAim and Objectives\u003c/h3\u003e\n\u003cp\u003eIt is the purpose of this systematic review to establish the present pooled prevalence of anaemia in South African pregnant women. The specific objectives are to\u003c/p\u003e\u003cul\u003e\u003cli\u003eDetermine the causal or associated factors of anaemia in the pregnant population\u003c/li\u003e\u003cli\u003eDescribe the type and severity of anaemia\u003c/li\u003e\u003cli\u003eDescribe the fetal and maternal outcomes associated with anaemia in pregnancy\u003c/li\u003e\u003c/ul\u003e\n\u003cp\u003eCorrelation of factors contributing to the development of anaemia and other disorders during pregnancy will facilitate exploration of medical interventions as well as inform behavioural changes to mitigate current and future risk.\u003c/p\u003e"},{"header":"Methodology","content":"\n\u003cp\u003eThis protocol is written in line with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) guidelines (9). The results will be reported based on the PRISMA 2009 statement, and article screening and selection process will also be demonstrated through a PRISMA-P flow diagram.\u003c/p\u003e\n\u003ch3\u003eEligibility of research question\u003c/h3\u003e\n\u003cp\u003eThe eligibility of the research question was determined by the Population Exposure Comparator Outcomes (PECO) framework as illustrated in Table 1.\u003c/p\u003e\n\n\u003cp\u003eAll studies reporting on anaemia and reporting on prevalence or haemoglobin concentration during pregnancy in a South African population will be included. There will be no restriction on study design, setting or date of publication. Articles published in any language will be accepted and translated into English using Google Translate if possible. If it is not possible to translate abstracts into English, they will be removed from the study, but listed in an appendix.\u003c/p\u003e\n\u003ch3\u003eIdentifying relevant studies\u003c/h3\u003e\n\u003cp\u003eSearch terms used and their synonyms were identified using the Medical Subject Headings (MeSH). The uniterms and Boolean operators in English to be used in the search strategies are (anemia OR anaemia OR haemoglobin OR hemoglobin OR haematocrit OR hematocrit) AND (Pregnancy OR Pregnant women OR Gravidity OR Maternal exposure OR Mother OR Pregnant OR Gravid OR Obstetric OR Antenatal OR Antepartum OR Gestation) AND (South Africa OR Southern Africa or South African or Sub-Saharan Africa). The search strategy will be adapted for the other electronic databases to be searched.\u003c/p\u003e\n\u003cp\u003eThe search strategy was piloted in November 2019 to check the appropriateness of selected electronic databases and key words as depicted in Table 2.\u003c/p\u003e\n\u003ch3\u003eStudy selection\u003c/h3\u003e\n\u003cp\u003eThe eligibility of retrieved studies will be assessed using the following criteria:\u003c/p\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003eFor studies to be included they should meet the following criteria:\u003c/p\u003e\u003cul\u003e\u003cli\u003eBe available in full text\u003c/li\u003e\u003cli\u003eMust include pregnant women living in South Africa\u003c/li\u003e\u003cli\u003eMust focus on anaemia in pregnancy using the WHO classification of anaemia: \u0026lt;10mg/dL Hb or include such data on pregnant women in studies ascertaining prevalence in various population groups\u003c/li\u003e\u003c/ul\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003eStudies will be excluded should they be:\u003c/p\u003e\u003cul\u003e\u003cli\u003eNot available in full text\u003c/li\u003e\u003cli\u003eNot reporting anaemia or haemoglobin concentrations in pregnancy\u003c/li\u003e\u003cli\u003eFull papers not available despite requests to the authors\u003c/li\u003e\u003c/ul\u003e\n\u003cp\u003eAn abstract screening tool, using Google Forms will be developed and distributed to the researchers. Abstract screening, followed by full article screening will be conducted manually, including those articles for which an abstract is not available.\u003c/p\u003e\n\u003cp\u003eA citation manager Zotero v5.0.81 \u003ca href=\"http://(Zotero.org\"\u003e(Zotero.org\u003c/a\u003e) will be used to create a library for this review. The primary investigator will conduct a search using the key fields in the databases created. Eligible studies will be exported to the citation manager, with duplicates removed before abstracts are screened by two independent reviewers. Consensus will be obtained from a third reviewer (JM) in case of disagreement between the reviewers. Full article screening guided by the eligibility criteria will then be carried out independently. A subject librarian will be consulted to optimise the article search procedure to help with retrieving and finding articles to be included in the full-article screening. For those papers that are electronically unavailable, authors will also be contacted directly. The screening results will be reported using a PRISMA-P flowchart (9).\u003c/p\u003e\n\n\u003ch3\u003eCharting of data items\u003c/h3\u003e\n\u003cp\u003eAs illustrated in Table 3 below, a data charting table will be used to extract background information and process the data items from each study selected. To ensure that all pertinent information regarding the relevant aspects for the study is collected, a data charting form will be developed and piloted, and continually updated.