1. Obeid R. et al. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?. J Perinat Med 2013; 41(5): 469–483.
2. Greenberg J. et al. Multivitamin Supplementation During Pregnancy: Emphasis on Folic Acid and L-Methylfolate. REVIEWS IN OBSTETRICS & GYNECOLOGY 2011; VOL 4 N° ¾.

3. Prinz-Langenohl R. et al. [6S]-5 methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C,T polymorphism of methylenetetrahydrofolate reductase. British Journal of Pharmacology 2009; 158, 2014–202.

4. Lamers Y. et al. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006 Jul;84(1):156-61.

5. Lamers Y. et al. Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. J Clin Nutr 2004;79:473–8.

6. Steven W. et al. The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects. Scientific Reports 2018; 8:409.

Polimorfismo MTHFR

1. Morales de Machín A. et al. Polimorfismo C677T del gen de la metilentetrahidrofolato reductasa en madres de niños afectados con defectos del tubo neural. Invest Clin 2015; 56(3): 284 – 295.

2. Blom H. et al. Neural tube defects and folate: case far from closed. Nat Rev Neurosci. 2006 September; 7.(9): 724–731. 3. Herrera J. et al. Factores determinantes del estado nutricional del folato y el rol de la variante genética C677T de la enzima metilen tetrahidrofolato reductasa (MTHFR). Rev Chil Nutr Vol 2016; 43, Nº4.

4. Hiraoka M. and Kagawa Y. Genetic polymorphisms and folate status. Congenital Anomalies 2017; 57, 142 –14.

5. Leclerc D and Rozen R. Génétique moléculaire de MTHFR. MEDECINE / SCIENCES 2007; 23 : 297-302.

6. Cabo R. Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study. Genes Nutr 2015; 10:7.

7. Tsang B. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C.T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies. Am J Clin Nutr 2015;101:1286–9.

Frecuencia Polimorfismo

1. Góes Soligo a. et al. Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women. Rev Bras Ginecol Obstet 2017;39:659–662.

2. Wilcken B. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase ( MTHFR ): findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003; 40:619–625.

3. Binia A. Geographical and ethnic distribution of single nucleotide polymorphisms within genes of the folate/homocysteine pathway metabolism. Genes Nutr 2014; 9:421

4. Yadav U. Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis. Indian J Clin Biochem. 2017 Oct;32(4):399-410.

Dosis Altas Ácido Fólico

1. Raghavan R. Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring. Paediatr Perinat Epidemiol. 2018 Jan;32(1):100-111.

2. Valera-Gran D. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am J Clin Nutr. 2017 Sep;106(3):878-887.

3. Morakinyo A High-Dose Perinatal Folic-Acid Supplementation Alters Insulin Sensitivity in Sprague-Dawley Rats and Diminishes the Expression of Adiponectin. J Diet Suppl. 2018 Feb 16:1-13.

4. Navarrete-Muñoz E. High doses of folic acid in the periconceptional period and risk of low weight for gestational age at birth in a population based cohort study. Eur J Nutr. 2017 Nov 27.

5. Bailey S. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. PNAS 2009 Sept; Vol 106, N°36.

6. Christensen K. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr 2015;101:646–58.

7. Field M and Stover P. Safety of folic acid. Ann. N.Y. Acad. Sci. 2018; 1414:59–71.

8. Wiens D. and De Soto C. Is High Folic Acid Intake a Risk Factor for Autism?—A Review. Brain Sci. 2017; 7:149.

9. Sawaengsri H. et al. High folic acid intake reduces natural killer cell cytotoxicity in aged mice. J Nutr Biochem. 2016 Apr;30:102-7.

10. Martínez García R. et al. Suplementos en gestación: últimas recomendaciones. Nutr Hosp 2016; 33(Supl. 4):3-7.

11. Takimoto H. Elevated maternal serum folate in the third trimester and reduced fetal growth: a longitudinal study. J Nutr Sci Vitaminol (Tokyo) 2011;57(2):130-7.

12. Tam C. Circulating Unmetabolized Folic Acid: Relations hip to Folate Status and Effect of Supplementation. Obstetrics and Gynecology International 2012; Article ID 485179.


Suplementación Vitaminas y Minerales

1. World Health Organization, Standart for Maternal and Neonatal Care, Prevention of neural tube defects, 2006.

2. World Health Organization, Standart for Maternal and Neonatal Care, Iron and folate supplementation, 2006.

3. Devakumar et al. Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis. BMC Medicine 2016; 14:90.

4. Pre-conceptional Vitamin/Folic Acid Supplementation 2007: The Use of Folic Acid in Combination With a Multivitamin Supplement for the Prevention of Neural Tube Defects and Other Congenital Anomalies. JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE 2007; Guideline N°201.

5. De-Regil L. Preconceptional Nutrition Interventions for Adolescent Girls and Adult Women: Global Guidelines and Gaps in Evidence and Policy with Emphasis on Micronutrients. J Nutr 2016 Jul;146(7):1461S-70S.

6. Nguyen P. Preconception Micronutrient Supplementation with Iron and Folic Acid Compared with Folic Acid Alone Affects Linear Growth and Fine Motor Development at 2 Years of Age: A Randomized Controlled Trial in Vietnam. J Nutr. 2017 Aug;147(8):1593-1601.

7. Genuis S. Preconception Care: A New Standard of Care within Maternal Health Services. BioMed Research International 2016; Article ID 6150976.