Abstract
Background/objectives:
A low folate or low thiamine status may be associated with the risk of preterm delivery, small for gestational age (SGA) offspring and adverse pregnancy outcomes.
Subjects/methods:
5-Methyltetrahydrofolate (5MTHF) and thiamine diphosphate (TDP) were measured directly in cord-blood erythrocytes (CBEs) of early preterm (n=26; <32 weeks gestational age; including 50% multiple births), late preterm (n=38; 32 to <37 weeks; including 24% multiple births) and term newborns (n=60, 37–42 weeks) via high-performance liquid chromatography and fluorescence detection. Associations between 5MTHF and TDP with gestational age, newborn anthropometrics (birth weight, newborn’s length and head circumference) and risk of being SGA were explored.
Results:
Group comparison as well as multivariate linear regression analysis of cord-blood vitamins revealed that 5MTHF was significantly lower in late preterms compared with terms but did not differ between singletons and multiples. TDP tended to be higher in preterms than in terms and lower in multiples than in singletons in both early and late preterms. Multivariate analysis on birth outcomes showed that 5MTHF was significantly positively associated with gestational age, birth weight and newborn’s length. 5MTHF, increasing gestational age and parity were associated with a significantly reduced risk for being SGA, while TDP, multiple births and gender were not associated with the risk for being SGA.
Conclusions:
Higher CBE concentrations of 5MTHF were associated with improved birth outcomes. Lower TDP concentrations were observed in multiple births. Future studies evaluating cord-blood vitamin concentrations and their associations with birth outcomes should additionally include dietary intakes and maternal blood concentrations at different stages of pregnancy.
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References
Crump C, Sundquist K, Sundquist J, Winkleby MA . Gestational age at birth and mortality in young adulthood. JAMA 2011; 306: 1233–1240.
Crump C, Winkleby MA, Sundquist K, Sundquist J . Risk of diabetes among young adults born preterm in Sweden. Diabetes Care 2011; 34: 1109–1113.
Boyle EM, Poulsen G, Field DJ, Kurinczuk JJ, Wolke D, Alfirevic Z et al. Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study. BMJ 2012; 344: e896.
Quigley MA, Poulsen G, Boyle E, Wolke D, Field D, Alfirevic Z et al. Early term and late preterm birth are associated with poorer school performance at age 5 years: a cohort study. Arch Dis Child Fetal Neonatal. Ed 2012; 97: F167–F173.
Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012; 379: 2162–2172.
Grosse SD, Collins JS . Folic acid supplementation and neural tube defect recurrence prevention. Birth Defects Res A Clin Mol Teratol 2007; 79: 737–742.
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; (10), CD007950.
Castillo-Lancellotti C, Tur JA, Uauy R . Impact of folic acid fortification of flour on neural tube defects: a systematic review—Corrigendum. Public Health Nutr 2013; 16: 1527.
Castillo-Lancellotti C, Tur JA, Uauy R . Impact of folic acid fortification of flour on neural tube defects: a systematic review. Public Health Nutr 2013; 16: 901–911.
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: 739–751.
Relton CL, Pearce MS, Parker L . The influence of erythrocyte folate and serum vitamin B12 status on birth weight. Br J Nutr 2005; 93: 593–599.
Scholl TO, Hediger ML, Schall JI, Khoo CS, Fischer RL . Dietary and serum folate: their influence on the outcome of pregnancy. Am J Clin Nutr 1996; 63: 520–525.
Bodnar LM, Himes KP, Venkataramanan R, Chen JY, Evans RW, Meyer JL et al. Maternal serum folate species in early pregnancy and risk of preterm birth. Am J Clin Nutr 2010; 92: 864–871.
Papadopoulou E, Stratakis N, Roumeliotaki T, Sarri K, Merlo DF, Kogevinas M et al. 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.
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: 7–14.
Tamura T, Goldenberg RL, Johnston KE, Cliver SP, Hoffman HJ . Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome. Acta Obstet Gynecol Scand Suppl 1997; 165: 63–70.
van Uitert EM, Steegers-Theunissen RP . Influence of maternal folate status on human fetal growth parameters. Mol Nutr Food Res 2013; 57: 582–595.
Tamura T, Picciano MF . Folate and human reproduction. Am J Clin Nutr 2006; 83: 993–1016.
Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA et al. 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.
Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP . The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update 2007; 13: 163–174.
Pynn CJ, Henderson NG, Clark H, Koster G, Bernhard W, Postle AD . Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo. J Lipid Res 2011; 52: 399–407.
Van den Veyver IB . Genetic effects of methylation diets. Annu Rev Nutr 2002; 22: 255–282.
Djukic A . Folate-responsive neurologic diseases. Pediatr Neurol 2007; 37: 387–397.
Baker H, Hockstein S, DeAngelis B, Holland BK . Thiamin status of gravidas treated for gestational diabetes mellitus compared to their neonates at parturition. Int J Vitam Nutr Res 2000; 70: 317–320.
Link G, Zempleni J, Bitsch I . The intrauterine turnover of thiamin in preterm and full-term infants. Int J Vitam Nutr Res 1998; 68: 242–248.
Baker H, Thind IS, Frank O, DeAngelis B, Caterini H, Louria DB . Vitamin levels in low-birth-weight newborn infants and their mothers. Am J Obstet Gynecol 1977; 129: 521–524.
Dutta B, Huang W, Molero M, Kekuda R, Leibach FH, Devoe LD et al. Cloning of the human thiamine transporter, a member of the folate transporter family. J Biol Chem 1999; 274: 31925–31929.
