Pregnancy-associated plasma protein A (PAPP-A): measurement by highly sensitive and specific enzyme immunoassay, importance of first-trimester serum determinations, and stability studies

1995 ◽  
Vol 7 (6) ◽  
pp. 1419 ◽  
Author(s):  
NA Bersinger ◽  
P Marguerat ◽  
G Pescia ◽  
H Schneider
Keyword(s):  
Enzyme Immunoassay ◽  
Plasma Protein ◽  
Protein A ◽  
First Trimester ◽  
Maternal Serum ◽  
Potential Candidate ◽  
Second Trimester ◽  
Freezing And Thawing ◽  
Control Serum ◽  
Repeated Freezing

It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboratories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).

Four Years' Experience With an Interlaboratory Comparison Program Involving First-Trimester Markers of Down Syndrome

2010 ◽  
Vol 134 (11) ◽  
pp. 1685-1691
Author(s):  
Glenn E. Palomaki ◽  
George J. Knight ◽  
Geralyn Lambert-Messerlian ◽  
Jacob A. Canick ◽  
James E. Haddow
Keyword(s):  
Down Syndrome ◽  
Chorionic Gonadotropin ◽  
Plasma Protein ◽  
Human Chorionic Gonadotropin ◽  
Interlaboratory Comparison ◽  
Protein A ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Second Trimester ◽  
Coefficients Of Variation

Abstract Context.—We initiated a voluntary, self-funded interlaboratory comparison program in the fall of 2005 because no proficiency testing program was available to laboratories in North America offering first-trimester, combined serum and ultrasound, Down syndrome screening. Objectives.—To evaluate the first 4 years of the interlaboratory comparison program against stated goals, to identify areas of concern, and to create new initiatives as indicated. Design.—Five serum samples are distributed 3 times a year to be tested for pregnancy-associated plasma protein A, human chorionic gonadotropin or its β subunit, and dimeric inhibin-A; participants convert these results into multiples of the median. Patient histories include nuchal translucency information that enables the calculation of the risk of Down syndrome. Also included are educational components linked to interlaboratory comparison program results. Assessment of integrated (first- and second-trimester markers) risks is accomplished by having participants combine interlaboratory comparison program results with their results from a second-trimester proficiency testing program administered by the College of American Pathologists. Results.—The precision profile for pregnancy-associated plasma protein A shows decreasing coefficients of variation with increasing pregnancy-associated plasma protein A concentrations and multiples of the median (25% to 11% and 30% to 15%, respectively). In contrast, coefficients of variation are a relatively constant 12% throughout the entire range of human chorionic gonadotropin results. On a logarithmic scale, the median coefficient of variation of the risk of Down syndrome is 9%. Conclusions.—Participants in the interlaboratory comparison program reliably measure analytes, compute multiples of the median, and calculate consistent Down syndrome risks. Assays for the measurement of pregnancy-associated plasma protein A are not standardized and are less precise than those for human chorionic gonadotropin. Participants calculate reliable median equations given sonographer-specific sets of paired crown-rump length and nuchal translucency measurements.

Association between first-trimester maternal serum pregnancy-associated plasma protein-A and obstetric complications

2013 ◽  
Vol 33 (9) ◽  
pp. 839-847 ◽  
Author(s):  
Francesco D'Antonio ◽  
Claudia Rijo ◽  
Basky Thilaganathan ◽  
Ranjit Akolekar ◽  
Asma Khalil ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Protein A ◽  
First Trimester ◽  
Maternal Serum ◽  
Obstetric Complications

scholarly journals First Trimester Biochemical Screening for Trisomy 21: The Role of Free Beta hCG, Alpha Fetoprotein and Pregnancy Associated Plasma Protein A

1994 ◽  
Vol 31 (5) ◽  
pp. 447-454 ◽  
Author(s):  
K Spencer ◽  
D A Aitken ◽  
J A Crossley ◽  
G McCaw ◽  
E Berry ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Plasma Protein ◽  
Human Chorionic Gonadotropin ◽  
Trisomy 21 ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Serum Markers ◽  
Maternal Serum ◽  
Detection Rates

The potential efficacy of screening for trisomy 21 in the first trimester, using maternal serum markers α fetoprotein, free β human chorionic gonadotropin, unconjugated oestriol and pregnancy associated plasma protein A, was studied in an unselected population of women between the seventh and fourteenth week of gestation. Using a combination of α fetoprotein and free β human chorionic gonadotropin, 53% of affected pregnancies could be identified at a false positive rate of 5%. Unconjugated oestriol and pregnancy associated plasma protein A levels were lower in cases of trisomy 21, but their inclusion with other markers did not significantly improve detection rate. Monitoring the same pregnancies also in the second trimester showed that screening in the first trimester identified the same cases as in the second. We conclude that first trimester screening using free β human chorionic gonadotropin and α fetoprotein, is a viable possibility and will lead to detection rates in excess of 50%. Prospective studies are needed to confirm these observations.

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