Advertisement

Improving Pregnancy Outcomes with One-Carbon Metabolic Nutrients

  • Julia H. King
  • Sze Ting (Cecilia) Kwan
  • Marie A. Caudill
Chapter
Part of the Nutrition and Health book series (NH)

Abstract

Folate, vitamin B12, vitamin B6, and choline—collectively known as one-carbon or methyl nutrients—are involved in many biological processes vital to development, including nucleotide synthesis, methylation reactions, neurotransmitter production, lipid production and transport, and amino acid metabolism. The demand for these nutrients is particularly high during pregnancy, when cells of the placenta and fetus are undergoing rapid division. As such, pregnant women need to consume more of these nutrients to meet their higher requirements. Vegetables, fruits, legumes, and grains are rich sources of folate and vitamin B6, whereas vitamin B12 and choline are found most abundantly in animal products. Fortified foods and prenatal supplements are also an important source of folate, vitamin B12, and B6 for pregnant women. Deficiency of these nutrients is suggested to contribute to preeclampsia, preterm birth, birth defects, fetal growth retardation, and other adverse pregnancy outcomes, some of which can significantly affect the long-term health of mothers and their children. Clinicians who work with women of reproductive age should understand the role of these nutrients in fetal development and promote their greater intake to optimize pregnancy outcomes.

Keywords

Folate Choline Vitamin B12 Vitamin B6 Pregnancy 

References

  1. 1.
    Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004;62(6 Pt 2):S3–12. Discussion S3.CrossRefGoogle Scholar
  2. 2.
    Rosenberg IH. A history of the isolation and identification of folic acid (folate). Ann Nutr Metab. 2012;61(3):231–5.  https://doi.org/10.1159/000343112.CrossRefPubMedGoogle Scholar
  3. 3.
    Shane B. Folate chemistry and metabolism. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 1–24.Google Scholar
  4. 4.
    Solanky N, Requena Jimenez A, D’Souza SW, Sibley CP, Glazier JD. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta. 2010;31(2):134–43.  https://doi.org/10.1016/j.placenta.2009.11.017.CrossRefPubMedGoogle Scholar
  5. 5.
    Caudill MA, Miller JW, Gregory JF III, Shane B. Folate, choline, vitamin B and vitamin B. In: Stipanuk MH, Caudill MA, editors. Biochemical, physiological, and molecular aspects of human nutrition. 3rd ed. St. Louis: Elsevier; 2013. p. 565–609.Google Scholar
  6. 6.
    Scott JM, Molloy AM. The discovery of vitamin B(12). Ann Nutr Metab. 2012;61(3):239–45.  https://doi.org/10.1159/000343114.CrossRefPubMedGoogle Scholar
  7. 7.
    Okuda K. Discovery of vitamin B12 in the liver and its absorption factor in the stomach: a historical review. J Gastroenterol Hepatol. 1999;14(4):301–8.CrossRefGoogle Scholar
  8. 8.
    Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95(5):1002–7.  https://doi.org/10.1016/j.biochi.2012.11.004.CrossRefPubMedGoogle Scholar
  9. 9.
    Molloy AM. Folate-vitamin B12 interrelationships. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 381–408.Google Scholar
  10. 10.
    Rosenberg IH. A history of the isolation and identification of vitamin B(6). Ann Nutr Metab. 2012;61(3):236–8.  https://doi.org/10.1159/000343113.CrossRefPubMedGoogle Scholar
  11. 11.
    Gregory JF III. Bioavailability of vitamin B-6. Eur J Clin Nutr. 1997;51(Suppl 1):S43–8.Google Scholar
  12. 12.
    Percudani R, Peracchi A. A genomic overview of pyridoxal-phosphate-dependent enzymes. EMBO Rep. 2003;4(9):850–4.  https://doi.org/10.1038/sj.embor.embor914.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Finkelstein JD. Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine. Clin Chem Lab Med. 2007;45(12):1694–9.  https://doi.org/10.1515/CCLM.2007.341.CrossRefPubMedGoogle Scholar
  14. 14.
    Leklem JE. Vitamin B6. Handbook of vitamins, vol. 3. 3rd ed. New York: Marcel Dekker; 2001. p. 339–96.Google Scholar
  15. 15.
    Zeisel SH. A brief history of choline. Ann Nutr Metab. 2012;61(3):254–8.  https://doi.org/10.1159/000343120.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5(7):2093–8.CrossRefGoogle Scholar
  17. 17.
    Institute of Medicine. Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington DC: National Academies Press; 1998.Google Scholar
  18. 18.
    Jiang X, Jones S, Andrew BY, Ganti A, Malysheva OV, Giallourou N, et al. Choline inadequacy impairs trophoblast function and vascularization in cultured human placental trophoblasts. J Cell Physiol. 2014;229(8):1016–27.  https://doi.org/10.1002/jcp.24526.CrossRefPubMedGoogle Scholar
  19. 19.
