Predicting first trimester pregnancy outcome: derivation of a multiple marker test

Abstract

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 B1-glycoprotein (SP1), 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.

Keywords: Ectopic pregnancy; biomarker; early pregnancy failure.

Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Sensitivity and Specificity Trees for Pregnancy Location EP – Ectopic Pregnancy Intrauterine – Miscarriage (SAB) + Viable intrauterine pregnancy (IUP)

Figure 2

Sensitivity and Specificity Trees for Pregnancy Viability IUP – Viable intrauterine pregnancy Nonviable – Miscarriage (SAB) + Ectopic Pregnancy (EP)