Jooma, Rashid

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eCommons@AKU Section of Neurosurgery Department of Surgery 11-2004 Preventing neural tube defects by folic acid fortification of flour Rashid Jooma Follow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg  Part of the Neurology Commons, Neurosurgery Commons, and the Surgery Commons EditorialPreventing Neural Tube Defects by Folic Acid fortification of FlourR. JoomaDepartment of Neurosurgery, Jinnah Postgraduate Medical Centre, Karachi.Neural tube defects (NTDS) are a group of seriouslydisabling birth malformations of which spina bifida andanencephaly are most frequent. No data is available for theincidence of NTDS in Pakistan but anecdotal testimonyfrom health professionals suggest that it is not inconsequen-tial and is probably at the higher end of the world range (0.5to 12 per 1000 live births).JPMC StudyA year-long prospective study conducted in theobstetrical service of Jinnah Postgraduate Medical Centre(JPMC), Karachi for the year 2002, observed 9892 deliver-ies (312 still-born). Amongst these, there were 34 birthswith various NTDs of whom there were 16 live births.Anencephaly was the commonest of the neural abnormali-ties (19 cases with only 3 live births) followed by 11myelomeningocoeles with 7 live births. There were 3 babieswith encephalocoeles and 4 cases of spina bifida aperta.Folic Acid Consumption and NTDSOver the past two decades a strong link has beenestablished between the occurrence of NTDs and a deficien-cy of folate in the diet of the mother at the time of concep-tion.1 The initial observations came from the findings thatthese defects were prevalent in the low socio-economicgroups and the high incidence of NTDs during periods ofnutritional deprivation such as famines.Since these initial observations, it has been clearlyshown by various scientific studies that increasing thedietary intake of folate in women of childbearing age andsupplementations with 0.4 to 4 mg folic acid a day, 4 weeksprior and 8 weeks after conception significantly reduces thebirth of babies with NTDs.2 Thus NTDs may be viewed asa folate deficiency disorder preventable by augmentation offolic acid intake. A recent study of women bearing NTDbabies revealed a high level of autoantibodies to folatereceptors3 and this could explain the mechanism whereby arelative folic acid deficiency may occur resulting in failureof neural tube closure and the rationale of augmenting folicacid in young women to levels that would overcome thereceptor block.Increasing Folate intakeFolate is largely found in fruits (especially citrus),leafy green vegetables, animal liver and to a lesser extent inbeans and lentils. The non-pregnant adult's daily require-ment of 100 micrograms is usually met but the 400 micro-grams a day required by the mother to afford protectionfrom NTDs affecting the foetus may not be available in theaverage Pakistani diet.The 3 strategies of nutritional interventions that maybe used are:1. To encourage consumption of a folate rich diet throughprocess of public education. However, this would requirethat the target audience be accessible through the massmedia and have the economic resources for provision of theappropriate foodstuff in the requisite quantities.2. Provision of supplements of folic acid to women ofchildbearing age using the national Lady Health Workersnetwork. However, because many pregnancies areunplanned and NTDs arise in the foetus between days 15and 28 post-conception when most women are unaware thatthey are pregnant and by the time she comes to a health careworker for antenatal care, it is too late to prevent the malfor-mations by supplementation.3. Universal folic acid fortification of a basic food ingredi-ent is the most effective strategy to ensure adequate bloodlevels in the mother in the critical peri-conceptional periodas the embryonic closure of the neural tube is taking place.Recommendation for Folic Acid FortificationTo ensure that all women in Pakistan of childbearingage increase their intake by 400 micrograms per day, enrich-ment of flour would be that most efficient vehicle of fortifi-cation. The current recommendation is for the fortificationof folic acid to the level of 240 micrograms per 100 gram offlour (240ppm).4 That such an intervention does work inreducing devastating birth defects has now been well estab-lished from studies of other countries.5Fortification in other CountriesA number of countries have adopted a range of folicacid fortification approaches. In the U.K. the Committee onMedical Aspects of Food and Nutrition Policy4 recommend-ed voluntary fortification at 240ug/100g white flour. TheUnited States of America and Canada adopted mandatoryfortification (140ur/100 gm of cereal grain and 150ug/100gm of white flour respectively) and the early reports show adecline in NTD births of 1991 to 70%.6,7 In Costa Rica,where mandatory fortification was introduced in 1999 at alevel of 180ug folic acid/100gm of wheat and maize flour, amaize flour, a reduction of NTD births at theNational Children's Hospital in San Jose has been reportedfrom 106 cases in 1995 to 26 cases in 2001.8 Chile intro-duced mandatory fortification at a level of 220ug/100gm ofwhite flour in 2000 and has reported a 31% decrease inNTD cases within the first two years.9 The cost of fortifica-tion in the USA is about 1 cent per person per year and theexpenditure on each NTD prevented in estimated at lessthan $1000.10Studies confirm that the greater the background rateof NTDs, the greater the beneficial effect of folic acid andthus in countries such as Pakistan the benefit should be