Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia
Presented at the 20th annual meeting of the Society for Pediatric and Perinatal Epidemiologic Research, Boston, MA, June 18-19, 2007.
Received 13 June 2007; received in revised form 15 August 2007; accepted 11 October 2007. published online 28 January 2008.
Objective
Preeclampsia is a multisystem disease classically defined on the basis of hypertension and proteinuria. As shown in animal studies, complement activation is associated with inflammation in the placenta and adverse pregnancy outcomes. The association between complement activation in humans and adverse pregnancy outcomes is unclear. The purpose of this study was to determine whether elevated levels of the activation fragment Bb in early pregnancy are predictive of preeclampsia.
Study Design
This prospective study of 701 women was conducted in Denver, CO. A single plasma sample was obtained from each woman before 20 weeks’ gestation. The cohort was followed up throughout pregnancy for the development of preeclampsia. Analysis included multivariate logistic regression to adjust for established risk factors for preeclampsia.
Results
Preeclampsia developed in 4.6% of the cohort. Women with elevated Bb (90th or greater percentile) were substantially more likely to develop preeclampsia than women who had levels less than the 90th percentile (unadjusted relative risk [RR], 3.3, 95% confidence interval [CI] 1.6 to 7, P = .0009). Other significant risk factors for preeclampsia included nulliparity (RR, 2.1, 95% CI, 1-4), a high body mass index (P = .006 for trend), and maternal medical (preexisting maternal hypertension, type 1 diabetes, systemic lupus erythematosus) disease (RR, 4.4, 95% CI, 2-10). Significant risk factors among multiparous women included a history of hypertension in a previous pregnancy (RR, 5, 95% CI, 1.6 to 16) and a change of paternity (RR, 5.1, 95% CI, 1.6 to 15). Adjustment for risk factors did not attenuate the association between an elevated Bb and preeclampsia (adjusted odds ratio [OR], 3.8, 95% CI, 1.6 to 9, P = .002) in the cohort. After removing women with plasma obtained before 10 weeks, the adjusted OR of Bb in the top decile for preeclampsia was 6.1 (95% CI 2.2, 17, P = .0005).
Conclusion
The complement activation product Bb in early pregnancy is a biomarker for elevated risk of preeclampsia. This observation suggests that events linked to activation of complement in early pregnancy are associated with the pathogenesis of preeclampsia.
aDepartment of Obstetrics and Gynecology, University of Colorado at Denver and Health Sciences Center, Denver, CO
bDepartment of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, CO
cDepartment of Medicine and Immunology, University of Colorado at Denver and Health Sciences Center, Denver, CO
dDivision of Biostatistics and Bioinformatics, National Jewish Medical and Research Center, Denver, CO
eDepartment of Pediatrics, Division of Allergy and Immunology, National Jewish Medical and Research Center, Denver, CO
fWeill Medical College, Cornell University, New York, NY.
Reprints: Anne Lynch MB, BCh, BAO, MSPH, Department of Obstetrics and Gynecology, University of Colorado at Denver and Health Sciences Center, Department of Obstetrics and Gynecology, Mail Stop B198-5, Academic Office One, 12631 East 17th Avenue, PO Box 6511, Aurora, CO 80045.
This study was supported by Grant K23 HD049684 from the National Institute of Child Health and Human Development and Newborn Hope Colorado (to A.M.L.) and National Institutes of Health Grant R01 AI 55007 (to V.M.H.).
Cite this article as: Lynch AM, Murphy JR, Byers T, et al. Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia. Am J Obstet Gynecol 2008;198:385.e1-385.e9.
ABSTRACT
Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia