Associations between Maternal and Fetal Inherited Thrombophilias, Placental Characteristics Associated with Vascular Malperfusion, and Fetal Growth

Abstract

Pregnancy results in alterations in coagulation processes, which may increase the risk of thrombosis. Inherited thrombophilia mutations may further increase this risk, possibly through alterations in the placenta, which may result in pregnancy complications such as poor fetal growth. The purpose of our study is to evaluate the association of fetal growth, approximated by birth weight for gestational age percentile, with genetic markers of thrombophilia and placental characteristics related to vascular malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's population-based case–control study conducted in 2006–2008. Study recruitment occurred in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah. The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation with a complete placental examination and successful testing for ≥1 thrombophilia marker (858 mothers, 902 infants). Data were weighted to account for oversampling, differential consent, and availability of placental examination. We evaluated five thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers separately using linear regression. Maternal factor V Leiden mutation was associated with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval: −25.50, −0.82). Adjustment for placental abnormalities related to vascular malperfusion did not affect the observed association. No other maternal or fetal thrombophilia markers were significantly associated with birth weight percentile. Maternal factor V Leiden may be associated with fetal growth independent of placental characteristics.

Keywords

pregnancy - inherited thrombophilias - perinatal hemostasis

Funding

This work was supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and with supplemental funding from the Office of Research in Women's Health, National Institutes of Health (grants U10-HD045953 (Brown University), U10-HD045925 (Emory University), U10-HD045952 (University of Texas Medical Branch at Galveston), U10-HD045955 (University of Texas Health Sciences Center at San Antonio), UK10-HD045944 (University of Utah Health Sciences Center), U10-HD045954 and HHSN275201400001C (RTI International), and 5T32HD052460–10 to A.A.F.). This work was also supported by funding from the Maternal Child Health Bureau, Health Resources and Services Administration (grant T03MC07651 to A.A.F.).

Members of the Study Group

The Stillbirth Collaborative Research Network—University of Texas Health Science Center at San Antonio: Dr. Donald J. Dudley, Dr. Deborah Conway, Josefine Heim-Hall, Karen Aufdemorte, and Angela Rodriguez; University of Utah School of Medicine: Dr. Robert M. Silver, Dr. Michael W. Varner, and Kristi Nelson; Emory University School of Medicine and Rollins School of Public Health: Dr. Carol J. Rowland Hogue, Dr. Barbara J. Stoll, Janice Daniels Tinsley, Dr. Bahig Shehata, and Dr. Carlos Abromowsky; Brown University: Dr. Donald Coustan, Dr. Halit Pinar, Dr. Marshall Carpenter, and Susan Kubaska; University of Texas Medical Branch at Galveston: Dr. George R. Saade, Dr. Radek Bukowski, Jennifer Lee Rollins, Dr. Hal Hawkins, and Elena Sbrana; RTI International: Dr. Corette B. Parker, Dr. Matthew A. Koch, Vanessa R. Thorsten, Holly Franklin, and Pinliang Chen; Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development: Drs. Marian Willinger and Uma M. Reddy; Columbia University Medical Center: Dr. Robert L. Goldenberg.

The Stillbirth Collaborative Research Network Writing Group—Dr. Carol J. R. Hogue (Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia); Dr. Robert L. Goldenberg (Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York); Drs. Radek Bukowski and George R. Saade (Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas); Dr. Barbara J. Stoll (McGovern Medical School, University of Texas Health Science Center, Houston, Texas); Drs. Marshall Carpenter, Donald Coustan, and Halit Pinar (Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brown University School of Medicine, Providence, Rhode Island); Dr. Deborah Conway (Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas); Dr. Donald J. Dudley (Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia); Drs. Robert M. Silver and Michael W. Varner (Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, and Maternal Fetal Medicine Unit, Intermountain Healthcare, Salt Lake City, Utah); Drs. Uma M. Reddy and Marian Willinger (Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland); and Drs. Matthew A. Koch and Corette B. Parker (Statistics and Epidemiology Unit, Health Sciences Division, RTI International, Research Triangle Park, North Carolina).

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