Maternal and Child Health Journal

, Volume 10, Issue 5, pp 397–401 | Cite as

Weekly Administration of Folic Acid and Epidemiology of Neural Tube Defects

  • Laura E. Martínez de VillarrealEmail author
  • Patricia Arredondo
  • Ricardo Hernández
  • Jesús Z. Villarreal
Original Paper


Objective: In 1999, a folic acid campaign for prevention of neural tube defects was started in Nuevo León, México, with the recommendation of taking a 5000 -mcg tablet of folic acid per week. The purpose of this study was to compare the epidemiology of neural tube defects after four years of the campaign. Methods: Cases of anencephaly, spina bifida, and encephalocele (ICD Q00, Q01, Q05, 10th Ed.) from public and private hospitals were registered by immediate notification, death certificates, and fetal death registries. Comparisons of neural tube defects rates, phenotype distribution of cases, and sex ratios, registered before and after the folic acid campaign, were done using the Student’s t Test and Chi square test. Results: There was a 50% reduction in the incidence of anencephaly and spina bifida cases from 93 in 1999 (1.04×1000) to 46 in the year 2003 (0.56×1000) (p < 0.001). Spina bifida cases declined up to 70% in 2002 and anencephaly cases up to 50% in 2003. In 1999, overall, the ratio (females: males) was 0.66 with female excess; the sex ratio was similar for anencephaly and spina bifida cases. In the year 2000, female cases showed a significant reduction for both spina bifida and anencephaly (75% and 56% respectively); the sex ratio was 0.57 with a greater male excess for both phenotypes. Conclusions: Weekly administration of 5000 mcg of folic acid reduces the incidence of neural tube defects 50%, primarily spina bifida, with a higher reduction of female cases.