    Zeisel SH, Blusztajn JK. Choline and human nutrition. Annu Rev Nutr. 1994;14:269–96.CrossRefGoogle Scholar
  20. 20.
    Resseguie M, Song J, Niculescu MD, da Costa KA, Randall TA, Zeisel SH. Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes. FASEB J. 2007;21(10):2622–32.CrossRefGoogle Scholar
  21. 21.
    DeLong CJ, Shen YJ, Thomas MJ, Cui Z. Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. J Biol Chem. 1999;274(42):29683–8.CrossRefGoogle Scholar
  22. 22.
    Wessler I, Kilbinger H, Bittinger F, Unger R, Kirkpatrick CJ. The non-neuronal cholinergic system in humans: expression, function and pathophysiology. Life Sci. 2003;72(18–19):2055–61.CrossRefGoogle Scholar
  23. 23.
    Sastry BV. Human placental cholinergic system. Biochem Pharmacol. 1997;53(11):1577–86.CrossRefGoogle Scholar
  24. 24.
    King RG, Gude NM, Krishna BR, Chen S, Brennecke SP, Boura AL, et al. Human placental acetylcholine. Reprod Fertil Dev. 1991;3(4):405–11.CrossRefGoogle Scholar
  25. 25.
    Tamura T, Picciano MF, McGuire MK. Folate in pregnancy and lactation. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 111–31.Google Scholar
  26. 26.
    Stabler SP. Clinical folate deficiency. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 409–28.Google Scholar
  27. 27.
    Christensen KE, Rozen R. Genetic variation: effect on folate metabolism and health. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 75–110.Google Scholar
  28. 28.
    Bailey RL, Dodd KW, Gahche JJ, Dwyer JT, McDowell MA, Yetley EA, et al. Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-2006. Am J Clin Nutr. 2010;91(1):231–7.  https://doi.org/10.3945/ajcn.2009.28427.CrossRefPubMedGoogle Scholar
  29. 29.
    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(4):789–800.  https://doi.org/10.3945/ajcn.112.037523.CrossRefPubMedGoogle Scholar
  30. 30.
    Kauwell GPA, Diaz ML, Yang Q, Bailey LB. Folate: recommended intakes, consumption, and status. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 467–90.Google Scholar
  31. 31.
    Goodnight W, Newman R. Society of Maternal-Fetal M. Optimal nutrition for improved twin pregnancy outcome. Obstet Gynecol. 2009;114(5):1121–34.  https://doi.org/10.1097/AOG.0b013e3181bb14c8.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Christensen KE, Mikael LG, Leung KY, Levesque N, Deng L, Wu Q, et al. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr. 2015;101(3):646–58.  https://doi.org/10.3945/ajcn.114.086603.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    McNulty H, Pentieva K. Folate Bioavailability. In: Bailey LB, editor. Folate in health and disease. 2nd ed. Boca Raton, FL: CRC Press; 2009. p. 25–47.Google Scholar
  34. 34.
    Centers for Disease Control. Folic acid: recommendations. centers for disease control. 2015. Available at: http://www.cdc.gov/ncbddd/folicacid/recommendations.html. Accessed 21 Feb 2016.
  35. 35.
    Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011;94(1):348S–58S.  https://doi.org/10.3945/ajcn.111.013441.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Green R, Miller JW. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population. Clin Chem Lab Med. 2005;43(10):1048–51.  https://doi.org/10.1515/CCLM.2005.183.CrossRefPubMedGoogle Scholar
  37. 37.
    Bae S, West AA, Yan J, Jiang X, Perry CA, Malysheva O, et al. Vitamin B-12 status differs among pregnant, lactating, and control women with equivalent nutrient intakes. J Nutr. 2015;145(7):1507–14.  https://doi.org/10.3945/jn.115.210757.CrossRefPubMedGoogle Scholar
  38. 38.
    Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110–7.  https://doi.org/10.1111/nure.12001.CrossRefPubMedGoogle Scholar
  39. 39.
    Scott JM. Bioavailability of vitamin B12. Eur J Clin Nutr. 1997;51(Suppl 1):S49–53.PubMedGoogle Scholar
  40. 40.
    Ueland PM, Ulvik A, Rios-Avila L, Midttun O, Gregory JF III. Direct and functional biomarkers of vitamin B6 status. Annu Rev Nutr. 2015;35:33–70.  https://doi.org/10.1146/annurev-nutr-071714-034330.CrossRefGoogle Scholar
  41. 41.
    Leklem JE. Vitamin B6. In: Machlin LJ, editor. Handbook of vitamins. New York: Marcel Decker Inc; 1991. p. 341–78.Google Scholar
  42. 42.
    Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5′-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr. 2008;87(5):1446–54.CrossRefGoogle Scholar
  43. 43.
    Welsch F. Choline metabolism in human term placenta—studies on de novo synthesis and the effects of some drugs on the metabolic fate of [N-methyl 3H]choline. Biochem Pharmacol. 1978;27(8):1251–7.CrossRefGoogle Scholar
  44. 44.
    Garner SC, Chou SC, Mar MH, Coleman RA, Zeisel SH. Characterization of choline metabolism and secretion by human placental trophoblasts in culture. Biochim Biophys Acta. 1993;1168(3):358–64.CrossRefGoogle Scholar
  45. 45.
    Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, et al. Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr. 2012;95(5):1060–71.CrossRefGoogle Scholar
  46. 46.
    Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Brenna JT, et al. Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women. Am J Clin Nutr. 2013;98(6):1459–67.CrossRefGoogle Scholar
  47. 47.
    Jiang X, Bar HY, Yan J, Jones S, Brannon PM, West AA, et al. A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1). FASEB J. 2013;27(3):1245–53.  https://doi.org/10.1096/fj.12-221648.CrossRefPubMedGoogle Scholar
  48. 48.
    Jiang X, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, et al. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 2012;26(8):3563–74.CrossRefGoogle Scholar
  49. 49.
    Weisberg IS, Jacques PF, Selhub J, Bostom AG, Chen Z, Curtis Ellison R, et al. The 1298A→C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis. 2001;156(2):409–15.CrossRefGoogle Scholar
  50. 50.
    Guinotte CL, Burns MG, Axume JA, Hata H, Urrutia TF, Alamilla A, et al. Methylenetetrahydrofolate reductase 677C→T variant modulates folate status response to controlled folate intakes in young women. J Nutr. 2003;133(5):1272–80.CrossRefGoogle Scholar
  51. 51.
    Solis C, Veenema K, Ivanov AA, Tran S, Li R, Wang W, et al. Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype. J Nutr. 2008;138(1):67–72.CrossRefGoogle Scholar
  52. 52.
    Kosmas IP, Tatsioni A, Ioannidis JP. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J Hypertens. 2004;22(9):1655–62.CrossRefGoogle Scholar
  53. 53.
    Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study. Am J Med. 2004;117(1):26–31.  https://doi.org/10.1016/j.amjmed.2004.01.019.CrossRefPubMedGoogle Scholar
  54. 54.
    Candito M, Rivet R, Herbeth B, Boisson C, Rudigoz RC, Luton D, et al. Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study. Am J Med Genet A. 2008;146A(9):1128–33.  https://doi.org/10.1002/ajmg.a.32199.CrossRefPubMedGoogle Scholar
  55. 55.
    Furness DL, Fenech MF, Khong YT, Romero R, Dekker GA. One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. Am J Obstet Gynecol. 2008;199(3):276.e1–8.  https://doi.org/10.1016/j.ajog.2008.06.020.CrossRefGoogle Scholar
  56. 56.
    Wang BJ, Liu MJ, Wang Y, Dai JR, Tao JY, Wang SN, et al. Association between SNPs in genes involved in folate metabolism and preterm birth risk. Genet Mol Res. 2015;14(1):850–9.  https://doi.org/10.4238/2015.February.2.9.CrossRefPubMedGoogle Scholar
  57. 57.
    Hazra A, Kraft P, Selhub J, Giovannucci EL, Thomas G, Hoover RN, et al. Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat Genet. 2008;40(10):1160–2.  https://doi.org/10.1038/ng.210.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical chemistry tests during normal pregnancy. BJOG. 2008;115(7):874–81.  https://doi.org/10.1111/j.1471-0528.2008.01709.x.CrossRefGoogle Scholar
  59. 59.
    Carter TC, Pangilinan F, Molloy AM, Fan R, Wang Y, Shane B, et al. Common variants at putative regulatory sites of the tissue nonspecific alkaline phosphatase gene influence circulating pyridoxal 5′-phosphate concentration in healthy adults. J Nutr. 2015;145(7):1386–93.  https://doi.org/10.3945/jn.114.208769.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006;20(9):1336–44.CrossRefGoogle Scholar
  61. 61.
    Lee NY, Choi HM, Kang YS. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT. Placenta. 2009;30(4):368–74.CrossRefGoogle Scholar
  62. 62.
    da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J. 2014;28(7):2970–8.CrossRefGoogle Scholar
  63. 63.
    Ganz AB, Shields K, Fomin VG, Lopez YS, Mohan S, Lovesky J, et al. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. FASEB J. 2016;30(10):3321–33.CrossRefGoogle Scholar
  64. 64.
    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 small-for-gestational age infants in South Indian women: a prospective observational cohort study. Am J Clin Nutr. 2013;98(6):1450–8.  https://doi.org/10.3945/ajcn.112.056382.CrossRefPubMedGoogle Scholar
  65. 65.
    Jacques PF, Kalmbach R, Bagley PJ, Russo GT, Rogers G, Wilson PW, et al. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr. 2002;132(2):283–8.CrossRefGoogle Scholar
  66. 66.
    Hansen CM, Shultz TD, Kwak HK, Memon HS, Leklem JE. Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance. J Nutr. 2001;131(6):1777–86.CrossRefGoogle Scholar
  67. 67.
    Kim YI, Miller JW, da Costa KA, Nadeau M, Smith D, Selhub J, et al. Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver. J Nutr. 1994;124(11):2197–203.CrossRefGoogle Scholar
  68. 68.
    Jacob RA, Jenden DJ, Allman-Farinelli MA, Swendseid ME. Folate nutriture alters choline status of women and men fed low choline diets. J Nutr. 1999;129(3):712–7.CrossRefGoogle Scholar
  69. 69.
    Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, et al. Homocysteine-betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency. FASEB J. 2003;17(3):512–4.  https://doi.org/10.1096/fj.02-0456fje.CrossRefPubMedGoogle Scholar
  70. 70.
    Abratte CM, Wang W, Li R, Moriarty DJ, Caudill MA. Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women. J Nutr Biochem. 2008;19(3):158–65.  https://doi.org/10.1016/j.jnutbio.2007.02.004.CrossRefPubMedGoogle Scholar
  71. 71.
    Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH. Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc Natl Acad Sci U S A. 2005;102(44):16025–30.CrossRefGoogle Scholar
  72. 72.
    Neural Tube Defect Ascertainment Project. National birth defects prevention network. 2013. Available at: http://www.nbdpn.org/docs/NTD_Fact_Sheet_11-13_for_website.pdf. Accessed 21 Feb 2016.
  73. 73.
    Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J Agric Food Chem. 2013;61(28):6769–75.  https://doi.org/10.1021/jf401545z.CrossRefPubMedGoogle Scholar
  74. 74.
    Schupbach R, Wegmuller R, Berguerand C, Bui M, Herter-Aeberli I. Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland. Eur J Nutr. 2017;56(1):283–93.  https://doi.org/10.1007/s00394-015-1079-7.CrossRefPubMedGoogle Scholar
  75. 75.
    Chester D, Goldman J, Ahuja J, Moshfegh A. Dietary intakes of choline. What we eat in America, NHANES 2007–2008. Agricultural Research Service, U.S. Department of Agriculture; 2011.Google Scholar
  76. 76.
    Jensen HH, Batres-Marquez SP, Carriquiry A, Schalinske KL. Choline in the diets of the US population: NHANES, 2003–2004. FASEB J. 2007;21:lb219.Google Scholar
  77. 77.
    Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr. 2006;83(4):905–11.CrossRefGoogle Scholar
  78. 78.
    Masih SP, Plumptre L, Ly A, Berger H, Lausman AY, Croxford R, et al. Pregnant Canadian women achieve recommended intakes of one-carbon nutrients through prenatal supplementation but the supplement composition, including choline, requires reconsideration. J Nutr. 2015;145(8):1824–34.  https://doi.org/10.3945/jn.115.211300.CrossRefPubMedGoogle Scholar
  79. 79.
    Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW, et al. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ. 2013;346:f3443.  https://doi.org/10.1136/bmj.f3443.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Odewole OA, Williamson RS, Zakai NA, Berry RJ, Judd SE, Qi YP, et al. Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: reasons for geographic and racial differences in stroke study 2003-2007. Am J Clin Nutr. 2013;98(4):1042–7.  https://doi.org/10.3945/ajcn.113.059683.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    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.  https://doi.org/10.1002/14651858.CD006896.pub2.
  82. 82.
    American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008;112(1):201–7.  https://doi.org/10.1097/AOG.0b013e3181809c0d.CrossRefGoogle Scholar
  83. 83.
    de Azevedo PA, Rondo PH, Guerra-Shinohara EM, Silva CS. The influence of iron, vitamin B(12), and folate levels on soluble transferrin receptor concentration in pregnant women. Clin Chim Acta. 2003;334(1–2):197–203.Google Scholar
  84. 84.
    Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–44.  https://doi.org/10.1016/S0140-6736(10)60279-6.CrossRefPubMedGoogle Scholar
  85. 85.
    Redman CW, Sargent IL, Staff AC. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia? Placenta. 2014;35(Suppl):S20–5.  https://doi.org/10.1016/j.placenta.2013.12.008.CrossRefPubMedGoogle Scholar
  86. 86.
    Lee G, Tubby J. Preeclampsia and the risk of cardiovascular disease later in life - a review of the evidence. Midwifery. 2015;31(12):1127–34.  https://doi.org/10.1016/j.midw.2015.09.005.CrossRefPubMedGoogle Scholar
  87. 87.
    Paauw ND, Luijken K, Franx A, Verhaar MC, Lely AT. Long-term renal and cardiovascular risk after preeclampsia: towards screening and prevention. Clin Sci (Lond). 2016;130(4):239–46.  https://doi.org/10.1042/CS20150567.CrossRefGoogle Scholar
  88. 88.
    Dhobale M, Chavan P, Kulkarni A, Mehendale S, Pisal H, Joshi S. Reduced folate, increased vitamin B(12) and homocysteine concentrations in women delivering preterm. Ann Nutr Metab. 2012;61(1):7–14.  https://doi.org/10.1159/000338473.CrossRefPubMedGoogle Scholar
  89. 89.
    Bergen NE, Jaddoe VW, Timmermans S, Hofman A, Lindemans J, Russcher H, et al. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG. 2012;119(6):739–51.  https://doi.org/10.1111/j.1471-0528.2012.03321.x.CrossRefPubMedGoogle Scholar
  90. 90.
    Martinussen MP, Bracken MB, Triche EW, Jacobsen GW, Risnes KR. Folic acid supplementation in early pregnancy and the risk of preeclampsia, small for gestational age offspring and preterm delivery. Eur J Obstet Gynecol Reprod Biol. 2015;195:94–9.  https://doi.org/10.1016/j.ejogrb.2015.09.022.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Kim MW, Ahn KH, Ryu KJ, Hong SC, Lee JS, Nava-Ocampo AA, et al. Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes. PLoS One. 2014;9(5):e97273.  https://doi.org/10.1371/journal.pone.0097273.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Singh MD, Thomas P, Owens J, Hague W, Fenech M. Potential role of folate in pre-eclampsia. Nutr Rev. 2015;73(10):694–722.  https://doi.org/10.1093/nutrit/nuv028.CrossRefPubMedGoogle Scholar
  93. 93.
    Wen SW, Champagne J, Rennicks White R, Coyle D, Fraser W, Smith G, et al. Effect of folic acid supplementation in pregnancy on preeclampsia: the folic acid clinical trial study. J Pregnancy. 2013;2013:294312.  https://doi.org/10.1155/2013/294312.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Ottawa Hospital Research Institute. Canadian Institutes of Health Research. High dose folic acid supplementation throughout pregnancy for preeclampsia prevention (FACT). Bethesda, MD: ClinicalTrials.gov; 2000. Available at: https://www.clinicaltrials.gov/ct2/show/study/NCT01355159. Accessed 21 Feb 2016.
  95. 95.
    Salam RA, Zuberi NF, Bhutta ZA. Pyridoxine (vitamin B6) supplementation during pregnancy or labour for maternal and neonatal outcomes. Cochrane Database Syst Rev. 2015;6:CD000179.  https://doi.org/10.1002/14651858.CD000179.pub3.CrossRefGoogle Scholar
  96. 96.
    Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA. Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res. 2005;57(5 Pt 2):1R–7R.  https://doi.org/10.1203/01.PDR.0000159567.85157.B7.CrossRefPubMedGoogle Scholar
  97. 97.
    Kwan ST, King JH, Yan J, Jiang X, Wei E, Fomin VG, et al. Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner. Placenta. 2017;53:57–65.  https://doi.org/10.1016/j.placenta.2017.03.019CrossRefGoogle Scholar
  98. 98.
    Chen LW, Lim AL, Colega M, Tint MT, Aris IM, Tan CS, et al. Maternal folate status, but not that of vitamins B-12 or B-6, is associated with gestational age and preterm birth risk in a multiethnic Asian population. J Nutr. 2015;145(1):113–20.  https://doi.org/10.3945/jn.114.196352.CrossRefPubMedGoogle Scholar
  99. 99.
    Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, et al. Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol. 2007;166(3):304–12.  https://doi.org/10.1093/aje/kwm078.CrossRefPubMedGoogle Scholar
  100. 100.
    Gaskins AJ, Rich-Edwards JW, Hauser R, Williams PL, Gillman MW, Ginsburg ES, et al. Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth. Obstet Gynecol. 2014;124(1):23–31.  https://doi.org/10.1097/AOG.0000000000000343.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GD, et al. Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study. PLoS Med. 2009;6(5):e1000061.  https://doi.org/10.1371/journal.pmed.1000061.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Rumbold A, Middleton P, Pan N, Crowther CA. Vitamin supplementation for preventing miscarriage. Cochrane Database Syst Rev. 2011;1:CD004073.  https://doi.org/10.1002/14651858.CD004073.pub3.CrossRefGoogle Scholar
  103. 103.
    Gaskins AJ, Chiu YH, Williams PL, Ford JB, Toth TL, Hauser R, et al. Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies. Am J Clin Nutr. 2015;102(4):943–50.  https://doi.org/10.3945/ajcn.115.112185.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Rowland AS, Baird DD, Shore DL, Weinberg CR, Savitz DA, Wilcox AJ. Nitrous oxide and spontaneous abortion in female dental assistants. Am J Epidemiol. 1995;141(6):531–8.CrossRefGoogle Scholar
  105. 105.
