title: Maternal serum folate species in early pregnancy and risk of preterm birth.
abstract: BACKGROUND
  Poor maternal folate status has been associated with an increased risk of preterm birth. However, major gaps remain in our understanding of how individual folate species relate to preterm birth.
  
  
  OBJECTIVE
  Our objective was to assess the association between maternal folate status as measured by 5-methyltetrahydrofolate (5MeTHF), 5-formyltetrahydrofolate (5FoTHF), and folic acid concentrations, which are the 3 primary folate species in serum, and the risk of preterm birth and spontaneous preterm birth (sPTB).
  
  
  METHODS
  A cohort of 313 pregnant women who received care at resident antepartum clinics at Magee-Womens Hospital (Pittsburgh, PA) (2003-2007) was enrolled at <16 wk gestation. We analyzed nonfasting blood samples that were drawn from subjects at enrollment for the 3 folate species by using HPLC-tandem mass spectrometry.
  
  
  RESULTS
  Serum 5MeTHF and 5FoTHF concentrations comprised 65% and 33% of total folate concentrations, respectively. In confounder-adjusted, multivariable, log-binomial regression models, 1-SD increases in serum total folate and serum 5MeTHF concentrations were associated with significant reductions in the risk of sPTB (P < 0.05). There was a significant interaction between serum 5MeTHF and 5FoTHF concentrations and risk of preterm birth (P = 0.01). When serum 5MeTHF concentrations were low, there was a positive linear relation between 5FoTHF and risk of preterm birth. When 5MeTHF concentrations were high, there was a strong negative relation between 5FoTHF and preterm birth.
  
  
  CONCLUSIONS
  Our results imply that the relative concentrations of folate species may be more critical than total folate in preventing preterm birth. An improved understanding of folate metabolism during pregnancy may lead to targeted intervention strategies that decrease the rate of preterm birth.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. bodnar@edc.pitt.edu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bodnar
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Himes
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Jia-Yuh
authors.initials: JY
authors.lastname: Chen
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Meyer
authors.forename: Hyagriv N
authors.initials: HN
authors.lastname: Simhan
mesh_terms: D044383:Black People; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D002955:Leucovorin / Q000097:blood; D010414:Pennsylvania; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013763:Tetrahydrofolates / Q000097:blood; D044465:White People; D001741:Black or African American
chemical_list: D013763:Tetrahydrofolates; D005492:Folic Acid; D002955:Leucovorin; C005984:5-methyltetrahydrofolate