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European Journal of Nutrition

, Volume 46, Issue 5, pp 300–306 | Cite as

Relationship between dietary folate intakes, maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan

  • Hidemi TakimotoEmail author
  • Natsuko Mito
  • Keizo Umegaki
  • Asako Ishiwaki
  • Kaoru Kusama
  • Shiro Abe
  • Machi Yamawaki
  • Hideoki Fukuoka
  • Chitaru Ohta
  • Nobuo Yoshiike
ORIGINAL CONTRIBUTION

Abstract

Background

Adequate folate status in pregnancy is important for satisfactory pregnancy outcome.

Aim of the Study

The objective of the present study was to evaluate folate status in healthy pregnant women by assessing dietary folate intakes and measuring changes in folate-related biomarkers including plasma tHcy, serum vitamin B12 (B12), and serum and RBC folate concentrations in each trimester and to examine their relation to fetal growth.

Methods

From 94 pregnant women, 3-day-dietary records were obtained and blood was collected for plasma total homocysteine (tHcy), serum B12, and serum and red-blood cell (RBC) folate measurements. Infant anthropometric measurements were made immediately after birth.

Results

Average folate intake was less than 300 µg/day with a mean energy intake of about 1800 kcal. Mean serum and RBC folate concentrations declined significantly during gestation (p < 0.05). Mean serum B12 also significantly decreased (p < 0.01), whereas plasma tHcy increased from 5.1 in the first trimester to 5.9 µmol/l in the third trimester (p < 0.01). Multiple regression analyses, after controlling for maternal age, parity and pre-pregnancy body-mass index indicated that a 1.0 µmol/l increase in plasma tHcy in the third trimester corresponded to a 151 g decrease in birth weight (p < 0.01). Neither B12 nor folate concentrations in all three trimesters showed any significant associations with birthweight. Plasma pyridoxal-5′-phosphate concentrations were markedly low, and were consistent with low intake of vitamin B6 in our population.

Conclusion

Our data suggest that higher plasma tHcy in the third trimester is a predictor of lower birth weight. In general, the dietary intake of B-vitamins and energy may be inadequate in our population, suggesting intervention is necessary.

Keywords

pregnancy folate homocysteine fetal growth neonatal anthropometric measures 

Notes

Acknowledgements

Sponsorship: This study was supported by the Ministry of Health, Labour, and Welfare, Health and Labour Research Grant, Research on Children and Families. We thank Ms. Yukari Tamagawa, Ms. Chiharu Ninakawa, and Ms. Soko Nakagami for checking and coding dietary data. There are no conflicts of interest regarding any of the authors. Authors’ contributions: HT was involved in planning and coordinating of the study, data collection and statistical analysis, and the writing of the paper. NM contributed to data collection and analysis of the overall study. KU was the supervisor and coordinator of all analyses. AI and KK were involved in data collection and analysis of dietary data. SA, MY, HF, and CO were responsible for selection of patients, and contributed to data collection. NY designed the study, and was the overall supervisor of the project.

