Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

BMC Pregnancy and Childbirth

Bo Jacobsson⁸  Staffan Nilsson⁵  Stein Emil Vollset³  Per Magnus¹  Roy Miodini Nilsen²  Helle Margrete Meltzer⁷  Anne-Lise Brantsæter⁷  Margaretha Haugen⁷  Aase Serine Devold Pay⁶  Solveig Myking⁸  Ronny Myhre⁸  Jonas Bacelis⁴  Verena Sengpiel⁴ 

[1] Division of Epidemiology, Norwegian Institute of Public Health, Oslo NO-0403, Norway;Department of Global Public Health and Primary Care, University of Bergen, Bergen NO-5018, Norway;Norwegian Institute of Public Health and University of Bergen, Kalfarveien 31, Bergen NO-5018, Norway;Department of Obstetrics and Gynaecology, Sahlgrenska Academy, Sahlgrenska University Hospital/Östra, Göteborg SE-416 85, Sweden;Mathematical Sciences, Chalmers University of Technology, Göteborg SE-412 96, Sweden;Department of Obstetrics and Gynecology, Women and Children’s Division, Oslo University Hospital, Nydalen, Oslo NO-0424, Norway;Department of Exposure and Risk Assessment, Division of Environmental Medicine, Norwegian Institute of Public Health, Nydalen, Oslo NO-0403, Norway;Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Nydalen, Oslo NO-0403, Norway

关键词: Folic acid supplementation;    Folate;    Gestational length;    Preterm birth;    Preterm delivery;    Pregnancy;   

Others  :  1091961
DOI  :  10.1186/s12884-014-0375-1

 received in 2014-06-06, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

Background

Health authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy with the risk of spontaneous preterm delivery (PTD).

Methods

The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 66,014 women with singleton pregnancies resulting in live births in 2002–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22⁺⁰ and 36⁺⁶ (n = 1,755).

Results

The median total folate intake was 313 μg/d (interquartile range IQR 167–558) in the overall population and 530 μg/d (IQR 355–636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.

Conclusions

Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

【 授权许可】

   
2014 Sengpiel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Tamura T, Picciano MF: Folate and human reproduction. Am J Clin Nutr 2006, 83(5):993-1016.
• [2]Folate In Nordic Nutrition Recommendations 2004 Integrating nutrition and physical activity. Norden, Copenhagen; 2004:287-296.
• [3]Folate and Folic acid In Vitamin and mineral requirements in human nutrition. FAO, Rome; 2004:53-62.
• [4]Scholl TO, Johnson WG: Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000, 71(5 Suppl):1295S-1303S.
• [5]Israels MC, Da Cunha FA: Megaloblastic anaemia of pregnancy. Lancet 1952, 2(6727):214-215.
• [6]Czeizel AE, Dudas I, Metneki J: Pregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report. Arch Gynecol Obstet 1994, 255(3):131-139.
• [7]Czeizel AE, Dudas I: Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992, 327(26):1832-1835.
• [8]Prevention of neural tube defects: results of the Medical Research Council Vitamin Study Lancet 1991, 338(8760):131-137.
• [9]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):170-173.
• [10]De Bree A, Van Dusseldorp M, Brouwer IA, van het Hof KH, Steegers-Theunissen RP: Folate intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 1997, 51(10):643-660.
• [11][http:/ / www.helsedirektoratet.no/ folkehelse/ ernering/ kostholdsrad/ gravide/ Sider/ default.aspx] webcite Kostholdsråd gravide (Dietary recommendation for pregnant women, in Norwegian) []
• [12]The prevention of perinatal mortality and morbidity. Report of a WHO Expert Committee World Health Organ Tech Rep Ser 1970, 457:1-60.
• [13]Moster D, Lie RT, Markestad T: Long-term medical and social consequences of preterm birth. N Engl J Med 2008, 359(3):262-273.
• [14]Bryce J, Boschi-Pinto C, Shibuya K, Black RE: WHO estimates of the causes of death in children. Lancet 2005, 365(9465):1147-1152.
• [15]Magnus P, Irgens LM, Haug K, Nystad W, Skjaerven R, Stoltenberg C: Cohort profile: the Norwegian mother and child cohort study (MoBa). Int J Epidemiol 2006, 35(5):1146-1150.
• [16]Lockwood CJ: Predicting premature delivery–no easy task. N Engl J Med 2002, 346(4):282-284.
• [17]Dodd JM, Flenady VJ, Cincotta R, Crowther CA: Progesterone for the prevention of preterm birth: a systematic review. Obstet Gynecol 2008, 112(1):127-134.
• [18]Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O’Brien JM, Cetingoz E, Da Fonseca E, Creasy GW, Klein K, Rode L, Soma-Pillay P, Fusey S, Cam C, Alfirevic Z, Hassan SS: Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012, 206(2):124 e121-119.
• [19]Li Z, Ye R, Zhang L, Li H, Liu J, Ren A: Periconceptional folic acid supplementation and the risk of preterm births in China: a large prospective cohort study. Int J Epidemiol 2014, 43(4):1132-1139.
• [20]Papadopoulou E, Stratakis N, Roumeliotaki T, Sarri K, Merlo DF, Kogevinas M, Chatzi L: 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(1):327-336.
• [21]Bukowski R, Malone FD, Porter FT, Nyberg DA, Comstock CH, Hankins GD, Eddleman K, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D'Alton ME: Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study. PLoS Med 2009, 6(5):e1000061.
• [22]Czeizel AE, Puho EH, Langmar Z, Acs N, Banhidy F: Possible association of folic acid supplementation during pregnancy with reduction of preterm birth: a population-based study. Eur J Obstet Gynecol Reprod Biol 2010, 148(2):135-140.
• [23]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.
• [24]Charles DH, Ness AR, Campbell D, Smith GD, Whitley E, Hall MH: Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review. Paediatr Perinat Epidemiol 2005, 19(2):112-124.
• [25]Fekete K, Berti C, Trovato M, Lohner S, Dullemeijer C, Souverein OW, Cetin I, Decsi T: Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr J 2012, 11(1):75. BioMed Central Full Text
• [26]Pennell CE, Jacobsson B, Williams SM, Buus RM, Muglia LJ, Dolan SM, Morken NH, Ozcelik H, Lye SJ, Relton C: Genetic epidemiologic studies of preterm birth: guidelines for research. Am J Obstet Gynecol 2007, 196(2):107-118.
• [27]Mantovani E, Filippini F, Bortolus R, Franchi M: Folic acid supplementation and preterm birth: results from observational studies. Biomed Res Int 2014, 2014:481914.
• [28][http:/ / www.fhi.no/ eway/ default.aspx?pid=240&trg=Main_6664& Main_6664=6894:0:25,7372:1:0:0:::0: 0] webcite Norwegian Mother and Child Study. []
• [29]Irgens LM: The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years. Acta Obstet Gynecol Scand 2000, 79(6):435-439.
• [30]Meltzer HM, Brantsaeter AL, Ydersbond TA, Alexander J, Haugen M: Methodological challenges when monitoring the diet of pregnant women in a large study: experiences from the Norwegian Mother and Child Cohort Study (MoBa). Matern Child Nutr 2008, 4(1):14-27.
• [31][http://www.ibt.ku.dk/jesper/FoodCalc/Default.htm] webcite FoodCalc. []
• [32]Rimestad AH, Borgejordet A, Vesterhus KN, Sygnestveit K, Løken EB, Trygg K, Pollestad ML, Lund-Larsen K, Omholt-Jensen G, Nordbotten A: Matvaretabellen (The Norwegian Food Table, in Norwegian). Norwegian Food Safety Authority; Norwegian Directorate of Health; Department of Nutrition, University of Oslo; 2001.
