FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 341:1485-1490 November 11, 1999 Number 20 Next

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article PubMed Citation

ABSTRACT

Background Periconceptional use of multivitamins containing folic acid can reduce a woman's risk of having a baby with a neural-tube defect.

Methods As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 µg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy.

Results Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent).

Conclusions Periconceptional intake of 400 µg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Source Information

From the Birth Defects and Genetic Diseases Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta (R.J.B., J.D.E., C.A.M., J.M., L.-Y.C.W., J.G., A.C.); and the National Center for Maternal and Infant Health and the Department of Health Care Epidemiology, Beijing Medical University, Beijing, China (Z.L., S.L., H.W., P.Z., S.-X.H.). Other authors were Ling Hao, M.D., M.P.H. (National Center for Maternal and Infant Health and the Department of Health Care Epidemiology, Beijing Medical University, Beijing, China), and Elaine Gunter, B.S., M.T.(A.S.C.P.) (Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta).

Address reprint requests to Dr. Berry at the Birth Defects and Genetic Diseases Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy., MS F-45, Atlanta, GA 30341-3724.

Full Text of this Article

Related Letters:

Neural-Tube Defects
Schulman J. D., Werler M. M., Mitchell A. A., Hook E. B., Botto L. D., Erickson J. D., Mulinare J., Berry R. J., Gindler J., Botto L.
Extract | Full Text  
N Engl J Med 2000; 342:1135-1137, Apr 13, 2000. Correspondence

This article has been cited by other articles:

