Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies

Journal of Obstetrics and Gynaecology Canada

Volumn 37, Issue 6, 2015, Pages 534-549

  Douglas Wilson, R ^a   Audibert, François ^a   Brock, Jo Ann ^a   Carroll, June ^a   Cartier, Lola ^a   Gagnon, Alain ^a   Johnson, Jo Ann ^a   Langlois, Sylvie ^a   Murphy Kaulbeck, Lynn ^a   Okun, Nanette ^a   Pastuck, Melanie ^a   Deb Rinker, Paromita ^a   Dodds, Linda ^a   Leon, Juan Andres ^a   Lowell, Hélène ^a   Luo, Wei ^a   MacFarlane, Amanda ^a   McMillan, Rachel ^a   Moore, Aideen ^a   Mundle, William ^a   O'Connor, Deborah ^a   Ray, Joel ^a   Van den Hof, Michiel ^a   more..

^a NONE   (Canada)

Author keywords

Birth defects; Congenital anomalies; Congenital anomaly risk reduction; Fetal anomalies; Folate; Folate sensitive birth defects; Folic acid; Micronutrients; Myelomeningocele; Neural tube defect; Preconception counseling; Pregnancy; Prenatal multivitamins; Prevention; Spina bifida

Indexed keywords

FOLIC ACID; MULTIVITAMIN; TRACE ELEMENT; VITAMIN B COMPLEX;

ARTICLE; CONGENITAL MALFORMATION; CONTROLLED CLINICAL TRIAL (TOPIC); COST BENEFIT ANALYSIS; DIET SUPPLEMENTATION; DRUG COST; EPIGENETICS; HEALTH CARE COST; HEALTH CARE PERSONNEL; HUMAN; MIDWIFE; NEURAL TUBE DEFECT; NURSE; OBSERVATIONAL STUDY; PATIENT COUNSELING; PATIENT EDUCATION; PHYSICIAN; PRACTICE GUIDELINE; PREGNANCY; PREPREGNANCY CARE; PRIMARY PREVENTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK BENEFIT ANALYSIS; SECONDARY PREVENTION; SYSTEMATIC REVIEW (TOPIC); TWIN PREGNANCY; VITAMIN SUPPLEMENTATION; MATERNAL NUTRITION; ANENCEPHALY; ATTITUDE TO HEALTH; DECISION TREE; FEMALE; MATERNAL CARE; PRENATAL CARE;

ANENCEPHALY; DECISION TREES; DIETARY SUPPLEMENTS; FEMALE; FOLIC ACID; HEALTH KNOWLEDGE, ATTITUDES, PRACTICE; HUMANS; PRECONCEPTION CARE; PREGNANCY; PRENATAL CARE; VITAMIN B COMPLEX;

EID: 84973560653     PISSN: 17012163     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1701-2163(15)30230-9     Document Type: Article

References (193)

1. Andres J., Evans J., Royle C. Prevalence of congenital anomalies. Canadian Perinatal Health Report, 2008 ed. Ottawa:. Public Health Agency of Canada 2008, 158-163.
2. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991, 338:131-137.
3. Czeizel A.E., Dudas L. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 1992, 327:1832-1835.
4. Czeizel A.E. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 1993, 306:1645-1648.
5. Czeizel A.E. Periconceptional folic acid and multivitamin supplementation for the prevention of neural tube defects and other congenital abnormalities. Birth Defects Res A Clin Mol Teratol 2009, 85:260-268.
6. De Wals P., Tairou F., Van Allen M.I., Uh S.H., Lowry R.B., Sibbald B. Reduction of neural-tube defects after folic acid fortification in Canada. N Engl J Med 2007, 357:135-142.
7. Persad V.L., Van den Hof M.C., Dube J.M., Zimmer P. Incidence of open neural tube defects in Nova Scotia after folic acid fortification. CMAJ 2002, 167:241-245.
8. Berry R.J., Li Z., Erickson J.D., Li S., Moore C.A., Wang H. Prevention of neural-tube defects with folic acid in China. N Engl J Med 1999, 341:1485-1490.
9. Martin R.H., Nimrod C. Crohn's disease, folic acid, and neural tube defects (NTD). BMJ 1984, 289-328.
10. Mulinare J., Cordero J.F., Erickson J.D., Berry R.J. Periconceptional use of multivitamins and the occurrence of neural tube defects. JAMA 1988, 260:3141-3145.
11. Mills J.L., Rhoads G.G., Simpson J.L., Cunningham G.C., Conley M.R., Lassman M.R. The absence of a relation between the periconceptional use of vitamins and neural tube defects. N Engl J Med 1989, 321:430-435.
12. Milunsky A., Jick H., Jick S.S., Bruell C.L., MacLaughlin D.S., Rothman K.J. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA 1989, 262:2847-2852.
13. Centers for Disease Control (CDC). Use of folic acid for prevention of spina bifida and other neural tube defects 1983-1991. MMWR Morb Mortal Wkly Rep 1991, 40:513-516.
