Efficacy of a daily prenatal supplement of folic acid; how many cases of spina bifida can be prevented?

motherisk int j 2020;1:20


Yonah Amitai MD, The Meuchedet Insurance Fund and Bar Ilan University, Israel.



I am confused: The FDA claims that folic acid prevents 50-70% of neural tube defects. But population-based American studies show only a 20-30% prevention rate. Where is the catch here?



In the US there is mandatory folate food fortification, so any study on the effectiveness of folic acid supplementation is biased by the fact that the women already receive folic acid through fortified foods. A breakthrough study from Israel, where there is no central folate fortification, shows that pre-conceptional use of folic acid results indeed in at least 54% reduction in rate of spina bifida.


In 1992 the CDC published a directive to supplement with folic acid  women of childbearing age to prevent open neural tube  defects (NTDs) (1). According to the CDC the potential prevention rate of NTDs by folic acid ranges from 50 to 70%, but studies from the USA have shown that in practice the rate of decrease in NTDs ranges has ranged from 25-35%. These different rates  have caused confusion among clinicians and researchers. In the United States, there has been a requirement for enrichment of flour with folic acid since 1998.

American studies have shown that following the enrichment of flour with folic acid  there has been an average 28% decrease in the rate of NTDs (2). But this result is based on the general population, and not just on women who had taken folic acid, especially because the rate of folic acid use in the USA in the critical period before pregnancy is low. Hence it is difficult, based on US studies, to separate the effect of taking folic acid as a daily personal supplement, from the masking  effect of adding folic acid to food .

In Israel, a directive was issued for a daily supplement of 0.4 mg folic acid for women only in 2000, and to this day food is not routinely enriched with folic acid. Following this directive, the Ministry of Health has been running an ongoing campaign that included interviews in the media, meetings with opinion leaders in the Jewish and Muslim sectors, and the distribution of millions of leaflets. According to four national surveys starting in 2000 following the publication of the briefing, the percentage of folic acid use increased from 5% pre 2000 to 30.5% in 2002 and 57% in 2010.

The latest survey conducted in 2010 sampled all 768 mothers who gave birth at the same time in all 29 hospitals in Israel. The rate of use of folic acid before pregnancy was 57% (close to 60% in Jewish women and 49.3% among Arabs), and when the women who started taking folic acid  in the first 3-4 weeks of pregnancy were also included, the rate of use of HF in all women was 79% (80.4% among Jewish and 76.3% in Arabs). The rate of use of folic acid in Israel, according to this survey, is among the highest in the world.

A study based on national Israeli data of 1,668,073 births was recently published(3),  examining the decrease in the rate of NTDs as a measure of the effectiveness of the recommendations for taking folic acid from the year 2000 and the policy of increasing the use of folic acid before pregnancy. The study included NTDs data from all live births and also from abortions in all hospitals in Israel.

The study found an overall 53% decrease in the rate of  spina bifida and a 40% decrease in the rate of anencephaly  in the years 2008-2012 compared to the rates in Israel in  2000-2001(Diagram).

This rate of decrease is explained by the provision of folic acid supplements to women before pregnancy, which has increased substantially in Israel since the directive was issued in 2000. This decrease in NTDs cannot be explained as a natural trend over the years.  For comparison, in Europe Khoshnood and  investigators  from 19 countries  recording 12.5 million births over 10 years, have shown in 2015 no change in the incidence rate of NTDs.

The novelty of the present study in relation to studies from the USA is that it is baseda national data, with  a large number of births, which also included data on abortions alongside live births, and expresses the effectiveness of a daily supplement of folic acid per se, as there is no folate fortification program in Israel.



This study has made it possible to evaluate the effectiveness of a daily supplement of folic acid in the pre-pregnancy period in the prevention of NTDs, without the effect of folic acid food fortification  . While a 53% decrease in the incidence rate of spina bifida was detected, the true prevention rate is higher since not all women had taken this supplement. The use of folic acid to prevent NTDs is one of the greatest achievements in primary prevention of serious morbidity, disability, mortality, human suffering and high costs to the health and welfare systems. Appreciating the true effectiveness in preventing NTDs is therefore critical.



  1. https://www.cdc.gov>faq-folic-ntd
  2. Viegi C, Bertini M. Folic acid in the prevention of neural tube defects. J Birth Defects. 2018;1;1:5
  3. Reiss A, Cohen MJ, Kaliner E, Gabai Kapara E, Singer A, Grotto I, Gamzu R. Lower Rates of Neural Tube Defects in Israel Following Folic Acid Supplementation Policy. Prev Med. 24 Mar; 106064.
  4. Khoshnwood B, Loane M, de Walle H, et al. Long term trends in prevalence of neural tube defects in Europe,BMJ 2015;351;h5949