Robert M Silver1, George R Saade2, Vanessa Thorsten3, Corette B Parker3, Uma M Reddy4, Carey Drews-Botsch5, Deborah Conway6, Donald Coustan7, Donald J Dudley6, Radek Bukowski2, Carol J Rowland Hogue8, Halit Pinar7, Michael W Varner9, Robert Goldenberg10, Marian Willinger4. 1. University of Utah School of Medicine, Salt Lake City, UT. Electronic address: bsilver@hsc.utah.edu. 2. University of Texas Medical Branch at Galveston, Galveston, TX. 3. RTI International, Research Triangle Park, NC. 4. Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. 5. Rollins School of Public Health, Emory University, Atlanta, GA. 6. Health Science Center at San Antonio, San Antonio, TX. 7. Brown University School of Medicine, Providence, RI. 8. School of Medicine, Emory University, Atlanta, GA. 9. University of Utah School of Medicine, Salt Lake City, UT. 10. Columbia University, New York, NY.
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.
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, prothrombinG20210A, 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.
Authors: Andrew Z Carey; Nathan R Blue; Michael W Varner; Jessica M Page; Nathorn Chaiyakunapruk; Aaron R Quinlan; D Ware Branch; Robert M Silver; Tsegaselassie Workalemahu Journal: Front Reprod Health Date: 2021-12-15
Authors: J W Nijkamp; N J Sebire; K Bouman; F J Korteweg; J J H M Erwich; S J Gordijn Journal: Semin Fetal Neonatal Med Date: 2017-03-18 Impact factor: 3.926