Predicting first trimester pregnancy outcome: derivation of a multiple marker test.
OBJECTIVE
To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort.


METHODS
Case-control study.


METHODS
Three academic centers.


METHODS
Women with pain and bleeding in early pregnancy.


METHODS
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.


METHODS
Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome.


RESULTS
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.


CONCLUSIONS
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.
Department Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Suneeta.Senapati@uphs.upenn.edu.
Suneeta
S
Senapati
Center for Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania.
Mary D
MD
Sammel
Department Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania.
Samantha F
SF
Butts
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
Peter
P
Takacs
Reproductive Endocrinology & Infertility, University of Southern California, Los Angeles, California.
Karine
K
Chung
Department Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania.
Kurt T
KT
Barnhart
D000072199:ADAM12 Protein / Q000097:blood*; D000022:Abortion, Spontaneous / Q000097:blood* / Q000175:diagnosis; D028341:Activins / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000071816:Glycodelin / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000097:blood*; D011271:Pregnancy, Ectopic / Q000097:blood* / Q000175:diagnosis; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011374:Progesterone / Q000097:blood*; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D014481:United States
D015415:Biomarkers; D000071816:Glycodelin; C045246:PAEP protein, human; C422405:activin A; D028341:Activins; D011374:Progesterone; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
Ectopic pregnancy; biomarker; early pregnancy failure