14. Bower C., Stanley F.J. Dietary folate as a risk factor for neural tube defects: evidence from a case-control study in Western Australia. Med J Aust 1989, 150:613-618.
15. Goh Y.I., Bollano E., Einarson T.R., Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can 2006, 28:680-689.
16. Ray J.G., Meier C., Vermeulen M.J., Boss S., Wyatt P.R., Cole D.E. Association of neural tube defects and folic acid food fortification in Canada. Lancet 2002, 360:2047-2048.
17. Lopez-Camelo J.S., Orioli I.M., Dutra M.D.G., Nazer-Herrera J., Rivera N., Ojeda M.E. Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile. Am J Med Genet 2005, 135:120-125.
18. Boulet S.L., Yang Q., Mai C., Kirby R.S., Collins J.S., Robbins J.M. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol 2008, 82:517-532.
19. Greene N.D.E., Stanier P., Copp A.J. Genetics of human neural tube defects. Hum Mol Genet 2009, 17:113-129.
20. Shaw G.M., Lu W., Zhu H., Yang W., Briggs F.S.B., Carmichael S.L. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Medical Genet 2009, 10-49.
21. Blom H.K., Shaw G.M., den Heijer M., Finnell R.H. Neural tube defects and folate: case far from closed. Nat Rev Neurosci 2006, 7:724-732.
22. Blom H.J. Folic acid, methylation and neural tube closure in humans. Birth Defects Res A Clin Mol Teratol 2009, 85:295-302.
23. Castillo-Lancellotti C., Tur J.A., Uauy R. Impact of folic acid fortification of flour on neural tube defects: a systematic review. Pub Health Nutr 2013, 16:901-911. 10.1017/S1368980012003576.
24. Rosenthal J., Casas J., Taren D., Alverson C.J., Flores A., Frias J. Neural tube defects in Latin America and the impact of fortification: a literature review. Latin America. Pub Health Nutr 2014, 17:537-550. 10.1017/S1368980013000256.
25. Branum A.M., Bailey R., Singer B.J. Dietary supplement use and folate status during pregnancy in the United States. J Nutr 2013, 143:486-492.
26. Shaw G.M., O'Malley C.D., Wasserman C.R., TolarovaM M.M., Lammer E.J. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 1995, 59:536-545.
27. Botto L.D., Khoury M.J., Mulinara J., Erickson J.D. Periconceptional multivitamin use and the occurrence of conotruncal heart defects:results from a population-based, case-control study. Pediatr 1996, 98:911-917.
28. Czeizel A.E. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996, 62:179-183.
29. Goldmuntz E., Woyciechowski S., Renstrom D., Lupo P.J., Mitchell L.E. Variants of folate metabolism genes and the risk of conotruncal cardiac defects. Cir Cardiovasc Genet 2008, 1:126-132.
30. Li X., Li S., Mu D., Liu Z., Li Y., Lin Y. The association between periconceptional folic acid supplementation and congenital heart defects: a case-control study in China. Prev Med 2013, 66:385-389.
31. Li D.K., Daling J.R., Mueller B.A., Hickok D.E., Fantel A.G., Weiss N.S. Periconceptional multivitamin use in relation to the risk of congenital urinary tract anomalies. Epidemiology 1995, 6:212-218.
32. Hayes C., Werler M.M., Willett W.C., Mitchell A.A. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol 1996, 143:1229-1234.
33. Shaw G.M., Lammer E.J., Wasserman C.R., O'Malley C.D., Tolarova M.M. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995, 345:393-396.
34. Tolarova M., Harris J. Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins. Teratology 1995, 51:71-78.
35. Badovinac R.L., Werler M.M., Williams P.L., Kelsey K.T., Hayes C. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis. Birth Defects Res A Clin Mol Teratol 2007, 79:8-15.
36. Yazdy M.M., Honein M.A., Xing J. Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply. Birth Defects Res A Clin Mol Teratol 2007, 79:16-23.
37. O'Neill J. Do folic acid supplements reduce facial clefts?. Evid Based Dentistry 2008, 9:82-83.
38. Johnson C.Y., Little J. Folate intake, markers of folate status and oral clefts: is the evidence converging?. International J Epidemiol 2008, 37(5):1041-1058.
39. Wehby G.L., Félix T.M., Goco N., Richieri-Costa A., Chakraborty H., Souza J. High dose folic acid supplementation, oral cleft recurrence and fetal growth. Int J Environ Res Public Health 2013, 10:590-605.
40. Godwin K.A., Sibbald B., Bedard T., Kuzeljevic B., Lowry R.B., Arbour L. Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry. Can J Public Health 2008, 99:271-275.
41. Van Allen M.I., McCourt C., Lee N.S. Public Health Agency of Canada. Preconception health: folic acid for the primary prevention of neural tube defects. A resource document for health professionals, Ottawa ON: PHAC. Available at: http://www.phac-aspc.gc.ca/fa-af/pdf/backgrounder_full.pdf 2013.
42. Health Canada. Prenatal nutrition guidelines for health professionals-background on Canada's food guide. Eating well with Canada's Food Guide. Ottawa ON: Health Canada. Available at: http://www.hc-sc.gc.ca/fn-an/pubs/nutrition/guide-prenatal-eng.php 2009.
43. Botto L.D., Olney R.S., Erickson J.D. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet 2004, 125:12-21.
44. Botto L.D., Lisi A., Bower C., Canfield M.A., Dattani N., DeVigan C. Trends of selected malformations in relation to folic acid recommendations and fortifications: an international assessment 2006, 76:693-705.
45. Peller A.J., Westgate M.N., Holmes L. Trends in congenital malformations, 174-1999: effect of prenatal diagnosis and elective termination. Obstet Gynecol 2004, 104:957-964.
46. Van Allen M.I., Boyle E., Thiessen P., McFadden D., Cochrane D., Chambers G.K. The impact of prenatal diagnosis on neural tube defect (NTD) pregnancy versus birth incidence in British Columbia. J Appl Genet 2006, 47:151-158.
47. Ray J.G., Wyatt P.R., Thompson M.D., Vermeulen M.J., Meier C., Wong P-Y. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 2005.
48. Ahn E., Kapur B., Koren G. Motherisk Update 2007. Study on circadian variation in folate pharmacokinetics. Can J Clin Pharmacol 2005, 12:4-9.
49. Koren G., Pairaideau N. Motherisk Update 2007. Compliance with prenatal vitamins. Patients with morning sickness sometimes find it difficult. Can Fam Physician 2006, 52:1392-1393.
50. Sherwood L.K., Houghton L.A., Tarasuk V., O'Connor D.L. One third of pregnant and lactating women may not be meeting their folate requirements from diet alone based on mandated levels of folic acid fortification. J Nutr 2006, 136:2820-2826.
51. Shakur Y.A., Garriguet D., Corey P., O'Connor D.L. Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians. Am J Clin Nutr 2010, 92:818-825.
52. Oakley G.P., Bell K.N., Weber M.B. Recommendations for accelerating global action to prevent folic acid-preventable birth defects and other folate deficiency diseases: meeting of experts on preventing folic acid-preventable neural tube defects. Birth Defects Res A Clin Mol Teratol 2004, 70:835-837.
53. Canfield M.A., Collins J.S., Boto L.D., Williams L.J., Mai C.T., Kirby R.S. Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study. Birth Defects Res A Clin Mol Teratol 2005, 73:679-689.
54. Robbins J.M., Tilford J.M., Bird T.M., Cleves M.A., Reading A., Hobbs C.A. Hospitalizations of newborns with folate-sensitive birth defects before and after fortification of foods with folic acid. Pediatr 2006, 118:906-915.
55. Bell K.N., Oakley G.P. Tracking the prevention of folic acid-preventable spina bifida and anencephaly. Birth Defects Res A Clin Mol Teratol 2006, 76:654-657.
56. Wald N.J. Folic acid and the prevention of neural tube defects. N Engl J Med. Birth Defects Res A Clin Mol Teratol 2004, 350:101-103.
57. Hubner R.A., Houlston R.D., Muir K.R. Should folic acid fortification be mandatory?. BMJ 2007;334:1253 2007, 334:1253.
58. Czeizel A.E., Medveczky E. Periconceptional multivitamin supplementation and multimalformed offspring. Obstet Gynecol 2003, 102:1255-1261.
59. BarOz B., Koren G., Nguyen P., Kapur B.M. Folate fortification and supplementation-are we there yet?. Reprod Toxicol 2008, 25:408-412.
60. Brown J.E., Jacobs D., Hartman T., Barosso G., Stang J., Gross M. Predictors of red cell folate level in women attempting pregnancy. JAMA 1997, 277:548-552.
61. Tam L., McDonald S.D., Wen S.W., Smith G.N., Windrim R.C., Walker M.C. A survey of preconceptional folic acid use in a group of Canadian women. J Obstet Gynaecol Can 2005, 27:232-236.
62. Cleves M.A., Hobbs C.A., Collins H.B., Andrews N., Smith L.N., Robbins J.M. Folic acid use by women receiving routine gynecologic care. Obstet Gynecol 2004, 103:746-753.
63. de Jong-van den Berg L.T.W., Hernandez-Diaz S., Werler M.M., Louik C., Mitchell A.A. Trends and predictors of folic acid awareness and periconceptional use in pregnant women. Am J Obstet Gynecol 2005, 192:121-128.
64. Robbins J.M., Cleves M.A., Collins B., Andrews N.A., Smith L.N., Hobbs C.A. Randomized trial of a physician-based intervention to increase the use of folic acid supplements among woman. Am J Obstet Gynecol 2005, 192:1126-1132.
65. Nguyen P., Tam C., O'Connor D.L., Kapur B., Koren G. Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age. Am J Clin Nutr 2009, 89:844-852.
66. Han A., Rotermann M., Fuller-Thomson E., Ray J.G. Pre-conceptional folic acid supplement use according to maternal country of birth. J Obstet Gynecol Can 2009, 31:222-226.
67. Colapinto C.K., O'Connor D.L., Tremblay M.S. Folate status of the population in the Canadian Health Measures Survey. CMAJ 2011, 183:100-106.
68. Tam C., McKenna K., Goh Y.I., KliegerGrossman C., O'Connor D.L., Einarson A. Periconceptional folic acid supplementation: a new indication for therapeutic drug monitoring. Ther Drug Monit 2009, 31:319-326.
69. Farrell C.J., Kirsch S.H., Herrmann M. Red cell or serum folate: what to do in clinical practice?. Clin Chem Lab Med 2013, 51:555-569.
70. Niesser M., Demmelmair H., Weith T., Moretti D., RauhPfeiffer A., van Lipzig M. Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation. PLoS One 2013, 8:561-594.
71. Colapinto C.K., O'Connor D.L., Dubois L., Tremblay M.S. Folic acid supplement use is the most significant predictor of folate concentrations in Canadian women of childbearing age. Appl Physiol Nutr Metab 2012, 37:284-292.
72. Miller E.C., Liu N., Wen S.W., Walker M. Why do Canadian women fail to achieve optimal pre-conceptional folic acid supplementation? An observational study. J Obstet Gynaecol Can 2011, 33:1116-1123.
73. Richard-Tremblay A-A., Sheehy O., Audibert F., Ferreira E., Bérard A. Concordance between periconceptional folic acid supplementation and Canadian clinical guidelines. J Popul Ther Clin Pharmacol 2012, 19:150-159.
74. Anderson C.A., Beresford S.A., McLerran D., Lampe J.W., Deeb S., Feng Z. Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: results from a crossover trial. Mol Nutr Food Res 2013, 57:637-644.
75. Tam C., O'Connor D., Koren G. Circulating unmetabolized folic acid: relationship to folate status and effect of supplementation. Obstet Gynecol Int 2012;2012:485479 2012, 10.1155/2012/485179.
76. Obeid R., Holzgreve W., Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?. J Perinat Med 2013, 41:469-483.
77. Firth H.V., Hurst J.A., Hall J.G. Oxford desk reference. Clinical genetics. Oxford: Oxford University Press 2006.
78. Health Canada. Canadian perinatal health report 2003. Canadian Perinatal Surveillance System. Ottawa: Minister of Public Works and Government Services Canada 2003.
79. Hall J.G., Friedman J.M., Kenna B.A., Popkin J., Jawanda M., Arnold W. Clinical, genetic, and epidemiological factors in neural tube defects. Am J Hum Genet 1988, 43:827-837.
80. Chambers K., Popkin J., Arnold W., Irwin B., Hall J.G. Neural tube defects in British Columbia. Lancet 1994, 343:489-490.
81. Hall J.G. Folic acid: the opportunity that still exists. CMAJ 2000, 162:1571-1572.
82. Neural tube defects. American College of Obstetrics and Gynecology Educational Bulletin 2003, 44:754-764. (Re-affirmed 2011.).
83. Little J., Elwood J.M. eds. Epidemiology and control of neural tube defects. In: Monograph in epidemiology and biostatistics. Oxford: Oxford University Press 1992, 20.
84. Baird P.A. Neural tube defects in the Sikhs. Am J Med Genet 1983, 16:49-56.
85. Hunter AGW. Neural tube defects in eastern Ontario and western Quebec: demography and family data. Am J Med Genet 1984, 19:45-63.
86. Frecker M., Fraser F.C. Epidemiological studies of neural tube defects in Newfoundland. Teratology 1987, 36:355-361.
87. Dallaire L., Melancon S.B., Potier M., Matthiew M-P., Ducharme G. Date of conception and prevention of neural tube defects. Clin Genet 1984, 26:304-307.
88. McBride M.L. Sib risks of anencephaly and spina bifida in British Columbia. Am J Med Genet 1979, 3:377-387.
89. Dallaire L., Michaud J., Melancon S.B., Potier M., Lambert M., Mitchell G. et al. Prenatal diagnosis of fetal anomalies during the second trimester of pregnancy: their characterization and delineation of defects in pregnancies at risk. Prenat Diagn 1991, 11:629-635.
90. Gucciardi E., Pietrusiak M.A., Reynolds D.L., Rouleau J. Incidence of neural tube defects in Ontario, 1986-1999. CMAJ 2002, 167:237-240.
91. Trimble B.K., Baird P.A. Congenital anomalies of the central nervous system. Incidence in British Columbia 1952-1972. Teratology 1978, 17:1743-1749.