\u003c/p\u003e\n\n\u003ch3\u003eCollating, summarising and reporting the results\u003c/h3\u003e\n\u003ch3\u003eRisk of bias and quality assessment\u003c/h3\u003e\n\u003cp\u003eThe quality and risk of bias of selected studies will be performed by both reviewers using the Hoy(10) tool which determines the risk of bias in prevalence studies. The tool uses 10 criteria to assess both internal and external validity of studies based on participant selection criteria as a representation of overall population, how information is collected, and whether parameters used to determine prevalence was consistent in each study amongst participants (10). An overall risk of bias will then be determined based on the individual scores obtained for each of the 10 items and graded according to the number of high risks found: low (≤ 2), moderate (3–4), and high (≥ 5). Where information related to the 10 items is not available, it will be captured as high risk.\u003c/p\u003e\n\u003cp\u003eThe quality and scientific evidence of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to assess risk of bias, imprecision, inconsistency and indirectness, as well as publication bias, and placed into one of four categories, ranging from very low (where the true effect is probably markedly different from the estimated effect) to very high (that which was observed is most likely to be true). Randomised controlled trials without limitations will therefore present the most reliable evidence, with observational studies falling into the lowest category, given the potential for confounding. The strength of the recommendations emanating from these studies will be assessed based on the quality of evidence presented. The two authors will independently assess the quality of the studies using the data extraction tool, with consensus on disagreement being achieved with the assistance of a third reviewer.\u003c/p\u003e\n\n\u003ch3\u003eData Synthesis and Analysis\u003c/h3\u003e\n\u003cp\u003eHeterogeneity among studies will be checked using I\u003csup\u003e2\u003c/sup\u003e to determine dispersion. As there may be substantial heterogeneity based on differences in sampled populations in South Africa based on geography and sociodemographic factors, a weighted inverse-variance meta-analysis using a random-effects model will be carried out to generate a pooled prevalence estimate. A Funnel plot and Egger’s regression test will be conducted to assess publication bias. The articles obtained by these searches will be analysed for causative factors and outcomes by a parallel and independent review team, using suitable eligibility criteria. Screening, data extraction, and quality appraisal will be conducted independently by two authors (VD and CB). Disagreement will be resolved by independent assessment by a third reviewer (JM). Sub group analysis by region, stage of pregnancy, socio-economic status, severity and cause of anaemia will be conducted if sufficient data is available. Data will be analysed using STATA v16 (2019, College Station, TX: StataCorp LLC.) and presented in evidence tables and in meta-analytic forest plots.\u003c/p\u003e"},{"header":"Discussion","content":"\n\u003cp\u003eThus far very few investigations have focussed on anaemia and concomitant disorders during pregnancy in the Southern African region. Active research in this vulnerable population is urgently required to identify the type and burden of anaemia affecting South African pregnant women and its association with contributing factors such as nutrient deficiency, growth and development of the fetus and neonate, co-morbid diseases such as TB and HIV, hypertensive disorders of pregnancy as well as clinical outcomes and long term sequelae. This protocol has been developed to determine the prevalence, type and causes of anaemia affecting pregnant women in South Africa. The information thus obtained will best inform decision makers in developing health policies and practises most suitable to positively impact on maternal and fetal outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\n\u003ch3\u003eAmendments\u003c/h3\u003e\n\u003cp\u003eThis is the first iteration of the protocol. Should it be necessary to amend any part of this protocol, every amendment including the date, the nature of the change and the rationale behind it will be registered independently of the protocol.\u003c/p\u003e\n\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eAll data generated or analysed during this study will be included in the published systematic review article and will also be available upon request. The Prisma-P checklist is available in Additional File 1.docx\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis protocol for a systematic review forms part of a larger study investigating anaemia and hypertensive disorders of pregnancy in South African women, which is funded by the National Research Foundation (TTK170508230162) in collaboration with the University of KwaZulu-Natal and Medical Research Council of South Africa. The institutions listed have no vested interest in the study and are not involved in the protocol design, analysis plan, data collection and analyses. Further there will be no input from these organisations in the interpretation and publication of the results.\u003c/p\u003e\n\u003ch3\u003eAuthors’ contributions\u003c/h3\u003e\n\u003cp\u003eVD and CB conceptualised the study and prepared the draft protocol under the guidance and supervision of JM. All three authors contributed to the development of the background and planned output of the research as well as the design of the study.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eThe authors would like to thank Dr Tivani Mashamba-Thomson and Dr Bongani Nkambule for their guidance in the development of this protocol.