References

  1. 1.
    Tamura T, Picciano M (2006) Folate and human reproduction. Am J Clin Nutr 83:993–1016Google Scholar
  2. 2.
    Ministry of Health: Department of Maternal and Child Health, Bureau of Children and Families (2000) Information on promoting intake of folic acid in order to reduce children afflicted with neural tube defects among young women who are capable of becoming pregnant. [Japanese]Google Scholar
  3. 3.
    Kondo A, Kamihira O, Shimosuka Y, Okai I, Gotoh M, Ozawa H (2005) Awareness of the role of folic acid, dietary folate intake and plasma folate concentration in Japan. J Obstet Gynaecol Res 31:172–177CrossRefGoogle Scholar
  4. 4.
    International Clearinghouse for Birth Defects Monitoring System (2002) Annual Report 2002 with Data for 2002. The International Centre for Birth Defects, RomeGoogle Scholar
  5. 5.
    Takimoto H, Tamura T (2006) Increasing trend of spina bifida and decreasing birth weight in relation to declining body-mass index of young women in Japan. Med Hypoth 67:1023–1026CrossRefGoogle Scholar
  6. 6.
    Takimoto H, Yokoyama T, Yoshiike N, Fukuoka H (2005) Increase in low-birth-weight infants in Japan and associated risk factors, 1980–2000. J Obstet Gynaecol Res 31:314–322CrossRefGoogle Scholar
  7. 7.
    Takimoto H, Yoshiike N, Kaneda F, Yoshita K (2004) Thinness among young Japanese women. Am J Public Health 94:1592–1595CrossRefGoogle Scholar
  8. 8.
    Murphy MM, Scott JM, Arija V, Molloy AM, Fernandez-Ballart JD (2004) Maternal homocysteine before conception and throughout pregnancy predicts fetal homocysteine and birth weight. Clin Chem 50:1406–1412CrossRefGoogle Scholar
  9. 9.
    Relton C, Pearce M, Parker L (2005) The influence of erythrocyte folate and serum vitamin B12 status on birth weight. Br J Nutr 93:593–599CrossRefGoogle Scholar
  10. 10.
    Tamura T, Goldenberg RL, Freeberg LE, Cliver S, Cutter GR, Hoffman HJ (1992) Maternal serum folate and zinc concentrations and their relationship to pregnancy outcome. Am J Clin Nutr 56:365–370Google Scholar
  11. 11.
    Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, Monsen AL, Ueland PM (2000) Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr 71:962–968Google Scholar
  12. 12.
    Mito N, Takimoto H, Umegaki K et al. (2006) Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester. Eur J Clin Nutr 61:83–90CrossRefGoogle Scholar
  13. 13.
    Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422:43–52CrossRefGoogle Scholar
  14. 14.
    Tamura T (1990) Microbiological assay of folates. In: Picciano M, Stokstad E, Gregory JI (eds) Folic acid metabolism in health and disease. Wiley-Liss, New York, pp 121–137Google Scholar
  15. 15.
    Resources Council of the Science and Technology Agency (2000) Standard tables of food composition in Japan. Fifth revision ed. Ministry of Finance Printing Bureau [Japanese], TokyoGoogle Scholar
  16. 16.
    Pagan K, Hou J, Goldenberg RL, Cliver S, Tamura T (2002) Mid-pregnancy serum homocysteine and B-vitamin concentrations and fetal growth. Nutr Res 22:1133–1141CrossRefGoogle Scholar
  17. 17.
    Schuster K, Bailey LB, Mahan CS (1984) Effect of maternal pyridoxine X HCl supplementation on the vitamin B-6 status of mother and infant and on pregnancy outcome. J Nutr 114:977–988Google Scholar
  18. 18.
    Steegers-Theunissen RP, Van Iersel CA, Peer PG, Nelen WL, Steegers EA (2004) Hyperhomocysteinemia, pregnancy complications, and the timing of investigation. Obstet Gynecol 104:336–343Google Scholar
  19. 19.
    Burke G, Robinson K, Refsum H, Stuart B, Drumm J, Graham I (1992) Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Eng J Med 326:69–70Google Scholar
  20. 20.
    Hogg BB, Tamura T, Johnston KE, Dubard MB, Goldenberg RL (2000) Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction. Am J Obstet Gynecol 183:805–809CrossRefGoogle Scholar
