Home Investigation on the ability of first trimester glycodelin and angiopoietin-2 to predict small-for-gestational age pregnancies at delivery
Article
Licensed
Unlicensed Requires Authentication

Investigation on the ability of first trimester glycodelin and angiopoietin-2 to predict small-for-gestational age pregnancies at delivery

  • Young Bae Hansen ORCID logo EMAIL logo , Vibeke Myrhøj , Finn Stener Jørgensen and Steen Sørensen
Published/Copyright: February 10, 2016
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 9

Abstract

Background:

The aim was to investigate whether first trimester glycodelin and angiopoietin-2 can predict small-for-gestational age (SGA) at delivery, individually or in combination.

Methods:

In this case-control study we measured glycodelin and angiopoietin-2 on serum from 170 singleton pregnant women delivering SGA neonates and 985 singleton pregnant women delivering normal-weighted neonates. All values were converted to multiples of the medians (MoM).

Results:

Pregnant women delivering SGA neonates had lower first trimester glycodelin and angiopoietin-2 MoM values [median (interquartile range)] compared with pregnant women delivering normal-weighted neonates for glycodelin: 0.86 (0.58–1.24) vs. 1.03 (0.74–1.45), p<0.001, and for angiopoietin-2: 0.89 (0.69–1.19) vs. 1.01 (0.78–1.31), p<0.001. The prediction performances of the biomarkers showed that the areas under the curve (AUC) were 0.59 (glycodelin), 0.58 (angiopoietin-2), and 0.60 (glycodelin and angiopoietin-2).

Conclusions:

We demonstrated that first trimester glycodelin and angiopoietin-2 were associated with SGA, but they were, individually and in combination, poor predictors of SGA at delivery. The AUCs were low which indicate low detection rates and high false positive rates.

Keywords: endometrial biomarkers; fetal and placental pathology; first trimester median curves; influencing variables; maternal serum screening; small-for-gestational age
Corresponding author: Young Bae Hansen, MD, Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospital Glostrup, Nordre Ringvej 57, 2600 Glostrup, Denmark, E-mail: . http://orcid.org/0000-0002-8428-560X; and Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Denmark

  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. McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999;340:1234–8.10.1056/NEJM199904223401603Search in Google Scholar PubMed

2. Gizzo S, Noventa M, Di Gangi S, Saccardi C, Cosmi E, Nardelli GB, et al. Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale. Clin Chem Lab Med 2015;53:975–9.10.1515/cclm-2014-0693Search in Google Scholar PubMed

3. Patrelli TS, Dall’asta A, Gizzo S, Pedrazzi G, Piantelli G, Jasonni VM, et al. Calcium supplementation and prevention of preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med 2012;25:2570–4.10.3109/14767058.2012.715220Search in Google Scholar PubMed

4. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta-analysis. Br J Obstet Gynaecol 2013;120:681–94.10.1111/1471-0528.12172Search in Google Scholar PubMed

5. Morris RK, Cnossen JS, Langejans M, Robson SC, Kleijnen J, Ter RG, et al. Serum screening with Down’s syndrome markers to predict pre-eclampsia and small for gestational age: systematic review and meta-analysis. BMC Pregnancy Childbirth 2008;8:33.10.1186/1471-2393-8-33Search in Google Scholar PubMed PubMed Central

6. Munoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunol Rev 2011;241:20–38.10.1111/j.1600-065X.2011.01002.xSearch in Google Scholar PubMed

7. Burton GJ, Watson AL, Hempstock J, Skepper JN, Jauniaux E. Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy. J Clin Endocrinol Metab 2002;87:2954–9.10.1210/jcem.87.6.8563Search in Google Scholar PubMed

8. Julkunen M, Seppala M, Janne OA. Complete amino acid sequence of human placental protein 14: a progesterone-regulated uterine protein homologous to beta-lactoglobulins. Proc Natl Acad Sci USA 1988;85:8845–9.10.1073/pnas.85.23.8845Search in Google Scholar PubMed PubMed Central

9. Bersinger NA, Birkhauser MH, Yared M, Wunder DM. Serum glycodelin pattern during the menstrual cycle in healthy young women. Acta Obstet Gynecol Scand 2009;88:1215–21.10.3109/00016340903294264Search in Google Scholar PubMed

10. Jeschke U, Richter DU, Reimer T, Bergemann C, Briese V, Karsten U, et al. Glycodelin A and differentiation of first trimester trophoblast cells in vitro. Arch Gynecol Obstet 2005;272:151–9.10.1007/s00404-004-0682-2Search in Google Scholar PubMed