Cuco G, Fernandez-Ballart J, Arija V, Canals J . Effect of B1-, B6- and iron intake during pregnancy on neonatal behavior. Int J Vitam Nutr Res 2005; 75: 320–326.
Bailey LB . New standard for dietary folate intake in pregnant women. Am J Clin Nutr 2000; 71 (5 Suppl), 1304S–1307S.
Bernhard W, Full A, Arand J, Maas C, Poets CF, Franz AR . Choline supply of preterm infants: assessment of dietary intake and pathophysiological considerations. Eur J Nutr 2013; 52: 1269–1278.
Engle WA . A recommendation for the definition of "late preterm" (near-term) and the birth weight-gestational age classification system. Semin Perinatol 2006; 30: 2–7.
Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan MA . United States national reference for fetal growth. Obstet Gynecol 1996; 87: 163–168.
Leeming RJ, Pollock A, Melville LJ, Hamon CG . Measurement of 5-methyltetrahydrofolic acid in man by high-performance liquid chromatography. Metabolism 1990; 39: 902–904.
Stuetz W, Carrara VI, McGready R, Lee SJ, Biesalski HK, Nosten FH . Thiamine diphosphate in whole blood, thiamine and thiamine monophosphate in breast-milk in a refugee population. PLoS One 2012; 7: e36280.
Ek J, Magnus EM . Plasma and red blood cell folate in breastfed infants. Acta Paediatr Scand 1979; 68: 239–243.
Vanier TM, Tyas JF . Folic acid status in premature infants. Arch Dis Child 1967; 42: 57–61.
Hall MH, Pirani BB, Campbell D . The cause of the fall in serum folate in normal pregnancy. Br J Obstet Gynaecol 1976; 83: 132–136.
Navarro J, Causse MB, Desquilbet N, Herve F, Lallemand D . The vitamin status of low birth weight infants and their mothers. J Pediatr Gastroenterol Nutr 1984; 3: 744–748.
Brough L, Rees GA, Crawford MA, Morton RH, Dorman EK . Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population. Br J Nutr 2010; 104: 437–445.
de Weerd S, Steegers-Theunissen RP, de Boo TM, Thomas CM, Steegers EA . Maternal periconceptional biochemical and hematological parameters, vitamin profiles and pregnancy outcome. Eur J Clin Nutr 2003; 57: 1128–1134.
Hong J, Park EA, Kim YJ, Lee HY, Park BH, Ha EH et al. Association of antioxidant vitamins and oxidative stress levels in pregnancy with infant growth during the first year of life. Public Health Nutr 2008; 11: 998–1005.
Nilsen RM, Vollset SE, Monsen AL, Ulvik A, Haugen M, Meltzer HM et al. Infant birth size is not associated with maternal intake and status of folate during the second trimester in Norwegian pregnant women. J Nutr 2010; 140: 572–579.
Hogeveen M, Blom HJ, van der Heijden EH, Semmekrot BA, Sporken JM, Ueland PM et al. Maternal homocysteine and related B vitamins as risk factors for low birthweight. Am J Obstet Gynecol 2010; 202: 572–576.
Sanchez DJ, Murphy MM, Bosch-Sabater J, Fernandez-Ballart J . Enzymic evaluation of thiamin, riboflavin and pyridoxine status of parturient mothers and their newborn infants in a Mediterranean area of Spain. Eur J Clin Nutr 1999; 53: 27–38.
Heinze T, Weber W . Determination of thiamine (vitamin B1) in maternal blood during normal pregnancies and pregnancies with intrauterine growth retardation. Z Ernahrungswiss 1990; 29: 39–46.
Shinagawa S, Suzuki S, Chihara H, Otsubo Y, Takeshita T, Araki T . Maternal basal metabolic rate in twin pregnancy. Gynecol Obstet Invest 2005; 60: 145–148.
Baker H, DeAngelis B, Holland B, Gittens-Williams L, Barrett T Jr . Vitamin profile of 563 gravidas during trimesters of pregnancy. J Am Coll Nutr 2002; 21: 33–37.
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press: Washington, D.C. USA, 1998.
Campbell MK, Cartier S, Xie B, Kouniakis G, Huang W, Han V . Determinants of small for gestational age birth at term. Paediatr Perinat Epidemiol 2012; 26: 525–533.
Shipton D, Tappin DM, Vadiveloo T, Crossley JA, Aitken DA, Chalmers J . Reliability of self reported smoking status by pregnant women for estimating smoking prevalence: a retrospective, cross sectional study. BMJ 2009; 339: b4347.
Acknowledgements
This study was supported by an institutional grant (project no. E1100008) from the joint Center for Nutritional Medicine (Zentrum für Ernaehrungsmedizin, ZEM) of the University of Hohenheim and the University of Tuebingen, Germany. The project with the working title ‘Deficiency of choline and methylene donors in preterm newborns’ (W. Bernhard/N. Breusing) was approved for the 2009/2010 research period under the subject ‘Malnutrition/Clinical nutrition’. We thank Franziska Goepke for the measurement of TDP.
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Weber, D., Stuetz, W., Bernhard, W. et al. 5-Methyltetrahydrofolate and thiamine diphosphate in cord-blood erythrocytes of preterm versus term newborns. Eur J Clin Nutr 67, 1029–1035 (2013). https://doi.org/10.1038/ejcn.2013.158
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DOI: https://doi.org/10.1038/ejcn.2013.158
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