Abstract
A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Folic acid to prevent neural tube defects. Lancet. 1991 Aug 24;338(8765):505–506. [PubMed] [Google Scholar]
- Haviland M. G. Yates's correction for continuity and the analysis of 2 x 2 contingency tables. Stat Med. 1990 Apr;9(4):363–383. doi: 10.1002/sim.4780090403. [DOI] [PubMed] [Google Scholar]
- Laurence K. M., James N., Miller M. H., Tennant G. B., Campbell H. Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br Med J (Clin Res Ed) 1981 May 9;282(6275):1509–1511. doi: 10.1136/bmj.282.6275.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacCarthy P. A., Dalrymple I. J., Duignan N. M., Elwood J. H., Guiney E. J., Hanratty T. D., Kirke P. N., MacDonald D. W. Recurrence rates of neural tube defects in Dublin maternity hospitals. Ir Med J. 1983 Feb;76(2):78–79. [PubMed] [Google Scholar]
- Miettinen O. Estimability and estimation in case-referent studies. Am J Epidemiol. 1976 Feb;103(2):226–235. doi: 10.1093/oxfordjournals.aje.a112220. [DOI] [PubMed] [Google Scholar]
- Smithells R. W., Nevin N. C., Seller M. J., Sheppard S., Harris R., Read A. P., Fielding D. W., Walker S., Schorah C. J., Wild J. Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet. 1983 May 7;1(8332):1027–1031. doi: 10.1016/s0140-6736(83)92654-5. [DOI] [PubMed] [Google Scholar]
- Smithells R. W., Sheppard S., Schorah C. J., Seller M. J., Nevin N. C., Harris R., Read A. P., Fielding D. W. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet. 1980 Feb 16;1(8164):339–340. doi: 10.1016/s0140-6736(80)90886-7. [DOI] [PubMed] [Google Scholar]
- Wald N. J., Polani P. E. Neural-tube defects and vitamins: the need for a randomized clinical trial. Br J Obstet Gynaecol. 1984 Jun;91(6):516–523. doi: 10.1111/j.1471-0528.1984.tb04796.x. [DOI] [PubMed] [Google Scholar]