• [33]Brantsaeter AL, Haugen M, Hagve TA, Aksnes L, Rasmussen SE, Julshamn K, Alexander J, Meltzer HM: Self-reported dietary supplement use is confirmed by biological markers in the Norwegian Mother and Child Cohort Study (MoBa). Ann Nutr Metab 2007, 51(2):146-154.
• [34]Haugen M, Brantsaeter AL, Alexander J, Meltzer HM: Dietary supplements contribute substantially to the total nutrient intake in pregnant Norwegian women. Ann Nutr Metab 2008, 52(4):272-280.
• [35]Requirements of Vitamin A, Iron, Folate and Vitamin B12 Report of a Joint Fao/Who Expert Consultation (Fao Fisheries Report). Food and Agriculture Organization of the United Nations, Rome, Lanham, MD; 1988.
• [36]Grambsch PM, Therneau TM: Proportional hazards tests and diagnostics based on weighted residualsProportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994, 81:515-526.
• [37]Callaway L, Colditz PB, Fisk NM: Folic acid supplementation and spontaneous preterm birth: adding grist to the mill? PLoS Med 2009, 6(5):e1000077.
• [38]Alwan NA, Greenwood DC, Simpson NA, McArdle HJ, Cade JE: The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women. BJOG 2010, 117(7):821-829.
• [39]Catov JM, Bodnar LM, Olsen J, Olsen S, Nohr EA: Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr 2011, 94(3):906-912.
• [40]Nilsen RM, Vollset SE, Monsen AL, Ulvik A, Haugen M, Meltzer HM, Magnus P, Ueland PM: 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(3):572-579.
• [41]Timmermans S, Jaddoe VW, Hofman A, Steegers-Theunissen RP, Steegers EA: Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study. Br J Nutr 2009, 102(5):777-785.
• [42]Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R: Maternal micronutrient status and preterm versus term birth for black and white US women. Reprod Sci 2012, 19(9):939-948.
• [43]Shaw GM, Carmichael SL, Yang W, Siega-Riz AM: Periconceptional intake of folic acid and food folate and risks of preterm delivery. Am J Perinatol 2011, 28(10):747-752.
• [44]Fleming AF, Martin JD, Stenhouse NS: Pregnancy anaemia, iron and folate deficiency in Western Australia. Med J Aust 1974, 2(13):479-484.
• [45]Fletcher J, Gurr A, Fellingham FR, Prankerd TA, Brant HA, Menzies DN: The value of folic acid supplements in pregnancy. J Obstet Gynaecol Br Commonw 1971, 78(9):781-785.
• [46]Baumslag N, Edelstein T, Metz J: Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br Med J 1970, 1(5687):16-17.
• [47]Rolschau J, Kristoffersen K, Ulrich M, Grinsted P, Schaumburg E, Foged N: 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 1999, 87(2):105-110. discussion 103–104
• [48]Scholl TO, Hediger ML, Bendich A, Schall JI, Smith WK, Krueger PM: Use of multivitamin/mineral prenatal supplements: influence on the outcome of pregnancy. Am J Epidemiol 1997, 146(2):134-141.
• [49]Siega-Riz AM, Savitz DA, Zeisel SH, Thorp JM, Herring A: Second trimester folate status and preterm birth. Am J Obstet Gynecol 2004, 191(6):1851-1857.
• [50]Furness DL, Yasin N, Dekker GA, Thompson SD, Roberts CT: Maternal red blood cell folate concentration at 10–12 weeks gestation and pregnancy outcome. J Matern Fetal Neonatal Med 2012, 25(8):1423-1427.
• [51]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(4):520-525.
• [52]Bailey RL, Dodd KW, Gahche JJ, Dwyer JT, McDowell MA, Yetley EA, Sempos CA, Burt VL, Radimer KL, Picciano MF: Total folate and folic acid intake from foods and dietary supplements in the United States: 2003–2006. Am J Clin Nutr 2010, 91(1):231-237.
• [53]Nilsen RM, Vollset SE, Gjessing HK, Magnus P, Meltzer HM, Haugen M, Ueland PM: Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian mother and child cohort study. Am J Clin Nutr 2006, 84(5):1134-1141.
• [54]Nilsen RM, Mastroiacovo P, Gunnes N, Alsaker ER, Bjorke-Monsen AL, Eussen SJ, Haugen M, Johannessen A, Meltzer HM, Stoltenberg C, Ueland PM, Vollset SE: Folic acid supplementation and interpregnancy interval. Paediatr Perinat Epidemiol 2014, 28(3):270-274.
• [55]Bergen NE, Jaddoe VW, Timmermans S, Hofman A, Lindemans J, Russcher H, Raat H, Steegers-Theunissen RP, Steegers EA: Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study. BJOG 2012, 119(6):739-751.
• [56]Nilsen RM, Suren P, Gunnes N, Alsaker ER, Bresnahan M, Hirtz D, Hornig M, Lie KK, Lipkin WI, Reichborn-Kjennerud T, Roth C, Schjolberg S, Smith GD, Susser E, Vollset SE, Oyen AS, Magnus P, Stoltenberg C: Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders. Paediatr Perinat Epidemiol 2013, 27(6):553-563.
• [57]Nilsen RM, Vollset SE, Gjessing HK, Skjaerven R, Melve KK, Schreuder P, Alsaker ER, Haug K, Daltveit AK, Magnus P: Self-selection and bias in a large prospective pregnancy cohort in Norway. Paediatr Perinat Epidemiol 2009, 23(6):597-608.
• [58]Brantsaeter AL, Haugen M, Alexander J, Meltzer HM: Validity of a new food frequency questionnaire for pregnant women in the Norwegian Mother and Child Cohort Study (MoBa). Matern Child Nutr 2008, 4(1):28-43.