Development of a Multiple Marker Test for Ectopic Pregnancy

Rausch, Mary; Sammel, Mary D.; Takács, Péter; Chung, Karine; Shaunik, Alka; Barnhart, Kurt T.

doi:10.1097/aog.0b013e31820b3c61

Cited by 55 publications

(73 citation statements)

References 35 publications

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“…The previous predictive model of EP was based on the combination of two decision trees (10). One decision tree was developed to maximize the sensitivity of prediction, and the second to maximize specificity of prediction for the outcome of interest.…”

Section: Methodsmentioning

confidence: 99%

“…Overall accuracy in those classified, and accuracy of each predicted outcome (ie. EP or IUP) is then reported (10, 18). …”

Section: Methodsmentioning

confidence: 99%

“…Prior studies identified a 4-marker test of progesterone, vascular endothelial growth factor (VEGF), Inhibin A and Activin A to have 98% sensitivity and 100% specificity for identifying EP in a subset of patients with EP and IUP. (10) Other groups have suggested multiple marker tests including combinations of markers of inflammation and corpus luteum function,(11) or of trophoblast and corpus luteum function(12). In addition, A Disintegrin And Metalloprotease-12 (ADAM12) (13, 14) and placental like growth factor (PlGF) (15,16), have been suggested as potential biomarker candidates.…”

Section: Introductionmentioning

confidence: 99%

“…Our first aim was to validate a 4-marker test for prediction of ectopic pregnancy that we previously derived. (10) Our second aim was to assess a multiple marker test incorporating two novel markers (PlGF and ADAM12). We hypothesized that marker performance would be synergized by optimizing sensitivity and specificity for pregnancy location (extra-uterine vs. intrauterine) and viability (IUP vs. early pregnancy failure).…”

Section: Introductionmentioning

confidence: 99%

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

Senapati

Sammel

Butts

et al. 2016

Fertility and Sterility

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Objective To predict first trimester pregnancy outcome using biomarkers in a multi-center cohort. Design Case-control study Setting Three academic centers Patients Women with pain and bleeding in early pregnancy Interventions Sera from women 5-12 weeks’ gestational age (GA) with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage (SAB) was analyzed via ELISA and immunoassay for Activin A (AA), Inhibin A (IA), Progesterone (P4), ADAM12, PAPP-A, pregnancy specific beta-glycoprotein-1 (SP1), Placental-like growth factor (PlGF), Vascular endothelial growth factor (VEGF), Glycodelin (Glyc), and human chorionic gonadotropin (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. Results In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity, (95% 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. AA, Glyc, and ADAM12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. P4 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 Glycodelin are the most promising markers for pregnancy location; Progesterone and PAPP-A for viability.

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Section: Methodsmentioning

confidence: 99%

“…Overall accuracy in those classified, and accuracy of each predicted outcome (ie. EP or IUP) is then reported (10, 18). …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Senapati

Sammel

Butts

et al. 2016

Fertility and Sterility

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, Dewan and co-workers reported that a copy-number deletion of PSG11 and its alternatively spliced variants may confer risk for preeclampsia but further studies are required to confirm their findings (Zhao et al, 2012). Expression of some PSGs has been reported in molar trophoblastic tissue (Hagiwara et al, 1986, Leslie et al, 1990 and differential expression of PSGs in intrauterine pregnancy and ectopic pregnancy have been recently suggested to have useful diagnostic value as part of a multiple biomarker test (Rausch et al, 2011). In summary, while low PSG concentrations appear associated with some pregnancy complications, studies with more specific reagents are required as PSG levels could potentially be used as useful markers of placental function.…”

Section: Psgs and Pregnancy Pathologiesmentioning

confidence: 99%

Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions

2014

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The pregnancy-specific glycoproteins (PSGs) are the most abundant trophoblastic proteins in maternal blood during human pregnancy and they appear to be exclusive to species with hemochorial placentation. There are ten protein-coding human PSG genes (PSG1 -PSG9, PSG11) and also multiple PSG genes in non-human primates, rodents and bats. Several studies indicate that PSGs have immunoregulatory, pro-angiogenic, and anti-platelet functions. Some PSGs have been shown to bind different moieties on the surface of cells, including the tetraspanin CD9, heparan sulphate, and specific integrins. Recently, PSG1 was shown to associate with and activate the anti-inflammatory cytokines transforming growth factor (TGF)-b1 and TGF-b2 making PSG1 one of the few known biological activators of these important cytokines. TGF-bs regulate many biological processes essential for pregnancy success including trophoblast invasion and proliferation, angiogenesis, extracellular matrix formation and tolerance to the fetal semi-allograft. As summarized in this review, progress has been made in recent years towards a better understanding of the functions of these proteins which were originally described in the early 1970s, but more research will likely contribute to demonstrate their importance for a successful pregnancy.

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The potential value of activin B and fibronectin for the triage of pregnancies of unknown location and prediction of first trimester viability

Al‐Memar

Bobdiwala

Madhra

et al. 2018

Australas J Ultrason Med

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AimWe have assessed the potential predictive ability of the biomarkers activin B and fibronectin (FN1) alone and when added to established markers for triaging patients as being at low or high risk of ectopic pregnancy (EP). We also assessed their use as predictors of viability at 12 weeks gestation.MethodsExploratory secondary analysis of a prospective study including all women classified as a pregnancy of known location (PUL) based on transvaginal ultrasonography between January and December 2007 at the early pregnancy unit of St Georges’ Hospital (London). We used multinomial logistic regression to assess the diagnostic potential of the biomarkers to triage PUL at high risk of complications (EP or persistent PUL), and standard binary logistic regression to predict first trimester viability at 12 weeks.ResultsFor discriminating high‐risk (n = 16) from low‐risk PUL (n = 93), the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval 0.60–0.85) for activin B and 0.55 (0.41–0.68) for FN1. Adding activin B to a multinomial logistic regression model incorporating β‐hCG ratio and initial progesterone yielded odds ratios of 0.16 (0.05–0.55) for failing vs high‐risk PUL and 0.29 (0.07–1.19) for intrauterine vs high‐risk PUL and increased the model's AUC from 0.84 to 0.89. At a risk threshold of 5% for high‐risk PUL, sensitivity increased from 84% to 87% and specificity from 48% to 64%. For discriminating viable (n = 28) from non‐viable (n = 81) pregnancies at 12 weeks, both markers had an AUC of 0.54.ConclusionsOur results suggested that activin B may be a promising marker to improve PUL triage in addition to established markers.

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Development of a Multiple Marker Test for Ectopic Pregnancy

Abstract: : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194168.

Cited by 55 publications

References 35 publications

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

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

Pregnancy-specific glycoproteins: complex gene families regulating maternal-fetal interactions

The potential value of activin B and fibronectin for the triage of pregnancies of unknown location and prediction of first trimester viability

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