Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia.
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.


METHODS
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).


CONCLUSIONS
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.
Lynch
Anne M
AM
Department of Obstetrics and Gynecology, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA. anne.lynch@uchsc.edu
Murphy
James R
JR
Byers
Tim
T
Gibbs
Ronald S
RS
Neville
Margaret C
MC
Giclas
Patricia C
PC
Salmon
Jane E
JE
Holers
V Michael
VM
D000328:Adult; D015415:Biomarkers / Q000097:blood; D011415:Complement Factor B / Q000032:analysis*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D011237:Predictive Value of Tests; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; D011415:Complement Factor B