WHO Issues Folate Recommendations for Women

Laurie Barclay, MD

April 24, 2015

Optimal red blood cell (RBC) folate concentrations should exceed 400 ng/mL in women of reproductive age to prevent neural tube defects (NTDs), according to World Health Organization (WHO) guidelines described in an article published in the April 24 issue of the Morbidity and Mortality Weekly Report.

"[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," write Amy M. Cordero, MPA, from the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues.

"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. The US Public Health Service recommends that women capable of becoming pregnant consume 400 μg of folic acid daily for NTD prevention."

Although the WHO estimates the global incidence of NTDs at about 300,000 annually, the true count is unknown because many countries do not collect birth defects data.

The WHO issued the new recommendations to help countries lower the risk for NTDs by determining population risk and the need for prevention programs, as well as by implementing and assessing the effectiveness of such programs. Key strategies include folic acid fortification of staple foods and periconceptional supplementation. It would be useful to examine the risk for NTDs while birth defects surveillance systems are being developed or to supplement data from existing systems.

Specific WHO recommendations are as follows:

  • To prevent the greatest number of NTDs, RBC folate concentrations at the population level should exceed 400 ng/mL (906 nmol/L) in women of reproductive age (strong recommendation, low-quality evidence).

  • Among women of reproductive age, the RBC folate threshold of >400 ng/mL (906 nmol/L) can be used as a marker of folate insufficiency (strong recommendation, low-quality evidence). The authors warn that this marker is only useful at the population level because all cases of NTDs are not caused by low folate concentrations. Clinicians cannot use this threshold to predict a specific woman's risk for having a NTD-affected pregnancy.

  • At the population level, the WHO has not recommended a serum folate threshold to prevent NTDs in women of reproductive age (strong recommendation, low-quality evidence). Before attempting to use such an indicator, countries should first determine the association between both serum and RBC folate concentrations and use the threshold value for RBC folate concentration to determine the corresponding serum threshold.

  • The most reliable option yielding comparable results for RBC folate concentration across countries is microbiological assay (strong recommendation, moderate-quality evidence).

"[A]lthough the guidelines provide an important tool to assist with NTD prevention interventions, birth defects surveillance continues to be critical for monitoring the prevalence of birth defects because not all NTDs are folate sensitive," the guidelines authors conclude.

The authors have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. 2015;64:421-423. Full text

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