Folic acid supplementation in pregnancy and implications in health and disease

Journal of Biomedical Science

Volumn 21, Issue 1, 2014, Pages

  Barua, Subit ^a   Kuizon, Salomon ^a   Junaid, Mohammed A ^a  

^a NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

Author keywords

Autism; Dna methylation; Epigenetic; Folic acid; Imprinting; Neural tube defects; Prenatal nutrition

Indexed keywords

FOLIC ACID;

COHORT ANALYSIS; EPIGENETICS; FOLATE METABOLISM; GENETIC REGULATION; HEALTH STATUS; HUMAN; MATERNAL DISEASE; MEDICAL HISTORY; NEURAL TUBE DEFECT; NONHUMAN; PREGNANCY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; TREATMENT OUTCOME; VITAMIN SUPPLEMENTATION; ANIMAL EMBRYO; DIET SUPPLEMENTATION; DRUG EFFECTS; EMBRYO DEVELOPMENT; EMBRYOLOGY; FEMALE; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; INCIDENCE; NEURAL TUBE DEFECTS;

DIETARY SUPPLEMENTS; EMBRYO, MAMMALIAN; EMBRYONIC DEVELOPMENT; EPIGENESIS, GENETIC; FEMALE; FOLIC ACID; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; INCIDENCE; NEURAL TUBE DEFECTS; PREGNANCY;

EID: 84920417054     PISSN: 10217770     EISSN: 14230127     Source Type: Journal    
DOI: 10.1186/s12929-014-0077-z     Document Type: Review

References (138)

1. Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A: A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 2012, 484:339-344.
2. Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003, 33(Suppl):245-254.
3. Gabory A, Attig L, Junien C: Developmental programming and epigenetics. Am J Clin Nutr 2011, 94:1943S-1952S.
4. Smithells RW, Sheppard S, Schorah CJ: Vitamin dificiencies and neural tube defects. Arch Dis Child 1976, 51:944-950.
5. Li D, Rozen R: Maternal folate deficiency affects proliferation, but not apoptosis, in embryonic mouse heart. J Nutr 2006, 136:1774-1778.
6. Blom HJ, Shaw GM, Den Heijer M, Finnell RH: Neural tube defects and folate: case far from closed. Nat Rev Neurosci 2006, 7:724-731.
7. Rosati R, Ma H, Cabelof DC: Folate and colorectal cancer in rodents: a model of DNA repair deficiency. J Oncol 2012, 2012:105949.
8. Hoyo C, Murtha AP, Schildkraut JM, Forman MR, Calingaert B, Demark-Wahnefried W, Kurtzberg J, Jirtle RL, Murphy SK: Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST). BMC Public Health 2011, 11:46.
9. West AA, Yan J, Perry CA, Jiang X, Malysheva OV, Caudill MA: Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women. Am J Clin Nutr 2012, 96:789-800.
10. Wallingford JB, Niswander LA, Shaw GM, Finnell RH: The continuing challenge of understanding, preventing, and treating neural tube defects. Science 2013, 339:1222002.
11. CDC: 2014. http://www.cdc.gov/ncbddd/birthdefects/data.html. Ref Type: Report.
12. Pitkin RM: Folate and neural tube defects. Am J Clin Nutr 2007, 85:285S-288S.
13. Au KS, Ashley-Koch A, Northrup H: Epidemiologic and genetic aspects of spina bifida and other neural tube defects. Dev Disabil Res Rev 2010, 16:6-15.
14. Northrup H, Volcik KA: Spina bifida and other neural tube defects. Curr Probl Pediatr 2000, 30:313-332.
15. Frey L, Hauser WA: Epidemiology of neural tube defects. Epilepsia 2003, 44(Suppl 3):4-13.
16. Imbard A, Benoist JF, Blom HJ: Neural tube defects, folic acid and methylation. Int J Environ Res Public Health 2013, 10:4352-4389.
17. De Regil LM, Fernandez-Gaxiola AC, Dowswell T, Pena-Rosas JP: Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2010, CD007950.
18. Vandevijvere S, Amsalkhir S, Van Oyen H, Moreno-Reyes R: Determinants of folate status in pregnant women: results from a national cross-sectional survey in Belgium. Eur J Clin Nutr 2012, 66:1172-1177.
19. Blom HJ: Folic acid, methylation and neural tube closure in humans. Birth Defects Res A Clin Mol Teratol 2009, 85:295-302.
20. Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM: Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med 1993, 86:703-708.
21. Scott JM: Folate and vitamin B12. Proc Nutr Soc 1999, 58:441-448.
22. Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P: Folic acid metabolism and mechanisms of neural tube defects. Ciba Found Symp 1994, 181:180-187.
23. Heid MK, Bills ND, Hinrichs SH, Clifford AJ: Folate deficiency alone does not produce neural tube defects in mice. J Nutr 1992, 122:888-894.
24. Burgoon JM, Selhub J, Nadeau M, Sadler TW: Investigation of the effects of folate deficiency on embryonic development through the establishment of a folate deficient mouse model. Teratology 2002, 65:219-227.
25. Fleming A, Copp AJ: Embryonic folate metabolism and mouse neural tube defects. Science 1998, 280:2107-2109.
26. Callender STE: A critical review of pernicious anaemia of pregnancy. Q J Med 1944, 13:75-105.
27. Gatenby PB, Lillie EW: Clinical analysis of 100 cases of severe megaloblastic anaemia of pregnancy. Br Med J 1960, 2:1111-1114.
28. Hibbard ED, Smithells RW: Folic acid metabolism and human embryopathy. Lancet 1965, 285:1254.
29. Smithells RW, Sheppard S, Wild J, Schorah CJ: Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989, 2:498-499.
30. Nevin NC, Seller MJ: Prevention of neural-tube-defect recurrences. Lancet 1990, 335:178-179.
31. 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, 315:339-340.
32. Wald NJ: Commentary: a brief history of folic acid in the prevention of neural tube defects. Int J Epidemiol 2011, 40:1154-1156.
33. MRC Vitamin Study Research Group: Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991, 338:131-137.
34. Czeizel AE, Dudas I: Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992, 327:1832-1835.
35. 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.
36. Crandall BF, Corson VL, Evans MI, Goldberg JD, Knight G, Salafsky IS: American College of Medical Genetics statement on folic acid: fortification and supplementation. Am J Med Genet 1998, 78:381.
37. Wilson RD, Johnson JA, Wyatt P, Allen V, Gagnon A, Langlois S, Blight C, Audibert F, Desilets V, Brock JA, Koren G, Goh YI, Nguyen P, Kapur B: 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. J Obstet Gynaecol Can 2007, 29:1003-1026.
38. Kennedy D, Koren G: Identifying women who might benefit from higher doses of folic acid in pregnancy. Can Fam Physician 2012, 58:394-397.
39. Wald NJ, Law MR, Morris JK, Wald DS: Quantifying the effect of folic acid. Lancet 2001, 358:2069-2073.
40. Fowler B: The folate cycle and disease in humans. Kidney Int Suppl 2001, 78:S221-S229.
41. Crider KS, Yang TP, Berry RJ, Bailey LB: Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr 2012, 3:21-38.
42. Hubner RA, Houlston RS: Folate and colorectal cancer prevention. Br J Cancer 2009, 100:233-239.
43. Liu JJ, Ward RL: Folate and one-carbon metabolism and its impact on aberrant DNA methylation in cancer. Adv Genet 2010, 71:79-121.
44. Stanger O: Physiology of folic acid in health and disease. Curr Drug Metab 2002, 3:211-223.
45. Zhang T, Lou J, Zhong R, Wu J, Zou L, Sun Y, Lu X, Liu L, Miao X, Xiong G: Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature. PLoS One 2013, 8:e59570.
46. Molloy AM, Brody LC, Mills JL, Scott JM, Kirke PN: The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects. Birth Defects Res A Clin Mol Teratol 2009, 85:285-294.
47. Hoffman DR, Marion DW, Cornatzer WE, Duerre JA: S-Adenosylmethionine and S-adenosylhomocystein metabolism in isolated rat liver. Effects of L-methionine, L-homocystein, and adenosine. J Biol Chem 1980, 255:10822-10827.
48. James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA: Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 2002, 132:2361S-2366S.
49. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ: Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000, 275:29318-29323.
50. Kim KC, Friso S, Choi SW: DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging. J Nutr Biochem 2009, 20:917-926.
51. Waterland RA, Travisano M, Tahiliani KG: Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. FASEB J 2007, 21:3380-3385.
52. Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, Slagboom PE, Heijmans BT: Periconceptional maternal folic acid use of 400 microg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS One 2009, 4:e7845.
53. Meethal SV, Hogan KJ, Mayanil CS, Iskandar BJ: Folate and epigenetic mechanisms in neural tube development and defects. Childs Nerv Syst 2013, 29:1427-1433.
54. Iskandar BJ, Rizk E, Meier B, Hariharan N, Bottiglieri T, Finnell RH, Jarrard DF, Banerjee RV, Skene JH, Nelson A, Patel N, Gherasim C, Simon K, Cook TD, Hogan KJ: Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. J Clin Invest 2010, 120:1603-1616.
55. Ichi S, Costa FF, Bischof JM, Nakazaki H, Shen YW, Boshnjaku V, Sharma S, Mania-Farnell B, McLone DG, Tomita T, Soares MB, Mayanil CS: Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development. J Biol Chem 2010, 285:36922-36932.
56. Junaid MA, Kuizon S, Cardona J, Azher T, Murakami N, Pullarkat RK, Brown WT: Folic acid supplementation dysregulates gene expression in lymphoblastoid cells-implications in nutrition. Biochem Biophys Res Commun 2011, 412:688-692.
57. Barua S, Kuizon S, Chadman KK, Flory MJ, Brown WT, Junaid MA: Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid. Epigenetics Chromatin 2014, 7:3.
58. Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH, Jacques PF: Folic acid intake from fortification in United States exceeds predictions. J Nutr 2002, 132:2792-2798.
59. Ly A, Lee H, Chen J, Sie KK, Renlund R, Medline A, Sohn KJ, Croxford R, Thompson LU, Kim YI: Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Cancer Res 2011, 71:988-997.
60. Barua S, Chadman KK, Kuizon S, Buenaventura D, Stapley NW, Ruocco F, Begum U, Guariglia SR, Brown WT, Junaid MA: Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring. PLoS One 2014, 9:e101674.
61. Ulrich CM, Potter JD: Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev 2006, 15:189-193.
62. Deghan MS, Ishiguro L, Sohn KJ, Medline A, Renlund R, Croxford R, Kim YI: Folic Acid supplementation promotes mammary tumor progression in a rat model. PLoS One 2014, 9:e84635.
63. Been RA, Ross JA, Nagel CW, Hooten AJ, Langer EK, DeCoursin KJ, Marek CA, Janik CL, Linden MA, Reed RC, Schutten MM, Largaespada DA, Johnson KJ: Perigestational dietary folic acid deficiency protects against medulloblastoma formation in a mouse model of nevoid basal cell carcinoma syndrome. Nutr Cancer 2013, 65:857-865.
64. Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bonaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, Den Heijer M, Ueland PM, Bennett D, Collins R, Peto R: 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.
65. Goh YI, Bollano E, Einarson TR, Koren G: Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis. Clin Pharmacol Ther 2007, 81:685-691.
66. French AE, Grant R, Weitzman S, Ray JG, Vermeulen MJ, Sung L, Greenberg M, Koren G: Folic acid food fortification is associated with a decline in neuroblastoma. Clin Pharmacol Ther 2003, 74:288-294.
67. Grupp SG, Greenberg ML, Ray JG, Busto U, Lanctot KL, Nulman I, Koren G: Pediatric cancer rates after universal folic acid flour fortification in Ontario. J Clin Pharmacol 2011, 51:60-65.
68. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr: Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006, 354:1567-1577.
69. Sauer J, Mason JB, Choi SW: Too much folate: a risk factor for cancer and cardiovascular disease? Curr Opin Clin Nutr Metab Care 2009, 12:30-36.
70. Thakur S, Thakur SD, Wani NA, Kaur J: Reduced expression of folate transporters in kidney of a rat model of folate oversupplementation. Genes Nutr 2014, 9:369.
71. Timmermans S, Jaddoe VW, Hofman A, Steegers-Theunissen RP, Steegers EA: Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study. Br J Nutr 2009, 102:777-785.
72. Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GD, Eddleman K, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D'Alton ME: Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study. PLoS Med 2009, 6:e1000061.
73. Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA: Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr 2011, 94:906-912.
74. Catov JM, Nohr EA, Bodnar LM, Knudson VK, Olsen SF, Olsen J: Association of periconceptional multivitamin use with reduced risk of preeclampsia among normal-weight women in the Danish National Birth Cohort. Am J Epidemiol 2009, 169:1304-1311.
75. Alwan NA, Greenwood DC, Simpson NA, McArdle HJ, Cade JE: The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women. BJOG 2010, 117:821-829.
76. Whitrow MJ, Moore VM, Rumbold AR, Davies MJ: Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am J Epidemiol 2009, 170:1486-1493.
77. Haberg SE, London SJ, Stigum H, Nafstad P, Nystad W: Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 2009, 94:180-184.
78. Smith AD, Kim YI, Refsum H: Is folic acid good for everyone? Am J Clin Nutr 2008, 87:517-533.
79. Kallen B: Use of folic acid supplementation and risk for dizygotic twinning. Early Hum Dev 2004, 80:143-151.
80. Muggli EE, Halliday JL: Folic acid and risk of twinning: a systematic review of the recent literature, July 1994 to July 2006. Med J Aust 2007, 186:243-248.
81. Berry RJ, Kihlberg R, Devine O: Impact of misclassification of in vitro fertilisation in studies of folic acid and twinning: modelling using population based Swedish vital records. BMJ 2005, 330:815.
82. Vollset SE, Gjessing HK, Tandberg A, Ronning T, Irgens LM, Baste V, Nilsen RM, Daltveit AK: Folate supplementation and twin pregnancies. Epidemiology 2005, 16:201-205.
83. Parker SE, Yazdy MM, Tinker SC, Mitchell AA, Werler MM: The impact of folic acid intake on the association among diabetes mellitus, obesity, and spina bifida. Am J Obstet Gynecol 2013, 209:239.e1-8.
84. Ahrens K, Yazdy MM, Mitchell AA, Werler MM: Folic acid intake and spina bifida in the era of dietary folic acid fortification. Epidemiology 2011, 22:731-737.
85. Cortes F, Mellado C, Pardo RA, Villarroel LA, Hertrampf E: Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile. Am J Med Genet A 2012, 158 A: 1885-1890.
86. Hosseini MB, Khamnian Z, Dastgiri S, Samadi RB, Ravanshad Y: Folic acid and birth defects: a case study (Iran). J Pregnancy 2011, 2011:370458.
87. Imdad A, Yakoob MY, Bhutta ZA: The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths. BMC Public Health 2011, 11(Suppl 3):S4.
88. Hollis ND, Allen EG, Oliver TR, Tinker SW, Druschel C, Hobbs CA, O'Leary LA, Romitti PA, Royle MH, Torfs CP, Freeman SB, Sherman SL, Bean LJ: Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project. Am J Med Genet A 2013, 161 A: 438-444.
89. Bean LJ, Allen EG, Tinker SW, Hollis ND, Locke AE, Druschel C, Hobbs CA, O'Leary L, Romitti PA, Royle MH, Torfs CP, Dooley KJ, Freeman SB, Sherman SL: Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project. Birth Defects Res A Clin Mol Teratol 2011, 91:885-893.
90. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I: Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr 2012, 96:80-89.
91. Suren P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjolberg S, Davey SG, Oyen AS, Susser E, Stoltenberg C: Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013, 309:570-577.