  21. 21.
    Infante-Rivard C, Rivard G-E, Gauthier R, Thort Y (2003) Unexpected relationship between plasma homocysteine and intrauterine growth restriction. Clin Chem 49:1476–1482CrossRefGoogle Scholar
  22. 22.
    Ronnenberg AG, Goldman MB, Chen D, Aitken IW, Willett WC, Selhub J, Xu X (2002) Preconception homocysteine and B vitamin status and birth outcomes in Chinese women. Am J Clin Nutr 76:1385–1391Google Scholar
  23. 23.
    Cikot R, Steegers-Theunissen R, Thomas C, de Boo T, Merkus H, Steegers E (2001) Longitudinal vitamin and homocysteine levels in normal pregnancy. Br J Nutr 85:49–58CrossRefGoogle Scholar
  24. 24.
    Kang S, Wong P, Zhou J, Cook H (1986) Total homocyst(e)ine in plasma and amniotic fluid of pregnant women. Metabolism 35:889–891CrossRefGoogle Scholar
  25. 25.
    Bruinse H, van der Berg H, Haspels A (1985) Maternal serum folacin levels during and after normal pregnancy. Eur J Obstet Gynecol Reprod Biol 20:153–158CrossRefGoogle Scholar
  26. 26.
    Pagan K, Hou J, Goldenberg RL, Cliver SP, Tamura T (2001) Effect of smoking on serum concentrations of total homocysteine and B vitamins in mid-pregnancy. Clin Chim Acta 306:103–109CrossRefGoogle Scholar
  27. 27.
    Tamura T, Goldenberg RL, Johnston KE, Cliver SP, Hoffman HJ (1997) Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome. Acta Obstet Gynecol Scand Suppl 165:63–70Google Scholar
  28. 28.
    Ek J (1982) Plasma and red cell folate in mothers and infants in normal pregnancies. Relation to birth weight. Acta Obstet Gynecol Scand 61:17–20CrossRefGoogle Scholar
  29. 29.
    Ministry of Health, Labour, & Welfare, Japan (2005) Dietary reference intakes for Japanese, 2005. Dai-ichi Shuppan, TokyoGoogle Scholar
  30. 30.
    Wilcox A (2001) On the importance- and the unimportance- of birthweight. Int J Epidemiol 30:1233–1241CrossRefGoogle Scholar
  31. 31.
    Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet 2:577–580CrossRefGoogle Scholar
  32. 32.
    Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ (1999) Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 318:427–431Google Scholar
  33. 33.
    Forsen T, Eriksson JG, Tuomilehto J, Osmond C, Barker DJ (1999) Growth in utero and during childhood among women who develop coronary heart disease: longitinal study. BMJ 319:1403–1407Google Scholar
  34. 34.
    Promotion Committee of the “Healthy Families (Sukoyaka Oyako) 21” Project (2006) Dietary guidelines for pregnant and lactating women. Ministry of Health, Labour, and Welfare. [Japanese], TokyoGoogle Scholar
  35. 35.
    Christian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, Adhikari RK, Sommer A, West KP Jr (2003) Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ 326:571CrossRefGoogle Scholar
  36. 36.
    Hininger I, Favier M, Arnaud J, Faure H, Thoulon JM, Hariveau E, Favier A, Roussel AM (2004) Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant women. Eur J Clin Nutr 58:52–59CrossRefGoogle Scholar

Copyright information

© Spinger 2007

Authors and Affiliations

  • Hidemi Takimoto
    • 1
    Email author
  • Natsuko Mito
    • 2
  • Keizo Umegaki
    • 2
  • Asako Ishiwaki
    • 3
  • Kaoru Kusama
    • 4
  • Shiro Abe
    • 5
  • Machi Yamawaki
    • 6
  • Hideoki Fukuoka
    • 7
  • Chitaru Ohta
    • 8
  • Nobuo Yoshiike
    • 2
  1. 1.Dept. of Health Promotion and ResearchNational Institute of Public HealthSaitamaJapan
  2. 2.National Institute of Health and NutritionTokyoJapan
  3. 3.Ochanomizu Women’s UniversityTokyoJapan
  4. 4.National Institute of Public HealthSaitamaJapan
  5. 5.Metropolitan Ohtsuka HospitalTokyoJapan
  6. 6.Matsushima Women’s ClinicTokyoJapan
  7. 7.Comprehensive Research Organization, Waseda UniversityTokyoJapan
  8. 8.Ohta HospitalTokyoJapan

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