• Zeng, L., Cheng, Y., Dang, S., Yan, H., Dibley, M. J, Chang, S., Kong, L. (2008). Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ 337: a2001-a2001 [Abstract] [Full Text]  
• Mosley, B. S., Hobbs, C. A. (2008). Mosley and Hobbs Respond to "Folic Acid Fortification and Neural Tube Defects". Am J Epidemiol 0: kwn320v1-kwn320 [Full Text]  
• Mosley, B. S., Cleves, M. A., Siega-Riz, A. M., Shaw, G. M., Canfield, M. A., Waller, D. K., Werler, M. M., Hobbs, C. A., for the National Birth Defects Prevention Study, (2008). Neural Tube Defects and Maternal Folate Intake Among Pregnancies Conceived After Folic Acid Fortification in the United States. Am J Epidemiol 0: kwn331v1-kwn331 [Abstract] [Full Text]  
• Kim, Y.-I. (2008). Folic Acid Supplementation and Cancer Risk: Point. Cancer Epidemiol. Biomarkers Prev. 17: 2220-2225 [Full Text]  
• Hao, L., Yang, Q.-H., Li, Z., Bailey, L. B, Zhu, J.-H., Hu, D. J, Zhang, B.-L., Erickson, J D., Zhang, L., Gindler, J., Li, S., Berry, R. J (2008). Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial. Am. J. Clin. Nutr. 88: 448-457 [Abstract] [Full Text]  
• Bognar, M., Ponyi, A., Hauser, P., Muller, J., Constantin, T., Jakab, Z., Schuler, D., Garami, M. (2008). Improper Supplementation Habits of Folic Acid Intake by Hungarian Pregnant Women: Improper Recommendations. J. Am. Coll. Nutr. 27: 499-504 [Abstract] [Full Text]  
• Nguyen, P., Grajeda, R., Melgar, P., Marcinkevage, J., Flores, R., Martorell, R. (2008). Weekly May Be as Efficacious as Daily Folic Acid Supplementation in Improving Folate Status and Lowering Serum Homocysteine Concentrations in Guatemalan Women. J. Nutr. 138: 1491-1498 [Abstract] [Full Text]  
• Zhang, J., Liu, Y., Meikle, S., Zheng, J., Sun, W., Li, Z. (2008). Cesarean Delivery on Maternal Request in Southeast China. Obstet Gynecol 111: 1077-1082 [Abstract] [Full Text]  
• Liu, Y., Liu, J., Ye, R., Ren, A., Li, S., Li, Z. (2008). Association of Education and the Occurrence of Low Birthweight in Rural Southern China During the Early and Late 1990s. Am. J. Public Health 98: 687-691 [Abstract] [Full Text]  
• Carmichael, S. L., Yang, W., Herring, A., Abrams, B., Shaw, G. M. (2007). Maternal Food Insecurity Is Associated with Increased Risk of Certain Birth Defects. J. Nutr. 137: 2087-2092 [Abstract] [Full Text]  
• De Wals, P., Tairou, F., Van Allen, M. I., Uh, S.-H., Lowry, R. B., Sibbald, B., Evans, J. A., Van den Hof, M. C., Zimmer, P., Crowley, M., Fernandez, B., Lee, N. S., Niyonsenga, T. (2007). Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada. NEJM 357: 135-142 [Abstract] [Full Text]  
• Mason, J. B., Dickstein, A., Jacques, P. F., Haggarty, P., Selhub, J., Dallal, G., Rosenberg, I. H. (2007). A Temporal Association between Folic Acid Fortification and an Increase in Colorectal Cancer Rates May Be Illuminating Important Biological Principles: A Hypothesis. Cancer Epidemiol. Biomarkers Prev. 16: 1325-1329 [Abstract] [Full Text]  
• Yang, Q.-H., Carter, H. K, Mulinare, J., Berry, R., Friedman, J., Erickson, J D. (2007). Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001-2002. Am. J. Clin. Nutr. 85: 1409-1416 [Abstract] [Full Text]  
• Hao, L., Ma, J., Zhu, J., Stampfer, M. J., Tian, Y., Willett, W. C., Li, Z. (2007). Vitamin B-12 Deficiency Is Prevalent in 35- to 64-Year-Old Chinese Adults. J. Nutr. 137: 1278-1285 [Abstract] [Full Text]  
• Imhoff-Kunsch, B., Flores, R., Dary, O., Martorell, R. (2007). Wheat Flour Fortification Is Unlikely to Benefit the Neediest in Guatemala. J. Nutr. 137: 1017-1022 [Abstract] [Full Text]  
• Bille, C, Murray, J C, Olsen, S F (2007). Folic acid and birth malformations. BMJ 334: 433-434 [Full Text]  
• Antony, A. C (2007). In utero physiology: role of folic acid in nutrient delivery and fetal development. Am. J. Clin. Nutr. 85: 598S-603S [Abstract] [Full Text]  
• Blacher, J., Czernichow, S., Raphael, M., Roussel, C., Chadefaux-Vekemans, B., Morineau, G., Giraudier, S., Tibi, A., Henry, O., Vayssiere, M., Oudjhani, M., Nadai, S., Vincent, J.-P., Bodak, A., Di Menza, C., Menard, J., Zittoun, J., Ducimetiere, P. (2007). Very Low Oral Doses of Vitamin B-12 Increase Serum Concentrations in Elderly Subjects with Food-Bound Vitamin B-12 Malabsorption. J. Nutr. 137: 373-378 [Abstract] [Full Text]  
