title: Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network.
abstract: An evaluation for heritable thrombophilias is recommended in the evaluation of stillbirth. However, the association between thrombophilias and stillbirth remains uncertain.
  
  
  
  We sought to assess the association between maternal and fetal/placental heritable thrombophilias and stillbirth in a population-based, case-control study in a geographically, racially, and ethnically diverse population.
  
  
  
  We conducted secondary analysis of data from the Stillbirth Collaborative Research Network, a population-based case-control study of stillbirth. Testing for factor V Leiden, prothrombin G20210A, methylene tetrahydrofolate reductase C677T and A1298C, and plasminogen activating inhibitor (PAI)-1 4G/5G mutations was done on maternal and fetal (or placental) DNA from singleton pregnancies. Data analyses were weighted for oversampling and other aspects of the design. Odds ratios (OR) were generated from univariate models regressing stillbirth/live birth status on each thrombophilia marker.
  
  
  
  Results were available for ≥1 marker in 488 stillbirths and 1342 live birth mothers and 405 stillbirths and 990 live birth fetuses. There was an increased odds of stillbirth for maternal homozygous factor V Leiden mutation (2/488; 0.4% vs 1/1380; 0.0046%; OR, 87.44; 95% confidence interval, 7.88-970.92). However, there were no significant differences in the odds of stillbirth for any other maternal thrombophilia, even after stratified analyses. Fetal 4G/4G PAI-1 (OR, 0.63; 95% confidence interval, 0.43-0.91) was associated with decreased odds of stillbirth. Other fetal thrombophilias were similar among groups.
  
  
  
  Most maternal and fetal thrombophilias were not associated with stillbirth. Maternal factor V Leiden was weakly associated with stillbirth, and the fetal PAI-1 4G/4G polymorphism was associated with live birth. Our data do not support routine testing for heritable thrombophilias as part of an evaluation for possible causes of stillbirth.
authors.affiliation: University of Utah School of Medicine, Salt Lake City, UT. Electronic address: bsilver@hsc.utah.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Silver
authors.affiliation: University of Texas Medical Branch at Galveston, Galveston, TX.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: RTI International, Research Triangle Park, NC.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Thorsten
authors.affiliation: RTI International, Research Triangle Park, NC.
authors.forename: Corette B
authors.initials: CB
authors.lastname: Parker
authors.affiliation: Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Uma M
authors.initials: UM
authors.lastname: Reddy
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, GA.
authors.forename: Carey
authors.initials: C
authors.lastname: Drews-Botsch
authors.affiliation: Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Deborah
authors.initials: D
authors.lastname: Conway
authors.affiliation: Brown University School of Medicine, Providence, RI.
authors.forename: Donald
authors.initials: D
authors.lastname: Coustan
authors.affiliation: Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Dudley
authors.affiliation: University of Texas Medical Branch at Galveston, Galveston, TX.
authors.forename: Radek
authors.initials: R
authors.lastname: Bukowski
authors.affiliation: School of Medicine, Emory University, Atlanta, GA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Rowland Hogue
authors.affiliation: Brown University School of Medicine, Providence, RI.
authors.forename: Halit
authors.initials: H
authors.lastname: Pinar
authors.affiliation: University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.affiliation: Columbia University, New York, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldenberg
authors.affiliation: Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Marian
authors.initials: M
authors.lastname: Willinger
mesh_terms: D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D050498:Live Birth; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D050497:Stillbirth / Q000235:genetics*; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics; D014481:United States
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: placenta; stillbirth; thrombophilia