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Br Med J (Clin Res Ed). 1981 May 9; 282(6275): 1509–1511.
PMCID: PMC1505459

Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects.


A randomized controlled double-blind trial was undertaken in south Wales to prevent the recurrence of neural-tube defects in women who had had one child with a neural-tube defect. Sixty women were allocated before conception to take 4 mg of folic acid a day before and during early pregnancy and 44 complied with these instructions. Fifty-one women were allocated to placebo treatment. There were no recurrences among the compliant mothers but two among the non-compliers and four among the women in the placebo group. Thus there were no recurrences among those who received supplementation and six among those who did not; this difference is significant (p = 0.04). It is concluded that folic acid supplementation might be a cheap, safe, and effective method of primary prevention of neural-tube defects but that this must be confirmed in a large, multicentre trial.

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Selected References

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  • Laurence KM, Carter CO, David PA. Major central nervous system malformations in South Wales. II. Pregnancy factors, seasonal variation, and social class effects. Br J Prev Soc Med. 1968 Oct;22(4):212–222. [PMC free article] [PubMed]
  • Smithells RW, Sheppard S, Schorah CJ. Vitamin dificiencies and neural tube defects. Arch Dis Child. 1976 Dec;51(12):944–950. [PMC free article] [PubMed]
  • THIERSCH JB. Therapeutic abortions with a folic acid antagonist, 4-aminopteroylglutamic acid (4-amino P.G.A) administered by the oral route. Am J Obstet Gynecol. 1952 Jun;63(6):1298–1304. [PubMed]
  • Laurence KM, Carter CO, David PA. Major central nervous system malformations in South Wales. I. Incidence, local variations and geographical factors. Br J Prev Soc Med. 1968 Jul;22(3):146–160. [PMC free article] [PubMed]
  • Tennant GB, Withey JL. An assessment of work simplified procedures for the microbiological assay of serum vitamin B12 and serum folate. Med Lab Technol. 1972 Apr;29(2):171–181. [PubMed]
  • Hoffbrand AV, Newcombe FA, Mollin DL. Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency. J Clin Pathol. 1966 Jan;19(1):17–28. [PMC free article] [PubMed]
  • Smithells RW, Sheppard S, Schorah CJ, Seller MJ, Nevin NC, Harris R, Read AP, Fielding DW. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet. 1980 Feb 16;1(8164):339–340. [PubMed]

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