\u003c/p\u003e\n\u003ch3\u003eAuthor details\u003c/h3\u003e\n\u003cp\u003e\u003cem\u003eVinogrin Dorsamy: \u003c/em\u003eLaboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, South Africa \u003ca href=\"mailto:[email protected]\"\u003e\u003ca href=\"http://[email protected]\"\[email protected]\u003c/a\u003e\u003c/a\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eChauntelle Bagwandeen: \u003c/em\u003eDepartment of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, South Africa \u003ca href=\"mailto:[email protected]\"\u003e\u003ca href=\"http://[email protected]\"\[email protected]\u003c/a\u003e\u003c/a\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eJagadesa Moodley:\u003c/em\u003e Women’s Health and HIV, School of Clinical Medicine, University of KwaZulu-Natal, South Africa \u003ca href=\"mailto:jmog%[email protected]\"\u003ejmog \u003ca href=\"http://@ukzn.ac.za\"\[email protected]\u003c/a\u003e\u003c/a\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003eYounger P. Stedman’s Medical Dictionary, 28th ed.200734 Stedman’s Medical Dictionary, 28th ed.. Philadelphia, PA: Lippincott Williams and Wilkins 2006. l+2170 pp.+appendices 176 pp. £26.95; $49.95, ISBN: 0 7817 3390 1 Includes CD‐ROM. Ref Rev. 2007 Jan 23;21(1):41–2.\u003c/li\u003e\u003cli\u003eShisana O, South Africa, Department of Health, Human Sciences Research Council, South African Medical Research Council. The South African National Health and Nutrition Examination Survey: SANHANES–1. Cape Town: HSRC Press; 2013.\u003c/li\u003e\u003cli\u003eStevens, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health. 2013 Jul;1(1):e16–25.\u003c/li\u003e\u003cli\u003eHoque M. Risk factors for anaemia in pregnancy in rural KwaZulu-Natal, South Africa : implication for health education and health promotion : original research. 2009 [cited 2015 Nov 14]; Available from: http://reference.sabinet.co.za/document/EJC80328\u003c/li\u003e\u003cli\u003eMkhize BT, Mabaso M, Mamba T, Napier CE, Mkhize-Kwitshana ZL. The Interaction between HIV and Intestinal Helminth Parasites Coinfection with Nutrition among Adults in KwaZulu-Natal, South Africa. BioMed Res Int. 2017 Mar 22;2017:e9059523.\u003c/li\u003e\u003cli\u003eSoares Magalhães RJ, Clements AC. Spatial heterogeneity of haemoglobin concentration in preschool-age children in sub-Saharan Africa. Bull World Health Organ. 2011 Jun 1;89(6):459–68.\u003c/li\u003e\u003cli\u003eCantor AG, Bougatsos C, Dana T, Blazina I, McDonagh M. Routine iron supplementation and screening for iron deficiency anemia in pregnancy: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Apr 21;162(8):566–76.\u003c/li\u003e\u003cli\u003eHaider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW, et al. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ. 2013 Jun 21;346:f3443.\u003c/li\u003e\u003cli\u003eMoher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan 1;4(1):1.\u003c/li\u003e\u003cli\u003eHoy D, Brooks P, Woolf A, Blyth F, March L, Bain C, et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J Clin Epidemiol. 2012 Sep;65(9):934–9.\u003c/li\u003e\u003c/ol\u003e"},{"header":"Supplementary Files Legend","content":"\u003cp\u003eAdditional files:\u003c/p\u003e\n\n\u003cp\u003eAdditional file 1.docx\u003c/p\u003e\n\n\u003cp\u003eTitle\u003c/p\u003e\n\u003cp\u003ePrisma P Checklist\u003c/p\u003e\n\u003cp\u003eDescription\u003c/p\u003e\n\u003cp\u003ePrisma P checklist in fulfilment of Systematic Reviews protocol\u003c/p\u003e"},{"header":"Tables","content":"Due to technical limitations, Tables 1 - 3 are only available for download from the Supplementary Files section."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anaemia, Pregnancy, South Africa","lastPublishedDoi":"10.21203/rs.3.rs-16197/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-16197/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground A significant cause of morbidity and mortality during pregnancy is maternal anaemia. The causes of anaemia and the sequelae are varied, and the prevention and management are public health challenges, especially in resource limited settings and certain geographic locations.\u0026nbsp;South Africa is plagued by a quadruple burden of disease, with high maternal mortality rates affected by hypertensive disorders of pregnancy, HIV, tuberculosis and neglected tropical diseases.\u0026nbsp;This is most prevalent in people of lower socio-economic status. Poor nutrition, chronic infections, lack of access to health care facilities and poor compliance with micronutrient supplementation all contribute to maternal anaemia.\u0026nbsp;\u0026nbsp;The aim of this study is to systematically map the literature to ascertain the pooled prevalence and associated causes of anaemia in the South African pregnant population, which will enable health care workers and other key stakeholders to more pertinently address Sustainable Development Goal 3 focussing on good health and reducing maternal mortality.\u003c/p\u003e\u003cp\u003eMethods PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS will be searched, using the keywords ‘anaemia’, ,’haemoglobin’, ‘pregnancy’, ‘South Africa’, to conduct a systematic review and meta-analysis to explore, describe and map literature on the distribution and burden of anaemia in pregnant women in South Africa. The reference list of articles selected for review will be scanned for other articles of interest to our study question.\u0026nbsp;Studies published in any language will be included in this review. As there may be differences in sampled populations in South Africa based on geography and sociodemographic factors, a weighted inverse-variance meta-analysis using a random-effects model will be carried out to generate a pooled prevalence estimate. A Funnel plot and Egger’s regression test will be conducted to assess publication bias. Heterogeneity among studies will be checked using I\u003csup\u003e2\u003c/sup\u003e to determine dispersion and meta-regression analysis will be performed to investigate the source of heterogeneity.