Home Medicine Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia
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Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

  • Carin P. De Villiers , Paula L. Hedley , Sophie Placing , Karen R. Wøjdemann , Anne-Cathrine Shalmi , Anting L. Carlsen , Line Rode , Karin Sundberg , Ann Tabor and Michael Christiansen EMAIL logo
Published/Copyright: July 12, 2017
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 1

Abstract

Background:

Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified.

Methods:

PP13 was measured in first trimester (week 10+3–13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation.

Results:

In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8–85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1–50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4–142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI.

Conclusions:

PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Keywords: biomarkers; preeclampsia; pregnancy complications; pregnancy outcome; prenatal diagnosis
Corresponding author: Michael Christiansen, FRCPath, MD, Professor, Chief Physician, Department for Congenital Disorders, Statens Serum Institut, 5 Artillerivej, 2300S Copenhagen, Denmark, Phone: +4532683657

Acknowledgments

We gratefully acknowledge the expert technical assistance of Pia Lind. We acknowledge the financial support of the Danish Medical Research Council, The John and Birthe Meyer Foundation, The Ivan Nielsen Foundation, The Else and Mogens Wedell-Wedellsborg Foundation, The Dagmar Marshall Foundation, The Egmont Foundation, The Fetal Medicine Foundation, The Augustinus Foundation, The Gangsted Foundation, The A.P. Møller Foundation and The Mads Clausens Foundation. This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99.10.1002/9781444312904.ch68Search in Google Scholar

2. Moodley J. Maternal deaths due to hypertensive disorders in pregnancy: Saving Mothers report 2002–2004. Cardiovasc J Afr 2007;18:358–61.Search in Google Scholar

3. Papageorghiou AT, Campbell S. First trimester screening for preeclampsia. Curr Opin Obstet Gynecol 2006;18:594–600.10.1097/GCO.0b013e328010bedaSearch in Google Scholar

4. Shennan AH. Recent developments in obstetrics. Br Med J 2003;327:604–8.10.1136/bmj.327.7415.604Search in Google Scholar

5. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br Med J 2007;335:974.10.1136/bmj.39335.385301.BESearch in Google Scholar

6. Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 2008;51:970–5.10.1161/HYPERTENSIONAHA.107.107607Search in Google Scholar

7. Vatten LJ, Eskild A, Nilsen TI, Jeansson S, Jenum PA, Staff AC. Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am J Obstet Gynecol 2007;196:239 e1–6.10.1016/j.ajog.2006.10.909Search in Google Scholar

8. Roberts JM, Hubel CA. The two stage model of preeclampsia: variations on the theme. Placenta 2009;30 Suppl A:S32–7.10.1016/j.placenta.2008.11.009Search in Google Scholar

9. Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol 2010;63:534–43.10.1111/j.1600-0897.2010.00831.xSearch in Google Scholar

10. Kharfi A, Giguere Y, De Grandpre P, Moutquin JM, Forest JC. Human chorionic gonadotropin (hCG) may be a marker of systemic oxidative stress in normotensive and preeclamptic term pregnancies. Clin Biochem 2005;38:717–21.10.1016/j.clinbiochem.2005.04.011Search in Google Scholar

11. Masse J, Giguere Y, Kharfi A, Girouard J, Forest JC. Pathophysiology and maternal biologic markers of preeclampsia. Endocrine 2002;19:113–25.10.1385/ENDO:19:1:113Search in Google Scholar

12. Hubel CA, Powers RW, Snaedal S, Gammill HS, Ness RB, Roberts JM, et al. C-reactive protein is elevated 30 years after eclamptic pregnancy. Hypertension 2008;51:1499–505.10.1161/HYPERTENSIONAHA.108.109934Search in Google Scholar

13. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:IX–XIV.10.3109/10641950109152635Search in Google Scholar

14. Vatten LJ, Skjaerven R. Is pre-eclampsia more than one disease? Br J Obstet Gynaecol 2004;111:298–302.10.1111/j.1471-0528.2004.00071.xSearch in Google Scholar

15. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005;105:402–10.10.1097/01.AOG.0000152351.13671.99Search in Google Scholar

16. Vainio M, Kujansuu E, Iso-Mustajarvi M, Maenpaa J. Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and intrauterine growth retardation in women with bilateral uterine artery notches. Br J Obstet Gynaecol 2002;109:161–7.10.1111/j.1471-0528.2002.01046.xSearch in Google Scholar

17. Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Giguere Y. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can 2009;31:818–26.10.1016/S1701-2163(16)34300-6Search in Google Scholar

18. Chames MC, Haddad B, Barton JR, Livingston JC, Sibai BM. Subsequent pregnancy outcome in women with a history of HELLP syndrome at < or = 28 weeks of gestation. Am J Obstet Gynecol 2003;188:1504–7; discussion 7–8.10.1067/mob.2003.383Search in Google Scholar PubMed

19. Giguere Y, Charland M, Bujold E, Bernard N, Grenier S, Rousseau F, et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: a systematic review. Clin Chem 2010;56:361–75.10.1684/abc.2011.0572Search in Google Scholar PubMed

20. Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H. First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol 2007;29:128–34.10.1002/uog.3876Search in Google Scholar PubMed

21. Nicolaides KH, Bindra R, Turan OM, Chefetz I, Sammar M, Meiri H, et al. A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound. Ultrasound Obstet Gynecol 2006;27:13–7.10.1002/uog.2686Search in Google Scholar PubMed

22. Bohn H, Kraus W, Winckler W. Purification and characterization of two new soluble placental tissue proteins (PP13 and PP17). Oncodev Biol Med 1983;4:343–50.Search in Google Scholar

23. Than NG, Sumegi B, Than GN, Berente Z, Bohn H. Isolation and sequence analysis of a cDNA encoding human placental tissue protein 13 (PP13), a new lysophospholipase, homologue of human eosinophil Charcot-Leyden Crystal protein. Placenta 1999;20:703–10.10.1053/plac.1999.0436Search in Google Scholar PubMed

24. Chiariotti L, Salvatore P, Frunzio R, Bruni CB. Galectin genes: regulation of expression. Glycoconj J 2004;19:441–9.10.1023/B:GLYC.0000014073.23096.3aSearch in Google Scholar

25. Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z, et al. A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death. Proc Natl Acad Sci USA 2009;106:9731–6.10.1073/pnas.0903568106Search in Google Scholar PubMed PubMed Central

26. Than NG, Pick E, Bellyei S, Szigeti A, Burger O, Berente Z, et al. Functional analyses of placental protein 13/galectin-13. Eur J Biochem 2004;271:1065–78.10.1111/j.1432-1033.2004.04004.xSearch in Google Scholar PubMed

27. Than NG, Abdul Rahman O, Magenheim R, Nagy B, Fule T, Hargitai B, et al. Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome. Virchows Arch 2008;453:387–400.10.1007/s00428-008-0658-xSearch in Google Scholar PubMed PubMed Central

28. Burger O, Pick E, Zwickel J, Klayman M, Meiri H, Slotky R, et al. Placental protein 13 (PP-13): effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies. Placenta 2004;25: 608–22.10.1016/j.placenta.2003.12.009Search in Google Scholar PubMed

29. Romero R, Kusanovic JP, Than NG, Erez O, Gotsch F, Espinoza J, et al. First-trimester maternal serum PP13 in the risk assessment for preeclampsia. Am J Obstet Gynecol 2008;199:122e1–11.10.1016/j.ajog.2008.01.013Search in Google Scholar PubMed PubMed Central

30. Chafetz I, Kuhnreich I, Sammar M, Tal Y, Gibor Y, Meiri H, et al. First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction. Am J Obstet Gynecol 2007;197:35e1–7.10.1016/j.ajog.2007.02.025Search in Google Scholar PubMed

31. Huppertz B, Sammar M, Chefetz I, Neumaier-Wagner P, Bartz C, Meiri H. Longitudinal determination of serum placental protein 13 during development of preeclampsia. Fetal Diagn Ther 2008;24:230–6.10.1159/000151344Search in Google Scholar PubMed

