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Neural Tube Defects and Folic Acid. What is the Story in Europe?

Neural Tube Defects (NTD) (anencephaly, spina bifida and encephalocoele) affect approximately one in a thousand pregnancies in Europe (equating to over 5000 pregnancies annually). Anencephaly is always lethal. Spina bifida and encephalocoele cause serious disability in survivors. The majority of NTD affected pregnancies are prenatally diagnosed and terminated (approximately 70%) in most European countries, but this always represents a major tragedy for the parents.


In 1991 the Medical Research Council (MRC) Vitamin Study results confirmed that the majority of NTDs could be prevented if the mother took folic acid supplements prior to conception and in the first trimester of pregnancy1.Folic Acid is a synthetic form of folate which is a water soluble B vitamin most commonly found in green vegetables. Most European countries have policies in place advising periconceptional supplementation with 0.4 milligrams of folic acid taken daily prior to conception and for the first three months of pregnancy.


However, most women in Europe are still not taking supplements prior to conception,and the ability of folic acid to reduce the number of NTD has not been fully realised. The relative failure of the periconceptional folic acid supplementation policy has led many countries to introduce mandatory fortification of flour with folic acid (to see a global (and country specific) overview of fortification, access the Food Fortification Initiative website http://ffinetwork.org/country_profiles/index.php).Three of the first countries to introduce mandatory fortification were the USA and Canada in 1998 and Chile in 2000. Studies following fortification showed a decline in the NTD rates in those countries2-5.


While voluntary fortification of some foods is available in much of Europe, European countries have been reluctant to introduce mandatory fortification. Reluctance has centered on fears that there would be adverse effects. The fears have mainly concerned the possibility of an association between folic acid and colorectal cancer and the possibility of higher blood folate levels masking Vitamin B12 deficiency in the elderly. In the UK, the Scientific Advisory Committee on Nutrition, having considered the available evidence on adverse effects, met in June 2009 and supported a recommendation for mandatory fortification6.

What Does EUROCAT Monitor About NTDs and Why?



What Does the EUROCAT Data on NTDs Tell Us?



“The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. In order to achieve a reduction in NTD prevalence, new efforts are needed in all countries to implement a combined strategy to increase folate status by dietary means, increase uptake of folic acid supplements periconceptionally, and to increase availability and identification of fortified foods.”


“Member States should ensure that their registries are adequately resourced and supported to produce high quality data.”


It would be possible in the future to look at rates of other congenital anomalies in the context of folic acid supplementation and / or fortification policies. The results of several studies suggest that folic acid might be protective against some cardiac defects and some oral clefts7,8.

Further studies are necessary to determine if there is, in fact, a protective effect and if so, how strong, against specified congenital anomalies other than NTDs.


Relevant EUROCAT Reports


Special Report: Prevention of Neural Tube Defects by Periconpceptional Folic Acid Supplementation in Europe - December 2009

Survey of Folic Acid Policy and Practice in European Countries - December 2007

Special Report: NTD Rates and Survey of Folic Acid Policy and Practice in European Countries - December 2005

Special Report: NTD Rates and Survey of Folic Acid Policy and Practice in European Countries - May 2003

EUROCAT and EUROPLAN (2013). Primary Prevention of Congenital Anomalies: Recommendations on Policies to be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases. EUROCAT Central Registry, University of Ulster

EUROCAT (2013). EUROCAT Special Report: Primary Prevention of Congenital Anomalies in European Countries. EUROCAT Central Registry, University of Ulster.


EUROCAT (2010). EUROCAT Special Report: Prevalence of Neural Tube Defects in Younger Mothers in Europe 2000-2008: Analysis of the EUROCAT Database. EUROCAT Central Registry, University of Ulster.


de Smit (2013). Appraisal of strategies monitor (population) folate status with respect to the prevention and scientific study of congenital anomalies. A MediClara Report created within WP7 of the EUROCAT Joint Action - Primary Prevention of Congenital Anomalies.


To access EUROCAT’s publications on Folic Acid click here [Link]


1 MRC Vitamin Study Research Group (1991), "Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study", Lancet, Vol 338, No 8760, pp 131-137. (http://www.ncbi.nlm.nih.gov/pubmed/1677062?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

2 de Wals, Tairou F, van Allen MI, Lowry SH, Sibbald B, Evans JA, van den Hof MC, Zimmer P, Crowley M, Fernandez B, Lee NS, Niyonsenga T (2007), "Reduction in Neural Tube Defects after Folic Acid Fortification in Canada", N Engl J Med, Vol 357, No 2, pp 135-142.(http://www.ncbi.nlm.nih.gov/pubmed/17625125?ordinalpos=18&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

3 Botto LD, Lisi A, Bower C, Cranfield MA, Dattani N, de Vigan C, de Walle H, Halliday J, Irgens LM, Lowry RB, McDonnell R, Metneki J, Poetzsch S, Ritvanen A, Robert-Gnansia E, Siffel C, Stoll C, Mastrioacovo P (2006), "Trends of Selected Malformations in Relation to Folic Acid Recommendations and Fortification: An International Assessment", Birth Defects Res A Clin Mol Teratol, Vol 76, No 1, pp 693-705. (http://www.ncbi.nlm.nih.gov/pubmed/17029289?ordinalpos=23&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum0

4 Williams LJ, Mai CT, Edmonds LD, Shaw GM, Kirby RS, Hobbs CA, Sever LE, Miller LA, Meaney FJ, Levitt M (2002), "Prevalence of Spina Bifida and Anencephaly During the Transition to Mandatory Folic Acid Fortification in the United States", Teratology, Vol 66, No 1, pp 33-39. (http://www.ncbi.nlm.nih.gov/pubmed/12115778?ordinalpos=16&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

5 Lopez-Camelo JS, Orioli IM, de Graca Dutra M, Nazer-Herrera J, Rivera N, Ojeda ME, Canessa A, Wettig E, Fontannaz AM, Mellado C, Castilla EE (2005), "Reduction of Birth Prevalence Rates of Neural Tube Defects After Folic Acid Fortification in Chile", Am J Med Genet A, Vol 135, No 2, pp 120-125. (http://www.ncbi.nlm.nih.gov/pubmed/15846825?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

6 Scientific Advisory Committee on Nutrition (2009), "Folic Acid and Colorectal Cancer Risk: Review of Recommendation for Mandatory Folic Acif Foprtification", Report to CMO. (http://www.sacn.gov.uk/pdfs/summary_of_sacn_report_to_cmo_19_october_2009.pdf)

7 Botto LD, Mulinare J, Erickson JD (2003), "Do Multivitamin or Folic Acid Supplements Reduce the Risk for Congenital Heart Defects? Evidence and Gaps", Am J Med Genet A, Vol 121, No 2, pp 95-101. (http://www.ncbi.nlm.nih.gov/pubmed/12910485?ordinalpos=79&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

8 Badovinas RL, Werler MM, Williams PL, Kelsey KT, Hayes C (2007), "Folic Acid Containing Supplement Consumption During Pregnancy and Risk for Oral Clefts: A Meta-Analysis", Birth Defects Res Clin Mol Teratol, Vol 79, No 1, pp 8-15. (http://www.ncbi.nlm.nih.gov/pubmed/17133404?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum