Top

European Journal of Nutrition

Published in:

01-09-2020 | Folic Acid | Original Contribution

Modelling the impact of mandatory folic acid fortification of bread or flour in Ireland on the risk of occurrence of NTD-affected pregnancies in women of childbearing age and on risk of masking vitamin B₁₂ deficiency in older adults

Authors: Laura Kehoe, Janette Walton, Sinead M. Hopkins, Breige A. McNulty, Anne P. Nugent, Albert Flynn

Published in: European Journal of Nutrition | Issue 6/2020

Abstract

Purpose

The rate of neural tube defects (NTDs) in Europe has remained similar since the 1990s despite folic acid supplement recommendations (400 µg/day) for women of childbearing age. Mandatory folic acid fortification of staple foods has proved effective for reducing the prevalence of NTDs in over 80 countries. This study estimated the impact of addition of folic acid to bread or flour in the Republic of Ireland on reducing the risk of occurrence of NTD-affected pregnancies and the possible risk of masking (undiagnosed) vitamin B₁₂ deficiency in older adults.

Methods

Analyses were based on the Irish National Adult Nutrition Survey (2008–2010). Folic acid fortification was modelled using DaDiet© software. Estimates were made of the increase in average daily folic acid intake in women (18–50 years) and the risk of exceeding the tolerable upper intake level (UL) of 1000 µg for folic acid in adults over 50 years of age.

Results

The fortification scenarios examined would reduce the risk of NTD-affected pregnancies by 8–32%, corresponding to an increase of 39–152 μg in the mean daily folic acid intake of WCBA. The risk of masking anaemia associated with vitamin B₁₂ deficiency in older adults would be negligible as the probability of exceeding the UL for folic acid, even by a small amount, is very low (≤ 0.2%).

Conclusions

These levels of addition of folic acid to bread or flour would effectively reduce the risk of NTDs while allowing safe consumption of folic acid at current levels from other fortified foods and supplements.

Available only for authorised users

Pitkin RM (2007) Folate and neural tube defects. Am J Clin Nutr 85(1):285S–288S. https://doi.org/10.1093/ajcn/85.1.285S CrossRefPubMed

Botto LD, Lisi A, Robert-Gnansia E, Erickson JD, Vollset SE, Mastroiacovo P, Botting B, Cocchi G, de Vigan C, de Walle H, Feijoo M, Irgens LM, McDonnell B, Merlob P, Ritvanen A, Scarano G, Siffel C, Metneki J, Stoll C, Smithells R, Goujard J (2005) International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ Br Med J 330(7491):571–573. https://doi.org/10.1136/bmj.38336.664352.82 CrossRef

MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338(8760):131–137. https://doi.org/10.1016/0140-6736(91)90133-A CrossRef

FSAI (2011) Scientific recommendations for healthy eating guidelines in Ireland, vol 2. Food Safety Authority of Ireland, Dublin

Scientific Advisory Committee on Nutrition (2006) Folate and disease prevention. The Stationery Office, London

CDC (1992) Recommendations for the use of folic acid to reduce the number of cases of Spina Bifida and other neural tube defects, vol 41 (RR-14), pp 1–7. Morbidity and Mortality Weekly Report (MMWR), Washington, DC

National Health and Medical Research Council NZMoH, Department of Health and Ageing (2006) Nutrient reference values for Australia and New Zealand including Recommended Dietary Intakes Commonwealth of Australia, Canberra (AUST)

Sedgh G, Singh S, Hussain R (2014) Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann 45(3):301–314. https://doi.org/10.1111/j.1728-4465.2014.00393.x CrossRefPubMedPubMedCentral

Tarrant RC, Sheridan-Pereira M, McCarthy RA, Younger KM, Kearney JM (2011) Maternal and infant nutritional supplementation practices in ireland: implications for clinicians and policymakers. Irish Med J 104(6):173–177

10.

Bestwick JP, Huttly WJ, Morris JK, Wald NJ (2014) Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women. PLoS One 9(2):e89354. https://doi.org/10.1371/journal.pone.0089354 CrossRefPubMedPubMedCentral

11.

CDC (2005) Use of dietary supplements containing folic acid among women of childbearing age—United States. Morb Mortal Wkly Rep (MMWR) 54(38):955–958

12.