92. Oakley G.P. Folate deficiency is an "imminent health hazard" causing a worldwide birth defects epidemic. Birth Defects Res A Clin Mol Teratol 2003, 67:903-904.
93. Eichholzer M., Tonz O., Zimmerman R. Folic acid: a public-health challenge. Lancet 2006, 367:1852-1861.
94. Oakley G.P. The scientific basis for eliminating folic acid-preventable spina bifida: a modern miracle from epidemiology. Ann Epidemiol 2009, 19:226-230.
95. Oakley G.P. Folic acid-preventable spina bifida. A good start but much to be done. Am J Prev Med 2010, 38:569-570.
96. Wilson R.D., Désilets V., Wyatt P., Langlois S., Gagnon A., Allen V. et al.; Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada; The Motherrisk Program. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. SOGC Clinical Practice Guidelines, No. 201, December 2007. J Obstet Gynaecol Can 2007, 29:1003-1013.
97. Evans J.A. Pre-conceptional vitamin/folic acid supplementation 2007. J Obstet Gynaecol Can 2008, 30:656-658.
98. Health Canada. Prenatal nutrition guidelines for health professionals. Folate contributes to a healthy pregnancy. Ottawa: Health Canada. Available at: http://www.hc-sc.gc.ca/fn-an/pubs/nutrition/folate-eng.php 2009.
99. Health Canada. High dose folic acid supplementation - questions and answers for health professionals. Ottawa: Health Canada. Available at: http://www.hc-sc.gc.ca/fn-an/nutrition/prenatal/fol-qa-qr-eng.php 2010.
100. Lammer E.J., Sever L.E., Oakley G.P. Teratogen updates: valproic acid. Teratology 1987, 35:465-473.
101. Rosa F.W. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991, 324:674-677.
102. Warkany J. Amniopterin and methotrexate: folic acid deficiency. Teratology 1978, 17:353-358.
103. Briggs G.G., Freeman R.K., Yaffe S.J. Drugs in pregnancy and lactation, 9th ed. A reference guide to fetal and neonatal risk. London: Royal College of Obstetricians and Gynaecologists 2011.
104. American College of Obstetricians and Gynecologists (ACOG). ACOG education pamphlet AP 056. Good health before pregnancy: preconception care. Washington, DC: ACOG. Available at: http://www.acog.org/Patients/FAQs/Good-Health-Before-Pregnancy-Preconception-Care 2015.
105. American College of Obstetricians and Gynecologists (ACOG). ACOG education pamphlet AP 146. Reducing your risk of birth defects. Washington, DC: ACOG. Available at: http://www.acog.org/Patients/FAQs/Reducing-Risks-of-Birth-Defects 2014.
106. US Preventative Services Task Force. Folic acid for the prevention of neural tube defects. US Preventive Services Task Force recommendation statement. Ann Intern Med 2009, 150:626-631.
107. Holmes L.B., Driscoll S.G., Atkins L.A. Etiologic heterogeneity of neural tube defects. N Engl J Med 1976, 294:365-369.
108. Khoury M.J., Erickson J.D., James L.M. Etiologic heterogeneity of neural tube defects: clues from epidemiology. Am J Epidem 1982, 115:538-548.
109. Jones K.L. Smith's recognizable patterns of human malformation, 6th ed. Philadelphia: WB Saunders 2006, 704-705.
110. Pietrzik K., Bailey L., Shane B. Folic acid and L-5 methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2010, 48:535-548.
111. Bodnar L.M., Himes K.P., Venkataramanan R., Chen J.Y., Evans R.W., Meyer J.L. Maternal serum folate species in early pregnancy and risk of preterm birth. Am J Clin Nutr 2010, 92:864-871.
112. Suh J.R., Herbig A.K., Stover P.J. New perspectives on folate catabolism. Annu Rev Nutr 2001, 21:255-282.
113. van der Linden I.J., Den Heijer M., Alman L.A., Gellekink H., Vermeulen S.H., Kluijtmans L.A. The methionine synthase reductase 66A to G polymorphism is a maternal risk factor for spina bifida. J Mol Med (Berl) 2006, 84:1047-1054.
114. Wallingford J.B., Niswander L.A., Shaw G.M., Finnell R.H. The continuing challenge of understanding, preventing, and treating neural tube defects. Science 2013, 339. 1222002. 10.1126/Science1222002.
115. Burdge G.C., Lillycrop K.A. Folic acid supplementation in pregnancy: are there devils in the detail?. Br J Nutr 2012, 180:1924-1930.
116. Salbaum J.M., Kappen C. Genetic and epigenomic footprints of folate. Prog Mol Biol Transl Sci 2012, 108:129-158.
117. Greenburg J.A., Bell S.J., Guan Y., Yu Y-H. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol 2011, 4:52-59.
118. Vasquez K., Kuizon S., Junaid M., El Idrissi A. Chapter 8. The effect of folic acid on GABA(A)-B 1 receptor subunit. In: El Idrissi A, L'Amoreaux WJ, editors. Taurine 8. Advances in experimental medicine and biology 775. New York: Springer Science+Business Media 2013, 101-108. 10.1007/978-1-4614-6130-2_8.
