Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Print + Online
See all formats and pricing
More options …
Volume 51, Issue 9

Issues

Autocorrelation and cross-correlation between hCGβ and PAPP-A in repeated sampling during first trimester of pregnancy

Pernille Nørgaard
  • Corresponding author
  • Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dave Wright / Susan Ball / Paul Newell / Ida Kirkegaard / Olav Bjørn Petersen
  • Fetal Medicine Unit, Department of Obstetrics and Gynecology, Aarhus University Hospital-Skejby, Aarhus, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Niels Uldbjerg
  • Fetal Medicine Unit, Department of Obstetrics and Gynecology, Aarhus University Hospital-Skejby, Aarhus, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Niels Tørring / Finn Stener Jørgensen
  • Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lennart Friis-Hansen
  • Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Charlotte Ekelund
  • Department of Obstetrics and Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ann Tabor
  • Center of Fetal Medicine, Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Steen Sørensen
  • Department of Clinical Biochemistry, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-04-11 | DOI: https://doi.org/10.1515/cclm-2012-0805

Abstract

Background: Theoretically, repeated sampling of free β-human chorionic gonadotropin (hCGβ) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester of pregnancy might improve performance of risk assessment of trisomy 21 (T21). To assess the performance of a screening test involving repeated measures of biochemical markers, correlations between markers must be estimated. The aims of this study were to calculate the autocorrelation and cross-correlation between hCGβ and PAPP-A in the first trimester of pregnancy and to investigate the possible impact of gestational age at the first sample and time between sampling on the correlation.

Methods: A prospective study was conducted including 3891 unaffected singleton pregnancies. Two measurements of hCGβ and PAPP-A were obtained during the first trimester in each pregnancy. Correlations between the four parameters, hCGβ first, hCGβ second, PAPP-A first and PAPP-A second, were estimated and presented in terms of Pearson’s r coefficients. Furthermore, the correlation between paired samples as a function of time between samples was investigated.

Results: The study demonstrated high correlation between first and second samples of hCGβ and PAPP-A with a correlation coefficient of 0.80 and 0.79, respectively. By contrast, the correlations between hCGβ and PAPP-A were low. In addition, the study demonstrated that the correlation between paired samples of hCGβ and PAPP-A decreases with earlier gestational age at the first sample and with increasing time between samples.

Conclusions: We have developed a parameter set in terms of correlations between biochemical markers, which can be incorporated into a T21 screening algorithm based on repeated measures within the first trimester.

Keywords: combined first trimester screening; correlation; Down syndrome screening; first trimester risk assessment; free β-human chorionic gonadotropin (hCGβ); pregnancy associated plasma protein-A (PAPP-A); repeated biochemical markers; Trisomy 21 screening

References

  • 1.

    Nicolaides KH, Spencer K, Avgidou K, Faiola S, Falcon O. Multicenter study of first-trimester screening for trisomy 21 in 75821 pregnancies: results and estimation of potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet Gynecol 2005;25:221–6.Google Scholar

  • 2.

    Spencer K, Crossley JA, Aitken DA, Nix AB, Dunstan FD, Williams K. Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy. Ann Clin Biochem 2002;39:567–76.PubMedCrossrefGoogle Scholar

  • 3.

    Spencer K, Crossley JA, Aitken DA, Nix AB, Dunstan FD, Williams K. The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down’s syndrome. Ann Clin Biochem 2003;40:219–31.CrossrefPubMedGoogle Scholar

  • 4.

    Kirkegaard I, Petersen OB, Uldbjerg N, Torring N. Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks. Prenat Diagn 2008;28:839–44.PubMedGoogle Scholar

  • 5.

    Wright D, Spencer K, Kagan K, Tørring N, Petersen OB, Christou A, et al. First trimester combined screening for trisomy 21 at 7–14 weeks gestation. Ultrasound Obstet Gynecol 2010;36:404–11.CrossrefGoogle Scholar

  • 6.

    Wright D, Bradbury I. Repeated measures screening for Down’s syndrome. BJOG 2005;112:80–3.PubMedGoogle Scholar

  • 7.

    Palomaki GE, Wright DE, Summers AM, Neveux LM, Meier C, O’Donnell A, et al. Repeated measurement of pregnancy-associated plasma protein-A (PAPP-A) in Down syndrome screening: a validation study. Prenat Diagn 2006;26:730–9.PubMedGoogle Scholar

  • 8.

    Spencer K, Cuckle HS. Screening for chromosomal anomalies in the first trimester: does repeat maternal serum screening improve detection rates? Prenat Diagn 2002;22:903–6.PubMedGoogle Scholar

  • 9.

    Sennels HP, Jørgensen FS, Sørensen S. Biological variation of free β chorionic gonadotropin and pregnancy-associated plasma protein A in first trimester pregnancies. Clin Chem Lab Med 2011;49:291–5.PubMedWeb of ScienceGoogle Scholar

  • 10.

    Spencer K, Cowans NJ. Analytical goal setting in aneuploidy screening: within person biological variability of first trimester biochemical markers. Prenat Diagn 2012;32:1–6.Google Scholar

  • 11.

    R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2011 (ISBN 3-900051-07-0, URL http://www.R-project.org/).

  • 12.

    Lambert-Messerlian GM, Eklund EE, Malone FD, Palomaki GE, Canick JA, D’Alton ME. Stability of first- and second-trimester serum markers after storage and shipment. Prenat Diagn 2006;26:17–21.Google Scholar

  • 13.

    Wright D, Bradbury I, Malone F, D’Alton M, Summers A, Huang T, et al. Cross-trimester repeated measures testing for Down’s syndrome screening: an assessment. Health Technol Assess 2010;14:1–80.PubMedWeb of ScienceGoogle Scholar

  • 14.

    Kagan KO, Hoopmann M, Baker A, Huebner M, Abele H, Wright D. Impact of bias in crown-rump length measurement at first-trimester screening for trisomy 21. Ultrasound Obstet Gynecol 2012;40:135–9.PubMedCrossrefGoogle Scholar

About the article

Corresponding author: Pernille Nørgaard, MD, Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Copenhagen 2650, Denmark


Received: 2012-11-24

Accepted: 2013-03-18

Published Online: 2013-04-11

Published in Print: 2013-09-01


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 51, Issue 9, Pages 1781–1788, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0805.

Export Citation

©2013 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Niels Tørring
Scandinavian Journal of Clinical and Laboratory Investigation, 2016, Volume 76, Number 6, Page 435

Comments (0)

Please log in or register to comment.
Log in