11. Lam KK, Chiu PC, Chung MK, Lee CL, Lee KF, Koistinen R, et al. Glycodelin-A as a modulator of trophoblast invasion. Hum Reprod 2009;24:2093–103.10.5353/th_b4559896Search in Google Scholar

12. Okamoto N, Uchida A, Takakura K, Kariya Y, Kanzaki H, Riittinen L, et al. Suppression by human placental protein 14 of natural killer cell activity. Am J Reprod Immunol 1991;26:137–42.10.1111/j.1600-0897.1991.tb00713.xSearch in Google Scholar

13. Jeschke U, Wang X, Briese V, Friese K, Stahn R. Glycodelin and amniotic fluid transferrin as inhibitors of E-selectin-mediated cell adhesion. Histochem Cell Biol 2003;119:345–54.10.1007/s00418-003-0529-0Search in Google Scholar

14. Yaniv E, Borovsky Z, Mishan-Eisenberg G, Rachmilewitz J. Placental protein 14 regulates selective B cell responses. Cell Immunol 2003;222:156–63.10.1016/S0008-8749(03)00129-1Search in Google Scholar

15. Song M, Ramaswamy S, Ramachandran S, Flowers LC, Horowitz IR, Rock JA, et al. Angiogenic role for glycodelin in tumorigenesis. Proc Natl Acad Sci USA 2001;98:9265–70.10.1073/pnas.151151198Search in Google Scholar

16. Bolton AE, Chapman MG, Stoker RJ, Andrew CE, Wass D, Bohn H. The radioimmunoassay of human placental protein 14 (PP14). Clin Chim Acta 1983;135:283–91.10.1016/0009-8981(83)90287-5Search in Google Scholar

17. Jeschke U, Kunert-Keil C, Mylonas I, Hammer A, Schiessl B, Lomba I, et al. Expression of glycodelin A in decidual tissue of preeclamptic, HELLP and intrauterine growth-restricted pregnancies. Virchows Arch 2005;446:360–8.10.1007/s00428-004-1201-3Search in Google Scholar

18. Woolnough C, Wang Y, Kan CY, Morris JM, Tasevski V, Ashton AW. Source of angiopoietin-2 in the sera of women during pregnancy. Microvasc Res 2012;84:367–74.10.1016/j.mvr.2012.08.003Search in Google Scholar

19. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277:55–60.10.1126/science.277.5322.55Search in Google Scholar

20. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87:1171–80.10.1016/S0092-8674(00)81813-9Search in Google Scholar

21. Wang Y, Tasevski V, Wallace EM, Gallery ED, Morris JM. Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency. Br J Obstet Gynaecol 2007;114:1427–31.10.1111/j.1471-0528.2007.01511.xSearch in Google Scholar

22. Schneuer FJ, Roberts CL, Ashton AW, Guilbert C, Tasevski V, Morris JM, et al. Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes. Am J Obstet Gynecol 2014;210:345–9.10.1016/j.ajog.2013.11.012Search in Google Scholar

23. Hansen YB, Myrhøj V, Jørgensen FS, Oxvig C, Sørensen S. First trimester PAPP-A2, PAPP-A and hCGbeta in small-for-gestational-age pregnancies. Clin Chem Lab Med 2016;54:117–23.10.1515/cclm-2015-0230Search in Google Scholar

24. Marsal K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 1996;85:843–8.10.1111/j.1651-2227.1996.tb14164.xSearch in Google Scholar

25. Loughna P, Chitty L, Evans T, Chudleigh T. Fetal size and dating: charts recommended for clinical obstetric practice. Ultrasound 2009;17:161–7.10.1179/174313409X448543Search in Google Scholar

26. Lykke J, Bødker B, Søgaard M, Barbosa M, Klemmensen Å, Pedersen BW, et al. Hypertension and preeclampsia. In: Sandbjerg guidelines. [In Danish]. [updated 2012]. Available from: www.dsog.dk/guidelines.Search in Google Scholar

27. Gao J, Mazella J, Seppala M, Tseng L. Ligand activated hPR modulates the glycodelin promoter activity through the Sp1 sites in human endometrial adenocarcinoma cells. Mol Cell Endocrinol 2001;176:97–102.10.1016/S0303-7207(01)00450-6Search in Google Scholar

28. Johansson ED. Plasma levels of progesterone in pregnancy measured by a rapid competitive protein binding technique. Acta Endocrinol (Copenh) 1969;61:607–17.10.1530/acta.0.0610607Search in Google Scholar PubMed

29. Tabbaa ZM, Zheng Y, Daftary GS. KLF11 epigenetically regulates glycodelin-A, a marker of endometrial biology via histone-modifying chromatin mechanisms. Reprod Sci 2014;21:319–28.10.1177/1933719113503407Search in Google Scholar PubMed