32. Gonen R, Shahar R, Grimpel YI, Chefetz I, Sammar M, Meiri H, et al. Placental protein 13 as an early marker for pre-eclampsia: a prospective longitudinal study. Br J Obstet Gynaecol 2008;115:1465–72.10.1111/j.1471-0528.2008.01902.xSearch in Google Scholar PubMed

33. Khalil A, Cowans NJ, Spencer K, Goichman S, Meiri H, Harrington K. First trimester maternal serum placental protein 13 for the prediction of pre-eclampsia in women with a priori high risk. Prenat Diagn 2009;29:781–9.10.1002/pd.2287Search in Google Scholar PubMed

34. Koster MP, Wortelboer EJ, Cuckle HS, Stoutenbeek P, Visser GH, Schielen PC. Placental protein 13 as a first trimester screening marker for aneuploidy. Prenat Diagn 2009;29: 1237–41.10.1002/pd.2384Search in Google Scholar PubMed

35. Akolekar R, Perez Penco JM, Skyfta E, Rodriguez Calvo J, Nicolaides KH. Maternal serum placental protein 13 at eleven to thirteen weeks in chromosomally abnormal pregnancies. Fetal Diagn Ther 2010;27:72–7.10.1159/000294340Search in Google Scholar PubMed

36. Cowans NJ, Spencer K, Meiri H. First-trimester maternal placental protein 13 levels in pregnancies resulting in adverse outcomes. Prenat Diagn 2008;28:121–5.10.1002/pd.1921Search in Google Scholar PubMed

37. Hedley PL, Placing S, Wojdemann K, Carlsen AL, Shalmi AC, Sundberg K, et al. Free leptin index and PAPP-A: a first trimester maternal serum screening test for pre-eclampsia. Prenat Diagn 2010;30:103–9.10.1002/pd.2337Search in Google Scholar PubMed

38. Laigaard J, Sorensen T, Placing S, Holck P, Frohlich C, Wojdemann KR, et al. Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia. Obstet Gynecol 2005;106:144–9.10.1097/01.AOG.0000165829.65319.65Search in Google Scholar PubMed

39. Wojdemann KR, Shalmi AC, Christiansen M, Larsen SO, Sundberg K, Brocks V, et al. Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women. Ultrasound Obstet Gynecol 2005;25:227–33.10.1002/uog.1834Search in Google Scholar PubMed

40. Robinson HP, Fleming JE. A critical evaluation of sonar “crown-rump length” measurements. Br J Obstet Gynaecol 1975;82:702–10.10.1111/j.1471-0528.1975.tb00710.xSearch in Google Scholar PubMed

41. Larsen SO, Christiansen M, Norgaard-Pedersen B. Calculation of roc curves in multidimensional likelihood ratio based screening with Down’s syndrome as a special case. J Med Screen 1998;5:57–62.10.1136/jms.5.2.57Search in Google Scholar PubMed

42. Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11–13 weeks of gestation in preeclampsia. Prenat Diagn 2009;29:1103–8.10.1002/pd.2375Search in Google Scholar PubMed

43. Christiansen M, Pihl K, Hedley PL, Gjerris AC, Lind PO, Larsen SO, et al. ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome. Prenat Diagn 2010;30:110–4.10.1002/pd.2405Search in Google Scholar PubMed

44. Than NG, Romero R, Hillermann R, Cozzi V, Nie G, Huppertz B. Prediction of preeclampsia - a workshop report. Placenta 2008;29 Suppl A:S83–5.10.1016/j.placenta.2007.10.008Search in Google Scholar PubMed PubMed Central

45. Conover CA, Oxvig C, Overgaard MT, Christiansen M, Giudice LC. Evidence that the insulin-like growth factor binding protein-4 protease in human ovarian follicular fluid is pregnancy associated plasma protein-A. J Clin Endocrinol Metab 1999;84:4742–5.10.1210/jcem.84.12.6342Search in Google Scholar PubMed

