Addendum to Scientific Impact Paper No. 4: Periconceptual Folic Acid and Food Fortification in the Prevention of
Neural Tube Defects (2003)
As a public health intervention, the Royal College of Obstetricians and Gyanecologists (RCOG) renews its
recommendation of mandatory food fortification of folic acid to prevent neural tube defects in babies.
Public Health England’s National Diet and Nutrition Survey (NDNS), published in March 2015, indicated low folate
levels in more than 10% of the UK adult population.1 In particular, the study found low folate levels in a significant
proportion of women of childbearing age in the UK with many at an increased risk of biochemical folate deficiency.
One in ten of childbearing women were not getting enough folate from their dietary intake while one in six were
found to have low stores of folate in their bodies.2
Set alongside these findings are the high rate of unintended pregnancies in Britain each year3,4and the increasing
prevalence of neural tube defects found in England and Wales recently.5 Moreover, preconception folic acid
supplementation has been associated with other protective benefits such as preventing the risk of small for
gestational age at birth6, spontaneous preterm birth7 and autism spectrum disorders.8,9,10
Recent developments
Since the publication of the RCOG’s Scientific Impact Paper in 2003, and following the release of the report by the
Scientific Advisory Committee on Nutrition (SACN) on folate and human health in 200611, several other UK
organisations and bodies such as the British Medical Association (BMA), Food Standards Agency (FSA), Medical
Research Council (MRC) and Royal College of Paediatrics and Child Health (RCPCH) have supported mandatory folic
acid fortification as a public health measure to lower the risk of neural tube defects in babies.12,13,14,15
The SACN published a further report in 2009 that found no good evidence of an increased risk of colon, prostate or
colorectal cancers and coronary heart or vascular diseases associated with folic acid through fortification.16 The
SACN advised the setting up of a surveillance programme to monitor intake levels in the population and to identify
those who may suffer from folate deficiency. It was recognised that a portion of the UK population will exceed the
recommended dietary allowance (RDA) of folate through consuming foods that have been voluntarily fortified with
folic acid (such as in breakfast cereals) or through inappropriate supplementation.
In response, the Chief Medical Officer of England urged the Department of Health to put together a plan to advance
the SACN recommendations in her Annual Report 2012.17 This has been substantiated in a recent meta-analyses of
randomised trials which found no increase or decrease in site specific cancer with folic acid supplementation.18
Some doubts about the safety of folic acid have recently arisen through emerging studies in epigenetics where it has
been postulated that prenatal exposure to folate modifies fetal DNA with possible inter-generational outcomes19,20
and evidence points to higher cancer risk associated with elevated folate intake (>1mg/day)21 and safety concerns
have also been raised about consumption of supplements over the RDA during pregnancy.22
However, it must be noted that these concerns around folate and epigenetics are largely theoretical. Furthermore,
studies on paternal and maternal folate intake prior to conception have demonstrated no associations with
childhood brain tumours23 and a reduced risk of childhood leukemia24,25 respectively.
Globally, a growing number of countries are fortifying their grain stocks including maize and rice.26 53 countries have
regulation for mandatory fortification of folic acid in wheat flour, including the US, Canada, Australia and South
Africa.27,28
Opinion
The RCOG continues to support preconception supplementation of 400 micrograms of folic acid daily for women
wishing to become pregnant until their 12th week of pregnancy. This advice is in NICE clinical guidelines.29,30 and is a
World Health Organization (WHO) recommendation31. Additionally, women with a previous history of a NTD
pregnancy should take 5 milligrams per day as recommended by the SACN.
On mandatory fortification of folic acid in flour and bread, the RCOG supports the SACN recommendation that
safeguards are needed including controls on voluntary fortification by the food industry, guidance on supplement
use for certain population groups and the monitoring of the long-term effects of folic acid intake above the daily
guidance limits.
Dr Sadaf Ghaem-Maghami MRCOG
Chair, RCOG Scientific Advisory Committee
27 October 2015
Page 1 of 3
References:
1
National Diet and Nutrition Survey Rolling Programme (NDNS RP) Supplementary report: blood folate results for the UK as a
whole, Scotland, Northern Ireland (Years 1 to 4 combined) and Wales (Years 2 to 5 combined)
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/414745/NDNS_Y1_4_Folate_report.pdf
2
Presentation by Public Health England ‘Blood folate status in the UK – results from NDNS’ http://www.nii.org.uk/wpcontent/uploads/2015/09/Gillian-Swann-PHE-Blood-Folate-Status-in-the-UK-latest-results-from-NDNS.pdf
3
Wellings K et al. 'The prevalence of unplanned pregnancy and associated factors in Britain: findings from the third National
Survey of Sexual Attitudes and Lifestyles (Natsal-3)' The Lancet
Volume 382, Issue 9907, 30 November–6 December 2013, Pages 1807–1816
http://www.sciencedirect.com/science/article/pii/S0140673613620711. Also see MRC press release:
http://www.wellcome.ac.uk/News/Media-office/Press-releases/2013/Press-releases/WTP054814.htm
4
Department of Health (2013) A Framework for Sexual Health Improvement in England
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/142592/9287-2900714-TSOSexualHealthPolicyNW_ACCESSIBLE.pdf
5
BINOCAR (2014) Congenital Anomaly Statistics 2012: England and Wales
http://www.binocar.org/content/Annual%20report%202012_FINAL_nologo.pdf
6
Hodgetts VA et al. 'Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age
neonates: a population study, systematic review and meta-analysis'.
