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Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study

  • Sarah Timmermans (a1) (a2), Vincent W. V. Jaddoe (a1) (a3) (a4), Albert Hofman (a3), Régine P. M. Steegers-Theunissen (a2) (a3) (a4) (a5) and Eric A. P. Steegers (a2)...
Abstract

Countries worldwide, including the Netherlands, recommend that women planning pregnancy use a folic acid supplement during the periconception period. Some countries even fortify staple foods with folic acid. These recommendations mainly focus on the prevention of neural tube defects, despite increasing evidence that folic acid may also influence birth weight. We examined whether periconception folic acid supplementation affects fetal growth and the risks of low birth weight, small for gestational age (SGA) and preterm birth, in the Generation R Study in Rotterdam, the Netherlands. Main outcome measures were fetal growth measured in mid- and late pregnancy by ultrasound, birth weight, SGA and preterm birth in relation to periconception folic supplementation (0·4–0·5 mg). Data on 6353 pregnancies were available. Periconception folic acid supplementation was positively associated with fetal growth. Preconception folic acid supplementation was associated with 68 g higher birth weight (95 % CI 37·2, 99·0) and 13 g higher placental weight (95 % CI 1·1, 25·5), compared to no folic acid supplementation. In these analyses parity significantly modified the effect estimates. Start of folic acid supplementation after pregnancy confirmation was associated with a reduced risk of low birth weight (OR 0·61, 95 % CI 0·40, 0·94). Similarly, reduced risks for low birth weight and SGA were observed for women who started supplementation preconceptionally, compared to those who did not use folic acid (OR 0·43, 95 % CI 0·28, 0·69 and OR 0·40, 95 % CI 0·22, 0·72). In conclusion, periconception folic acid supplementation is associated with increased fetal growth resulting in higher placental and birth weight, and decreased risks of low birth weight and SGA.

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Corresponding author
*Corresponding author: Dr Sarah Timmermans, fax +31 10 7036815, email s.timmermans@erasmusmc.nl
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1 DJ Barker & PM Clark (1997) Foetal undernutrition and disease in later life. Rev Reprod 2, 105112.

2 T Roseboom , S de Rooij & R Painter (2006) The Dutch famine and its long-term consequences for adult health. Early Hum Dev 82, 485491.

6 JJ Hoet & MA Hanson (1999) Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development. J Physiol 514, 617627.

7 RP Steegers-Theunissen & EA Steegers (2003) Nutrient–gene interactions in early pregnancy: a vascular hypothesis. Eur J Obstet Gynecol Reprod Biol 106, 115117.

8 RA Waterland & RL Jirtle (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20, 6368.

9 BT Heijmans , EW Tobi , AD Stein , (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105, 1704617049.

12MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338, 131137.

13 AE Czeizel & I Dudas (1992) Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 327, 18321835.

14 S Hernandez-Diaz , MM Werler , AM Walker , (2000) Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 343, 16081614.

15 BM Hibbard (1964) The role of folic acid in pregnancy; with particular reference to anaemia, abruption and abortion. J Obstet Gynaecol Br Commonw 71, 529542.

16 RP Steegers-Theunissen , GH Boers , HJ Blom , (1992) Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 339, 11221123.

17 A de Bree , M van Dusseldorp , IA Brouwer , (1997) Folate intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 51, 643660.

18 LD Botto , A Lisi , E Robert-Gnansia , (2005) International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? Br Med J 330, 571.

19 N Baumslag , T Edelstein & J Metz (1970) Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br Med J 1, 1617.

21 L Iyengar & K Rajalakshmi (1975) Effect of folic acid supplement on birth weights of infants. Am J Obstet Gynecol 122, 332336.

22 J Rolschau , J Date & K Kristoffersen (1979) Folic acid supplement and intrauterine growth. Acta Obstet Gynecol Scand 58, 343346.

23 J Rolschau , K Kristoffersen , M Ulrich , (1999) The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part I. Eur J Obstet Gynecol Reprod Biol 87, 105110.

27 WW Fawzi , GI Msamanga , W Urassa , (2007) Vitamins and perinatal outcomes among HIV-negative women in Tanzania. N Engl J Med 356, 14231431.

29 KD Sinclair , C Allegrucci , R Singh , (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 104, 1935119356.

31 VW Jaddoe , R Bakker , CM van Duijn , (2007) The Generation R Study Biobank: a resource for epidemiological studies in children and their parents. Eur J Epidemiol 22, 917923.

32 VW Jaddoe , JP Mackenbach , HA Moll , (2006) The Generation R Study: design and cohort profile. Eur J Epidemiol 21, 475484.

35 BO Verburg , EA Steegers , M De Ridder , (2008) New charts for ultrasound dating of pregnancy and assessment of foetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol 31, 388396.

36 FP Hadlock , RB Harrist , RS Sharman , (1985) Estimation of foetal weight with the use of head, body, and femur measurements – a prospective study. Am J Obstet Gynecol 151, 333337.

37 OP Bleker , M Buimer , JA van der Post , (2006) Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index. Placenta 27, 10521054.

42 S Timmermans , VW Jaddoe , JP Mackenbach , (2008) Determinants of folic acid use in early pregnancy in a multi-ethnic urban population in The Netherlands: The Generation R study. Prev Med 47, 427432.

44 S Palma , R Perez-Iglesias , D Prieto , (2008) Iron but not folic acid supplementation reduces the risk of low birthweight in pregnant women without anaemia: a case control study. J Epidemiol Community Health 62, 120124.

45 EF van der Molen , B Verbruggen , I Novakova , (2000) Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy. BJOG 107, 785791.

46 TM Nafee , WE Farrell , WD Carroll , (2008) Epigenetic control of foetal gene expression. BJOG 115, 158168.

47 RA Waterland & KB Michels (2007) Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 27, 363388.

48 E Pennisi (2005) Environmental epigenomics meeting. Supplements restore gene function via methylation. Science 310, 1761.

52 KJ Hoggatt (2003) Commentary: Vitamin supplement use and confounding by lifestyle. Int J Epidemiol 32, 553555.

53 AL Brantsaeter , M Haugen , TA Hagve , (2007) Self-reported dietary supplement use is confirmed by biological markers in the Norwegian Mother and Child Cohort Study (MoBa). Ann Nutr Metab 51, 146154.

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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