Neural tube defects, folate deficiency

Folate deficiency The recommended dietary intake of folate has been increased (also protects against neural tube defects in the fetus), and additional folate is now added to flour (bread, pasta, and other products made liom flour)... 

Folate deficiency during pregnancy is a major contributor to neural tube defects because of the critical role of folate in neuronal development. 

Because both drugs may interfere with folic acid metabolism, their use during pregnancy is usually contraindicated by the potential for effects on the fetus, such as the development of neural tube defects associated with folate deficiency. The use of trimethoprim is contraindicated in patients with blood dyscrasias, hepatic damage, and renal impairment. 

Folate deficiency is associated with the increased risk of neural tube defects (spina bifida, anencephaly), cardiovascular diseases, megaloblastic anemia, and some cancers (Bailey et al., 2003 Finglas et al., 2006 Scott et al, 1999). Unfortunately, folate intake is suboptimal in most of the world s populations, even in developed countries (Scott et al., 2000). Therefore there is an urgent need to increase folate content and bioavailability in staple foods. Because of its large consumption worldwide, potato is an appealing target for enrichment. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Anyone taking diuretics for longer than six months may experience a folate, or folic acid, deficiency. Folic acid plays a part in the health and reproduction of virtually every cell in the body. It is responsible for protein metabolism, the prevention of neural tube defects in pregnancy, blood cell production, and the synthesis of neurotransmitters. Individuals with folate deficiencies may suffer from anemia, depression and other mood disorders, and may give birth to babies with neural tube defects. Supplementation with folic acid may be useful in reversing these effects. 

There has been an association between folate deficiency during the first weeks of pregnancy and neural tube defects, leading to a campaign to encourage folic acid intake. In as how much UV exposure might contribute to folate deficiency is still under discussion.126-128... 

Although folate is widely distributed in foods, dietary deficiency is not uncommon, and a number of commonly used drugs can cause folate depletion. Marginal folate status is a factor in the development of neural tube defects and supplements of 400 fj,g per day periconceptually reduce the incidence of neural tube defects significantly. High intakes of folate lower the plasma concentration of homocysteine in people genetically at risk of hyperhomo-cysteinemia and may reduce the risk of cardiovascular disease, although as yet there is no evidence from intervention studies. There is also evidence that low folate status is associated with increased risk of colorectal and other cancers and that folate may be protective. Mandatory enrichment of cereal products with folic acid has been introduced in the United States and other countries, and considered in others. 

Deficiency of either folic acid or vitamin B12 results in a clinically similar megaloblastic anemia because of the neurological damage that accompanies the megaloblastic anemia of vitamin B12 deficiency, the condition is generally known as pernicious anemia. Suhoptimal folate status is also associated with increased incidence of neural tube defects (Section 10.9.4), hyperhomocys-teinemia leading to increased risk of cardiovascular disease (Section 10.3.4.2), and undermethylation of DNAleadingto increased cancerrisk (Section 10.9.5). 

Folate (pteroylglutamic acid) is essential for the synthesis and methylation of DNA during fetal and early postnatal development (Nunn et al., 1986). Folate deficiency may result from poor diet, malabsorption, from treatment with anticonvulsant drugs such as phenytoin or primidone, as well as from antifolate drugs such as methotrexate. Folate deficiency during pregnancy leads to an increased prevalence of fetal malformations such as spina bifida and related neural tube defects. Findings... 

Folic acid deficiency may result in neural tube defects in newborns. Folic acid is one of the few nutritional supplements shown in clinical trials to be effective in preventing disease. Maternal prenatal supplementation with 400 mg/day folic acid reduced significantly the incidence of neural tube defects in newborns, which indicates that low maternal folate concentrations were associated with these defects. 

Biod mistry of Fc ie 1-Caib(m Metabolkm Ihirine and Pyrimidine ffiosyndiesis Mitodumdrial Folate tabolism Risk Factors for Folate Deficiency Sig]t of Folate Defidoicy Assesanait of Folate Status Folic dd and Neural Tube Defects... 

The metliylenetetraliydrofolate reductase enzyme reduces 5,10-methylenetetrahydrofolate to form 5-methyltetrahy-drofolate, which provides methyl groups necessary for homocysteine remetliylation to methionine. The severity of the enzyme defect and of clinical symptoms varies considerably. Completely absent enzyme activity results in neonatal apneic episodes, myoclonus leading to coma, and death, whereas partial deficiency may result in mental retardation and seizures. Premature cardiovascular disease or peripheral neuropathy could be the only manifestation. A common polymorphism (677C>T) is associated with enzyme thermal lability and mild elevation of homocysteine in the presence of folate insufficiency, implicating a risk for both vascular disease and neural tube defects. ... 

Folic acid Megaloblastic anemia, diarrhea, glossitis Serum folate Decreased with increased cellular/tissue turnover (pregnancy, malignancy, hemolytic anemia) masks neurologic complications of vitamin B12 deficiency decreases risks of neural tube defects... 

Pregnancy (folate deficiency during pregnancy is an important cause otl neural tube defects)... 

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