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W2121024166 abstract "Periconceptional nutritional supplementation of maternal diets with multivitamins, in particular folic acid, is associated with a diminished prevalence and recurrence of neural tube defects and other congenital malformations in live births and late fetal deaths (stillbirths). 1 Smithells RW Sheppard S Schorah CJ et al. Possible prevention of neural tube defects by periconceptional vitamin supplementation. Lancet. 1980; i: 339-340 Summary Scopus (317) Google Scholar , 2 MRC Vitamin Study Research GroupPrevention of neural tube defects: results of the Medical Research Council Vitamin study. Lancet. 1991; 338: 131-137 Summary PubMed Scopus (3591) Google Scholar , 3 Czeizel AE Dudás I Prevention of the first occurrence of neural tube defects by periconceptional multivitamin supplementation. N Engl J Med. 1992; 327: 1832-1835 Crossref PubMed Scopus (2695) Google Scholar , 4 Czeizel AE Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet. 1996; 62: 179-183 Crossref PubMed Scopus (246) Google Scholar , 5 Czeizel AE Dudás I Metneki J Pregnancy outcomes in a randomized controlled trial of periconceptional multivitamin supplementation: final report. Arch Gynecol Obstet. 1994; 255: 131-139 Crossref PubMed Scopus (175) Google Scholar , 6 Smithells RW Sheppard S Wild J Schorah CJ Prevention of neural tube defect recurrence in Yorkshire: final report. Lancet. 1989; ii: 498-499 Abstract Scopus (137) Google Scholar Although the precise mechanism for this protective effect is unknown, the association has led to widespread endorsement of folic-acid dietary supplementation of women of child-bearing age, and to the call for the addition of folic acid to bread and other cereal products. 7 Tonz O Luthy J Raunhardt O Folic acid in the prevention of neural tube defects. Schweiz Mediz Wochenschr. 1996; 126: 177-187 PubMed Google Scholar Much less widely known is that the only randomised occurrence study of folic-acid supplementation found a statistically significant association not only with diminished prevalence of birth defect, but also with an increased prevalence of recognised spontaneous abortion—ie, embryonic and early fetal death. The latter association could only be established at the conclusion of the study, and was noted in its final report. 5 Czeizel AE Dudás I Metneki J Pregnancy outcomes in a randomized controlled trial of periconceptional multivitamin supplementation: final report. Arch Gynecol Obstet. 1994; 255: 131-139 Crossref PubMed Scopus (175) Google Scholar The study was stopped early because of the clear protective advantage of folic-acid supplementation on birth defect, and by the time of the widely disseminated publication of this protective effect, the abortion association was not as yet detected. 3 Czeizel AE Dudás I Prevention of the first occurrence of neural tube defects by periconceptional multivitamin supplementation. N Engl J Med. 1992; 327: 1832-1835 Crossref PubMed Scopus (2695) Google Scholar The association with recognised spontaneous abortion is of relatively small magnitude: the relative risk is 1·16—ie, a 16% relative increase—compared with more than halving in the rate of all birth defects (table 1). The nominal statistical significance of this result (p) was 0·04. Table 1Comparison of diagnosed outcomes in supplemented and unsupplemented pregnancies * Adjusted from reported data3–5 excluding the six first trimester elective terminations in both supplemented and unsupplemented groups, but including outcomes among those enrolled who were found to be pregnant shortly before starting folic acid or control supplements—266 and 204, respectively. The 11 stillbirths in the supplemented and nine in the unsupplemented groups were included with the livebirths because they were examined for defect after delivery. Evaluation is limited to major congenital anomalies detected at birth because these are most likely to be associated with embryonic or fetal death. The three defects that were diagnosed prenatally and led to elective termination in the supplemented group4 were classified as having a selection coefficient of 0·1—ie, 10% probability of spontaneous loss and 90% probability of survival to birth. For the 12 cases in the unsupplemented group in this category (excluding one false-positive diagnosis), a higher selection coefficient of 0·2 was used because of the greater seriousness of defects in this group. The analysis is relatively insensitive to the classification of these few cases and the value of the selection coefficients used in any event. Adjusting for selection in the absence of prenatal diagnosis resulted in decimal entries that were rounded off to the nearest digit in this table. The total in the unsupplemented group excludes the one case terminated with a false-positive diagnosis of birth defect.5 Folic-acid supplemented Not folic-acid supplemented Difference χ2/p Risk ratio (95% CI) Rate of spontaneous abortions 363/2787 (13·0%) 297/2653 (11·2%) +1·8% 4·1/0·04 1·16 (1·01–1·3) Rate of congenital defects in births 23/2424 (0·9%) 49/2356 (2·1%) −1·2% 10·3/0·002 0·46 (0·28–0·75) * Adjusted from reported data 3 Czeizel AE Dudás I Prevention of the first occurrence of neural tube defects by periconceptional multivitamin supplementation. N Engl J Med. 1992; 327: 1832-1835 Crossref PubMed Scopus (2695) Google Scholar , 4 Czeizel AE Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet. 1996; 62: 179-183 Crossref PubMed Scopus (246) Google Scholar , 5 Czeizel AE Dudás I Metneki J Pregnancy outcomes in a randomized controlled trial of periconceptional multivitamin supplementation: final report. Arch Gynecol Obstet. 1994; 255: 131-139 Crossref PubMed Scopus (175) Google Scholar excluding the six first trimester elective terminations in both supplemented and unsupplemented groups, but including outcomes among those enrolled who were found to be pregnant shortly before starting folic acid or control supplements—266 and 204, respectively. The 11 stillbirths in the supplemented and nine in the unsupplemented groups were included with the livebirths because they were examined for defect after delivery. Evaluation is limited to major congenital anomalies detected at birth because these are most likely to be associated with embryonic or fetal death. The three defects that were diagnosed prenatally and led to elective termination in the supplemented group 4 Czeizel AE Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet. 1996; 62: 179-183 Crossref PubMed Scopus (246) Google Scholar were classified as having a selection coefficient of 0·1—ie, 10% probability of spontaneous loss and 90% probability of survival to birth. For the 12 cases in the unsupplemented group in this category (excluding one false-positive diagnosis), a higher selection coefficient of 0·2 was used because of the greater seriousness of defects in this group. The analysis is relatively insensitive to the classification of these few cases and the value of the selection coefficients used in any event. Adjusting for selection in the absence of prenatal diagnosis resulted in decimal entries that were rounded off to the nearest digit in this table. The total in the unsupplemented group excludes the one case terminated with a false-positive diagnosis of birth defect. 5 Czeizel AE Dudás I Metneki J Pregnancy outcomes in a randomized controlled trial of periconceptional multivitamin supplementation: final report. Arch Gynecol Obstet. 1994; 255: 131-139 Crossref PubMed Scopus (175) Google Scholar Open table in a new tab" @default.
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W2121024166 title "Can terathanasia explain the protective effect of folic-acid supplementation on birth defects?" @default.
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