Fetal neural tube defects

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. 

L4. Leighton, P. C., Gordon, Y. B., Kitau, M. J., Leek, A. E., and Chard, T., Levels of alpha-fetoprotein in maternal blood as a screening test for fetal neural-tube defect. Lancet 2, 1012-1015 (1975). 

Prevention of fetal neural tube defect (spina bifida). Folic acid supplementation taken before conception and during the early weeks of pregnancy has been shown in an 8-year trial to prevent the condition in pregnancies subsequent to an affected birth. Women hoping to conceive and who have had an affected child are advised to take folic acid 5 mg/day. To prevent a first occurrence 400 micrograms/day should be taken both before conception, or as soon as possible after diagnosis. In both cases folate supplement should be taken for the first 12 weeks of pregnancy. 

Several observational studies have shown that dietary supplementation of folate in women of childbearing age who might become pregnant can reduce the risk of fetal neural tube defects (e.g., spina bifida). 

Milunsky A, Morris JS, Jick H, et al. 1992. Maternal zinc and fetal neural tube defects. Teratology 46(4) 341-348. 

Liu J, JinL, Zhang L, liZ, Wang L, YeR, et al. Placental concentrations of manganese and the risk of fetal neural tube defects. J Trace Elem Med Biol 2013 27(4) 322-5. 

A small sample of amniotic fluid (10-20 ml) is collected at approximately 16 weeks gestation. Fetal cells are present in the amniotic fluid and can be used to diagnose single-gene disorders, chromosome abnormalities, and some biochemical disorders. Elevated a-fetoprotein levels indicate a fetus with a neural tube defect. The risk of fetal demise because of amniocentesis is estimated to be approximately 1/200. 

Embryonic age Neural tube defects from retinoic acid, arsenic, and valproic acid (Adams, 1993 Bennett Finnell, 1998) Decreased fertility in female rats exposed to dioxin (TCDD) (Gray Ostby, 1995) Hydronephrosis with dioxin exposure during embryonic or fetal periods in rats (Couture-Haws et al., 1991 Bimbaum, 1995) ... 

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... 

Valproate can cause fetal malformations, particularly neural tube defects (2-3% risk). 

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