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Folic acid and pregnancy – preventing neural tube defects with supplements

Medicover Genetics Editorial Team |
February 22, 2023

Each year, 300,000 babies are born with Neural Tube Defects (NTDs) worldwide [1]. NTDs are developmental defects of the brain and spinal cord occurring during early fetal development. Most of these cases are preventable, and folic acid (FA) plays a critical role.

What is folic acid?

Folic acid, or FA, is the synthetic form of folate, the natural form of Vitamin B9. Folate is essential for cell production and growth, DNA formation, and supporting functions of the nervous and immune systems. Folate is important for producing and maintaining red blood cells, hence, a deficiency can cause anemia. FA deficiency can also lead to a higher risk of depression, memory problems, fatigue, and loss of appetite. Alcohol abuse, frequent use of antibiotics, diuretics, and oral contraceptives, as well as poor diet and smoking, can deplete the body’s folate stores. Although the human body needs folate, it cannot produce it and must receive it from foods and dietary supplements. Folate can be found naturally in dark leafy vegetables such as spinach, Brussels sprouts, and lettuce, as well as in lentils, oranges, milk, and whole wheat bread.

What is folic acid’s role in pregnancy?

Folate is critically important during pregnancy as it reduces the risk of premature birth. It is also essential for spinal cord growth; a folate deficiency could lead to severe fetal defects and complications, such as miscarriage or low birth weight. Due to its critical role in fetal development, FA is found in most prenatal vitamins or as a supplement by itself. It is recommended that pregnant women should consume folate-rich foods and take appropriate amounts of FA supplements under the direction of their physician.

What causes NTDs and what role does folic acid play?

FA is essential for neural tube development and closure, which happens by the 28th day of conception. The neural tube is a structure from which both the brain and the spinal cord will subsequently form. If the neural tube fails to close, the embryo develops an NTD.

What are some common NTDs?

A common NTD of the brain is anencephaly, a serious birth defect in which part of the brain may be missing. Sadly, babies born with anencephaly do not survive past infancy. Spina bifida is a birth defect in which the baby’s spinal column does not properly close during development, leaving the spinal cord exposed. Children with spina bifida have mobility and skin problems and will need surgical interventions.

How can folic acid prevent NTDs?

To prevent NTDs from occurring, pregnant women must take FA supplements during the first 4 weeks following conception when the brain and spine develop. Since a lot of women might not be aware of their pregnancy at that stage, it is recommended that all women who are planning to get pregnant take FA supplements. There are no side effects from taking FA for a longer period; in fact, research has shown that taking FA for at least 12 months before becoming pregnant could reduce the risk of premature birth by over 50% [2]. Additionally, there is conclusive evidence that adequate consumption of FA during pregnancy can significantly reduce NTD occurrence. Studies have shown that 400μg of FA prevents the occurrence of over 50% of NTDs if it is taken before conception and throughout the first trimester of pregnancy [3]. Several countries such as the United States, Canada, China, and South Africa have launched a mandatory FA fortification of dietary foods such as staple cereal grains, bread, pasta, and flour among others. A study examining the results of FDA-required fortification in the United States from 1995-2011 has reported that the birth prevalence of NTDs has decreased by 35% since FA fortification was introduced in 1998 [4].

What is the recommended amount of folic acid supplement?

Several prominent health organizations, such as the CDC, recommend a daily amount of 400μg of FA to be consumed by pregnant women or women wishing to become pregnant. If there is a family history of an NTD, the recommended daily amount increases to 4,000μg.

Are genetics important in the development of NTDs?

It is accepted that there is a genetic risk for most NTDs; a 2-5% risk of recurrence for a sibling of someone with an NTD has been reported. However, it is thought that many are caused by a combination of genetic risk factors (potentially involving multiple genes) and environmental factors, such as medication or underlying diseases [5].

Many studies have investigated potential candidate genes, choosing mostly genes involved in folate one-carbon metabolism or glucose metabolism. Review articles summarizing these studies highlight the lack of significant results, with the exception of a polymorphism in one gene (MTHFR, which is involved in folate metabolism) which is associated with an increased risk of NTDs [6, 7].

Overall, the role of genetics in the development of NTDs is not well understood, and it has been suggested that larger studies are required to detect significant genetic associations and that the analysis of multiple candidate genes in the same individuals is necessary to investigate gene interactions and cumulative effects [6, 7]. An increased knowledge of genetic risk factors could enable more precise preventative therapies [5].

Conclusion

Worldwide, 300,000 babies are born with NTDs each year. Folic acid is essential for neural tube development and closure and therefore important in the prevention of NTDs. There is a genetic risk for NTDs, but the exact role of genetics in their development is not well understood. An increased knowledge of genetic risk factors could enable more precise preventative therapies.

Please note: Always discuss with your healthcare provider the right supplements and dosage for you.

References

[1] Christianson AL et al. Global report on birth defects: the hidden toll of dying and disabled children. White Plains (NY): March of Dimes Birth Defects Foundation. 2005 https://www.cabdirect.org/cabdirect/abstract/20063029121

[2] Callaway L et al. Folic acid supplementation and spontaneous preterm birth: adding grist to the mill? PLoS Med 2009 May 5;6(5):e1000077. doi: 10.1371/journal.pmed.1000077. Epub 2009 May 12. PMID: 19434229; PMCID: PMC2671593. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671593/

[3] Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of Spina Bifida and other neural tube defects. 1992. MMWR. 41: 1-8. https://www.cdc.gov/mmwr/preview/mmwrhtml/00019479.htm

[4] Centers for Disease Control and Prevention. Updated Estimates of Neural Tube Defects Prevented by Mandatory Folic Acid Fortification – United States, 1995-2011. 2015. MMWR Morbidity and Mortality Weekly Report. 64(01); 1-5. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a2.htm

[5] Copp AJ, Greene ND. Neural tube defects–disorders of neurulation and related embryonic processes. Wiley Interdisciplinary reviews. Developmental Biology. 2013 Mar-Apr;2(2):213-227. DOI: 10.1002/wdev.71. PMID: 24009034; PMCID: PMC4023228. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023228/pdf/emss-58507.pdf/?tool=EBI

[6] Greene ND, Stanier P, Copp AJ. Genetics of human neural tube defects. Hum Mol Genet. 2009 Oct 15;18(R2):R113-29. doi: 10.1093/hmg/ddp347. PMID: 19808787; PMCID: PMC2758708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758708/pdf/ddp347.pdf

[7] Copp AJ, Greene ND. Genetics and development of neural tube defects. J Pathol. 2010 Jan;220(2):217-30. doi: 10.1002/path.2643. PMID: 19918803; PMCID: PMC4239538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239538/pdf/emss-61095.pdf

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