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

Robert M. Silver, George 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 journalArticle

    9 Citations (Scopus)

    Abstract

    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)
    JournalAmerican Journal of Obstetrics and Gynecology
    DOIs
    StateAccepted/In press - Jan 27 2016

    Fingerprint

    Methylenetetrahydrofolate Reductase (NADPH2)
    Stillbirth
    Prothrombin
    Mutation
    Research
    Mothers
    Live Birth
    Plasminogen
    Thrombophilia
    Odds Ratio
    factor V Leiden
    Case-Control Studies
    Confidence Intervals
    Population

    Keywords

    • Placenta
    • Stillbirth
    • Thrombophilia

    ASJC Scopus subject areas

    • Obstetrics and Gynecology

    Cite this

    Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth : The Stillbirth Collaborative Research Network. / Silver, Robert M.; Saade, George; Thorsten, Vanessa; Parker, Corette B.; Reddy, Uma M.; Botsch, Carey Drews; Conway, Deborah; Coustan, Donald; Dudley, Donald J.; Bukowski, Radek; Rowland Hogue, Carol J.; Pinar, Halit; Varner, Michael W.; Goldenberg, Robert; Willinger, Marian.

    In: American Journal of Obstetrics and Gynecology, 27.01.2016.

    Research output: Contribution to journalArticle

    Silver, RM, Saade, G, Thorsten, V, Parker, CB, Reddy, UM, Botsch, CD, Conway, D, Coustan, D, Dudley, DJ, Bukowski, R, Rowland Hogue, CJ, Pinar, H, Varner, MW, Goldenberg, R & Willinger, M 2016, 'Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth: The Stillbirth Collaborative Research Network', American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2016.04.026
    Silver, Robert M. ; Saade, George ; Thorsten, Vanessa ; Parker, Corette B. ; Reddy, Uma M. ; Botsch, Carey Drews ; Conway, Deborah ; Coustan, Donald ; Dudley, Donald J. ; Bukowski, Radek ; Rowland Hogue, Carol J. ; Pinar, Halit ; Varner, Michael W. ; Goldenberg, Robert ; Willinger, Marian. / Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth : The Stillbirth Collaborative Research Network. In: American Journal of Obstetrics and Gynecology. 2016.
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    abstract = "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.",
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    T1 - Factor V Leiden, prothrombin G20210A, and methylene tetrahydrofolate reductase mutations and stillbirth

    T2 - The Stillbirth Collaborative Research Network

    AU - Silver, Robert M.

    AU - Saade, George

    AU - Thorsten, Vanessa

    AU - Parker, Corette B.

    AU - Reddy, Uma M.

    AU - Botsch, Carey Drews

    AU - Conway, Deborah

    AU - Coustan, Donald

    AU - Dudley, Donald J.

    AU - Bukowski, Radek

    AU - Rowland Hogue, Carol J.

    AU - Pinar, Halit

    AU - Varner, Michael W.

    AU - Goldenberg, Robert

    AU - Willinger, Marian

    PY - 2016/1/27

    Y1 - 2016/1/27

    N2 - 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.

    AB - 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.

    KW - Placenta

    KW - Stillbirth

    KW - Thrombophilia

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