119. Hoyo C., Murtha A.P., Schildkraut J.M., Forman M.R., Calingaert B., Demark-Wahnefried W. Folic acid supplementation before and during pregnancy in the Newborn Epigenetics Study (NEST). BMC Public Health 2011, 11:46.
120. Sie K.K., Li J., Ly A., Sohn K.J., Croxford R., Kim Y.I. Effect of maternal and postweaning folic acid supplementation on global and gene-specific DNA methylation in the liver of the rat offspring. Mol Nutr Food Res 2013, 67:677-685.
121. Babcook C.J., Ball R.H., Feldkamp M.L. Prevalence of aneuploidy and additional anatomic abnormalities in fetuses with open spina bifida: population based study in Utah. J Ultrasound Med 2000, 9:619-623.
122. Kumar V., Singh A., Sharma S.P., Srivastava A., Saxena A., Gangopadhyay A.N. Clinical spectrum of neural tube defects with special reference to karyotyping study. J Pediatr Neurosci 2012, 7:82-84.
123. Donnelly J.C., Platt L.D., Rebarber A., Zachary J., Grobman W.A., Wapner R.J. Association of copy number variants with specific ultrasonographically detected fetal anomalies. Obstet Gynaecol 2014, 124:83-90.
124. Desilets V., Oligny L.L. Genetics Committee of the Society of Obstetricians and Gynaecology Canada; Family Physicians Advisory Committee; Medico-Legal Committee of the SOGC. Fetal and perinatal autopsy in prenatally diagnosed fetal abnormalities with normal karyotype. SOGC Technical Update, No. 267, October 2011. J Obstet Gynaecol Can 2011, 33:1047-1057.
125. Mills J.L., Carter T.C., Kay D.M., Browne M., Brody L.C., Liu A. Folate and vitamin B12 related genes and risk for omphalocele. Hum Genet 2012, 131:739-746.
126. Hollis N.D., Allen E.G., Oliver T.R., Tinker S.W., Druschel C., Hobbs C.A. Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project. Amer J Med Genet A 2012, 161:438-444.
127. Goh Y.I., Bollano E., Einarson T.R., Koren G. Motherisk Update 2007. Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis. Clin Pharm Ther 2007, 81:685-691.
128. Olshan A.F., Smith J.C., Bondy M.L., Neglia J.P., Pollock B.H. Maternal vitamin use and the reduced risk of neuroblastoma. Epidemiol 2002, 13:575-580.
129. Allen V.M., Armson B.A. Genetics Committee and Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada. Teratogenicity associated with pre-existing and gestational diabetes. SOGC Clinical Practice Guideline, No. 200, November 2007. J Obstet Gynaecol Can 2007, 29:927-934.
130. Wentzel P. Can we prevent diabetic birth defects with micronutrients?. Diabetes Obes Metab 2009, 11:770-778.
131. Bánhidy F., Dakhlaoui A., Puhó E.H., Czeizel AAE. Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case-control study. Congenit Anom (Kyoto) 2011, 51:34-42.
132. Matok I., Gorodischer R., Koren G., Landau D., Wiznitzer A., Levy A. Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations. Br J Clin Pharmacol 2009, 68:956-962.
133. Ray J.G., Langman L.J., Mamdani M.M., Cole DEC. Absence of effect of folic acid flour fortification on anticolvulsant drug levels. Am J Med 2005, 118:444-445.
134. Morrow J.I., Hunt S.J., Russell A.J., Smithson W.H., Parsons L., Robertson I. Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 2009, 80:506-511.
135. Hauser W.A. Folic acid supplementation: too much of a good thing?. J Neurol Neurosurg Psychiatry 2009, 80:468.
136. Kjaer D., Horvath-Puhó E., Christensen J., Vestergaard M., Czeizel A.E., Sørensen H.T. Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case-control study. BJOG 2008, 115:98-103.
137. Werler M.M., Ahrens K.A., Bosco JLF., Mitchell A.A., Anderka M.T., Gilboa S.M. Use of antiepileptic medications in pregnancy in relation to risks of birth defects. Ann Epidemiol 2011, 21:842-850.
138. Meijer W.M., de Walle H.E., Kerstjens-Frederikse W.S., de Jong-van den Berg L.T. Folic acid sensitive birth defects in association with intrauterine exposure to folic acid antagonists. Reprod Toxicol 2005, 20:203-207.
139. Harden C.L., Pennell P.B., Koppel B.S., Hovinga C.A., Gidal B., Meador K.J. Management issues for women with epilepsy-focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009, 50:1247-1255.
140. Emes R.D., Clifford H., Haworth K.E., Farrell W.E., Fryer A.A., Carroll W.D. Antiepileptic drugs and the fetal epigenome. Epilepsia 2013, 54:16-19.
