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Predicting First Trimester Pregnancy Outcome: Derivation of a Multiple Marker Test

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Journal Fertil Steril
Date 2017 Mar 26
PMID 28340932
Citations 11
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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 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.

Citing Articles

Evaluation of novel biomarkers for early pregnancy outcome prediction†.

Bollig K, Senapati S, Takacs P, Robins J, Haisenleder D, Beer L Biol Reprod. 2023; 110(3):548-557.

PMID: 38011676 PMC: 10941089. DOI: 10.1093/biolre/ioad162.


Ectopic pregnancy: search for biomarker in salivary proteome.

Priya Aarthy A, Sen S, Srinivasan M, Muthukumar S, Madhanraj P, Akbarsha M Sci Rep. 2023; 13(1):16828.

PMID: 37803047 PMC: 10558548. DOI: 10.1038/s41598-023-43791-7.


Identification and verification of plasma protein biomarkers that accurately identify an ectopic pregnancy.

Beer L, Yin X, Ding J, Senapati S, Sammel M, Barnhart K Clin Proteomics. 2023; 20(1):37.

PMID: 37715129 PMC: 10503165. DOI: 10.1186/s12014-023-09425-w.


Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

Guo J, Feng Q, Chaemsaithong P, Appiah K, Sahota D, Leung B Acta Obstet Gynecol Scand. 2023; 102(8):1073-1083.

PMID: 37377341 PMC: 10378019. DOI: 10.1111/aogs.14618.


Validation of a multiple marker test for early pregnancy outcome prediction.

Bollig K, Senapati S, Sammel M, Takacs P, Robins J, Haisenleder D J Assist Reprod Genet. 2023; 40(4):837-844.

PMID: 36708430 PMC: 10224881. DOI: 10.1007/s10815-023-02719-w.


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