ABSTRACT
Las malformaciones congénitas constituyen la segunda causa de mortalidad infantil en nuestro medio, lo cual significa que nuestro comportamiento en términos de salud pública, es muy similar a los países desarrollados. Hay malformaciones de alto costo médico social en las cuales afortunadamente se puede intervenir eficazmente con medidas de prevención primaria o secundaria. Los defectos del tubo neural son una de ellas y en el mundo curiosamente, no son muchos los países que lo hacen. Afortunadamente, Chile ha tenido una actitud pionera en América con la implementación de un programa de fortificación de harinas que ha significado una disminución cercana al 50 por ciento en las tasas de frecuencia de la enfermedad. Los mecanismos bioquímicos exactos de la prevención no están claramente descritos, pero un papel importante juega el ácido fólico en la síntesis del ADN y en el metabolismo de la metionina/homocisteina, vías metabólicas claves del neuro desarrollo inicial. Lo más importante sin embargo, es que la prevención actúa sólo para aquellos casos típicamente dependientes de la neurulacion primaria y no para todos los defectos cráneo encefálicos.
Congenital anomalies are the second cause of infant mortality in Chile, which is similar to the findings in developed countries. The medical-social burden of some of these malformations is high, but some of them are able to undergo primary or secondary prevention. Neural tube defects are among them and unfortunately, a. global prevention is not the rule. Chile has been one of the pioneer countries with supplementation of folic acid fortification, which has resulted in a reduction in the prevalence of open neural tube defects in about 50 percent. The exact mechanisms involved in the prevention of open neural tube defects are not clear, but an important role has been ascribed to folic acid in the synthesis of DNA and metabolism of metionin-homocistein, key pathways for the early development of the neural tube. An important point is that fortification with folic acid only works in those defects associated with the primary neurulation and not to all cranio-encephalic defects.
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Neural Tube Defects/diagnosis , Neural Tube Defects/physiopathology , Neural Tube Defects/metabolism , Prenatal Diagnosis , Folic Acid/metabolism , Anencephaly/etiology , Neural Tube Defects/epidemiology , Spinal Dysraphism/etiology , Homocysteine/metabolism , Methionine/metabolism , Risk FactorsABSTRACT
To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.