Folic Acid Supplementation to Prevent Neural Tube Defects

Liaquat Roopesh Johnson, Suresh Prabhu

Department of Community Medicine, DM Wayanad Institute of Medical Sciences, Meppadi, Wayanad, Kerala, India*

Corresponding Author: Liaquat Roopesh Johnson, Department of Community Medicine, DM Wayanad Institute of Medical Sciences, Naseera Nagar, Meppadi, Wayanad – 673 577, Kerala, India. Phone: +91-8943964816, Email: liaquat99@gmail.com

 

Sir,

Globally, of the 2.76 million neonatal deaths in 2013, an estimated 276,000 babies died from congenital anomalies.1 Neural tube defects (NTDs) are among the most common severe congenital defects and include anencephaly, spina bifida, encephalocele, craniorachischisis, and iniencephaly.1,2 The birth prevalence of NTDs in India has been reported to be 4.1 per 1000 births.3

Many investigators have reported that NTDs can be prevented by periconceptional folic acid supplementation.4-6 Based on the evidence, the World Health Organization (WHO) recommends periconceptional supplementation with folic acid to prevent NTDs.

Accordingly, all women, from the moment they begin trying to conceive until 12 weeks of gestation, should take a folic acid supplement (400 µg folic acid daily).

Women who have had a fetus diagnosed as affected by an NTD or have given birth to a baby with an NTD should:

  • Be advised on the protective effect of periconceptional folic acid supplementation

  • Be offered high-dose supplementation (5 mg folic acid daily)

  • Be advised to increase their food intake of folate; and

  • Receive information on the risk of recurrence.7

Since maternal folate levels are suspected to be an important factor in the development of NTDs, a WHO Guideline Committee has tried to establish the utility of red blood cell (RBC) and serum folate as biomarkers of the risk of having an NTD affected pregnancy at the population level.

The committee examined four critical questions:

  1. What are the key genetic, biological and socio-demographic determinants of folate status in women of reproductive age?

  2. Do interventions to improve folate status in women improve blood folate concentrations?

  3. What is the threshold blood folate concentration associated with the lowest risk of having an NTD affected pregnancy?

  4. Are serum and RBC folate readings affected by the laboratory assays used to measure them?

The committee reported that:

  • Folate status in the general population is multifactorial. The strongest determinant of folate status in women of reproductive age is the gene polymorphism methylenetetrahydrofolate reductase 677C→ T.

  • RBC folate, which indicates long-term status, responds mainly to supplementation and fortification.

  • In order to achieve the greatest reduction of NTDs at the population level, RBC folate concentrations should be above 400 ng/mL (906 nmol/L) in women of reproductive age.

  • The above threshold is useful only at the population level as it cannot predict the risk of an individual having an NTD affected pregnancy.

  • Microbiological assay is the most reliable choice to obtain comparable results for RBC folate across countries.

However, the WHO guideline also states that low folate concentrations cannot explain all cases of NTDs.8

Indian experts have cautioned that the causes for NTDs in the Indian scenario are probably different from those reported in the western literature. While folate deficiency is important, Vitamin B 12 deficiency and zinc deficiency have been mentioned as possible confounders.

The use of periconceptional folic acid supplementation as a means to prevent NTDs is unlikely to be successful in India. Most pregnancies are unplanned; most women are unaware of pregnancy till the third-fourth week of gestation; and awareness regarding periconceptional folic acid supplementation to prevent NTDs is also low.9,10

In the long term, it is desirable that there is an increase in general awareness about NTDs and periconceptional folic acid supplementation, coupled with improvements in overall nutrition.

In the short term, however, large-scale food fortification with folate might be the only feasible solution.

 

End Note

Author Information

  1. Liaquat Roopesh Johnson, Assistant Professor, Department of Community Medicine, DM Wayanad Institute of Medical Sciences, Naseera Nagar, Meppadi, Wayanad – 673 577, Kerala, India. Phone: +91-8943964816, Email: liaquat99@gmail.com

  2. Suresh Prabhu, Associate Professor, Department of Community Medicine, DM Wayanad Institute of Medical Sciences, Naseera Nagar, Meppadi, Wayanad – 673 577, Kerala, India. Phone: +91-8111881137, Email: dr.sureshp@dmwims.com

 

Conflict of Interest

None declared.

References

1. World Health Organization. WHO Web Site2015; Last cited on 2015 Apr 24Available from: http://www.who.int/mediacentre/factsheets/fs370/en/.

2. Botto LD, Moore CA, Khoury MJ, Erickson JD, Neural-tube defectsN Engl J Med 1999; 341: 1509-19.[CrossRef] [PubMed]

3. Bhide P, Sagoo GS, Moorthie S, Burton H, Kar A, Systematic review of birth prevalence of neural tube defects in IndiaBirth Defects Res A Clin Mol Teratol 2013; 97: 437-43.[CrossRef] [PubMed]

4. Ramakrishnan U, Grant F, Goldenberg T, Zongrone A, Martorell R, Effect of women’s nutrition before and during early pregnancy on maternal and infant outcomes: A systematic reviewPaediatr Perinat Epidemiol 2012; 26: Suppl1285-301.[CrossRef] [PubMed]

5. De-Regil LM, Fernández-Gaxiola AC, Dowswell T, Peña-Rosas JP, Effects and safety of periconceptional folate supplementation for ?preventing birth defectsCochrane Database Syst Rev 2010; CD00795[CrossRef]

6. Castillo-Lancellotti C, Tur JA, Uauy R, Impact of folic acid fortification of flour on neural tube defects: A systematic reviewPublic Health Nutr 2013; 16: 901-11.[CrossRef][CrossRef] [PubMed]

7. World Health Organization. WHO Web Site2015; Last cited on 2015 Apr 24Available from: http://www.who.int/elena/titles/folate_periconceptional/en/.

8. World Health Organization. Guideline: Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects. GuidelineGuideline 2015; Geneva: World Health Organization

9. Gupta H, Gupta P, Neural tube defects and folic acidIndian Pediatr 2004; 41: 577-86.[PubMed]

10. Kumar A, Neural tube defects: A neglected problemIndian Pediatr 2009; 46: 665-7.[PubMed]

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