WHO Guideline on Optimal serum and red blood cell folate concentrations

February 2, 2015   World

International Federation for Spina Bifida and Hydrocephalus | Source

WHO guideline 2015In April 2015, the World Health Organization (WHO) released the Guideline on Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects. The guideline provides global, evidence-informed recommendations on blood folate concentrations in women of reproductive age to reduce the risk of neural tube defects (NTDs) in populations. It aims to help Member States and their partners in their efforts to make informed decisions on the appropriate nutrition actions to take to achieve the Millennium Development Goals (MDGs), in particular reduction of child mortality (MDG 4) and improvement of maternal health (MDG 5), through the establishment of appropriate threshold values for red blood cell folate concentrations at the population level.

These values may be used to determine the need for, and guide monitoring and evaluation of the impact of, nutrition interventions aimed at improving folate status and preventing congenital anomalies.


This guideline complements previously published WHO recommendations on the assessment of folate status in populations.

  1. At the population level, red blood cell folate concentrations should be above 400 ng/mL (906 nmol/L) in women of reproductive age, to achieve the greatest reduction of NTDs (strong recommendation, low quality evidence).
  2. The above red blood cell folate threshold can be used as an indicator of folate insufficiency in women of reproductive age (strong recommendation, low quality evidence). Because low folate concentrations cannot explain all cases of NTDs, this threshold cannot predict the individual risk of having a NTD-affected pregnancy and thus it is only useful at the population level.
  3. No serum folate threshold is recommended for prevention of NTDs in women of reproductive age at the population level (strong recommendation, low quality evidence). Countries interested in using this indicator may consider first establishing the relationship between both serum and red blood cell folate and use the threshold value for red blood cell folate to establish the corresponding threshold in serum.
  4. Microbiological assay is recommended as the most reliable choice to obtain comparable results for red blood cell folate across countries (strong recommendation, moderate quality evidence).

Reducing folate insufficiency at the population level may take time. However, reductions in NTDs may be seen, as the average red blood cell folate concentrations improve. An important consideration is that the overall reduction in NTDs will depend on the baseline folate status, time available for increasing folate status (through folate nutrition interventions) and NTD risk of each population. A threshold for public health concern on the prevalence of folate insufficiency (i.e. red blood cell folate below 400 ng/mL [906 nmol/L] in women of reproductive age) is difficult to establish at this time.

Member States and their partners are advised to discuss the merits of folate nutrition interventions through fortification of staple foods or targeted supplementation. The authors remark that high folic acid intake has not reliably been shown to be associated with negative health effects.

CDC has developed a webpage to help public health professionals, policymakers, and scientific staff globally to better understand the guideline's implications for public health practice. CDC also released an MMWR Policy Note highlighting the new WHO guideline.