NTDs Epidemiology Folic acid Spina bifida Anencephaly Sex ratios 


  1. 1.
    Botto LD, Moore CA, Khoury MJ, Erickson JD. Neural tube defects (Review). N Engl J Med 1999;34(20):1509–19CrossRefGoogle Scholar
  2. 2.
    Stevenson RE, Allen WP, Pai GS, Best R, Seaver LH, Dean J, Thompson S. Decline in prevalence of neural tube defects in a high-risk region of the United States. Pediatrics 2000;106(4):677–83PubMedCrossRefGoogle Scholar
  3. 3.
    Ou CY, Stevenson RE, Brown VK, et al. 5,10 methylenetetrahydrofolate reductase genetic Polymorphism as a risk factor for neural tube defects. Am J Med Gen 1996;63:610–4CrossRefGoogle Scholar
  4. 4.
    Martínez de Villarreal LE, Delgado Enciso I, Valdez Leal R, et al. Folate levels and N 5 , N 10-Methylenetetrahydrofolate reductase genotype (MTHFR) in mothers of offspring with neural tube defects. A case- control study. Arch Med Res 2000;32:277–82CrossRefGoogle Scholar
  5. 5.
    van der Putt NM, Blom HJ. Neural tube defects and a disturbed folate dependent homocysteine metabolism. Eur J Obstet Gynecol Reprod 2000;92(1):57–61CrossRefGoogle Scholar
  6. 6.
    Bianca S, Bianca M, Bonaffini F, Ettore G. The role of maternal reproductive history in the etiology of neural tube defects. Med. Hypotheses 2002;58(2):113–4PubMedCrossRefGoogle Scholar
  7. 7.
    Shaw GM, Quach T, Nelson V, Carmichael SL, Schaffer DM, Selvin S, Yang W. Neural tube defects associated with maternal periconceptional dietary intake of simple sugars and glycemic index. Am J Clin Nutr 2003;78(5):972–8PubMedGoogle Scholar
  8. 8.
    Shaw GM, Velie EM, Schaffer D. Risk of neural tube defect-affected pregnancies among obese women. JAMA 1996;275(14):1093–6PubMedCrossRefGoogle Scholar
  9. 9.
    Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic Acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608–14PubMedCrossRefGoogle Scholar
  10. 10.
    Farley TF, Hambidge SJ, Daley MF. Association of low maternal education with neural tube defects in Colorado, 1989–1998. Public Health 2002;116:89–94PubMedCrossRefGoogle Scholar
  11. 11.
    Brazeau NK, Wentz SJ, Hansen AM, Holmes TM. An epidemiological study of neural tube defects: Delta County Michigan, 1969–1988. Fam Prac Res 1992;12:205–12Google Scholar
  12. 12.
    van der Putt NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med 2001;226(4):243–70Google Scholar
  13. 13.
    Wald N, Law MR, Morris JK, Wald DS. Quantifying the effect of folic acid. Lancet 2001;358:2069–73PubMedCrossRefGoogle Scholar
  14. 14.
    Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Yang L, Gindler J, Hong SX, Correa A, Hao L, Gunter E, China-U.S. Collaborative Project for Neural Tube Defects Prevention. Prevention of neural tube defects with folic acid in China. N Engl J Med 1999;341(20):1485–90PubMedCrossRefGoogle Scholar
  15. 15.
    Arredondo P, Velazco MR, Hernández R, Villarreal JZ, Martínez LE. Mortality due to neural tube defects in the state of Nuevo León México. Teratology 2000;61(6):473Google Scholar
  16. 16.
    Martínez de Villarreal L, Villarreal Pérez JZ, Arredondo Vázquez P, Hernández Herrera R, Velazco Campos MR, Ambriz Lopez R. Decline of neural tube defects (NTD) cases after a folic acid campaign in Nuevo Leon, México. Teratology 2002;(5):249–56Google Scholar
  17. 17.
    Olney RS, Mulinare J. Trends in neural tube defect prevalence, folic acid fortification, and vitamin supplement use. Semin Perinatol 2002;(4):277–85Google Scholar
  18. 18.
    Frey L, Hauser WA. Epidemiology of neural tube defects. Epilepsia 2003;44:4–13PubMedCrossRefGoogle Scholar
  19. 19.
    Davidoff MJ, Petrini J, Damus K, Russell RB, Mattison D. Neural tube defect-specific infant mortality in the United States. Teratology 2002;66 Suppl 1:S17–S22PubMedCrossRefGoogle Scholar
  20. 20.
    Centers for Disease Control and Prevention (CDC). Spina bififda and anencephaly before and after folic acid mandate- United States, 1995–1996 and 1999–2000. MMWR Morb Mortal Wkly Rep 2004;53(17):362–365Google Scholar
  21. 21.
    Daly LE, Kirke PN, Molloy AM, Weir DG, Scott JM. Folate levels and neural tube defects. Implications for prevention. JAMA 1995;274(21):1698–702PubMedCrossRefGoogle Scholar
  22. 22.
    Moore LL, Bradlee ML, Singer MR, Rothman KJ, Milunsky A. Folate intake and the risk of neural tube defects: an estimation of dose response. Epidemiology 2003;14:200–5PubMedCrossRefGoogle Scholar
  23. 23.
    Kallen B, Cocchi G, Knudsen LB, et al. International study of sex ratio and twinning of neural tube defects. Teratology 1994;50(5):322–31PubMedCrossRefGoogle Scholar
  24. 24.
    Rittler M, Lopez-Camelo J, Castilla EE. Sex ratio and associated risk factors for 50 congenital anomaly types: clues for causal heterogeneity. Birth Defects Res A Clin Mol Teratol 2004;70(1):13–9PubMedCrossRefGoogle Scholar
  25. 25.
    Seller MJ. Neural tube defects and sex ratios. Am J Med Genet 1987;26:699–707PubMedCrossRefGoogle Scholar
  26. 26.
    Garabedian BH, Fraser FC. Upper and lower neural tube defects: an alternative hypothesis. J Med Genet 1993;30:849–51PubMedCrossRefGoogle Scholar
  27. 27.
    Berry RJ, Li Z, Moore CA, Li S, Erickson JD, Hong SX, Correa A. Periconceptional Folic acid and the gender of offspring with neural tube defects in a high prevalence area of China-Sino-US. NTD Project. Teratology 2001;63(6):275Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Laura E. Martínez de Villarreal
    • 1
    Email author
  • Patricia Arredondo
    • 2
  • Ricardo Hernández
    • 3
  • Jesús Z. Villarreal
    • 4
  1. 1.Departamento de Genética, Facultad de MedicinaUniversidad Autónoma de Nuevo LeónMonterreyMéxico
  2. 2.Servicios de Salud de Nuevo LeónMonterreyMéxico
  3. 3.Hospital Regional # 23 I.M.S.S.MonterreyMéxico
  4. 4.Departamento de EndocrinologíaHospital Universitario “Dr. José E. González”MonterreyMéxico

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