• Hao, L., Ma, J., Zhu, J., Stampfer, M. J., Tian, Y., Willett, W. C., Li, Z. (2007). High Prevalence of Hyperhomocysteinemia in Chinese Adults Is Associated with Low Folate, Vitamin B-12, and Vitamin B-6 Status. J. Nutr. 137: 407-413 [Abstract] [Full Text]  
• Thulstrup, A. M., Bonde, J. P. (2006). Maternal occupational exposure and risk of specific birth defects. Occup Med (Lond) 56: 532-543 [Abstract] [Full Text]  
• Nilsen, R. M, Vollset, S. E, Gjessing, H. K, Magnus, P., Meltzer, H. M, Haugen, M., Ueland, P. M (2006). Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian Mother and Child Cohort Study.. Am. J. Clin. Nutr. 84: 1134-1141 [Abstract] [Full Text]  
• Tamura, T., Picciano, M. F. (2006). Folate and human reproduction. Am. J. Clin. Nutr. 83: 993-1016 [Abstract] [Full Text]  
• Artama, M., Ritvanen, A., Gissler, M., Isojarvi, J., Auvinen, A. (2006). Congenital structural anomalies in offspring of women with epilepsy--a population-based cohort study in Finland. Int J Epidemiol 35: 280-287 [Abstract] [Full Text]  
• Brent, R. L., Oakley, G. P. Jr (2006). Triumph and/or Tragedy: The Present Food and Drug Administration Program of Enriching Grains With Folic Acid. Pediatrics 117: 930-932 [Full Text]  
• Zhu, W. L., Li, Y., Yan, L., Dao, J., Li, S. (2006). Maternal and offspring MTHFR gene C677T polymorphism as predictors of congenital atrial septal defect and patent ductus arteriosus. Mol Hum Reprod 12: 51-54 [Abstract] [Full Text]  
• Grosse, S. D., Waitzman, N. J., Romano, P. S., Mulinare, J. (2005). Reevaluating the Benefits of Folic Acid Fortification in the United States: Economic Analysis, Regulation, and Public Health. Am. J. Public Health 95: 1917-1922 [Abstract] [Full Text]  
• O'Brien, M D, Gilmour-White, S K (2005). Management of epilepsy in women. Postgrad. Med. J. 81: 278-285 [Abstract] [Full Text]  
• Botto, L. D, Lisi, A., Robert-Gnansia, E., Erickson, J D., Vollset, S. E., Mastroiacovo, P., Botting, B., Cocchi, G., de Vigan, C., de Walle, H., Feijoo, M., Irgens, L. M, McDonnell, B., Merlob, P., Ritvanen, A., Scarano, G., Siffel, C., Metneki, J., Stoll, C., Smithells, R., Goujard, J. (2005). International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?. BMJ 330: 571- [Abstract] [Full Text]  
• Bhutta, Z. A., Darmstadt, G. L., Hasan, B. S., Haws, R. A. (2005). Community-Based Interventions for Improving Perinatal and Neonatal Health Outcomes in Developing Countries: A Review of the Evidence. Pediatrics 115: 519-617 [Abstract] [Full Text]  
• Kim, Y.-I. (2004). Will mandatory folic acid fortification prevent or promote cancer?. Am. J. Clin. Nutr. 80: 1123-1128 [Abstract] [Full Text]  
• Daltveit, A. K., Vollset, S. E., Lande, B., Oien, H. (2004). Changes in knowledge and attitudes of folate, and use of dietary supplements among women of reproductive age in Norway 1998 - 2000. Scand J Public Health 32: 264-271 [Abstract]  
• Helinski, D. T., Trauth, J. M., Jernigan, J. C., Kerr, M. J. (2004). Describing a Folic Acid Intervention for Health Care Providers: Implications for Professional Practice and Continuing Education. Health Promot Pract 5: 326-333 [Abstract]  
• Refsum, H., Smith, A. D., Ueland, P. M., Nexo, E., Clarke, R., McPartlin, J., Johnston, C., Engbaek, F., Schneede, J., McPartlin, C., Scott, J. M. (2004). Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion. Clin. Chem. 50: 3-32 [Abstract] [Full Text]  
• Carmichael, S. L., Shaw, G. M., Schaffer, D. M., Laurent, C., Selvin, S. (2003). Dieting Behaviors and Risk of Neural Tube Defects. Am J Epidemiol 158: 1127-1131 [Abstract] [Full Text]  
• Alozie Arole, C. N., Puder, K. S., Reznar, M., Eby, E., Zhu, B.-P. (2003). Folic Acid Awareness in Michigan, 1996-1999. Obstet Gynecol 102: 1046-1050 [Abstract] [Full Text]  
• Santos-Guzman, J., Arnhold, T., Nau, H., Wagner, C., Fahr, S. H., Mao, G. E., Caudill, M. A., Wang, J. C., Henning, S. M., Swendseid, M. E., Collins, M. D. (2003). Antagonism of Hypervitaminosis A-Induced Anterior Neural Tube Closure Defects with a Methyl-Donor Deficiency in Murine Whole-Embryo Culture. J. Nutr. 133: 3561-3570 [Abstract] [Full Text]  
