Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects

World Health Organization Guidelines

Amy M. Cordero, MPA; Krista S. Crider, PhD; Lisa M. Rogers, PhD; Michael J. Cannon, PhD; R.J. Berry, MD


Morbidity and Mortality Weekly Report. 2015;64(15):421-423. 

In This Article


Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs.[1] The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 μg of folic acid daily for NTD prevention.[2] Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings[1] and is a highly cost-effective intervention.[3]

Worldwide, approximately 300,000 newborns with NTDs are born per year.[4] However, these estimates are based on modeled data because most countries lack complete, accurate, and timely surveillance systems for birth defects. Although this surveillance can be time consuming and resource intensive, it is a critical component for obtaining accurate data and raising awareness among policymakers about the need for prevention initiatives.

Population surveys that assess blood folate insufficiency (i.e., concentrations that increase the risk for having an NTD-affected pregnancy) provide complementary information for examining NTD risk in populations and can provide data relatively quickly. Cutoffs for defining folate deficiency initially were based on concentrations at which macrocytic anemia was likely to appear; they were more recently revised using homocysteine concentrations as the metabolic indicator.* However, no cutoffs to define blood folate insufficiency in women of reproductive age for NTD prevention were available. This prompted the World Health Organization (WHO) to develop guidelines on the optimal blood folate concentrations in women of reproductive age for NTD prevention.

*Available at http://apps.who.int/iris/bitstream/10665/75584/1/WHO_NMH_NHD_EPG_12.1_eng.pdf.