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Revista chilena de pediatría

versión impresa ISSN 0370-4106

Rev. chil. pediatr. vol.88 no.6 Santiago dic. 2017 


Supplementation with folic acid and orofacial clefts

Suplementación con acido fólico y fisuras orofaciales

Marcos Roberto Tovani-Palone a  

aHospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil

Keywords: Cleft lip; cleft palate; folic acid

Dear editor,

I read with great interest the article "Folatos y Embarazo, conceptos actuales. ¿Es necesaria una suplementación con Acido Fólico?”( 1 ). It is known that food fortification and supplementation with folic acid have been effective in preventing birth defects, such as neu ral tube defects and congenital heart disease121. Another important point is the potential preventive role of folic acid in orofacial clefts. This has been a controversial subject in the literature.

However, a connection between neural tube de fects and orofacial clefts has been discussed. In this case, their times of occurrence during embryogenesis, their status as defects as well as the related genetic as pects have been key points to understand this issue. On that basis, some similarities between this two malfor mations have been established3. Such data, in turn, support the theory that acid folic can likewise prevent orofacial clefts.

It should be noted, therefore, that orofacial clefts re sult from interaction between genetic and environmen tal factors4. Moreover, they occur during the embryo nic and early fetal periods5. Thus, taking into account the influence of the environment factors (eg: vitamin deficiency during pregnancy)4, the supplementation with folic acid during periconceptional period and first trimester of pregnancy could have an important role in preventing orofacial clefts. What do the article authors ( Folatos y Embarazo, conceptos actuales. ¿Es necesaria una suplementación con Acido Fólico?) think about it?


1. Castaño E, Piñuñuri R, Hirsch S, Ronco AM. Folatos y Embarazo, conceptos actuales: ¿Es necesaria una suplementación con Acido Fólico?. Rev Chil Pediatr. 2017;88(2):199-206. [ Links ]

2. Tovani-Palone MR. Diet, adolescence and pregnancy versus folic acid supplementation. Rev Chil Pediatr. 2016;87(2):150. [ Links ]

3. Wehby GL, Murray JC. Folic acid and orofacial clefts: a review of the evidence. Oral Dis. 2010;16(1):11-9. [ Links ]

4. Tovani-Palone MR, Saldias-Vargas VP. Factores genéticos y fisuras orofaciales no sindrómicas. Rev Fac Med. 2016;64(2):381-3. [ Links ]

5. Pang J, Broyles J, Redett R. Cleft lip and palate. Eplasty. 2013;13:ic25 [ Links ]

* Correspondence to: Marcos Roberto Tovani-Palone


Response to the letter of editor entitled: Supplementation with folic acid and orofacial clefts by Dr. Marcos Roberto Tovani-Palone

Respuesta carta al editor titulada: Suplementación con acido fólico y fisuras orofaciales

Ana María Roncoa 

aLaboratorio de Nutrición y Regulación Metabólica, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile

We completely agree with Dr. Tovani-Palona that an "adequate" supply of folates (contained in foods plus supplementation with folic acid) is essential to prevent NTD and other malformations like orofacial clefts. We think that the concept "adequate" should have considerations in terms of the period of use and in terms of concentrations that have to be optimal. It is important to follow the current advice for pregnant women on folic acid supplementation between 4 weeks before until 12 weeks pregnancy. Additional periods of supplementation before and during pregnancy can in duce epigenetic modifications in offspring genes rela ted to metabolism with yet unknown impact on (later) health1,2.

The topic related to the optimal folic acid concen trations that are needed to prevent fetal malformations and avoid long-term pathologies in the offspring is more complex. The source of our concern is that in Chile the fortification of wheat flour with folic acid (FA) is much higher than that recommended by the United States (2.4 mg/kg of flour)3. In addition, Chile has a high consumption of bread by the whole population4,5 and pregnant women are also supplemented with 1mg of daily FA. Both strategies are probably sur passing the upper limit established for the synthetic form of folates, defined by its ability to mask the vita min B12 deficiency, which in women of childbearing age is around 10%. Because an elevated folates/vit B12 ratio has been associated with several health impair-ments6,7, a balanced ratio is very important to achieve, not only by supplementation but also by supplying an adequate amount vitamin B12 needed to maintain the correct functioning of the one carbon metabolism.

Our goal was to emphasize the importance of the interaction between these two vitamins and their effects on the body, mainly on fetal programming, but without ignoring the importance of fortification pro grams in reducing the prevalence of malformations like NTD and orofacial clefts.


1. Pauwels S, Ghosh M, Duca RC, Bekaert B, Freson K, Huybrechts I, et al. Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation. Epigenetics. 2017;12:1-10. [ Links ]

2. Pauwels S, Ghosh M, Duca RC, Bekaert B, Freson K, Huybrechts I, et al. Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants. Clin Epigenetics. 2017;9:16. [ Links ]

3. Subsecretaría de Salud Pública. Ministerio de Salud. Instituto de Salud Pública de Chile. Informe. Programa Fortificación de Harinas. Santiago de Chile: 2011. [ Links ]

4. Hertrampf E, Cortés F. National food-fortification program with folic acid in Chile. Food Nutr Bull. 2008;29:S231-7. [ Links ]

5. Cortés F, Mellado C, Pardo RA, Villarroel LA, Hertrampf E. Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile. Am J Med Genet A. 2012;158A:1885-90. [ Links ]

6. Selhub J, Rosenberg IH. Excessive folic acid intake and relation to adverse health outcome. Biochimie. 2016;126:71-8. [ Links ]

7. Paul L, Selhub J. Interaction between excess folate and low vitamin B12 status. Mol Aspects Med. 2017;53:43-7 [ Links ]

* Correspondencia: amronco@inta.uchile.d

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