Molecular and Structural Biology Division
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ABSTRACT Neural tube defects (NTDs) are common congenital problem of central nervous system. Even though the epidemiologic link between maternal folate deficiency and fetal NTDs and preventive role of folate supplementation on oc currence and recurrence of these defects is establis hed, the causal mechanism at cellular and molecular level remains undefined. However, an elevated level of homocysteine is an independent risk factor for NTDs due to mutations in MTHFR gene which inhibits the production of this enzyme. Supplementation of folic acid 0.4µg per day may reduce the risk of this fetal disease. Hence public awareness program by the government should be built up in India as the occurrence of this fetal disease in North India as high as 4-9 per 1000 births. |
aberrant intracellular processing, thereby elevating its level. This increased level shows a spectrum of clinical symptom. Older children have been identified with mental retardation, acute psychosis, muscle weakness and ataxia. Adults have presented with gait disturbance. Young infants have been identified with more severe symptoms of hypotonia, failure to thrive, failure of neurological developments and severe apena. Most infants died at less than one year of age. During the last decade, homocysteine has received increasing attention as elevated levels of this have been implicated as an in dependent risk factor for neural tube defects. In addition to the genetic factors, environmental factors, including diet also influence the level of homocysteine 3 . |
38 Manthan , International e - Journal, Vol. 11, June, 2010, ISSN No. 0974 - 6331 FOLIC ACID SU PPLEMENTATION Folic acid is essential for the production of methionine, which is co-factor in RNA and DNA synthesis and is required for methylation of proteins, lipids and myelin. Folic acid is essential for growth, differentiation and repair, hence it is essential for fetal development during pregnancy. This vitamin is now considered as an important factor in reducing chances of NTDs, Megaloblastic anaemia of pregnancy and some other complications like spontaneous abortions, Intra Uterine Growth Retardation (IUGR) of baby. Folic acid is a vitamin B also known as folate or folacin. Folic acid is needed to make new cells in the body and it can be found in most multivitamin pills and also in certain foods (peas, corn, dried beans, leafy vegetables, beef lever, banana, orange juice and fortified cereals breakfast). Women whose diets follow the United States Dietary Associa tions (USDA) food guide pyramid are more likely to eat 0.4 mg of folate daily. It is recommended that all women able to have a baby take a multivitamin pill with folic acid in addition to eating foods high in folate because over cooking can destroy folate in food and the amount of absorbed from food varies. In 2004, Wald estimated that folic acid supplementation (5 mg/day) preconception and continuing till 12 weeks after getting pregnancy reduce the risk of NTDs by 85%. In the women with the previous baby affected by NTDs periconceptional use of folic acid decreases the recurrence by 70%. However, the bigger problem to prevent occurrence of NTDs is that about 50% of all pregnancies are unplanned even in developed countries. CONCLUSION Several scientific research based on clinical trial have reinforced the observation that risk of delivering a child with NTDs significantly decreases with ingestion of periconceptional folic acid. US Public Health Service made a strong recommendation that all women of childbearing age, who are capable of becoming pregnant should consume 0.4mg of folic |
acid per day. An individual should develop a plan with her doctor to check homocysteine levels periodically and adjust tr eatment accordingly. The MTHFR mutations appear to be medically irrelevant, so as long as an individual’s homocysteine level is normal. Hence public awareness “to plan before you conceive and to take folic acid if you plan a pregnancy”, should be built up in India also as the occurrence of this fetal disease in North India as high as 4-9 per 1000 births. ACKNOWLEDGEMENTS The authors are thankful to Dr. Sarita Agarwal, Associate Professor and Dr. Mandakini Pradhan, Assistant Professor, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow for providing the chance to work with them as a research trainee. Authors are also thankful to Mr. Ujjawal and Subodh for their kind help. REFRENCES 1. Kang, S. S., Wong, P. W., Susmano, A., Sora, J., Norusis, M. and Ruggie, N. (1999). Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am. J. Hum. Genet. 48: 536-545. 2. Viel, A., Dall’Agnese, L. and Simone, P. (1997). Loss of heterozygosity at the 5,10- methyltetrahydrofolate reductase locus in human ovarian carcinomas. Br. J. Cancer. 75: 1105-1110. 3. Pradhan, M., Behari, S., Kalra, S. K., Ojha, P., Agarwal, S. and Jain, V. K. (2007). Association of methylenetetrahydrofolate reductase genetic polymorphisms with atlantoaxial dislocation. J. Neurosurg. Spine . 7: 623-630. 4. Federal Register. (1993). Folic acid: proposed rules. 53254-53317pp. 5. Centers for Disease Control and Prevention. (1983- 1991). Use of folic acid for prevention of spina bifida and other neural tube defects. MMWR . 40: 513-516. 6. Arya, R. and Vyas, A. (2006). Folic acid and neural tube defects: a re view of the mechanism of pathogenesis. Journal of Neonatology . 20: 316-324 |
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