Dr.Padmesh. VNEURAL TUBE DEFECT ROLE OF FOLIC ACID DR. PADMESH . V
Dr.Padmesh. V• INTRODUCTION:• Folate prevents NTDs.• Folate functions in single-carbon transfer reactions .• Exists in many chemical forms.• Folic acid (pteroylmonoglutamic acid), which is the most oxidized and stable form of folate, occurs rarely in food but is the form used in vitamin supplements and in fortified food products.• Most naturally occurring folates (food folate) are pteroylpolyglutamates.
• ACTION OF FOLATE: Dr.Padmesh. V• Folate coenzymes are involved in:• (1) deoxyribonucleic acid (DNA) synthesis,• (2) Purine synthesis,• (3) generation of Formate into the formate pool, and• (4) amino acid interconversion with the conversion of homocysteine to Methionine providing methionine for the synthesis of S- adenosyl-methionine (an agent important for in vivo methylation).• Mutations in the genes encoding the enzymes involved in homocysteine metabolism include 5,10 methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase, and methionine synthase.• An association between a thermolabile variant of MTHFR and mothers of children with NTDs may account for up to 15% of preventable NTDs.
• ACTION OF FOLATE: Dr.Padmesh. V• Folic Acid in Prevention of NTDs• Folic acid plays an important role in closure of neural tube (neurulation).• There are two general and important biological effects of folate.• First, folate acts as a cofactor for enzymes involved in DNA and RNA biosynthesis.• Folate provides one-carbon units for the de-novo synthesis of DNA bases (guanidine, adenine, and thymine).• Folate requirements increase dramatically during the periods of rapid growth of fetus.• Thus with folate deficiency, DNA synthesis is inhibited and cells are unable to manufacture enough DNA for mitosis, leading to limited and/or imbalanced cell growth, followed by cell death.
• ACTION OF FOLATE: Dr.Padmesh. V• Folic Acid in Prevention of NTDs• Folic acid plays an important role in closure of neural tube (neurulation).• There are two general and important biological effects of folate.• Second, folate is involved in the supply of methyl groups to the methylation cycle.• The methyl group is used by methionine synthetase, to recycle homocysteine back to methionine. A disturbance in this process causes hyperhomocysteinemia and shortage of methionine; therefore cells are not able to methylate important compounds like proteins, lipids and myelin.• Thus, folate deficiency or genetically rooted error in folate metabolism can cause developmental defects through disturbances of DNA biosynthesis and/or the methylation cycle
Dr.Padmesh. V• Maternal periconceptional use of folic acid supplementation reduces the incidence of neural tube defects in pregnancies at risk by at least 50%.• To be effective, folic acid supplementation should be initiated 1 mo before the time of the planned conception and continued until at least the 12th wk of gestation when neurulation is complete.
• PREVENTION. Dr.Padmesh. V• Fortification of food: To increase folic acid intake, fortification of flour, pasta, rice, and cornmeal .• Health education: Informative educational programs.• Folic acid vitamin supplementation;• Consume food folate from a varied diet. Dietary sources of folate are leafy green vegetables, legumes (beans, peas), citrus fruits (juices), liver and whole bread .
• PREVENTION. Dr.Padmesh. V• All women of childbearing age and who are capable of becoming pregnant take 0.4 mg of folic acid daily.• To avoid occurrence of NTD: 0.4 mg/day.• If, however, a pregnancy is planned in high-risk women (previously affected child), supplementation should be started with 4 mg of folic acid daily, beginning 1 mo before the time of the planned conception, and continued until at least the 12th wk of gestation when neurulation is complete.• To avoid recurrence of NTD: 4 mg/ day.
• PREVENTION. Dr.Padmesh. V• Drugs that antagonize folic acid such as trimethoprim and the anticonvulsants carbamazepine, phenytoin, phenobarbital, and primidone, increase the risk of myelomeningocele.• Women on anticonvulsants,antimetabolites, and oral contraceptives have suboptimal folate status.• Anticonvulsant valproic acid causes neural tube defects in ≈1–2% of pregnancies, if the drug is administered during pregnancy.• Some epilepsy clinicians recommend that all female patients of childbearing potential who take anticonvulsant medications should also receive folic acid supplements.
Dr.Padmesh. V• Neural tube closure occurs during days 22-28.• Therefore, advice regarding dietary modification, supplementation, and food fortification should be in the periconceptional period i.e. beginning at least 1 month before conception and continuing through the first trimester.• Studies have demonstrated that periconceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly.