The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus

Donna Dizon-Townson, Connie Miller, Baha Sibai, Catherine Y. Spong, Elizabeth Thom, George Wendel, Katharine Wenstrom, Philip Samuels, Margaret A. Cotroneo, Atef Moawad, Yoram Sorokin, Paul Meis, Menachem Miodovnik, Mary J. O'Sullivan, Deborah Conway, Ronald J. Wapner, Steven G. Gabbe

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin Hl deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 graviclas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95%, confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated.

Original languageEnglish
Pages (from-to)517-524
Number of pages8
JournalObstetrics and Gynecology
Volume106
Issue number3
StatePublished - Sep 1 2005
Externally publishedYes

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Pregnancy Outcome
Fetus
Mothers
Mutation
Thromboembolism
Pregnancy
Activated Protein C Resistance
factor V Leiden
Confidence Intervals
Pre-Eclampsia
Protein S Deficiency
Protein C Deficiency
Abruptio Placentae
Methylenetetrahydrofolate Reductase (NADPH2)
Lupus Coagulation Inhibitor
Reproductive History
Antithrombins
Venous Thromboembolism
Prothrombin
Spontaneous Abortion

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Dizon-Townson, D., Miller, C., Sibai, B., Spong, C. Y., Thom, E., Wendel, G., ... Gabbe, S. G. (2005). The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstetrics and Gynecology, 106(3), 517-524.

The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. / Dizon-Townson, Donna; Miller, Connie; Sibai, Baha; Spong, Catherine Y.; Thom, Elizabeth; Wendel, George; Wenstrom, Katharine; Samuels, Philip; Cotroneo, Margaret A.; Moawad, Atef; Sorokin, Yoram; Meis, Paul; Miodovnik, Menachem; O'Sullivan, Mary J.; Conway, Deborah; Wapner, Ronald J.; Gabbe, Steven G.

In: Obstetrics and Gynecology, Vol. 106, No. 3, 01.09.2005, p. 517-524.

Research output: Contribution to journalArticle

Dizon-Townson, D, Miller, C, Sibai, B, Spong, CY, Thom, E, Wendel, G, Wenstrom, K, Samuels, P, Cotroneo, MA, Moawad, A, Sorokin, Y, Meis, P, Miodovnik, M, O'Sullivan, MJ, Conway, D, Wapner, RJ & Gabbe, SG 2005, 'The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus', Obstetrics and Gynecology, vol. 106, no. 3, pp. 517-524.
Dizon-Townson D, Miller C, Sibai B, Spong CY, Thom E, Wendel G et al. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstetrics and Gynecology. 2005 Sep 1;106(3):517-524.
Dizon-Townson, Donna ; Miller, Connie ; Sibai, Baha ; Spong, Catherine Y. ; Thom, Elizabeth ; Wendel, George ; Wenstrom, Katharine ; Samuels, Philip ; Cotroneo, Margaret A. ; Moawad, Atef ; Sorokin, Yoram ; Meis, Paul ; Miodovnik, Menachem ; O'Sullivan, Mary J. ; Conway, Deborah ; Wapner, Ronald J. ; Gabbe, Steven G. / The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. In: Obstetrics and Gynecology. 2005 ; Vol. 106, No. 3. pp. 517-524.
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abstract = "Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin Hl deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 graviclas (2.7{\%}), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0{\%}, 95{\%} confidence interval 0-2.7{\%}). Three pulmonary emboli and one deep venous thrombosis occurred (0.08{\%}, 95{\%}, confidence interval 0.02-0.21{\%}), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0{\%}) and Hispanic (12.5{\%}) women than white women (2.6{\%}, P = .04), adjusted odds ratio 2.4 (95{\%} confidence interval 1.0-5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated.",
author = "Donna Dizon-Townson and Connie Miller and Baha Sibai and Spong, {Catherine Y.} and Elizabeth Thom and George Wendel and Katharine Wenstrom and Philip Samuels and Cotroneo, {Margaret A.} and Atef Moawad and Yoram Sorokin and Paul Meis and Menachem Miodovnik and O'Sullivan, {Mary J.} and Deborah Conway and Wapner, {Ronald J.} and Gabbe, {Steven G.}",
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T1 - The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus

AU - Dizon-Townson, Donna

AU - Miller, Connie

AU - Sibai, Baha

AU - Spong, Catherine Y.

AU - Thom, Elizabeth

AU - Wendel, George

AU - Wenstrom, Katharine

AU - Samuels, Philip

AU - Cotroneo, Margaret A.

AU - Moawad, Atef

AU - Sorokin, Yoram

AU - Meis, Paul

AU - Miodovnik, Menachem

AU - O'Sullivan, Mary J.

AU - Conway, Deborah

AU - Wapner, Ronald J.

AU - Gabbe, Steven G.

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin Hl deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 graviclas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95%, confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated.

AB - Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin Hl deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 graviclas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95%, confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated.

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