    Willis RS, Winn WW, Morris AT, Newson AA, Massey WE. Clinical observations in treatment of nausea and vomiting in pregnancy with vitamins B1 and B6. Am J Obstet Gynecol. 1942;44(2):265–71.  https://doi.org/10.5555/uri:pii:S0002937842905982.CrossRefGoogle Scholar
  106. 106.
    Maltepe C, Koren G. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum—a 2013 update. J Popul Ther Clin Pharmacol. 2013;20(2):e184–92.Google Scholar
  107. 107.
    Matok I, Clark S, Caritis S, Miodovnik M, Umans JG, Hankins G, et al. Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs. J Clin Pharmacol. 2014;54(12):1429–33.  https://doi.org/10.1002/jcph.369.CrossRefPubMedGoogle Scholar
  108. 108.
    Matthews A, Haas DM, O’Mathuna DP, Dowswell T. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;9:CD007575.  https://doi.org/10.1002/14651858.CD007575.pub4.CrossRefGoogle Scholar
  109. 109.
    Shaw GM, Carmichael SL, Nelson V, Selvin S, Schaffer DM. Occurrence of low birthweight and preterm delivery among California infants before and after compulsory food fortification with folic acid. Public Health Rep. 2004;119(2):170–3.CrossRefGoogle Scholar
  110. 110.
    Halicioglu O, Sutcuoglu S, Koc F, Ozturk C, Albudak E, Colak A, et al. Vitamin B12 and folate statuses are associated with diet in pregnant women, but not with anthropometric measurements in term newborns. J Matern Fetal Neonatal Med. 2012;25(9):1618–21.  https://doi.org/10.3109/14767058.2011.648244.CrossRefPubMedGoogle Scholar
  111. 111.
    Muthayya S, Kurpad AV, Duggan CP, Bosch RJ, Dwarkanath P, Mhaskar A, et al. Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians. Eur J Clin Nutr. 2006;60(6):791–801.  https://doi.org/10.1038/sj.ejcn.1602383.CrossRefPubMedGoogle Scholar
  112. 112.
    Yajnik CS, Deshpande SS, Panchanadikar AV, Naik SS, Deshpande JA, Coyaji KJ, et al. Maternal total homocysteine concentration and neonatal size in India. Asia Pac J Clin Nutr. 2005;14(2):179–81.PubMedGoogle Scholar
  113. 113.
    Chang SJ. Adequacy of maternal pyridoxine supplementation during pregnancy in relation to the vitamin B6 status and growth of neonates at birth. J Nutr Sci Vitaminol. 1999;45(4):449–58.CrossRefGoogle Scholar
  114. 114.
    Schuster K, Bailey LB, Mahan CS. Vitamin B6 status of low-income adolescent and adult pregnant women and the condition of their infants at birth. Am J Clin Nutr. 1981;34(9):1731–5.CrossRefGoogle Scholar
  115. 115.
    Leermakers ET, Moreira EM, Kiefte-de Jong JC, Darweesh SK, Visser T, Voortman T, et al. Effects of choline on health across the life course: a systematic review. Nutr Rev. 2015;73(8):500–22.  https://doi.org/10.1093/nutrit/nuv010.CrossRefPubMedGoogle Scholar
  116. 116.
    Van den Veyver IB. Genetic effects of methylation diets. Annu Rev Nutr. 2002;22:255–82.  https://doi.org/10.1146/annurev.nutr.22.010402.102932.CrossRefPubMedGoogle Scholar
  117. 117.
    Relton CL, Wilding CS, Laffling AJ, Jonas PA, Burgess T, Binks K, et al. Low erythrocyte folate status and polymorphic variation in folate-related genes are associated with risk of neural tube defect pregnancy. Mol Genet Metab. 2004;81(4):273–81.  https://doi.org/10.1016/j.ymgme.2003.12.010.CrossRefPubMedGoogle Scholar
  118. 118.
    Suarez L, Hendricks K, Felkner M, Gunter E. Maternal serum B12 levels and risk for neural tube defects in a Texas-Mexico border population. Ann Epidemiol. 2003;13(2):81–8.CrossRefGoogle Scholar
  119. 119.
    Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004;160(2):102–9.CrossRefGoogle Scholar
  120. 120.
    Itikala PR, Watkins ML, Mulinare J, Moore CA, Liu Y. Maternal multivitamin use and orofacial clefts in offspring. Teratology. 2001;63(2):79–86.  https://doi.org/10.1002/1096-9926(200102)63:2<79::aid-tera1013>3.0.co;2-3.CrossRefPubMedGoogle Scholar
  121. 121.
