Predicting First Trimester Pregnancy Outcome: Derivation of a Multiple Marker Test
Overview
Affiliations
Objective: To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort.
Design: Case-control study.
Setting: Three academic centers.
Patient(s): Women with pain and bleeding in early pregnancy.
Intervention(s): Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B-glycoprotein (SP), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG. Classification trees were developed to optimize sensitivity/specificity for pregnancy location and viability.
Main Outcome Measure(s): Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome.
Result(s): In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity (95% confidence interval (CI) 0.65-0.80) and 31% sensitivity (95% CI 0.21-0.43) for viability. Similar methods had 21% sensitivity (95% CI 0.12-0.32) and 33% specificity (95% CI 0.26-0.41) for location. Activin A, Glyc, and A Disintegrin And Metalloprotease-12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. Progesterone and PAPP-A classified the viability in 61% of the sample with 94% accuracy.
Conclusion(s): Multiple marker panels can distinguish pregnancy location and viability in a subset of women at risk for early pregnancy complications. This strategy of combining markers to maximize sensitivity and specificity results in high accuracy in a subset of subjects. Activin A, ADAM12, and Glyc are the most promising markers for pregnancy location; P and PAPP-A for viability.
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