30. Khalil A, Maiz N, Garcia-Mandujano R, ElKhouli M, Nicolaides KH. Longitudinal changes in maternal soluble endoglin and angiopoietin-2 in women at risk for pre-eclampsia. Ultrasound Obstet Gynecol 2014;44:402–10.10.1002/uog.13439Search in Google Scholar PubMed

31. Malamitsi-Puchner A, Boutsikou T, Economou E, Tzonou A, Makrakis E, Nikolaou KE, et al. Angiopoietin-2 in the perinatal period and the role of intrauterine growth restriction. Acta Obstet Gynecol Scand 2006;85:45–8.10.1080/00016340500334786Search in Google Scholar PubMed

32. Bolin M, Wiberg-Itzel E, Wikstrom AK, Goop M, Larsson A, Olovsson M, et al. Angiopoietin-1/angiopoietin-2 ratio for prediction of preeclampsia. Am J Hypertens 2009;22:891–5.10.1038/ajh.2009.97Search in Google Scholar

33. Kamal M, El-Khayat W. Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G variant of PAI-1 gene have a role in the pathogenesis of preeclampsia? J Investig Med 2011;59:1147–50.10.2310/JIM.0b013e31822c5bdfSearch in Google Scholar

34. Keikkala E, Hytinantti T, Wathen KA, Andersson S, Vuorela P. Significant decrease in maternal serum concentrations of angiopoietin-1 and -2 after delivery. Acta Obstet Gynecol Scand 2012;91:917–22.10.1111/j.1600-0412.2012.01463.xSearch in Google Scholar

35. Hirokoshi K, Maeshima Y, Kobayashi K, Matsuura E, Sugiyama H, Yamasaki Y, et al. Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia. Am J Hypertens 2005;18:1181–8.10.1016/j.amjhyper.2005.03.745Search in Google Scholar

36. Lash GE, Schiessl B, Kirkley M, Innes BA, Cooper A, Searle RF, et al. Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy. J Leukoc Biol 2006;80:572–80.10.1189/jlb.0406250Search in Google Scholar

37. Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell 2002;3:411–23.10.1016/S1534-5807(02)00217-4Search in Google Scholar

38. Gizzo S, Andrisani A, Esposito F, Noventa M, Di Gangi S, Angioni S, et al. Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial. Gynecol Endocrinol 2014;30:902–8.10.3109/09513590.2014.964638Search in Google Scholar PubMed

Received: 2015-10-10
Accepted: 2015-12-21
Published Online: 2016-2-10
Published in Print: 2016-9-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. The Theranos phenomenon, scientific transparency and freedom of speech
  4. Holotranscobalamin: in the middle of difficultly lies opportunity
  5. Review
  6. Laboratory and clinical risk assessment to treat myelodysplatic syndromes
  7. Mini Review
  8. Quantitative nucleic acid amplification by digital PCR for clinical viral diagnostics
  9. Genetics and Molecular Diagnostics
  10. Hybrid minigene splicing assay verified the pathogenicity of a novel splice site variant in the dystrophin gene of a Chinese patient with typical Duchenne muscular dystrophy phenotype
  11. General Clinical Chemistry and Laboratory Medicine
  12. Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension
  13. Sex steroid hormone stability in serum tubes with and without separator gels
  14. Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols
  15. An International Standard for holotranscobalamin (holoTC): international collaborative study to assign a holoTC value to the International Standard for vitamin B12 and serum folate
  16. A technical and clinical evaluation of a new assay for inhibin A and its use in second trimester Down syndrome screening
  17. Investigation on the ability of first trimester glycodelin and angiopoietin-2 to predict small-for-gestational age pregnancies at delivery
  18. Plasma total C-terminal agrin fragment (tCAF) as a marker for kidney function in patients with chronic kidney disease
  19. Hematology and Coagulation
  20. Thirty-minutes’ exposure to smartphone call triggers neutrophil activation in vitro
  21. Performance of the XN-2000 WPC channel-flagging to differentiate reactive and neoplastic leukocytosis
  22. Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation
  23. Reference Values and Biological Variations
  24. Derivation of level-specific reference change values (RCV) from a health screening database and optimization of their thresholds based on clinical utility
  25. Cancer Diagnosis
  26. BRAF analysis before surgery for papillary thyroid carcinoma: correlation with clinicopathological features and prognosis in a single-institution prospective experience
  27. Letters to the Editor
  28. Significant increase of serum prostate-specific antigen after exercise
  29. Serum delipidation but not high-speed centrifugation is effective in clearing lipemia interference in serum lipase activity measurement
  30. A relationship between absolute monocyte count and C-reactive protein in patients with migraine undergoing no pharmacological therapy
  31. Validation of the “Vacutainer® urinalysis preservative plus urine tube” for the determination of albumin and protein
  32. Performance evaluation of a novel automated HIV Ag/Ab chemiluminescence immunoassay
  33. SLC26A4 genotypes associated with enlarged vestibular aqueduct malformation in south Italian children with sensorineural hearing loss
  34. Is cystatin C level altered in women with polycystic ovary syndrome?
  35. Venous thromboembolism in a patient with persistent inhibitor to coagulation factor V – a case report
  36. Free light chains nephelometric assay: human urine stability in different storage conditions
  37. Comparing the viscoelastomeric fibrin polymerization assays FIBTEM® (ROTEM) vs. Functional Fibrinogen® (TEG): or why is a higher threshold for fibrinogen substitution better than a lower one?
  38. Reply to: Comparing the visco-elastomeric fibrin polymerization assays FIBTEM® (ROTEM) vs. Functional Fibrinogen® (TEG): or why is a higher threshold for fibrinogen substitution better than a lower one? By Schöchl et al.
  39. Congress Abstracts
  40. 5th Slovenian Congress of Clinical Chemistry and Laboratory Medicine
https://doi.org/10.1515/cclm-2015-0989
Keywords for this article
endometrial biomarkers; fetal and placental pathology; first trimester median curves; influencing variables; maternal serum screening; small-for-gestational age

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. The Theranos phenomenon, scientific transparency and freedom of speech
  4. Holotranscobalamin: in the middle of difficultly lies opportunity
  5. Review
  6. Laboratory and clinical risk assessment to treat myelodysplatic syndromes
  7. Mini Review
  8. Quantitative nucleic acid amplification by digital PCR for clinical viral diagnostics
  9. Genetics and Molecular Diagnostics
  10. Hybrid minigene splicing assay verified the pathogenicity of a novel splice site variant in the dystrophin gene of a Chinese patient with typical Duchenne muscular dystrophy phenotype
  11. General Clinical Chemistry and Laboratory Medicine
  12. Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension
  13. Sex steroid hormone stability in serum tubes with and without separator gels
  14. Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols
  15. An International Standard for holotranscobalamin (holoTC): international collaborative study to assign a holoTC value to the International Standard for vitamin B12 and serum folate
  16. A technical and clinical evaluation of a new assay for inhibin A and its use in second trimester Down syndrome screening
  17. Investigation on the ability of first trimester glycodelin and angiopoietin-2 to predict small-for-gestational age pregnancies at delivery
  18. Plasma total C-terminal agrin fragment (tCAF) as a marker for kidney function in patients with chronic kidney disease
  19. Hematology and Coagulation
  20. Thirty-minutes’ exposure to smartphone call triggers neutrophil activation in vitro
  21. Performance of the XN-2000 WPC channel-flagging to differentiate reactive and neoplastic leukocytosis
  22. Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation
  23. Reference Values and Biological Variations
  24. Derivation of level-specific reference change values (RCV) from a health screening database and optimization of their thresholds based on clinical utility
  25. Cancer Diagnosis
  26. BRAF analysis before surgery for papillary thyroid carcinoma: correlation with clinicopathological features and prognosis in a single-institution prospective experience
  27. Letters to the Editor
  28. Significant increase of serum prostate-specific antigen after exercise
  29. Serum delipidation but not high-speed centrifugation is effective in clearing lipemia interference in serum lipase activity measurement
  30. A relationship between absolute monocyte count and C-reactive protein in patients with migraine undergoing no pharmacological therapy
  31. Validation of the “Vacutainer® urinalysis preservative plus urine tube” for the determination of albumin and protein
  32. Performance evaluation of a novel automated HIV Ag/Ab chemiluminescence immunoassay
  33. SLC26A4 genotypes associated with enlarged vestibular aqueduct malformation in south Italian children with sensorineural hearing loss
  34. Is cystatin C level altered in women with polycystic ovary syndrome?
  35. Venous thromboembolism in a patient with persistent inhibitor to coagulation factor V – a case report
  36. Free light chains nephelometric assay: human urine stability in different storage conditions
  37. Comparing the viscoelastomeric fibrin polymerization assays FIBTEM® (ROTEM) vs. Functional Fibrinogen® (TEG): or why is a higher threshold for fibrinogen substitution better than a lower one?
  38. Reply to: Comparing the visco-elastomeric fibrin polymerization assays FIBTEM® (ROTEM) vs. Functional Fibrinogen® (TEG): or why is a higher threshold for fibrinogen substitution better than a lower one? By Schöchl et al.
  39. Congress Abstracts
  40. 5th Slovenian Congress of Clinical Chemistry and Laboratory Medicine
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 16.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2015-0989/html
Scroll to top button