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EDITORIAL
Year : 2003  |  Volume : 49  |  Issue : 3  |  Page : 195-196

Folic Acid and Birth Defects


Department of Obstetrics and Gynecology, Seth G. S. Medical College and K. E. M. Hospital, Mumbai - 400012

Correspondence Address:
Department of Obstetrics and Gynecology, Seth G. S. Medical College and K. E. M. Hospital, Mumbai - 400012
vinitasalvi@gsmc.edu




How to cite this article:
Salvi V S. Folic Acid and Birth Defects. J Postgrad Med 2003;49:195-6


How to cite this URL:
Salvi V S. Folic Acid and Birth Defects. J Postgrad Med [serial online] 2003 [cited 2014 Nov 27];49:195-6. Available from: http://www.jpgmonline.com/text.asp?2003/49/3/195/1131


The world is increasingly becoming aware of the role of intrauterine nutrition on fetal health and its subsequent sequelae in the new born. The issue of peri-conceptional folic acid intake and its effects on the fetus has been one area where the beneficial effects of adequate nutrition have been best documented.
Annually, worldwide, an estimated 300,000 or more babies are born with spina bifida and anencephaly.[1] However, the actual burden of neural tube defects is far higher with a number of babies being born with other defects such as encephalocele, craniorachischisis and iniencephaly. Also, closed neural tube defects where the defect is covered by normal skin are often undetected and therefore not accounted for in the numbers. Moreover, a number of pregnancies with such anomalous babies either end in a spontaneous abortion or elective termination or deliver as stillbirths. These neurological anomalies pose a tremendous burden on society. These infants have a high mortality and morbidity and need a number of surgical procedures and also suffer from various neurological sequelae such as hydrocephalus, developmental compromise and incontinence. It is thus impossible to quantify the medical, emotional, psycho-social and financial costs, of neuraltube defects.
A number of factors have been implicated in the causation of neural tube defects. These include chromosomal aneuploidy, exposure to teratogenic drugs such as anti-convulsants, pregestational diabetes and even obesity. There is also a racial component with a higher frequency reported in Hispanic and non- Hispanic whites in the United States as compared to blacks.[1] However, the role of folic acid deficiency in the causation of neural tube defects and the corollary of the use of folic acid supplementation in the prevention of these birth defects has now gained universal acceptance.
Folic acid metabolism was linked with neural tube defects as early as 1965.[2] Folic acid is involved in DNA, RNA and protein biosynthesis and facilitates rapid cell division at crucial periods of embryogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is responsible for converting folic acid to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate serves as a methyl group donor in the conversion of homocysteine to methionine. This methylation is important in providing carbon units to rapidly dividing cells and the synthesis of nucleotide bases. Thus, folic acid deficiency would result in a neural tube defect. Moreover, if there is a mutation in the gene regulating MTHFR, homocysteine will not get converted to methionine and affected individuals will have to increase their folic acid intake to overcome the genetically defective enzyme.
Many studies have now conclusively proved the beneficial effects of folic acid supplementation in preventing neural tube defects. The United Kingdom Medical Research Council (UK-MRC) conducted a double blind, placebo- controlled randomised clinical trial at 33 centres in seven countries. A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy were randomized to one of four groups receiving folic acid (4mg daily), other vitamins, both or neither.[3] Folic acid was shown to have a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The benefits of folic acid supplementation were so overwhelming that the trial was stopped prematurely because of ethical concerns about denying folic acid to the remaining women.
Similar benefits were also demonstrated in a trial conducted by the Indian Council of Medical Research.[4] A folic acid (4mg) containing multivitamin preparation given for at least one month prior to conception and up to 3 months after conception was found to result in a 60% reduction in the occurrence of neural tube defects as compared to the group receiving placebo in women with a past history of a baby with neural tube defect. This trial was terminated after publication of results of the MRC trial.
The dose of folic acid in women who are at high risk for a neural tube defect is 4 mg. In low risk women, a daily supplement of 0.4 mg of folic acid is sufficient. The Centers for Disease Control and Prevention (CDC) recommends that all women of childbearing age who are capable of becoming pregnant should consume 0.4 mg for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other neural tube defects.[5] This dose has been found to be effective even in China in different areas with high and low rates of neural tube defects.[6]
While the burden of neural tube defects can be dramatically reduced by a simple measure of folic acid supplementation, the problem lies in ensuring that this occurs on a universal basis. In the United States breakfast cereals and enriched grains are fortified with folic acid.[7] In other countries it would be necessary to identify an item of staple diet which can be supplemented and this would require action at the level of the respective governments. Legislation would be needed in countries such as India to provide for fortification of food with folic acid. However it is imperative to move on a war-footing at a global level to achieve universal folic acid supplementation in light of the overwhelming benefits that such a move would ensure.

  ::   References Top

1.Botto LD, Moore CA, Khoury MJ, Erickson JD. Neural tube defects. N Engl J Med 1999:341:1509-19.  Back to cited text no. 1    
2.Smithells RW, Hibbard ED. Folic acid metabolism and human embryopathy. Lancet 1965;1:1254-6.  Back to cited text no. 2    
3.Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 1991;338:131-7.  Back to cited text no. 3  [PUBMED]  
4.Indian Council of Medical Research (ICMR) Collaborating Centres and Central Technical Co-ordinating Unit, ICMR, New Delhi. Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India. Indian J Med Res 2000;112:206-11.  Back to cited text no. 4    
5.Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep 1992;41:1-7.  Back to cited text no. 5    
6.Berry RJ, Zhu Li, Erickson JD, Song Li, Moore CA, Wang H, et al. Prevention of neural tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999;341:1485-90.  Back to cited text no. 6    
7.Oakley GP Jr. Eat right and take a multivitamin. N Engl J Med 1998;338:1060-61.  Back to cited text no. 7    

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
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