    Hayes C, Werler MM, Willett WC, Mitchell AA. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol. 1996;143(12):1229–34.CrossRefGoogle Scholar
  122. 122.
    van Rooij IA, Swinkels DW, Blom HJ, Merkus HM, Steegers-Theunissen RP. Vitamin and homocysteine status of mothers and infants and the risk of nonsyndromic orofacial clefts. Am J Obstet Gynecol. 2003;189(4):1155–60.CrossRefGoogle Scholar
  123. 123.
    Mills JL, Kirke PN, Molloy AM, Burke H, Conley MR, Lee YJ, et al. Methylenetetrahydrofolate reductase thermolabile variant and oral clefts. Am J Med Genet. 1999;86(1):71–4.CrossRefGoogle Scholar
  124. 124.
    Shaw GM, Rozen R, Finnell RH, Todoroff K, Lammer EJ. Infant C677T mutation in MTHFR, maternal periconceptional vitamin use, and cleft lip. Am J Med Genet. 1998;80(3):196–8.CrossRefGoogle Scholar
  125. 125.
    Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet. 1996;62(2):179–83.  https://doi.org/10.1002/(sici)1096-8628(19960315)62:2<179::aid-ajmg12>3.0.co;2-l.CrossRefPubMedGoogle Scholar
  126. 126.
    Chan J, Deng L, Mikael LG, Yan J, Pickell L, Wu Q, et al. Low dietary choline and low dietary riboflavin during pregnancy influence reproductive outcomes and heart development in mice. Am J Clin Nutr. 2010;91(4):1035–43.  https://doi.org/10.3945/ajcn.2009.28754.CrossRefPubMedGoogle Scholar
  127. 127.
    Shaw GM, Yang W, Carmichael SL, Vollset SE, Hobbs CA, Lammer EJ, et al. One-carbon metabolite levels in mid-pregnancy and risks of conotruncal heart defects. Birth Defects Res A Clin Mol Teratol. 2014;100(2):107–15.  https://doi.org/10.1002/bdra.23224.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet. 2000;67(3):623–30.  https://doi.org/10.1086/303055.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Moon J, Chen M, Gandhy SU, Strawderman M, Levitsky DA, Maclean KN, et al. Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome. Behav Neurosci. 2010;124(3):346–61.CrossRefGoogle Scholar
  130. 130.
    Velazquez R, Ash JA, Powers BE, Kelley CM, Strawderman M, Luscher ZI, et al. Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis. 2013;58:92–101.CrossRefGoogle Scholar
  131. 131.
    Pu D, Shen Y, Wu J. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res. 2013;6(5):384–92.  https://doi.org/10.1002/aur.1300.CrossRefPubMedGoogle Scholar
  132. 132.
    Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, et al. 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(1):80–9.  https://doi.org/10.3945/ajcn.110.004416.CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Suren P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013;309(6):570–7.  https://doi.org/10.1001/jama.2012.155925.CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Langley EA, Krykbaeva M, Blusztajn JK, Mellott TJ. High maternal choline consumption during pregnancy and nursing alleviates deficits in social interaction and improves anxiety-like behaviors in the BTBR T+Itpr3tf/J mouse model of autism. Behav Brain Res. 2015;278:210–20.  https://doi.org/10.1016/j.bbr.2014.09.043.CrossRefPubMedGoogle Scholar
  135. 135.
    Thomas JD, Abou EJ, Dominguez HD. Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats. Neurotoxicol Teratol. 2009;31(5):303–11.CrossRefGoogle Scholar
  136. 136.
    Xu Y, Tang Y, Li Y. Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice. Br J Nutr. 2008;99(3):455–61.  https://doi.org/10.1017/s0007114507812074.CrossRefPubMedGoogle Scholar
  137. 137.
    Albright CD, Friedrich CB, Brown EC, Mar MH, Zeisel SH. Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum. Brain Res Dev Brain Res. 1999;115(2):123–9.CrossRefGoogle Scholar
  138. 138.
    Albright CD, Tsai AY, Friedrich CB, Mar MH, Zeisel SH. Choline availability alters embryonic development of the hippocampus and septum in the rat. Brain Res Dev Brain Res. 1999;113(1–2):13–20.CrossRefGoogle Scholar
  139. 139.
    Gueant JL, Namour F, Gueant-Rodriguez RM, Daval JL. Folate and fetal programming: a play in epigenomics? Trends Endocrinol Metab. 2013;24(6):279–89.  https://doi.org/10.1016/j.tem.2013.01.010.CrossRefPubMedGoogle Scholar
  140. 140.
    Blusztajn JK, Mellott TJ. Neuroprotective actions of perinatal choline nutrition. Clin Chem Lab Med. 2013;51(3):591–9.CrossRefGoogle Scholar
  141. 141.