Khodr ZG, Lupo PJ, Agopian AJ, Canfield MA, Case AP, Carmichael SL, Mitchell LE (2014) Preconceptional folic acid-containing supplement use in the national birth defects prevention study. Birth Defects Res A 100(6):472–482. https://doi.org/10.1002/bdra.23238 CrossRef

13.

EUROCAT Folic Acid Working Group (2009) Prevention of neural tube defects by periconceptional folic acid supplementation in Europe. https://eu-rd-platform.jrc.ec.europa.eu/eurocat/prevention-and-risk-factors/folic-acid-neural-tube-defects. Accessed 31 Jan 2019

14.

Castillo-Lancellotti C, Tur JA, Uauy R (2012) Impact of folic acid fortification of flour on neural tube defects: a systematic review. Public Health Nutr 16(5):901–911. https://doi.org/10.1017/S1368980012003576 CrossRefPubMed

15.

Williams J, Mai CT, Mulinare J, Isenburg J, Flood TJ, Ethen M, Frohnert B, Kirby RS (2015) updated estimates of neural tube defects prevented by mandatory folic acid fortification United States, 1995–2011, vol 64(01), pp 1-5. Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report (MMWR)

16.

De Wals P, Tairou F, Van Allen MI, Uh S-H, Lowry RB, 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 357(2):135–142. https://doi.org/10.1056/NEJMoa067103 CrossRefPubMed

17.

Barboza-Argüello MP, Umaña-Solís LM, Azofeifa A, Valencia D, Flores AL, Rodríguez-Aguilar S, Alfaro-Calvo T, Mulinare J (2015) Neural tube defects in Costa Rica, 1987–2012: origins and development of birth defect surveillance and folic acid fortification. Matern Child Health J 19(3):583–590. https://doi.org/10.1007/s10995-014-1542-8 CrossRef

18.

De Wals P, Tairou F, Van Allen MI, Lowry RB, Evans JA, Van den Hof MC, Crowley M, Uh S-H, Zimmer P, Sibbald B, Fernandez B, Lee NS, Niyonsenga T (2008) Spina bifida before and after folic acid fortification in Canada. Birth Defects Res A 82(9):622–626. https://doi.org/10.1002/bdra.20485 CrossRef

19.

Liu S, West R, Randell E, Longerich L, O’Connor KS, Scott H, Crowley M, Lam A, Prabhakaran V, McCourt C (2004) A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth 4(1):1–10. https://doi.org/10.1186/1471-2393-4-20 CrossRef

20.

National Committee on Folic Acid Food Fortification (2006) Report of the National Committee on Folic Acid Food Fortification. Food Safety Authority of Ireland, Dublin

21.

Khoshnood B, Loane M, Walle Hd, Arriola L, Addor M-C, Barisic I, Beres J, Bianchi F, Dias C, Draper E, Garne E, Gatt M, Haeusler M, Klungsoyr K, Latos-Bielenska A, Lynch C, McDonnell B, Nelen V, Neville AJ, O’Mahony MT, Queisser-Luft A, Rankin J, Rissmann A, Ritvanen A, Rounding C, Sipek A, Tucker D, Verellen-Dumoulin C, Wellesley D, Dolk H (2015) Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ. https://doi.org/10.1136/bmj.h5949 CrossRefPubMedPubMedCentral

22.

Morris MS, Jacques PF, Rosenberg IH, Selhub J (2007) Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 85(1):193–200. https://doi.org/10.1093/ajcn/85.1.193 CrossRefPubMedPubMedCentral

23.

Cole BF, Baron JA, Sandler RS et al (2007) Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 297(21):2351–2359. https://doi.org/10.1001/jama.297.21.2351 CrossRefPubMed

24.

Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, Molloy AM, Caudill MA, Shane B, Berry RJ, Bailey RL, Hausman DB, Raghavan R, Raiten DJ (2015) Biomarkers of nutrition for development—folate review. J Nutr. https://doi.org/10.3945/jn.114.206599 CrossRefPubMedPubMedCentral

25.

Scientific Advisory Committee on Nutrition (2009) Folic acid and colorectal cancer risk: review of recommendation for mandatory folic acid fortification. The Stationery Office, London

26.

Expert Group on Vitamins and Minerals (EVM) (2003) Safe upper levels for vitamins and minerals. Food Standards Agency, London

27.

European Food Safety Authority (2009) Folic acid: an update on scientific developments. EFSA Supporting Publications 6(8):2E. https://doi.org/10.2903/sp.efsa.2009.en-2

28.

