{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:01:01Z","timestamp":1790996461679,"version":"4.1.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Anencephaly, encephalocele, and spina bifida are congenital neural tube defects and are the main causes of neonatal morbidity and mortality and impose a heavy economic burden on health systems. This study to estimates the direct costs of neural tube defects from the perspective of the Brazilian Ministry of Health, and the prevented cases and cost savings during the period in which mandatory folic acid fortification was in effect in the country (2010\u20132019). It is a top-down cost-of-illness oriented study based on the prevalence of the disorders in Brazil. Data were collected from the Brazilian Ministry of Health\u2019s outpatient and hospital information system databases. The direct cost was estimated from the total patient-years, allocated by age and type of disorder. Prevented cases and cost savings were determined by the difference in the prevalence of the disorders in the pre- and post-fortification periods based on the total number of births and the sum of outpatient and hospital costs during the period. The total cost of outpatient and hospital services for these disorders totaled R$ 92,530,810.63 (Int$ 40,565,896.81) in 10 years; spina bifida accounted for 84.92% of the total cost. Hospital costs were expressive of all three disorders in the first year of the patient\u2019s life. Between 2010 and 2019, mandatory folic acid fortification prevented 3,499 live births with neural tube defects and resulted in R$ 20,381,586.40 (Int$ 8,935,373.25) in hospital and outpatient cost savings. Flour fortification has proved to be a valuable strategy in preventing pregnancies with neural tube defects. Since its implementation, there has been a 30% decrease in the prevalence of neural tube defects and a 22.81% decrease associated in hospital and outpatient costs.<\/jats:p>","DOI":"10.1371\/journal.pone.0281077","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T18:24:40Z","timestamp":1677090280000},"page":"e0281077","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Prevented cases of neural tube defects and cost savings after folic acid fortification of flour in Brazil"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-820X","authenticated-orcid":true,"given":"Viviane Belini","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everton Nunes da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Marques","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonor Maria Pacheco","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"pone.0281077.ref001","author":"World Health Organization","year":"2022","journal-title":"Congenital anomalies"},{"key":"pone.0281077.ref002","article-title":"Prevention of neural tube defects.","author":"World Health Organization","year":"2006","journal-title":"In Integrated Management of Pregnancy and Childbirth (IMPAC)."},{"issue":"2","key":"pone.0281077.ref003","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1741-4520.2006.00104.x","article-title":"Etiology pathogenesis and prevention of neural tube defects","volume":"46","author":"R. 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Jo","year":"2014","journal-title":"Clin Mol Hepatol"},{"key":"pone.0281077.ref021","article-title":"Ministry of Health. Executive Secretary. Unified Health System (SUS): principles and achievements","author":"Brazil","year":"2000","journal-title":"1st ed. Ministry of Health"},{"key":"pone.0281077.ref022","first-page":"1763","article-title":"Universal health system and universal coverage: unraveling assumptions and strategies.","volume":"23","author":"L Giovanella","year":"2018","journal-title":"Report in Public Health"},{"key":"pone.0281077.ref023","article-title":"Ministry of Health.","author":"Brazil","year":"2020","journal-title":"Unified Health System (SUS): structure, principles and how it works"},{"key":"pone.0281077.ref024","unstructured":"Brazil. Ministry of Health. Database of the Unified Health System-DATASUS. [cited 2022 May 03]. Database Datasus. Available from: http:\/\/www.datasus.gov.br."},{"key":"pone.0281077.ref025","article-title":"ICD-10: international statistical classification of diseases and health-related problems.","author":"RHC Wells","year":"2011"},{"key":"pone.0281077.ref026","article-title":"Ministry of Health.","author":"Brazil","year":"2020","journal-title":"DATASUS. System for Management of the Table of Procedures, Medicines, Orthoses, Prostheses and Special Materials (SIGTAP, OPM) of SUS"},{"key":"pone.0281077.ref027","article-title":"Ministry of Health","author":"Brazil","year":"2015","journal-title":"Secretariat of Health Care. Department of Regulation, Evaluation and Control. Systems of Health Care Information: Historical Contexts, Advances and Prospects in SUS\/Pan American Health Organization"},{"key":"pone.0281077.ref028","first-page":"1","article-title":"Ministry of Health. General Coordination of Information and Epidemiological Analysis of the Department of Health Analysis and Surveillance of Noncommunicable Diseases","author":"Brazil","year":"2021","journal-title":"Epidemiological Bulletin. Congenital anomalies in Brazil, 2010 to 2019: analysis of a priority group for birth surveillance"},{"key":"pone.0281077.ref029","article-title":"National system of consumer price indexes.","author":"Brazilian Institute of Geography and Statistics","year":"2022","journal-title":"Complete table of historical series"},{"key":"pone.0281077.ref030","author":"JL De Souza","year":"2008","journal-title":"In The magazine of information and debates of the Institute for Economic and Applied Research"},{"key":"pone.0281077.ref031","author":"The World Bank","year":"2022","journal-title":"World Development Indicators database, PPP conversion"},{"issue":"2\u20133","key":"pone.0281077.ref032","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.healthpol.2007.01.011","article-title":"Cost-effectiveness of a folic acid fortification program in Chile.","volume":"83","author":"A Llanos","year":"2007","journal-title":"Health 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A"},{"issue":"2","key":"pone.0281077.ref036","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00381-014-2492-6","article-title":"Hydrocephalus in patients with closed neural tube defects.","volume":"31","author":"A Chance","year":"2015","journal-title":"Childs Nerv Syst."},{"key":"pone.0281077.ref037","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2147\/CEOR.S42841","article-title":"A cost-of-illness study of spina bifida in Italy.","volume":"5","author":"GL Colombo","year":"2013","journal-title":"Clinicoecon Outcomes Res."},{"issue":"2","key":"pone.0281077.ref038","doi-asserted-by":"crossref","first-page":"330","DOI":"10.2105\/AJPH.2004.050955","article-title":"Assistive technology use among adolescents and young adults with spina bifida.","volume":"97","author":"KL Johnson","year":"2007","journal-title":"Am J Public Health."},{"issue":"2","key":"pone.0281077.ref039","first-page":"188","article-title":"Estimates of the economic costs of birth defects.","volume":"31","author":"NJ Waitzman","year":"1994","journal-title":"Inquiry"},{"key":"pone.0281077.ref040","article-title":"The Halflife of Cost-of-Illness Estimates: The Case of Spina Bifida.","author":"N Waitzman","year":"2004","journal-title":"Salt Lake City, UT: Department of Economics, University of Utah"},{"issue":"7","key":"pone.0281077.ref041","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/bdra.20360","article-title":"Health care expenditures of children and adults with spina bifida in a privately insured U.S. population.","volume":"79","author":"L Ouyang","year":"2007","journal-title":"Birth Defects Res A Clin Mol Teratol."},{"issue":"3","key":"pone.0281077.ref042","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.puhe.2013.12.001","article-title":"Economic burden of neural tube defects in Germany.","volume":"128","author":"D Bowles","year":"2014","journal-title":"Public Health."},{"issue":"9","key":"pone.0281077.ref043","doi-asserted-by":"crossref","first-page":"e1003356","DOI":"10.1371\/journal.pmed.1003356","article-title":"Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies.","volume":"17","author":"SV Glinianaia","year":"2020","journal-title":"PLoS Med."},{"issue":"1","key":"pone.0281077.ref044","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3171\/2015.9.SPINE15771","article-title":"Adults with myelomeningocele and other forms of spinal dysraphism: hospital care in the United States since the turn of the millennium","volume":"25","author":"JH Piatt","year":"2016","journal-title":"J Neurosurg Spine"},{"issue":"23","key":"pone.0281077.ref045","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1080\/00222930500218946","article-title":"Use of health care among adults with chronic and complex physical disabilities of childhood.","volume":"27","author":"NL Young","year":"2005","journal-title":"Disabil Rehabil.15"},{"issue":"3","key":"pone.0281077.ref046","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.dhjo.2009.10.009","article-title":"Frequency of purchase and associated costs of assistive technology for Washington State Medicaid program enrollees with spina bifida by age.","volume":"3","author":"AM Bamer","year":"2010","journal-title":"Disabil Health J."},{"key":"pone.0281077.ref047","unstructured":"Brea CM, Munakomi S. Spina Bifida. [Updated 2022 Feb 9]. In: StatPearls Treasure Island (FL): StatPearls Publishing; 2022. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK559265\/."},{"key":"pone.0281077.ref048","volume-title":"Prevention of open neural tube defects: NTD. 2st ed","author":"MC Neto","year":"2020"},{"issue":"6 Pt 2","key":"pone.0281077.ref049","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1111\/j.1753-4887.2004.tb00074.x","article-title":"Folic acid fortification of wheat flour: Chile.","volume":"62","author":"E Hertrampf","year":"2004","journal-title":"Nutr Rev."},{"issue":"5 Suppl 1","key":"pone.0281077.ref050","first-page":"S74","article-title":"Retrospective Assessment of Cost Savings From Prevention: Folic Acid Fortification and Spina Bifida in the U.S. Am J Prev Med.","volume":"50","author":"SD Grosse","year":"2016"},{"key":"pone.0281077.ref051","article-title":"Out-of-date management system of the unified table of procedures (SIGTAP) Unified Health System.","author":"Fran\u00e7a A e Giustina APD","year":"2016"},{"key":"pone.0281077.ref052","first-page":"1","article-title":"The defasation in the SUS table affects most hospital procedures.","author":"Federal Council of Medicine","year":"2015","journal-title":"CFM"},{"issue":"40","key":"pone.0281077.ref053","article-title":"Office of the Comptroller General (CGU).","volume":"1","author":"Brazil","year":"2019","journal-title":"Institute of Applied Economic Research. Council for Monitoring and Evaluation of Public Policies. Health Care of the Population for Procedures in Medium and High Complexity (MAC)"},{"key":"pone.0281077.ref054","article-title":"Ministry of Health.","author":"Brazil","year":"2009","journal-title":"The Brazilian experience in health information systems Ministry of Health. 1st ed. 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