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.
Similar content being viewed by others
References
Tamura T, Picciano M (2006) Folate and human reproduction. Am J Clin Nutr 83:993–1016
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]
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 31:172–177
International Clearinghouse for Birth Defects Monitoring System (2002) Annual Report 2002 with Data for 2002. The International Centre for Birth Defects, Rome
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 67:1023–1026
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 31:314–322
Takimoto H, Yoshiike N, Kaneda F, Yoshita K (2004) Thinness among young Japanese women. Am J Public Health 94:1592–1595
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 50:1406–1412
Relton C, Pearce M, Parker L (2005) The influence of erythrocyte folate and serum vitamin B12 status on birth weight. Br J Nutr 93:593–599
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 56:365–370
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 71:962–968
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 61:83–90
Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422:43–52
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 121–137
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], Tokyo
Pagan K, Hou J, Goldenberg RL, Cliver S, Tamura T (2002) Mid-pregnancy serum homocysteine and B-vitamin concentrations and fetal growth. Nutr Res 22:1133–1141
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 114:977–988
Steegers-Theunissen RP, Van Iersel CA, Peer PG, Nelen WL, Steegers EA (2004) Hyperhomocysteinemia, pregnancy complications, and the timing of investigation. Obstet Gynecol 104:336–343
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 326:69–70
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 183:805–809
Infante-Rivard C, Rivard G-E, Gauthier R, Thort Y (2003) Unexpected relationship between plasma homocysteine and intrauterine growth restriction. Clin Chem 49:1476–1482
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 76:1385–1391
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 85:49–58
Kang S, Wong P, Zhou J, Cook H (1986) Total homocyst(e)ine in plasma and amniotic fluid of pregnant women. Metabolism 35:889–891
Bruinse H, van der Berg H, Haspels A (1985) Maternal serum folacin levels during and after normal pregnancy. Eur J Obstet Gynecol Reprod Biol 20:153–158
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 306:103–109
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 165:63–70
Ek J (1982) Plasma and red cell folate in mothers and infants in normal pregnancies. Relation to birth weight. Acta Obstet Gynecol Scand 61:17–20
Ministry of Health, Labour, & Welfare, Japan (2005) Dietary reference intakes for Japanese, 2005. Dai-ichi Shuppan, Tokyo
Wilcox A (2001) On the importance- and the unimportance- of birthweight. Int J Epidemiol 30:1233–1241
Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet 2:577–580
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 318:427–431
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 319:1403–1407
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], Tokyo
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 326:571
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 58:52–59
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takimoto, H., Mito, N., Umegaki, K. et al. Relationship between dietary folate intakes, maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan. Eur J Nutr 46, 300–306 (2007). https://doi.org/10.1007/s00394-007-0667-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-007-0667-6