atthe very least be as much as that reported in Nova Scotia,Canada, where a reduction in the absolute numbers of openNTDsfrom 30 in 1991 to 9 in 2000 i.e., a 70% decline hasbeen documented.7Study of Technical Issues requiredIn the context of other public health measures, folicacid fortification of flour would not be overly expensivewith the cost of the folic acid itself being about $0.15 permetric ton of flour. Data from the local flour milling indus-try would allow the final determination of the increment tothe cost of a maund of ata. Studies are required of the bestmethods to be employed in our flour mills and chakkies toensure even distribution of the nutrient mix between batch-es of flour. Technically it is easy to add folic acid to the"pre-mix" in an on-going fortification programme such asiron, zinc and some B vitamins as has been done in Chile.The dose of folic acid required to be taken by womenperi-conceptionally to prevent NTDs has been addressed ina meta-analysis by Wald et al.11 and their dose-responsemodel predicts an escalating reduction of risk from 23%with an intake of 0.2 mg/day of folic acid, 36% from anintake of 0.4 mg/day and as much as 85% by taking 5 mg offolic acid daily. We do not at present have data of folic acidlevels in the young women of Pakistan. However, both thehigh incidence of maternal anaemia documented in theNational Health Survey12 and the high incidence of NTDsthat we have observed in our institutional setting are surelyveritable markers of folate impoverishment in the diet of ourwomen and make a cogent argument for the level of fortifi-cation chosen to achieve the desired daily intake of at least450 micrograms a day to be best equated to the highest lev-els recommended by health authorities round the world.Folic acid is stable in stored flour but is sensitive tolight and heat. Study of the losses that occur in the distribu-tion and storage conditions existing in Pakistan and duringthe shelf life would also be required. Further study to quan-tify the degradation of folic acid during preparation of nansand chappatis is also essential to allow determination of the"overage" needed to achieve a level of 250 microgram offolic acid in the final product for every 100 gram of flourused in the making of local breads.ConclusionSpina bifida and anencephaly are two of the mostcommon and severe birth defects. One causes permanentparalysis and the other foetal or infant death. There is nowexcellent evidence that increased consumption of supple-mental folic acid can prevent many of these defects and theeffect is more pronounced where the background rate ofNTDs is in the higher range.13 Folic acid-preventable birthdefects are as preventable as polio and as a public healthmeasure, equally urgent. The technology to fortify is sim-ple, inexpensive and almost immediately implemented forlarge population groups.Folic acid enrichment of flour should be consideredas a priority public health measure by the State.Opportunities to implement a sustainable, inexpensive pub-lic health intervention to prevent major human disease comerarely. Folic acid fortification of flour is one of the rareopportunities. Governments of nations with a high back-ground incidence of NTDs who ignore folic acid fortifica-tion "are committing public health malpractices".14References1. Centres for Disease Control and Prevention. Recommendations for the use offolic acid to reduce the number of cases of spina bifida and other neural tubedefects. MMWR Morbid Mortal Wkly Rep 1992;41:1-7.2. Wald N, Sneddon J, Densem J, et al. Prevention of neural tube defects: resultsof the MRC Vitamin Study. Lancet 1991;338:132-7.3. Rothenberg SPn, da Costa MP, Sequeira JM, et al. Autoantibodies againstfolate receptors in women with a pregnancy complicated by a neural-tubedefect. N Engl J Med 2004;350:134-42.4. Committee on Medical Aspects of Food and Nutritional Policy. Folic acid andthe prevention of disease. Report of the committee on medical aspects of foodand nutrition policy. London: The HMSO, 2000, PP. 1-101.5. Ray JG, Meier C, Vermeulen MJ, et al. Association of neural tube defects andfolic acid food fortification in Canada. Lancet 2002;360:2047-8.6. Honein MA, Paulozzi LJ, Mathews TJ, et al. Impact of folic acid fortificationof the US food supply on the occurrence of neural tube defects. JAMA2001;285:2981-6.7. Persad VL, Van den Hof MC, Dube JM, et al. Incidence of open neural tubedefect in Nova Scotia after folic acid fortification. CMAJ 2002;167:241-5.8. Chen LT, Rivera MA. The Costa Rican experience: reduction of neural tubedefects following food fortification programs. Nutr Rev 2004;62:S40-3.9. Castilla EE, Orioli IM, Lopez-Camelo JS, et al. Preliminary data on changesin neural tube defect prevalence rates after folic acid fortification in SouthAmerica. Latin American Collaborative Study of Congenital Malformations(ECLAMC). Am J Med Genet 2003;123A:123-8.10. Wald NJ. Folic acid and the prevention of neural tube defects. N Engl J Med2004;350:101-3.11. Wald NJ, Law MR, Morris JK, et al. Quantifying the effect of folic acid.Lancet 2001;358:2069-73.12. National Survey of Pakistan 1990-94. Islamabad: PMRC, 1998.13. Berry RJ, Zhu LI, Ericson DJ, et al. Prevention of neural tube defects withfolic acid in China. N Engl J Med 1999;341:1485-90.14. Oakley GP. Folic acid fortification: time for a concerted effort. CMAJ2002;167:848.

Preventing neural tube defects by folic acid fortification of flour

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Preventing neural tube defects by folic acid fortification of flour

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