Antiphospholipid Antibodies in Stillbirth

Silver, Robert M. MD; Parker, Corette B. PhD; Reddy, Uma M. MD, MPH; Goldenberg, Robert MD; Coustan, Donald MD; Dudley, Donald J. MD; Saade, George R. MD; Stoll, Barbara MD; Koch, Matthew A. MD, PhD; Conway, Deborah MD; Bukowski, Radek MD; Rowland Hogue, Carol J. PhD; Pinar, Halit MD; Moore, Janet MS; Willinger, Marian PhD; Branch, D. Ware MD

Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e3182a1060e
Original Research
Abstract

OBJECTIVE: To compare antiphospholipid antibodies in deliveries with and without stillbirth using a multicenter, population-based case–control study of stillbirths and live births.

METHODS: Maternal sera were assayed for immunoglobulin (Ig)G and IgM anticardiolipin and anti-β2-glycoprotein-I antibodies. Assays were performed in 582 stillbirth deliveries and 1,547 live birth deliveries.

RESULTS: Elevated levels of IgG anticardiolipin and IgG anti-β2-glycoprotein-I antibodies were associated with an approximate threefold increased odds of stillbirth (crude odds ratio [OR] 3.43, 95% confidence interval [CI] 1.79–6.60, 3.8% compared with 1.1% and OR 3.17, 95% CI 1.30–7.72, (1.9% compared with 0.6%, respectively) when all deliveries with stillbirth were compared with all deliveries with live birth. When the subset of stillbirths not associated with fetal anomalies or obstetric complications was compared with term live births, elevated IgG anticardiolipin antibodies were associated with stillbirth (5.0% compared with 1.0%; OR 5.30, 95% CI, 2.39–11.76; IgG anti-β2-glycoprotein-I antibodies (1.9% compared with 0.6%) had an OR of 3.00 (95% CI 1.01–8.90) and IgM anticardiolipin antibodies (6.0% compared with 3.0%) had an OR of 2.03 (95% CI 1.09–3.76). Elevated levels of anticardiolipin and anti-β2-glycoprotein-I antibodies were associated with a threefold to fivefold increased odds of stillbirth.

CONCLUSIONS: Our data support consideration of testing for antiphospholipid antibodies in cases of otherwise unexplained stillbirth.

LEVEL OF EVIDENCE: II

In Brief

Elevated levels of anticardiolipin and anti-β2-glycoprotein-I antibodies are associated with threefold to fivefold increased odds for stillbirth.

Author Information

For a list of centers participating in the Stillbirth Collaborative Research Network, see the Appendix online at http://links.lww.com/AOG/A412.

University of Utah School of Medicine, Salt Lake City, Utah; RTI International, Research Triangle Park, North Carolina; the Pregnancy and Perinatology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Columbia University, New York, New York; Brown University School of Medicine, Providence, Rhode Island; the University of Texas Health Science Center at San Antonio, San Antonio, Texas; the University of Texas Medical Branch at Galveston, Galveston, Texas; Emory University School of Medicine, Atlanta, Georgia; and Rollins School of Public Health, Emory University, Atlanta, Georgia.

Corresponding author: Robert M. Silver, MD, Department of Obstetrics and Gynecology, University of Utah School of Medicine, 30 North 1900 East, Room 2B308, Salt Lake City, UT 84132; e-mail: bsilver@hsc.utah.edu.

Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10-HD045953 Brown University, Providence, Rhode Island; U10-HD045925 Emory University, Atlanta, Georgia; U10-HD045952 University of Texas Medical Branch at Galveston, Galveston, Texas; U10-HDO45955 University of Texas Health Sciences Center at San Antonio, San Antonio, Texas; U10-HD045944 University of Utah Health Sciences Center, Salt Lake City, Utah; and U01-HD045954 RTI International, Research Triangle Park, North Carolina.

The authors thank the following members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Scientific Advisory and Safety Monitoring Board for their review of the study protocol, materials, and progress: Reverend Phillip Cato, PhD; James W. Collins, Jr, MD, MPH; Terry Dwyer, MD, MPH; William P. Fifer, PhD; John Ilekis, PhD; Marc Incerpi, MD; George Macones, MD, MSCE; Richard M. Pauli, MD, PhD; Raymond W. Redline, MD; Elizabeth Thom, PhD (chair) as well as all of the other physicians, study coordinators, research nurses, and patients who participated in the Stillbirth Collaborative Research Network. The authors also thank Dr. Huixia Yu for assistance in performing the assays and Susan Fox for assistance in the preparation of this manuscript.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.