title: Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.
abstract: 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.
authors.forename: Verena
authors.initials: V
authors.lastname: Sengpiel
authors.forename: Jonas
authors.initials: J
authors.lastname: Bacelis
authors.forename: Ronny
authors.initials: R
authors.lastname: Myhre
authors.forename: Solveig
authors.initials: S
authors.lastname: Myking
authors.forename: Aase Serine
authors.initials: AS
authors.lastname: Devold Pay
authors.forename: Margaretha
authors.initials: M
authors.lastname: Haugen
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Brantsæter
authors.forename: Helle Margrete
authors.initials: HM
authors.lastname: Meltzer
authors.forename: Roy Miodini
authors.initials: RM
authors.lastname: Nilsen
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Bo
authors.initials: B
authors.lastname: Jacobsson
mesh_terms: D000328:Adult; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005865:Gestational Age; D006801:Humans; D009664:Norway / Q000453:epidemiology; D016742:Preconception Care; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology / Q000517:prevention & control*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D013997:Time Factors; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid