British Journal of Nutrition

Systematic Review

Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid

Helmut B. Hesekera1 c1, Joel B. Masona2, Jacob Selhuba3, Irwin H. Rosenberga4 and Paul F. Jacquesa5

a1 Department of Nutrition and Consumer Education, University Paderborn, Warburger Strasse 100, D-33098 Paderborn, Germany

a2 Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA 02111, USA

a3 Vitamin Metabolism Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA 02111, USA

a4 Nutrition and Neurocognition Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA 02111, USA

a5 Nutritional Epidemiology Program, Jean Mayer USDA HNRCA at Tufts University, Boston, MA 02111, USA

Abstract

Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a ‘floor effect’ for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups.

(Received July 01 2008)

(Revised September 29 2008)

(Accepted October 30 2008)

(Online publication December 16 2008)

Correspondence:

c1 Corresponding author: Helmut B. Heseker, fax +49 5251 603425, email helmut.heseker@uni-paderborn.de

Footnotes

Abbreviations: NTD, neural-tube defect