\u0026nbsp;The articles obtained by these searches will be analysed for causative factors, severity and outcomes by a parallel and independent review team, using suitable eligibility criteria. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Disagreement will be resolved by independent assessment by a third reviewer. Sub group analysis by region, stage of pregnancy, socio-economic status, severity and cause of anaemia will be conducted if sufficient data is available. Data will be analysed using statistical software, and presented in evidence tables and in meta-analytic forest plots.\u003c/p\u003e\u003cp\u003eDiscussion This protocol is developed to systematically review the literature on the prevalence and severity of anaemia, risk factors and outcomes in pregnant women in South Africa.\u0026nbsp;Correlation of factors contributing to the development of anaemia and other disorders during pregnancy will facilitate exploration of appropriate medical and behavioural change interventions implemented within other countries or regions that mitigate risk. This study will assist local health systems to inform public health policies and practises for more favourable maternal and fetal outcomes.\u003c/p\u003e","manuscriptTitle":"The Prevalence, Risk factors and Outcomes of Anaemia in South African Pregnant Women: A Protocol for a Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-08-15 22:51:24","doi":"10.21203/rs.3.rs-16197/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2020-08-19T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-19T12:00:00+00:00","index":3,"fulltext":"Recommendation: Accept\nForm responses:\n---\n\nComments to Author:\n---\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article of importance in its field that should be highlighted to relevant networks**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"editorInvitedReview","content":"","date":"2020-08-19T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept\nForm responses:\n---\n\nComments to Author:\n---\nNo further change is necessary in the opinion of the reviewer.\nAuthors have satisfied the comments of the reviewers* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article of limited interest**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"decision","content":"Accept","date":"2020-08-19T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-17T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept\nForm responses:\n---\n\nComments to Author:\n---\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article whose findings are important to those with closely related research interests**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"reviewerAgreed","content":"","date":"2020-08-13T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-12T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-08-12T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-12T12:00:00+00:00","index":1,"fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-03-05 17:49:26","doi":"10.21203/rs.3.rs-16197/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2020-07-08T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-08T12:00:00+00:00","index":1,"fulltext":"Recommendation: Minor Revision\nForm responses:\n---\n\nComments to Author:\n---\nLine 65 in background:it would be nice from the beginning to describe different types of anaemia in pregnancy.\n\nTable 1: in Comparator: should stop by without anaemia at any trimester,the other elements are already in Outcomes* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article of importance in its field that should be highlighted to relevant networks**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **i declare that i have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"editorInvitedReview","content":"","date":"2020-07-08T12:00:00+00:00","index":3,"fulltext":"Recommendation: Major Revision\nForm responses:\n---\n\nComments to Author:\n---\nWho will be \"two independent investigators\"?\n\n\", etc.\" is informal in academic writing.\n\nIt will be better to plan to show kappa for the selection and data extraction. Please plan to show the data of kappa of agreement during the systematic searches.\n\nHow disagreements will be solved during the systematic search among two independent reviewers?\n\nHow will authors deal with missing data? 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If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article of limited interest**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: **\nI agree to the open peer review policy of the journal**\n* Were you mentored through this peer review?: **No**\n"},{"type":"decision","content":"Major revision","date":"2020-07-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-04T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept\nForm responses:\n---\n\nComments to Author:\n---\nA very important topic . The protocol is well-written and all requirements pertaining to publication of SR and metaanalyses have been met, including registration into Prospero. Congratulations to the Authors . Good luck for the full SR to come.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Level of interest: **An article of importance in its field that should be highlighted to relevant networks**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. 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