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

Fertil Steril. 2016 Dec;106(7):1725-1732.e3. doi: 10.1016/j.fertnstert.2016.08.044. Epub 2016 Oct 26.


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.

Publication types

  • Multicenter Study

MeSH terms

  • ADAM12 Protein / blood*
  • Abortion, Spontaneous / blood*
  • Abortion, Spontaneous / diagnosis
  • Activins / blood*
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycodelin / blood*
  • Humans
  • Immunoassay
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, First / blood*
  • Pregnancy, Ectopic / blood*
  • Pregnancy, Ectopic / diagnosis
  • Pregnancy-Associated Plasma Protein-A / analysis*
  • Progesterone / blood*
  • ROC Curve
  • Reproducibility of Results
  • Risk Factors
  • United States


  • Biomarkers
  • Glycodelin
  • PAEP protein, human
  • activin A
  • Activins
  • Progesterone
  • ADAM12 Protein
  • ADAM12 protein, human
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA protein, human