    Nilsson TK, Yngve A, Bottiger AK, Hurtig-Wennlof A, Sjostrom M. High folate intake is related to better academic achievement in Swedish adolescents. Pediatrics. 2011;128(2):e358–65.  https://doi.org/10.1542/peds.2010-1481.CrossRefPubMedGoogle Scholar
  142. 142.
    Nguyen CT, Gracely EJ, Lee BK. Serum folate but not vitamin B-12 concentrations are positively associated with cognitive test scores in children aged 6-16 years. J Nutr. 2013;143(4):500–4.  https://doi.org/10.3945/jn.112.166165.CrossRefPubMedGoogle Scholar
  143. 143.
    Villamor E, Rifas-Shiman SL, Gillman MW, Oken E. Maternal intake of methyl-donor nutrients and child cognition at 3 years of age. Paediatr Perinat Epidemiol. 2012;26(4):328–35.  https://doi.org/10.1111/j.1365-3016.2012.01264.x.CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Gewa CA, Weiss RE, Bwibo NO, Whaley S, Sigman M, Murphy SP, et al. Dietary micronutrients are associated with higher cognitive function gains among primary school children in rural Kenya. Br J Nutr. 2009;101(9):1378–87.  https://doi.org/10.1017/s0007114508066804.CrossRefPubMedGoogle Scholar
  145. 145.
    Boeke CE, Gillman MW, Hughes MD, Rifas-Shiman SL, Villamor E, Oken E. Choline intake during pregnancy and child cognition at age 7 years. Am J Epidemiol. 2013;177(12):1338–47.  https://doi.org/10.1093/aje/kws395.CrossRefPubMedGoogle Scholar
  146. 146.
    Wu BT, Dyer RA, King DJ, Richardson KJ, Innis SM. Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS One. 2012;7(8):e43448.  https://doi.org/10.1371/journal.pone.0043448.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Cheatham CL, Goldman BD, Fischer LM, da Costa KA, Reznick JS, Zeisel SH. Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012;96(6):1465–72.  https://doi.org/10.3945/ajcn.112.037184.CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Maloney CA, Hay SM, Young LE, Sinclair KD, Rees WD. A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. J Nutr. 2011;141(1):95–100.  https://doi.org/10.3945/jn.109.119453.CrossRefPubMedGoogle Scholar
  149. 149.
    Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao S, Fisher DJ, et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia. 2008;51(1):29–38.  https://doi.org/10.1007/s00125-007-0793-y.CrossRefPubMedGoogle Scholar
  150. 150.
    Schulz KM, Pearson JN, Gasparrini ME, Brooks KF, Drake-Frazier C, Zajkowski ME, et al. Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors. Behav Brain Res. 2014;268:104–10.  https://doi.org/10.1016/j.bbr.2014.03.031.CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Kovacheva VP, Davison JM, Mellott TJ, Rogers AE, Yang S, O’Brien MJ, et al. Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival. FASEB J. 2009;23(4):1054–63.CrossRefGoogle Scholar
  152. 152.
    Bai SY, Briggs DI, Vickers MH. Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation. J Dev Orig Health Dis. 2012;3(5):342–9.  https://doi.org/10.1017/s2040174412000256.CrossRefPubMedGoogle Scholar
  153. 153.
    Davison JM, Mellott TJ, Kovacheva VP, Blusztajn JK. Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain. J Biol Chem. 2009;284(4):1982–9.CrossRefGoogle Scholar
  154. 154.
    Schaible TD, Harris RA, Dowd SE, Smith CW, Kellermayer R. Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes. Hum Mol Genet. 2011;20(9):1687–96.  https://doi.org/10.1093/hmg/ddr044.CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, Tomfohr J, et al. In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest. 2008;118(10):3462–9.  https://doi.org/10.1172/JCI34378.CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Pannia E, Cho CE, Kubant R, Sanchez-Hernandez D, Huot PS, Harvey Anderson G. Role of maternal vitamins in programming health and chronic disease. Nutr Rev. 2016;74(3):166–80.  https://doi.org/10.1093/nutrit/nuv103.CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Kiefte-de Jong JC, Timmermans S, Jaddoe VW, Hofman A, Tiemeier H, Steegers EA, et al. 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(4):731–8.  https://doi.org/10.3945/jn.111.154948.CrossRefPubMedGoogle Scholar
  158. 158.
    Prescott SL, Clifton V. Asthma and pregnancy: emerging evidence of epigenetic interactions in utero. Curr Opin Allergy Clin Immunol. 2009;9(5):417–26.  https://doi.org/10.1097/ACI.0b013e328330634f.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Julia H. King
    • 1
  • Sze Ting (Cecilia) Kwan
    • 1
  • Marie A. Caudill
    • 1
  1. 1.Division of Nutritional SciencesCornell UniversityIthacaUSA

Personalised recommendations