141. Czeizel A.E., Puhó E.H., Langmar Z., Ács N., Bánhidy F. Possible association of folic acid supplementation during pregnancy with reduction of preterm birth: a population-based study. Eur J Obstet Gynecol Reprod Biol 2010, 148:135-140.
142. van Uitert E.M. Steegers-Theunissen RPM. Influence of maternal folate status on human fetal growth parameters. Mol Nutr Food Res 2012, 00:1-14.
143. Kim M.W., Hong S.C., Choi J.S., Han J-Y., Oh M.J., Kim H.J. Homocysteine, folate, and pregnancy outcomes. J Obstet Gynaecol Can 2012, 32:520-524.
144. Li Z., Ye R., Zhang L., Li H., Liu J., Ren A. Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia. Hypertension 2013, 61:873-879.
145. Linabery A.M., Johnson K.J., Ross J.A. Childhood cancer incidence trends in association with US folic acid fortification (1986-2008). Pediatrics 2012, 129:1125-1133.
146. Milne E., Greenop K.R., Bower C., Miller M., van Bockxmeer F.M., Scott R.J. Maternal use of folic acid and other supplements and risk of childhood brain tumors. Cancer Epidemiol Biomarkers Prev 2012, 21:1933-1941.
147. Amigou A., Rudant J., Orsi L., Goujon-Bellec S., Leverger G., Baruchel A. Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes Control 2012, 23:1265-1277.
148. Surén P., Roth C., Bresnahan M., Haugen M., Hornig M., Hirtz D. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013, 309:570-577.
149. Berry R.J., Crider K.S., Yeargin-Allsopp M. Periconceptional folic acid and risk of autism spectrum disorders. JAMA 2013, 309:611-613.
150. Simpson J.L., Bailey L.B., Pietrzik K., Shane B., Holzgreve W. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I-folate, vitamin B12, vitamin B6. J Matern Fetal Neonatal Med 2010, 23:1323-1343.
151. Ahn E., Nava-Ocampo A.A., Motherisk Koren G. Multivitamin supplement for pregnant women. New insights. Can Fam Physician 2004, 50:705-706. update 2007.
152. Simpson J.L., Shulman L.P., Brown H., Holzgreve W. Closing the folate gap in reproductive-age women. Contemp Ob Gyn 2010, 55:34-40.
153. Ravdin P.M., Cronin K.A., Howlader N., Ber C.D., Chlebowski R.T., Feuer E.J. The decrease in breast-cancer incidence in 2003 in the United States. New Engl J Med 2007, 356:1670-1674.
154. Kim Y.I. Does a high folate intake increase the risk of breast cancer?. Nutr Rev 2006, 64:468-475.
155. Lubecka-Pietruszewska K., Kaufman-Szymczyk A., Stefanska B., Fabianowska-Majewska K. Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer. Biochem Biophy Res Comm 2013, 430:623-628.
156. Navarro-Silvera S.A., Jain M., Howe G.R., Miller A.B., Rohan T.E. Dietary folate consumption and risk of ovarian cancer: a prospective cohort study. Eur J Cancer Prev 2006, 15:511-515.
157. Kim M.W., Ahn K.H., Ryu J.H., Hong S.C., Lee J.S., Nava-Ocampo A.A. Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes. PLoS One 2014, 9(5):972-973.
158. Dekker G.A., de Vries J.I., Doelitzsch P.M., Huijgens P.C., von Blomberg B.M., Jakobs C. Underlying disorders associated with severe early-onset preeclampsia. Am J Obstet Gynecol 1995, 173:1042-1048.
159. Rajkovic A., Mahomed K., Malinow M.R., Sorenson T.K., Woelk G.B., Williams M.A. Plasma homocyst(e)ine concentration in eclamptic and pre-eclamptic African women postpartum. Obstet Gynecol 1999, 94:355-360.
160. Wen S.W., Chen X.K., Rodger M., White R.R., Yanag Q., Smith G.N. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 2008, 196:45-47. 10.1016/jajog.2007.06.067.
161. Metz J., McNel A.R., Levin M. The relationship between serum cobalamin concentration and mean red cell volume at varying concentrations of serum folate. Clin Lab Haem 2004, 26:323-325.
162. Lassi Z.S., Salam R.A., Haider B.A., Bhutta Z.A. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev 2013, 3. CD006896. 10.1002/14651858.CD006896.pub2.
163. Duffy T.P. Hematologic aspects of pregnancy. In: Barrow GN, Duffy TP, eds. Medical complications during pregnancy, 5th ed. Philadelphia: WB Saunders 1999, 82-83.
164. Kennedy D.A., Stern S.J., Moretti M., Matok I., Sarkar M., Nickel C. Folate intake and the risk of colorectal cancer: a systemic review and meta-analysis. Cancer Epidemiol 2011, 35:2-10.
165. Mason J.B., Dickstein A., Jacques P., Haggarty P., Selhub J., Dallal G. 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 2007, 16:1325-1329.