BJOG: An International Journal of Obstetrics & Gynaecology. 122(4):478-90, 2015 Mar.
7
Li Z et al. 'Periconceptional folic acid supplementation and the risk of preterm births in China: a large prospective cohort study'
International Journal of Epidemiology. 43(4):1132-9, 2014 Aug.
8
Lyall K et al. 'Maternal lifestyle and environmental risk factors for autism spectrum disorders'. International Journal of
Epidemiology. 43(2):443-64, 2014 Apr.
9
Suren P et al. ‘Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children'.
JAMA. 309(6):570-7, 2013 Feb 13.
10
Schmidt RJ et al. 'Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay
in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study'. American Journal of Clinical
Nutrition. 96(1):80-9, 2012 Jul.
11
SACN (2006) Folate and Disease Prevention https://www.gov.uk/government/publications/sacn-folate-and-diseaseprevention-report
12
British Medical Association briefing to the House of Lords published on 7 November 2013 http://bma.org.uk/news-viewsanalysis/news/2013/november/peers-use-bma-evidence-in-call-for-folic-acid-fortification
13
Food Standards Agency in 2007
http://collections.europarchive.org/tna/20100927130941/http://food.gov.uk/healthiereating/folicfortification/
14
Medical Research Council in 2007
http://www.ctu.mrc.ac.uk/news/2007/mrc_welcomes_fsa_decision_to_add_folic_acid_to_flour_170507
15
Royal College of Paediatrics and Child Health in 2007 http://www.rcpch.ac.uk/news/food-standards-agency-fsarecommendation-mandatory-fortification-bread-folic-acid-17-may-2007
16
SACN (2009) Report to CMO on folic acid and colorectal cancer risk https://www.gov.uk/government/publications/sacnreport-to-cmo-on-folic-acid-and-colorectal-cancer-risk
17
See Recommendation 6: ‘Nutrition’ on page 5 in Annual Report of the Chief Medical Officer 2012, Our Children Deserve Better:
Prevention Pays
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/255237/2901304_CMO_complete_low_res_a
ccessible.pdf
18
Vollset, Stein Emil et al. ‘Effects of folic acid supplementation on overall and site-specific cancer incidence during the
randomised trials: meta-analyses of data on 50 000 individuals’, The Lancet, Volume 381 , Issue 9871 , 1029 – 1036
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)62001-7/abstract
19
Johnson, Ian et al . 'Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in
vitro.' Epigenetics 2012 Jul 1;7(7):689-94. Epub 2012 Jul 1. http://www.ncbi.nlm.nih.gov/pubmed/22617627
20
Tsang V et al. 'The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to
arsenic.'Toxicol Appl Pharmacol. 2012 Nov 1;264(3):439-50. doi: 10.1016/j.taap.2012.08.022. Epub 2012 Aug 31
http://www.ncbi.nlm.nih.gov/pubmed/22959928)
21
Jagerstad M. 'Folic acid fortification prevents neural tube defects and may also reduce cancer risks', Acta Paediatrica.
101(10):1007-12, 2012 Oct
22
Pastor-Valero M et al. Periconceptional folic acid supplementation and anthropometric measures at birth in a cohort of
pregnant women in Valencia, Spain. British Journal of Nutrition. 105(9):1352-60, 2011 May
23
Greenop KR et al. 'Paternal dietary folate, B6 and B12 intake, and the risk of childhood brain tumors', Nutrition & Cancer.
67(2):224-30, 2015
24
Metayer C et al. 'Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood
Leukemia International Consortium study' Epidemiology. 25(6):811-22, 2014 Nov
Page 2 of 3
25
Ajrouche R et al. 'Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood
acute leukemia: the ESTELLE study'. Cancer Causes & Control. 25(10):1283-93, 2014 Oct
26
Food Fortification Initiative website ‘ Global progress’ - http://www.ffinetwork.org/global_progress/index.php. More
information on fortification in the UK can be found via the Institute of Food Research (‘What are folates and folic acid?’)
http://www.ifr.ac.uk/science-society/spotlight/folicacid/ and the Real Bread Campaign (‘Flour fortification’)
http://www.sustainweb.org/realbread/flour_fortification/
27
Crider KS, Bailey LB, Berry RJ. Folic Acid Food Fortification—Its History, Effect, Concerns, and Future Directions. Nutrients.
2011;3(3):370-384. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257747/
28
Oakley GP, Tulchinsky TH. Folic acid and vitamin B12 fortification of flour: a global basic food security requirement. Public
Health Reviews 2010;32:284-295. http://www.publichealthreviews.eu/show/f/30
29
NICE Clinical Guideline CG62 (2008) Antenatal care http://www.nice.org.uk/guidance/cg62/resources/guidance-antenatalcare-pdf
30
NICE Public Health Guidance PH11 (2008) Maternal and child nutrition http://www.nice.org.uk/guidance/ph11/chapter/1recommendations#folic-acid-2
31
WHO (2012) Guideline: Daily iron and folic acid supplementation in pregnant women
http://apps.who.int/iris/bitstream/10665/77770/1/9789241501996_eng.pdf?ua=1
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