Scientific Advisory Committee on Nutrition (2017) Update on folic acid. The Stationery Office, London

29.

Food and Drug Administration (2016) Food additives permitted for direct addition to food for human consumption: folic acid, vol FDA-2012-F-0489. Department of Health and Human Services, Food and Drug Administration, Federal Register

30.

European Food Safety Authority (2009) ESCO report on analysis of risks and benefits of fortification of food with folic acid. EFSA Supporting Publications 6(8):3E. https://doi.org/10.2903/sp.efsa.2009.en-3

31.

National Toxicology Program (NTP) (2015) Identifying research needs for safe use of high intakes of folic acid. NTP Monograph. U.S. Department of Health and Human Services, Washington, D.C.

32.

VKM (2015) Risk assessment of folic acid in food supplements. Scientific opinion by the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of VKM. Eur J Nutr Food Saf 5(4):1–11. https://doi.org/10.9734/ejnfs/2015/19619 CrossRef

33.

Office of the Prime Minister’s Chief Science Advisor and the Royal Society Te Apārangi (2018) The health benefits and risks of folic acid fortification of food. Auckland

34.

Evans SE, Mygind VL, Peddie MC, Miller JC, Houghton LA (2013) Effect of increasing voluntary folic acid food fortification on dietary folate intakes and adequacy of reproductive-age women in New Zealand. Public Health Nutr 17(7):1447–1453. https://doi.org/10.1017/S1368980013001717 CrossRefPubMed

35.

Food Standards Australia New Zealand (FSANZ) (2006) Final Assessment Report. Consideration for Mandatory Fortification with Folic Acid

36.

FSAI (2008) Report of the Implementation Group on Folic Acid Food Fortification to the Department of Health and Children. Food Safety Authority of Ireland, Dublin

37.

Hennessy Á, Hannon EM, Walton J, Flynn A (2015) Impact of voluntary food fortification practices in Ireland: trends in nutrient intakes in Irish adults between 1997–9 and 2008–10. Br J Nutr 113(02):310–320. https://doi.org/10.1017/S0007114514003651 CrossRefPubMed

38.

Hopkins SM, Gibney MJ, Nugent AP, McNulty H, Molloy AM, Scott JM, Flynn A, Strain J, Ward M, Walton J, McNulty BA (2015) Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults. Am J Clin Nutr 101(6):1163–1172. https://doi.org/10.3945/ajcn.115.107151 CrossRefPubMed

39.

McDonnell R, Delany V, O’Mahony MT, Mullaney C, Lee B, Turner MJ (2015) Neural tube defects in the Republic of Ireland in 2009–11. J Public Health 37(1):57–63. https://doi.org/10.1093/pubmed/fdu016 CrossRef

40.

McDonnel LR, Delany V, O’Mahony M, Lynch C, McKeating A, Monteith C, Turner M (2015) An audit of neural tube defects in the Republic of Ireland for 2012–2015. Irish Med J 111(3):712

41.

Irish Universities Nutrition Alliance (IUNA) The National Adult Nutrition Survey (NANS). http://www.iuna.net

42.

Cashman KD, Muldowney S, McNulty B, Nugent A, FitzGerald AP, Kiely M, Walton J, Gibney MJ, Flynn A (2013) Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey. Br J Nutr 109(7):1248–1256. https://doi.org/10.1017/S0007114512003212 CrossRefPubMed

43.

Hayes A, Hennessy Á, Walton J, McNulty BA, Lucey AJ, Kiely M, Flynn A, Cashman KD (2016) Phylloquinone intakes and food sources and vitamin K status in a nationally representative sample of Irish adults. J Nutr 146(11):2274–2280. https://doi.org/10.3945/jn.116.239137 CrossRefPubMed

44.

Central Statistics Office (2007) Census 2006 Principal Demographic Results (trans: Office CS). The Stationery Office, Dublin

45.

Black LJ, Ireland J, Møller A, Roe M, Walton J, Flynn A, Finglas PM, Kiely M (2011) Development of an on-line Irish food composition database for nutrients. J Food Compost Anal 24(7):1017–1023. https://doi.org/10.1016/j.jfca.2011.01.015 CrossRef

46.

EFSA Panel on Dietetic Products Nutrition and Allergies (2014) Scientific opinion on dietary reference values for folate. EFSA J 12(11):3893. https://doi.org/10.2903/j.efsa.2014.3893 CrossRef

47.

