Folic acid supplementation and pregnancy: more than just neural tube defect prevention


  • James A. Greenberg Brigham and Women’s Hospital; Faulkner Hospital Harvard Medical School, Boston, MA, United States
  • Stacey J. Bell Boston, MA, United States
  • Yong Guan Southern Medical University, Shenzhen, China
  • Yan-Hong Yu Southern Medical University, Guangzhou, China



folic acid, L-methylfolate, dietary supplements


Folate (vitamin B9) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities).

This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of L-methylfolate for the prevention of pregnancy-related complications other than neural tube defects.

The term folate is typically used as a generic name for the group of chemically related compounds based on the folic acid structure. Folate, or vitamin B9, is thought of as one of the 13 essential vitamins. It cannot be synthesized de novo by the body, and must be obtained either from diet or supplementation. Folic acid is a synthetic dietary supplement that is present in artificially enriched foods and pharmaceutical vitamins. Neither folate nor folic acid is metabolically active. Both must be reduced to participate in cellular metabolism. L-5-Methyltetrahydrofolate (L-methylfolate) is the predominant micronutrient form of folate that circulates in plasma and that is involved in biologic processes.

Periconceptional folic acid supplementation protects against fetal structural anomalies, including neural tube and congenital heart defects. Recent data suggest that it may also protect against preterm birth. Although additional studies are needed to better define the precise timing, dosing, and formulation, existing data suggest that dietary folic acid supplementation is a good idea for all reproductive-aged women.

Author Biographies

James A. Greenberg, Brigham and Women’s Hospital; Faulkner Hospital Harvard Medical School, Boston, MA

MD, Department of Obstetrics and Gynecology;

Division of Gynecology;

Department of Obstetrics, Gynecology and Reproductive Biology

Stacey J. Bell, Boston, MA

DSc, RD, Nutritional Consultant

Yong Guan, Southern Medical University, Shenzhen

MD, Department of Ultrasound, Shenzhen Maternity & Child Healthcare Hospital 

Yan-Hong Yu, Southern Medical University, Guangzhou

MD, PhD, Department of Obstetrics and Gynecology


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How to Cite

Greenberg, J. A., Bell, S. J., Guan, Y., & Yu, Y.-H. (2017). Folic acid supplementation and pregnancy: more than just neural tube defect prevention. REPRODUCTIVE ENDOCRINOLOGY, (34), 57–63.



Pregnancy and childbirth