92. Roth C, Magnus P, Schjolberg S, Stoltenberg C, Suren P, McKeague IW, Davey SG, Reichborn-Kjennerud T, Susser E: Folic acid supplements in pregnancy and severe language delay in children. JAMA 2011, 306:1566-1573.
93. Chatzi L, Papadopoulou E, Koutra K, Roumeliotaki T, Georgiou V, Stratakis N, Lebentakou V, Karachaliou M, Vassilaki M, Kogevinas M: Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother-child cohort 'Rhea' study in Crete, Greece. Public Health Nutr 2012, 15:1728-1736.
94. Bedard T, Lowry RB, Sibbald B, Harder JR, Trevenen C, Horobec V, Dyck JD: Folic acid fortification and the birth prevalence of congenital heart defect cases in Alberta, Canada. Birth Defects Res A Clin Mol Teratol 2013, 97:564-570.
95. Li X, Li S, Mu D, Liu Z, Li Y, Lin Y, Chen X, You F, Li N, Deng K, Deng Y, Wang Y, Zhu J: The association between periconceptional folic acid supplementation and congenital heart defects: a case-control study in China. Prev Med 2013, 56:385-389.
96. Rozendaal AM, Van Essen AJ, Te Meerman GJ, Bakker MK, van der Biezen JJ, Goorhuis-Brouwer SM, Vermeij-Keers C, De Walle HE: Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study. Eur J Epidemiol 2013, 28:875-887.
97. Vila-Nova C, Wehby GL, Queiros FC, Chakraborty H, Felix TM, Goco N, Moore J, Gewehr EV, Lins L, Affonso CM, Murray JC: Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil. J Perinat Med 2013, 41:461-466.
98. Wehby GL, Felix TM, Goco N, Richieri-Costa A, Chakraborty H, Souza J, Pereira R, Padovani C, Moretti-Ferreira D, Murray JC: High dosage folic acid supplementation, oral cleft recurrence and fetal growth. Int J Environ Res Public Health 2013, 10:590-605.
99. Kelly D, O'Dowd T, Reulbach U: Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. Br J Gen Pract 2012, 62:e466-e472.
100. Li S, Chao A, Li Z, Moore CA, Liu Y, Zhu J, Erickson JD, Hao L, Berry RJ: Folic acid use and nonsyndromic orofacial clefts in China: a prospective cohort study. Epidemiology 2012, 23:423-432.
101. Michels AC, Van den Elzen ME, Vles JS, Van der Hulst RR: Positional plagiocephaly and excessive folic Acid intake during pregnancy. Cleft Palate Craniofac J 2012, 49:1-4.
102. Correa A, Gilboa SM, Botto LD, Moore CA, Hobbs CA, Cleves MA, Riehle-Colarusso TJ, Waller DK, Reece EA: Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects. Am J Obstet Gynecol 2012, 206:218.e1-13.
103. Banhidy F, Dakhlaoui A, Puho EH, Czeizel AA: 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, 51:80-86.
104. Hossein-nezhad A, Mirzaei K, Maghbooli Z, Najmafshar A, Larijani B: The influence of folic acid supplementation on maternal and fetal bone turnover. J Bone Miner Metab 2011, 29:186-192.
105. Mantovani E, Filippini F, Bortolus R, Franchi M: Folic acid supplementation and preterm birth: results from observational studies. Biomed Res Int 2014, 2014:481914.
106. Shaw GM, Carmichael SL, Yang W, Siega-Riz AM: Periconceptional intake of folic acid and food folate and risks of preterm delivery. Am J Perinatol 2011, 28:747-752.
107. Byrne J: Periconceptional folic acid prevents miscarriage in Irish families with neural tube defects. Ir J Med Sci 2011, 180:59-62.
108. 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.
109. Furness D, Fenech M, Dekker G, Khong TY, Roberts C, Hague W: Folate, vitamin B12, vitamin B6 and homocysteine: impact on pregnancy outcome. Matern Child Nutr 2013, 9:155-166.
110. Dwarkanath P, Barzilay JR, Thomas T, Thomas A, Bhat S, Kurpad AV: High folate and low vitamin B-12 intakes during pregnancy are associated with smallforgestational age infants in South Indian women: a prospective observational cohort study. Am J Clin Nutr 2013, 98:1450-1458.
111. Lassi ZS, Salam RA, Haider BA, Bhutta ZA: Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev 2013, 3: CD006896.
112. Furness DL, Yasin N, Dekker GA, Thompson SD, Roberts CT: Maternal red blood cell folate concentration at 10-12 weeks gestation and pregnancy outcome. J Matern Fetal Neonatal Med 2012, 25:1423-1427.
113. Papadopoulou E, Stratakis N, Roumeliotaki T, Sarri K, Merlo DF, Kogevinas M, Chatzi L: The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother-child cohort study in Crete, Greece (Rhea study). Eur J Nutr 2013, 52:327-336.
114. Fekete K, Berti C, Trovato M, Lohner S, Dullemeijer C, Souverein OW, Cetin I, Decsi T: Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr J 2012, 11:75.
115. Pastor-Valero M, Navarrete-Munoz EM, Rebagliato M, Iniguez C, Murcia M, Marco A, Ballester F, Vioque J: Periconceptional folic acid supplementation and anthropometric measures at birth in a cohort of pregnant women in Valencia, Spain. Br J Nutr 2011, 105:1352-1360.