Food Standards Agency (2002) McCance and Widdowson’s the composition of foods, 6th edn. Royal Society of Chemistry, Cambridge

48.

Tooze JA, Kipnis V, Buckman DW, Carroll RJ, Freedman LS, Guenther PM, Krebs-Smith SM, Subar AF, Dodd KW (2010) A mixed-effects model approach for estimating the distribution of usual intake of nutrients: the NCI method. Stat Med 29(27):2857–2868. https://doi.org/10.1002/sim.4063 CrossRefPubMed

49.

Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM (1995) Folate levels and neural tube defects: implications for prevention. JAMA 274(21):1698–1702. https://doi.org/10.1001/jama.1995.03530210052030 CrossRefPubMed

50.

Daly S, Mills JL, Molloy AM, Conley M, Lee YJ, Kirke PN, Weir DG, Scott JM (1997) Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 350(9092):1666–1669. https://doi.org/10.1016/S0140-6736(97)07247-4 CrossRefPubMed

51.

EFSA Panel on Dietetic Products Nutrition and Allergies (2006) Tolerable upper intake levels for vitamins and minerals. EFSA J. http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf

52.

Qi YP, Do AN, Hamner HC, Pfeiffer CM, Berry RJ (2014) The prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis did not increase among older U.S. adults after mandatory folic acid fortification. J Nutr 144(2):170–176. https://doi.org/10.3945/jn.113.183095 CrossRefPubMed

53.

Atta CAM, Fiest KM, Frolkis AD, Jette N, Pringsheim T, St Germaine-Smith C, Rajapakse T, Kaplan GG, Metcalfe A (2015) Global birth prevalence of spina bifida by folic acid fortification status: a systematic review and meta-analysis. Am J Public Health 106(1):e24–e34. https://doi.org/10.2105/AJPH.2015.302902 CrossRefPubMed

54.

Youngblood ME, Williamson R, Bell KN, Johnson Q, Kancherla V, Oakley GP (2013) 2012 Update on global prevention of folic acid—preventable spina bifida and anencephaly. Birth Defects Res A 97(10):658–663. https://doi.org/10.1002/bdra.23166 CrossRef

55.

FSAI (2016) Update report on folic acid and the prevention of birth defects in Ireland. Food Safety Authority of Ireland, Dublin

56.

Grimstad AL (2007) Folic acid fortification of foods. Estimated intake of folate from different fortification scenarios in Norwegian population groups. University of Oslo, Oslo

57.

Gezondheidsraad (2008) Naar een optimaal gebruik van foliumzuur (Towards an optimal use of folic acid). Publicatienr. 2008/02. Den Haag

58.

Weissenborn A, Burger M, Mensink GBM, Klemm C, Sichert-Hellert W, Kersting M, Przyrembel H (2005) Folic acid intake of the German population. BfR-Wissenschaft, Berlin

59.

Salerno P, Bianchi F, Pierini A, Baldi F, Carbone P, Mantovani A, Tarusico D (2008) Folic acid and congenital malformation: scientific evidence and public health strategies. Ann Ig 20(6):519–530PubMed

Title: Modelling the impact of mandatory folic acid fortification of bread or flour in Ireland on the risk of occurrence of NTD-affected pregnancies in women of childbearing age and on risk of masking vitamin B12 deficiency in older adults
Authors: Laura Kehoe
Janette Walton
Sinead M. Hopkins
Breige A. McNulty
Anne P. Nugent
Albert Flynn
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Folic Acid
Vitamin B12 Deficiency
Published in: European Journal of Nutrition / Issue 6/2020
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-019-02111-4

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2020

Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice

Is there a soft drink vs. alcohol seesaw? A cross-sectional analysis of dietary data in the Australian Health Survey 2011–12

Effect of food-related behavioral activation therapy on food intake and the environmental impact of the diet: results from the MooDFOOD prevention trial

A self-emulsifying Omega-3 ethyl ester formulation (AquaCelle) significantly improves eicosapentaenoic and docosahexaenoic acid bioavailability in healthy adults

The effect of inulin and resistant maltodextrin on weight loss during energy restriction: a randomised, placebo-controlled, double-blinded intervention

Dietary protein and appetite sensations in individuals with overweight and obesity: a systematic review

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage