Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy

Objectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (pro...

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Main Authors: Jesper Friis Petersen, Vilma Tiittanen, Saara Wittfooth, Ellen Løkkegaard, Lennart Jan Friis-Hansen
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Practical Laboratory Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S235255172400074X
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author Jesper Friis Petersen
Vilma Tiittanen
Saara Wittfooth
Ellen Løkkegaard
Lennart Jan Friis-Hansen
author_facet Jesper Friis Petersen
Vilma Tiittanen
Saara Wittfooth
Ellen Løkkegaard
Lennart Jan Friis-Hansen
author_sort Jesper Friis Petersen
collection DOAJ
description Objectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility. Design: and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4–14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses. Results: During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p < 0.001), maternal weight (p < 0.001), and smoking (p = 0.02). For miscarriage prediction fPAPP-A was equal to PAPP-A (area under the receiver operating characteristics curve 0.79 vs. 0.81, p = 0.44). Conclusions: Investigating fPAPP-A presence and concentration directly in first trimester serum has not been done previously. This study report lower fPAPP-A values than anticipated from prior enzymatic studies of fPAPP-A. fPAPP-A was not superior to PAPP-A as a first trimester biomarker in this dataset.
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spelling doaj-art-4e81ffccd80e4f7bb03218e3b734e4d92025-08-20T02:37:02ZengElsevierPractical Laboratory Medicine2352-55172024-11-0142e0042810.1016/j.plabm.2024.e00428Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancyJesper Friis Petersen0Vilma Tiittanen1Saara Wittfooth2Ellen Løkkegaard3Lennart Jan Friis-Hansen4Department of Obstetrics and Gynecology, North Zealand Hospital, Dyrehavevej 29, 3400, Hillerød, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark; Corresponding author. Department of Obstetrics and Gynecology, North Zealand Hospital, Dyrehavevej 29, 3400, Hillerød, Denmark.Biotechnology Unit, Department of Life Technologies, 20014, University of Turku, FinlandBiotechnology Unit, Department of Life Technologies, 20014, University of Turku, FinlandDepartment of Obstetrics and Gynecology, North Zealand Hospital, Dyrehavevej 29, 3400, Hillerød, Denmark; Department of Clinical Medicine, University of Copenhagen, DenmarkDepartment of Clinical Biochemistry, Bispebjerg Hospital University Hospital, Nielsine Nielsens Vej 2, 2400, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, DenmarkObjectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility. Design: and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4–14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses. Results: During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p < 0.001), maternal weight (p < 0.001), and smoking (p = 0.02). For miscarriage prediction fPAPP-A was equal to PAPP-A (area under the receiver operating characteristics curve 0.79 vs. 0.81, p = 0.44). Conclusions: Investigating fPAPP-A presence and concentration directly in first trimester serum has not been done previously. This study report lower fPAPP-A values than anticipated from prior enzymatic studies of fPAPP-A. fPAPP-A was not superior to PAPP-A as a first trimester biomarker in this dataset.http://www.sciencedirect.com/science/article/pii/S235255172400074XPAPP-AFree PAPP-AFirst trimesterMiscarriageLive birthImmunoassay
spellingShingle Jesper Friis Petersen
Vilma Tiittanen
Saara Wittfooth
Ellen Løkkegaard
Lennart Jan Friis-Hansen
Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
Practical Laboratory Medicine
PAPP-A
Free PAPP-A
First trimester
Miscarriage
Live birth
Immunoassay
title Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
title_full Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
title_fullStr Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
title_full_unstemmed Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
title_short Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy
title_sort exploring free pregnancy associated plasma protein a fpapp a as a biomarker in early pregnancy
topic PAPP-A
Free PAPP-A
First trimester
Miscarriage
Live birth
Immunoassay
url http://www.sciencedirect.com/science/article/pii/S235255172400074X
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