116. Der Woude PA Z-v, De Walle HE, Hoek A, Bos HJ, Boezen HM, Koppelman GH, Den Berg LT DJ-v, Scholtens S: Maternal high-dose folic acid during pregnancy and asthma medication in the offspring. Pharmacoepidemiol Drug Saf 2014.
117. Veeranki SP, Gebretsadik T, Dorris SL, Mitchel EF, Hartert TV, Cooper WO, Tylavsky FA, Dupont W, Hartman TJ, Carroll KN: Association of folic acid supplementation during pregnancy and infant bronchiolitis. Am J Epidemiol 2014, 179:938-946.
118. Brown SB, Reeves KW, Bertone-Johnson ER: Maternal folate exposure in pregnancy and childhood asthma and allergy: a systematic review. Nutr Rev 2014, 72:55-64.
119. Crider KS, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ: Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am J Clin Nutr 2013, 98:1272-1281.
120. Bekkers MB, Elstgeest LE, Scholtens S, Haveman-Nies A, De Jongste JC, Kerkhof M, Koppelman GH, Gehring U, Smit HA, Wijga AH: Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy. Eur Respir J 2012, 39:1468-1474.
121. Kiefte-de Jong JC, Timmermans S, Jaddoe VW, Hofman A, Tiemeier H, Steegers EA, De Jongste JC, Moll HA: High circulating folate and vitamin B-12 concentrations in women during pregnancy are associated with increased prevalence of atopic dermatitis in their offspring. J Nutr 2012, 142:731-738.
122. Dunstan JA, West C, McCarthy S, Metcalfe J, Meldrum S, Oddy WH, Tulic MK, D'Vaz N, Prescott SL: The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Allergy 2012, 67:50-57.
123. Martinussen MP, Risnes KR, Jacobsen GW, Bracken MB: Folic acid supplementation in early pregnancy and asthma in children aged 6 years. Am J Obstet Gynecol 2012, 206:72-77.
124. Magdelijns FJ, 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:e135-e144.
125. Sharland E, Montgomery B, Granell R: Folic acid in pregnancy - is there a link with childhood asthma or wheeze? Aust Fam Physician 2011, 40:421-424.
126. Haberg SE, London SJ, Nafstad P, Nilsen RM, Ueland PM, Vollset SE, Nystad W: Maternal folate levels in pregnancy and asthma in children at age 3 years. J Allergy Clin Immunol 2011, 127:262-264.
127. McNulty B, McNulty H, Marshall B, Ward M, Molloy AM, Scott JM, Dornan J, Pentieva K: Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters. Am J Clin Nutr 2013, 98:92-98.
128. Hoyo C, Murtha AP, Schildkraut JM, Jirtle RL, Demark-Wahnefried W, Forman MR, Iversen ES, Kurtzberg J, Overcash F, Huang Z, Murphy SK: Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics 2011, 6:928-936.
129. Greenop KR, Miller M, De Klerk NH, Scott RJ, Attia J, Ashton LJ, Dalla-Pozza L, Bower C, Armstrong BK, Milne E: Maternal dietary intake of folate and vitamins b6 and B12 during pregnancy and risk of childhood brain tumors. Nutr Cancer 2014, 66:800-809.
130. Chokkalingam AP, Chun DS, Noonan EJ, Pfeiffer CM, Zhang M, Month SR, Taggart DR, Wiemels JL, Metayer C, Buffler PA: Blood levels of folate at birth and risk of childhood leukemia. Cancer Epidemiol Biomarkers Prev 2013, 22:1088-1094.
131. Orjuela MA, Cabrera-Munoz L, Paul L, Ramirez-Ortiz MA, Liu X, Chen J, Mejia-Rodriguez F, Medina-Sanson A, Diaz-Carreno S, Suen IH, Selhub J, Ponce-Castaneda MV: Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake. Cancer 2012, 118:5912-5919.
132. Milne E, Greenop KR, Bower C, Miller M, Van Bockxmeer FM, Scott RJ, De Klerk NH, Ashton LJ, Gottardo NG, Armstrong BK: Maternal use of folic acid and other supplements and risk of childhood brain tumors. Cancer Epidemiol Biomarkers Prev 2012, 21:1933-1941.
133. Amigou A, Rudant J, Orsi L, Goujon-Bellec S, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Haouy S, Chastagner P, Ducassou S, Rialland X, Hemon D, Clavel J: Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes Control 2012, 23:1265-1277.
134. Linabery AM, Johnson KJ, Ross JA: Childhood cancer incidence trends in association with US folic acid fortification (1986-2008). Pediatrics 2012, 129:1125-1133.
135. Crider KS, Bailey LB, Berry RJ: Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients 2011, 3:370-384.
136. EFSA meeting summary report: Folic Acid: An Update on Scientific Developments 2009. http://www.efsa.europa.eu/en/home/publication/efsafolicacid.pdf. Ref Type: Report.
137. The Kimmel Institute: 2014. http://www.thekimmelinstitute.com/varicoseveinspregnancy/.
138. The Johns Hopkins University: 2014. http://www.hopkinsmedicine.org/healthlibrary/test-procedures/gynecology/external-and-internal-heart-rate-monitoring-of-the-fetus-92, P07776/.