Prevention of Neural Tube Defects by the Fortification of Flour with Folic Acid: a Population-based Retrospective Study in Brazil

Overview

Journal Bull World Health Organ

Specialty Public Health

Date 2016 Jan 16

PMID 26769993

Citations 22

Authors

Leonor Maria Pacheco Santos

Roberto Carlos Reyes Lecca

Juan Jose Cortez-Escalante

Mauro Niskier Sanchez

Humberto Gabriel Rodrigues

Affiliations

Soon will be listed here.

Abstract

Objective: To determine if the fortification of wheat and maize flours with iron and folic acid - which became mandatory in Brazil from June 2004 - is effective in the prevention of neural tube defects.

Methods: Using data from national information systems on births in central, south-eastern and southern Brazil, we determined the prevalence of neural tube defects among live births and stillbirths in a pre-fortification period - i.e. 2001-2004 - and in a post-fortification period - i.e. 2005-2014. We distinguished between anencephaly, encephalocele, meningocele, myelomeningocele and other forms of spina bifida.

Findings: There were 8554 neural tube defects for 17,925,729 live births notified between 2001 and 2014. For the same period, 2673 neural tube defects were reported for 194,858 stillbirths. The overall prevalence of neural tube defects fell from 0.79 per 1000 pre-fortification to 0.55 per 1000 post-fortification (prevalence ratio, PR: 1.43; 95% confidence interval, CI: 1.38-1.50). For stillbirths, prevalence fell from 17.74 per 1000 stillbirths pre-fortification to 11.70 per 1000 stillbirths post-fortification. The corresponding values among live births were 0.57 and 0.44, respectively.

Conclusion: The introduction of the mandatory fortification of flour with iron and folic acid in Brazil was followed by a significant reduction in the prevalence of neural tube defects in our study area.

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References

De-Regil L, Fernandez-Gaxiola A, Dowswell T, Pena-Rosas J . Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010; (10):CD007950. PMC: 4160020. DOI: 10.1002/14651858.CD007950.pub2. View

Afshar M, Golalipour M, Farhud D . Epidemiologic aspects of neural tube defects in South East Iran. Neurosciences (Riyadh). 2012; 11(4):289-92. View

Frey L, Hauser W . Epidemiology of neural tube defects. Epilepsia. 2003; 44 Suppl 3:4-13. DOI: 10.1046/j.1528-1157.44.s3.2.x. View

Orioli I, do Nascimento R, Lopez-Camelo J, Castilla E . Effects of folic acid fortification on spina bifida prevalence in Brazil. Birth Defects Res A Clin Mol Teratol. 2011; 91(9):831-5. DOI: 10.1002/bdra.20830. View

Pena-Rosas J, De-Regil L, Rogers L, Bopardikar A, Panisset U . Translating research into action: WHO evidence-informed guidelines for safe and effective micronutrient interventions. J Nutr. 2011; 142(1):197S-204S. DOI: 10.3945/jn.111.138834. View

Almeida M, Alencar G, Franca Jr I, Novaes H, Franco de Siqueira A, Schoeps D . [Validation of birth certificates based on data from a case-control study]. Cad Saude Publica. 2006; 22(3):643-52. DOI: 10.1590/s0102-311x2006000300019. View

Fujimori E, Baldino C, Sayuri Sato A, Borges A, Gomes M . [Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification]. Cad Saude Publica. 2013; 29(1):145-54. DOI: 10.1590/s0102-311x2013000100017. View

Creasy M, ALBERMAN E . Congenital malformations of the central nervous system in spontaneous abortions. J Med Genet. 1976; 13(1):9-16. PMC: 1013341. DOI: 10.1136/jmg.13.1.9. View

De Wals P, Tairou F, Van Allen M, Uh S, Lowry R, Sibbald B . Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med. 2007; 357(2):135-42. DOI: 10.1056/NEJMoa067103. View

10.

Grillo E, da Silva R . [Neural tube defects and congenital hydrocephalus. Why is prevalence important?]. J Pediatr (Rio J). 2003; 79(2):105-6. View

11.

Hertrampf E, Cortes F . Folic acid fortification of wheat flour: Chile. Nutr Rev. 2004; 62(6 Pt 2):S44-8. DOI: 10.1111/j.1753-4887.2004.tb00074.x. View

12.

Ray J, Vermeulen M, Meier C, Cole D, Wyatt P . Maternal ethnicity and risk of neural tube defects: a population-based study. CMAJ. 2004; 171(4):343-5. PMC: 509047. DOI: 10.1503/cmaj.1040254. View

13.

Shaw G, Velie E, Wasserman C . Risk for neural tube defect-affected pregnancies among women of Mexican descent and white women in California. Am J Public Health. 1997; 87(9):1467-71. PMC: 1380971. DOI: 10.2105/ajph.87.9.1467. View

14.

Blencowe H, Cousens S, Modell B, Lawn J . Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol. 2010; 39 Suppl 1:i110-21. PMC: 2845867. DOI: 10.1093/ije/dyq028. View

15.

Tamura T, Picciano M . Folate and human reproduction. Am J Clin Nutr. 2006; 83(5):993-1016. DOI: 10.1093/ajcn/83.5.993. View

16.

Lopez-Camelo J, Castilla E, Orioli I . Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries. Am J Med Genet A. 2010; 152A(10):2444-58. DOI: 10.1002/ajmg.a.33479. View

17.

Langley-Evans S . Use of folic acid supplements in the first trimester of pregnancy. J R Soc Promot Health. 2002; 122(3):181-6. DOI: 10.1177/146642400212200315. View

18.

Stevenson R, Allen W, Pai G, Best R, Seaver L, Dean J . Decline in prevalence of neural tube defects in a high-risk region of the United States. Pediatrics. 2000; 106(4):677-83. DOI: 10.1542/peds.106.4.677. View

19.

Pitkin R . Folate and neural tube defects. Am J Clin Nutr. 2007; 85(1):285S-288S. DOI: 10.1093/ajcn/85.1.285S. View

20.

Honein M, Paulozzi L, Mathews T, Erickson J, Wong L . Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001; 285(23):2981-6. DOI: 10.1001/jama.285.23.2981. View