46. Giudice LC, Conover CA, Bale L, Faessen GH, Ilg K, Sun I, et al. Identification and regulation of the IGFBP-4 protease and its physiological inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine regulation of IGF-II bioavailability in the placental bed during human implantation. J Clin Endocrinol Metab 2002;87:2359–66.10.1210/jcem.87.5.8448Search in Google Scholar PubMed

47. Henson MC, Castracane VD. Leptin in pregnancy: an update. Biol Reprod 2006;74:218–29.10.1095/biolreprod.105.045120Search in Google Scholar PubMed

48. Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med 2010;362:1282–91.10.1056/NEJMoa0908056Search in Google Scholar PubMed PubMed Central

49. Sekizawa A, Purwosunu Y, Yoshimura S, Nakamura M, Shimizu H, Okai T, et al. PP13 mRNA expression in trophoblasts from preeclamptic placentas. Reprod Sci 2009;16:408–13.10.1177/1933719108328615Search in Google Scholar PubMed

50. Shimizu H, Sekizawa A, Purwosunu Y, Nakamura M, Farina A, Rizzo N, et al. PP13 mRNA expression in the cellular component of maternal blood as a marker for preeclampsia. Prenat Diagn 2009;29:1231–6.10.1002/pd.2380Search in Google Scholar PubMed

Received: 2017-4-25
Accepted: 2017-5-23
Published Online: 2017-7-12
Published in Print: 2017-11-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

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  2. Editorial
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  4. Review
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  17. Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy
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  25. Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose
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  35. Letters to the Editor
  36. Handling the altered test results of hemolyzed samples. Recommendations of the Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML)
  37. Reply to: Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
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https://doi.org/10.1515/cclm-2017-0356
Keywords for this article
biomarkers; preeclampsia; pregnancy complications; pregnancy outcome; prenatal diagnosis

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Method comparison – a practical approach based on error identification
  4. Review
  5. Neutrophil gelatinase-associated lipocalin as a risk marker in cardiovascular disease
  6. Mini Reviews
  7. α-Defensin point-of-care test for diagnosis of prosthetic joint infections: neglected role of laboratory and clinical pathologists
  8. The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature
  9. Opinion Paper
  10. New issues on measurement of B-type natriuretic peptides
  11. Genetics and Molecular Diagnostics
  12. The SEeMORE strategy: single-tube electrophoresis analysis-based genotyping to detect monogenic diseases rapidly and effectively from conception until birth
  13. General Clinical Chemistry and Laboratory Medicine
  14. Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry
  15. The effects of dry ice exposure on plasma pH and coagulation analyses
  16. Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia
  17. Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy
  18. Performance analysis of automated evaluation of Crithidia luciliae-based indirect immunofluorescence tests in a routine setting – strengths and weaknesses
  19. Performance of automated digital cell imaging analyzer Sysmex DI-60
  20. Reference Values and Biological Variations
  21. Determination of reference intervals for urinary steroid profiling using a newly validated GC-MS/MS method
  22. Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy
  23. Definition of the upper reference limit of glycated albumin in blood donors from Italy
  24. Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents
  25. Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose
  26. Cancer Diagnostics
  27. Cancer sniffer dogs: how can we translate this peculiarity in laboratory medicine? Results of a pilot study on gastrointestinal cancers
  28. Cardiovascular Diseases
  29. NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis
  30. Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay
  31. Infectious Diseases
  32. Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
  33. Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis
  34. Acknowledgment
  35. Letters to the Editor
  36. Handling the altered test results of hemolyzed samples. Recommendations of the Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML)
  37. Reply to: Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
  38. Excessive hypercortisolemia due to ectopic Cushing’s syndrome requiring extending the reportable range for plasma cortisol for management
  39. Heavy chain disease: our experience
  40. An abnormal elevation of serum CA72-4 due to taking colchicine
  41. Rivaroxaban non-responders: do plasma measurements have a place?
  42. Next generation sequencing and immuno-histochemistry profiling identify numerous biomarkers for personalized therapy of endometrioid endometrial carcinoma
  43. A multicenter effort to improve comparability of vitamin B6 assays in whole blood
  44. PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis
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