166. Lucock M., Yates Z. Folic acid fortification: a double-edged sword. Curr Opin Clin Nutr Metab Care 2009, 12:555-564.
167. Sauer J., Mason J.B., Choi S-W. Too much folate-a risk factor for cancer and cardiovascular disease?. Curr Opin Clin Nutr Metab Care 2009, 12:30-36.
168. Fife J., Raniga S., Hider P.N., Frizelle F.A. Folic acid supplementation and colorectal risk: a meta-analysis. Colorectal Dis 2009, 13:132-137.
169. Figueiredo J.C., Mott L.A., Giovannucci E., Wu K., Cole B., Grainge M.J. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int J Cancer 2011, 129:192-203.
170. Burh G., Bales C.W. Nutritional supplements for older adults: review and recommendations-Part II. J Nutr Elder 2010, 29:42-71.
171. Dunlap B., Shelke K., Salem S.A., Keith L.G. Folic acid and human reproduction-ten important issues for clinicians. J Exp Clin Assist Reprod 2011, 8:2-16.
172. Toriello H.V. Policy statement on folic acid and neural tube defects. Genet Med 2011, 13:593-596.
173. Tulauliker V.S., Arulkumaran S. Folic Acid in obstetric practice: a review. Obstet Gynecol Surv 2011, 66:240-247.
174. Curtin K., Samowitz W.S., Ulrich C.M., Wolff R.K., Herrick J.S., Caan B.J. Nutrients in folate-mediated, one-carbon metabolism and the risk of rectal tumors in men and women. Nutr Cancer 2011, 63:357-366.
175. Miller J.W., Ulrich C.M. Folic acid and cancer-where are we today?. Lancet 2013, 381:974-976.
176. Vollset S.E., Clarke R., Lewington S., Ebbing M., Halsey J., Lonn E. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals. Lancet 2013, 381:1029-1036.
177. No evidence of cancer risk from folate supplements. BMJ 2013, 346:546.
178. Song Y., Manson J.E., Lee I.M., Cook N.R., Paul L., Selhub J. Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma. J Natl Cancer Inst 2012, 104:1562-1575.
179. Castillo-Lancellotti C., Tur Mari J.A., Uauy Dagach R. Folic acid supplementation and colorectal adenoma recurrence: systematic review. Nutr Hosp 2012, 27:13-21.
180. Greenop K.R., Miller M., de Klerk N.H., Scott R.J., Attia J., Ashton L.J. Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and risk of childhood brain tumors. Nutr Cancer 2014, 66:800-809. 10.1080/01635581.2014.916326.
181. Czeizel A.E., Vargha P. Periconceptional folic acid/multivitamin supplementation and twin pregnancy. Am J Obstet Gynecol 2004, 191:790-794.
182. Steinman G. Can the chance of having twins be modified by diet?. Lancet 2006, 367:1461-1462.
183. Haggarty P., McCallum H., McBain H., Andrews K., Duthie S., McNeill G. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet 2006, 367:1513-1519.
184. Hågberg S.E., London S.J., Stigum H., Nafstad P., Nystad W. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 2009, 94:180-184.
185. Zetstra-van der Woude P.A., De Walle H.E., Hoek A., Bos H.J., Boezen H.M., Koppelman G.H. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring. Pharmacoepidemiol Drug Saf 2014, 23:1059-1065. 10.1002/pds.3652.
186. Veeranki S.P., Gebretsadik T., Dorris S.L., Mitchel E.F., Hartert T.V., Cooper W.O. Association of folic acid supplementation during pregnancy and infant bronchiolitis. Am J Epidemiol 2014, 179:938-946.
187. Magdelijns FJH., Mommers M., Penders J., Smits L., Thijs C. Folic acid use in pregnancy and the development of atopy, asthma, and lung function in childhood. Pediatrics 2011, 128:135-144.
188. Crider K.S., Cordero A.M., Qi Y.P., Mulinare J., Fowling N.F., Berry R.J. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr 2013, 98:1272-1281.
189. Nelson CRM., Loen J.A., Evans J. The relationship between awareness and supplementation: which Canadian women know about folic acid and how does that translate into use?. Can J Public Health 2014, 105:40-46.
190. Wang M., Wang Z.P., Gao L.J., Gong R., Sun X.H., Zhao Z.T. Maternal body mass index and the association between folic acid supplements and neural tube defects. Acta Paediatr 2013, 102:908-913.
191. Nguyen P., Thomas M., Koren G. Predictors of prenatal multivitamin adherence in pregnant women. J Clin Pharmacol 2009, 49:735-742.
192. Kennedy D., Koren G. Motherisk update 2012. Identifying women who might benefit from higher doses of folic acid in pregnancy. Can Fam Physician 2012, 58:394-397.
193. Woolf S.H., Battista R.N., Angerson G.M., Logan A.G., Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the Canadian Task Force on Preventive Health Care. CMAJ 2003, 169:207-208.