• Hao, L., Ma, J., Stampfer, M. J., Ren, A., Tian, Y., Tang, Y., Willett, W. C., Li, Z. (2003). Geographical, Seasonal and Gender Differences in Folate Status among Chinese Adults. J. Nutr. 133: 3630-3635 [Abstract] [Full Text]  
• Arkbage, K., Verwei, M., Havenaar, R., Witthoft, C. (2003). Bioaccessibility of Folic Acid and (6S)-5-Methyltetrahydrofolate Decreases after the Addition of Folate-Binding Protein to Yogurt as Studied in a Dynamic In Vitro Gastrointestinal Model,2. J. Nutr. 133: 3678-3683 [Abstract] [Full Text]  
• Kim, Y.-I. (2003). Role of Folate in Colon Cancer Development and Progression. J. Nutr. 133: 3731S-3739 [Abstract] [Full Text]  
• Chacko, M. R., Anding, R., Kozinetz, C. A., Grover, J. L., Smith, P. B. (2003). Neural Tube Defects: Knowledge and Preconceptional Prevention Practices in Minority Young Women. Pediatrics 112: 536-542 [Abstract] [Full Text]  
• Bailey, L. B., Rampersaud, G. C., Kauwell, G. P. A. (2003). Folic Acid Supplements and Fortification Affect the Risk for Neural Tube Defects, Vascular Disease and Cancer: Evolving Science,. J. Nutr. 133: 1961S-1968 [Abstract] [Full Text]  
• Kramer, M. S. (2003). The Epidemiology of Adverse Pregnancy Outcomes: An Overview. J. Nutr. 133: 1592S-1596 [Abstract] [Full Text]  
• Correa, A., Botto, L., Liu, Y., Mulinare, J., Erickson, J. D. (2003). Do Multivitamin Supplements Attenuate the Risk for Diabetes-Associated Birth Defects?. Pediatrics 111: 1146-1151 [Abstract] [Full Text]  
• Venn, B. J, Green, T. J, Moser, R., Mann, J. I (2003). Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. Am. J. Clin. Nutr. 77: 658-662 [Abstract] [Full Text]  
• Hesketh, T. (2003). Getting married in China: pass the medical first. BMJ 326: 277-279 [Full Text]  
• Murdoch, J. N., Henderson, D. J., Doudney, K., Gaston-Massuet, C., Phillips, H. M., Paternotte, C., Arkell, R., Stanier, P., Copp, A. J. (2003). Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum Mol Genet 12: 87-98 [Abstract] [Full Text]  
• Shane, B. (2003). Folate fortification: enough already?. Am. J. Clin. Nutr. 77: 8-9 [Full Text]  
• Yang, Q., Erickson, J D. (2003). Influence of reporting error on the relation between blood folate concentrations and reported folic acid-containing dietary supplement use among reproductive-aged women in the United States. Am. J. Clin. Nutr. 77: 196-203 [Abstract] [Full Text]  
• Ronnenberg, A. G, Goldman, M. B, Chen, D., Aitken, I. W, Willett, W. C, Selhub, J., Xu, X. (2002). Preconception homocysteine and B vitamin status and birth outcomes in Chinese women. Am. J. Clin. Nutr. 76: 1385-1391 [Abstract] [Full Text]  
• Wilson, P. W. F. (2002). Homocysteine and Coronary Heart Disease: How Great Is the Hazard?. JAMA 288: 2042-2043 [Full Text]  
• Venn, B. J, Mann, J. I, Williams, S. M, Riddell, L. J, Chisholm, A., Harper, M. J, Aitken, W. (2002). Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine. Am. J. Clin. Nutr. 76: 758-765 [Abstract] [Full Text]  
• Cogram, P., Tesh, S., Tesh, J., Wade, A., Allan, G., Greene, N. D.E., Copp, A. J. (2002). D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects. Hum Reprod 17: 2451-2458 [Abstract] [Full Text]  
• Green, N. S. (2002). Folic Acid Supplementation and Prevention of Birth Defects. J. Nutr. 132: 2356S-2360 [Abstract] [Full Text]  
• Ronnenberg, A. G., Goldman, M. B., Chen, D., Aitken, I. W., Willett, W. C., Selhub, J., Xu, X. (2002). Preconception Folate and Vitamin B6 Status and Clinical Spontaneous Abortion in Chinese Women. Obstet Gynecol 100: 107-113 [Abstract] [Full Text]  
• Holden, K. R., Collins, J. S., Greene, J. F., Hinkle, S., Nave, A. F., Portillo, J. M., Page, G. P., Stevenson, R. E. (2002). Dietary Intake and Blood Folate Levels in Honduran Women of Childbearing Age. J Child Neurol 17: 341-345 [Abstract]  
• Johanning, G L, Wenstrom, K D, Tamura, T (2002). Changes in frequencies of heterozygous thermolabile 5,10-methylenetetrahydrofolate reductase gene in fetuses with neural tube defects. J. Med. Genet. 39: 366-367 [Full Text]  
• Botto, L. D., Mulinare, J., Erickson, J. D. (2002). Occurrence of Omphalocele in Relation to Maternal Multivitamin Use: A Population-Based Study. Pediatrics 109: 904-908 [Abstract] [Full Text]  
