Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: the Stillbirth Collaborative Research Network

Robert M. Silver, George R. Saade, Vanessa Thorsten, Corette B. Parker, Uma M. Reddy, Carey Drews-Botsch, Deborah Conway, Donald Coustan, Donald J. Dudley, Radek Bukowski, Carol J. Rowland Hogue, Halit Pinar, Michael W. Varner, Robert Goldenberg, Marian Willinger

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background An evaluation for heritable thrombophilias is recommended in the evaluation of stillbirth. However, the association between thrombophilias and stillbirth remains uncertain. Objective 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. Study Design 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 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)468.e1-468.e17
JournalAmerican journal of obstetrics and gynecology
Issue number4
StatePublished - Oct 1 2016


  • placenta
  • stillbirth
  • thrombophilia

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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