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      Prevention of neural tube defects in the UK: a missed opportunity

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          Abstract

          Objective

          In 1991, the Medical Research Council (MRC) Vitamin Study demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). We aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in the UK from 1998 as it had been in the USA.

          Design

          Estimates of NTD prevalence, the preventive effect of folic acid and the proportion of women taking folic acid supplements before pregnancy were used to predict the number of NTD pregnancies that would have been prevented if folic acid fortification had been implemented.

          Setting

          Eight congenital anomaly registers in England and Wales.

          Main outcome measures

          The prevalence of pregnancies with an NTD in the UK and the number of these pregnancies that would have been prevented if folic acid fortification had been implemented.

          Results

          From 1991 to 2012, the prevalence of NTD pregnancies was 1.28 (95% CI 1.24 to 1.31) per 1000 total births (19% live births, 81% terminations and 0.5% stillbirths and fetal deaths ≥20 weeks’ gestation). If the USA levels of folic acid fortification from 1998 onwards had been adopted in the UK, an estimated 2014 fewer NTD pregnancies would have occurred.

          Conclusions

          Failure to implement folic acid fortification in the UK has caused, and continues to cause, avoidable terminations of pregnancy, stillbirths, neonatal deaths and permanent serious disability in surviving children.

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          Most cited references14

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          Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.

          J. F. Sneddon, J Densem, N Wald … (1991)
          A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid.
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            Reduction in neural-tube defects after folic acid fortification in Canada.

            Philippe De Wals, Fassiatou Tairou, Margot I. Van Allen … (2007)
            In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high. Copyright 2007 Massachusetts Medical Society.
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              Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States.

              Russell S Kirby, Roderick C. Hobbs, Thomas A. Miller … (2002)
              In 1992, the United States Public Health Service recommended that all women of childbearing age consume 400 microg of folic acid daily. The Food and Drug Administration authorized the addition of synthetic folic acid to grain products in March 1996 with mandatory compliance by January 1998. The impact of these public health policies on the prevalence of neural tube defects needs to be evaluated. We sought to determine the prevalences of spina bifida and anencephaly during the transition to mandatory folic acid fortification. Twenty-four population-based surveillance systems were used to identify 5,630 cases of spina bifida and anencephaly from 1995-99. Cases were divided into three temporal categories depending on whether neural tube development occurred before folic acid fortification (January 1995 to December 1996), during optional fortification (January 1997 to September 1998), or during mandatory fortification (October 1998 to December 1999). Prevalences for each defect were calculated for each time period. Data were also stratified by programs that did and did not ascertain prenatally diagnosed cases. The prevalence of spina bifida decreased 31% (prevalence ratio [PR] = 0.69, 95% confidence interval [CI] = 0.63-0.74) from the pre- to the mandatory fortification period and the prevalence of anencephaly decreased 16% (PR = 0.84, 95% CI = 0.75-0.95). Stratification by prenatal ascertainment did not alter results for spina bifida but did impact anencephaly trends. The decline in the prevalence of spina bifida was temporally associated with folic acid fortification of US grain supplies. The temporal association between fortification and the prevalence of anencephaly is unclear. Published 2002 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Arch Dis Child
                Journal ID (iso-abbrev): Arch. Dis. Child
                Journal ID (hwp): archdischild
                Journal ID (publisher-id): adc
                Title: Archives of Disease in Childhood
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Print): 0003-9888
                ISSN (Electronic): 1468-2044
                Publication date (Print): July 2016
                Publication date (Electronic): 17 December 2015
                Volume: 101
                Issue: 7
                Pages: 604-607
                Affiliations
                [1 ]Wolfson Institute of Preventive Medicine, Queen Mary University of London , London, UK
                [2 ]Institute of Health & Society, Newcastle University , Newcastle upon Tyne, UK
                [3 ]Department of Epidemiology & Public Health, University of Leicester , Leicester, UK
                [4 ]National PerinatalEpidemiology Unit, University of Oxford , Oxford, UK
                [5 ]Public Health England , London, UK
                [6 ]Congenital Anomaly Register and Information Service for Wales, Public Health Wales , Swansea, UK
                [7 ]University of Southampton and Wessex Clinical Genetics Service , Southampton, UK
                [8 ]School of Clinical Sciences, University of Bristol , Bristol, UK
                Author notes
                [Correspondence to ] Professor Joan Morris, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; j.k.morris@ 123456qmul.ac.uk
                Article
                Publisher ID: archdischild-2015-309226
                DOI: 10.1136/archdischild-2015-309226
                PMC ID: 4941168
                PubMed ID: 26681697
                SO-VID: 97a06f64-ae80-490e-be93-9208aef967cf
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                Date received : 23 June 2015
                Date revision received : 13 October 2015
                Date accepted : 17 October 2015
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                Subject: 1507
                Subject: 1612
                Subject: Original Article
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                ScienceOpen disciplines: Medicine
                Keywords: congenital abnorm,epidemiology,fetal medicine,neurodevelopment,folic acid
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: congenital abnorm, epidemiology, fetal medicine, neurodevelopment, folic acid

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