• Unfried, G., Griesmacher, A., Weismuller, W., Nagele, F., Huber, J. C., Tempfer, C. B. (2002). The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and Idiopathic Recurrent Miscarriage. Obstet Gynecol 99: 614-619 [Abstract] [Full Text]  
• Richter, B, Schultealbert, A H, Koch, M C (2002). Human T and risk for neural tube defects. J. Med. Genet. 39: e14-14 [Full Text]  
• Hernan, M. A., Hernandez-Diaz, S., Werler, M. M., Mitchell, A. A. (2002). Causal Knowledge as a Prerequisite for Confounding Evaluation: An Application to Birth Defects Epidemiology. Am J Epidemiol 155: 176-184 [Abstract] [Full Text]  
• de Weerd, S., Thomas, C. M. G., Cikot, R. J. L. M., Steegers-Theunissen, R. P. M., de Boo, T. M., Steegers, E. A. P. (2002). Preconception Counseling Improves Folate Status of Women Planning Pregnancy. Obstet Gynecol 99: 45-50 [Abstract] [Full Text]  
• Evans, M. I., Llurba, E., Landsberger, E. J., O'Brien, J. E., Harrison, H. H. (2002). Impact of Folic Acid Fortification in the United States: Markedly Diminished High Maternal Serum Alpha-Fetoprotein Values. Obstet Gynecol 103: 474-479 [Abstract] [Full Text]  
• Myers, M. F., Li, S., Correa-Villasenor, A., Li, Z., Moore, C. A., Hong, S. X., Berry, R. J., the China-US Collaborative Project for Neural Tube, (2001). Folic Acid Supplementation and Risk for Imperforate Anus in China. Am J Epidemiol 154: 1051-1056 [Abstract] [Full Text]  
• Murdoch, J. N., Doudney, K., Paternotte, C., Copp, A. J., Stanier, P. (2001). Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification. Hum Mol Genet 10: 2593-2601 [Abstract] [Full Text]  
• Olsen, S. F (2001). Commentary: Does use of food supplements influence the twin rate? New evidence from a randomized controlled trial. Int J Epidemiol 30: 807-808 [Full Text]  
• Williamson, R. (2001). Prevention of Birth Defects: Folic Acid. Biol Res Nurs 3: 33-38 [Abstract]  
• Cynkar, A. (2001). Center supports research to identify causes of birth defects. AAP News 19: 14-14 [Full Text]  
• Mills, J. L., England, L. (2001). Food Fortification to Prevent Neural Tube Defects: Is It Working?. JAMA 285: 3022-3023 [Full Text]  
• Sarwark, J. F. (2001). What's New in Pediatric Orthopaedics. JBJS 83: 959-966 [Full Text]  
• Matsuo, K., Suzuki, R., Hamajima, N., Ogura, M., Kagami, Y., Taji, H., Kondoh, E., Maeda, S., Asakura, S., Kaba, S., Nakamura, S., Seto, M., Morishima, Y., Tajima, K. (2001). Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma. Blood 97: 3205-3209 [Abstract] [Full Text]  
• van der Put, N. M.J., van Straaten, H. W.M., Trijbels, F. J.M., Blom, H. J. (2001). Folate, Homocysteine and Neural Tube Defects: An Overview. Exp. Biol. Med. 226: 243-270 [Abstract] [Full Text]  
• Hernandez-Diaz, S., Werler, M. M., Walker, A. M., Mitchell, A. A. (2000). Folic Acid Antagonists during Pregnancy and the Risk of Birth Defects. NEJM 343: 1608-1614 [Abstract] [Full Text]  
• Ronnenberg, A. G., Goldman, M. B., Aitken, I. W., Xu, X. (2000). Anemia and Deficiencies of Folate and Vitamin B-6 Are Common and Vary with Season in Chinese Women of Childbearing Age. J. Nutr. 130: 2703-2710 [Abstract] [Full Text]  
• Friel, J. K. (2000). Folic acid supplementation: more work is needed. CMAJ 163: 1129-1130 [Full Text]  
• Brent, R. L., Oakley Jr., G. P., Mattison, D. R. (2000). The Unnecessary Epidemic of Folic Acid-Preventable Spina Bifida and Anencephaly. Pediatrics 106: 825-827 [Abstract] [Full Text]  
• (2000). Folic acid: the opportunity that still exists. CMAJ 162: 1571-1572  
• Schulman, J. D., Werler, M. M., Mitchell, A. A., Hook, E. B., Botto, L. D., Erickson, J. D., Mulinare, J., Berry, R. J., Gindler, J., Botto, L. (2000). Neural-Tube Defects. NEJM 342: 1135-1137 [Full Text]  
• Picciano, M. F. (2000). Is homocysteine a biomarker for identifying women at risk of complications and adverse pregnancy outcomes?. Am. J. Clin. Nutr. 71: 857-858 [Full Text]  
• (2000). Folic Acid Reduces Neural-Tube Defects in Large Populations. Journal Watch Dermatology 2000: 15-15 [Full Text]  
• (1999). Folic Acid Reduces Neural-Tube Defects in Large Populations. JWatch General 1999: 4-4 [Full Text]  
• Botto, L. D., Moore, C. A., Khoury, M. J., Erickson, J. D. (1999). Neural-Tube Defects. NEJM 341: 1509-1519 [Full Text]