{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:47:39Z","timestamp":1782398859865,"version":"3.54.5"},"reference-count":26,"publisher":"Croatian Society for Medical Biochemistry and Laboratory Medicine","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. med. (Online)"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:p>Introduction: Placental growth factor (PlGF) is a key biomarker for diagnosing and predicting preeclampsia (PE). While serum-based PlGF assays are well established, urine has emerged as a promising non-invasive alternative matrix. However, the absence of urinary PlGF stability data remains a major preanalytical limitation. This study aimed to assess urinary PlGF stability under common preanalytical conditions, including refrigerated storage and a double freeze-thaw cycle. Materials and methods: A prospective study was conducted using urine samples from ten pregnant women. Each sample was processed under standard laboratory conditions and aliquoted into five tubes. One aliquot was immediately frozen at -80 \u00b0C (T0), three were stored at 2\u20138 \u00b0C for 48, 96, and 168 hours before freezing, and one underwent a double freeze-thaw cycle. Urinary PlGF concentrations were measured using the Elecsys PlGF immunoassay on Roche Cobas e801 analyzer. Percent degradation (PD%) was calculated relative to baseline. A linear regression model was applied to estimate the time to exceed a maximum permissible instability (MPI) of \u00b110%. Results: Urinary PlGF remained stable at 2\u20138 \u00b0C for up to 48 hours, with a mean PD% of -6% (95% confidence interval (CI): -9.1 to -2.8). The regression model (PD% = -0.0834 \u00d7 Time (h)) estimated the -10% threshold at approximately 120 hours. After a double freeze-thaw cycle, the mean PD% was -1.5% (95% CI: -3.4 to 0.4%). Conclusions: Urinary PlGF shows acceptable stability for up to 48 hours under refrigeration and is stable over two freeze-thaw cycles. These findings provide essential preanalytical data supporting its potential use in clinical and research settings.<\/jats:p>","DOI":"10.11613\/bm.2026.020701","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:01:57Z","timestamp":1775721717000},"page":"259-267","source":"Crossref","is-referenced-by-count":0,"title":["Urinary placental growth factor stability as a critical factor in the reliability of preeclampsia diagnosis"],"prefix":"10.11613","volume":"36","author":[{"given":"Marta","family":"Fabre","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Medel-Martinez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Paules","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Oros","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Martinez-Marzo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Peran","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Lerma-Irureta","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS Arag\u00f3n), Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4885","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"key20260409080154_r1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1053\/j.semperi.2009.02.010","article-title":"The Global Impact of Pre-eclampsia and Eclampsia. Vol. 33, Seminars in Perinatology. 2009. p. 130\u20137. Duley L. The Global Impact of Pre-eclampsia and Eclampsia.","volume":"33","author":"Duley","year":"2009","journal-title":"Semin Perinatol"},{"key":"key20260409080154_r2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-pathol-121808-102149","article-title":"Pathogenesis of preeclampsia.","volume":"5","author":"Young","year":"2010","journal-title":"Annu Rev Pathol"},{"key":"key20260409080154_r3","first-page":"30","article-title":"Diagnostic validity of the sFlt-1\/PlGF ratio in the identification of preeclampsia: A systematic review.","volume":"47","author":"Maesa","year":"2020","journal-title":"Clin Invest Ginecol Obstet"},{"key":"key20260409080154_r4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1414838","article-title":"Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia.","volume":"374","author":"Zeisler","year":"2016","journal-title":"N Engl J Med"},{"key":"key20260409080154_r5","unstructured":"National Institute for Health and Care Excellence (NICE). PLGF-based testing to help diagnose suspected preterm pre-eclampsia Diagnostics guidance [Internet]. London; 2022 Jul. Available from: www.nice.org.uk\/guidance\/dg49. Accessed May 15th 2025."},{"key":"key20260409080154_r6","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1161\/CIRCULATIONAHA.113.003215","article-title":"Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: A prospective multicenter study.","volume":"128","author":"Chappell","year":"2013","journal-title":"Circulation"},{"key":"key20260409080154_r7","doi-asserted-by":"crossref","DOI":"10.1016\/j.jogoh.2025.102925","article-title":"Predictive performance of sFlt-1, PlGF and the sFlt-1\/PlGF ratio for preeclampsia: A systematic review and meta-analysis.","volume":"54","author":"Zhang","year":"2025","journal-title":"J Gynecol Obstet Hum Reprod."},{"key":"key20260409080154_r8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11306-006-0042-2","article-title":"Urine stability for metabolomic studies: Effects of preparation and storage.","volume":"3","author":"Saude","year":"2007","journal-title":"Metabolomics"},{"key":"key20260409080154_r9","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1093\/jalm\/jfab082","article-title":"Sample Processing and Stability for Urine Biomarker Studies.","volume":"6","author":"Chang","year":"2021","journal-title":"J Appl Lab Med"},{"key":"key20260409080154_r10","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/prca.201400092","article-title":"Urine proteomic studies in preeclampsia.","volume":"9","author":"Kolialexi","year":"2015","journal-title":"Proteomics Clin Appl"},{"key":"key20260409080154_r11","doi-asserted-by":"crossref","DOI":"10.1080\/10641955.2025.2487794","article-title":"Pregnancy urine biomarkers for effectively preeclampsia prediction: a systematic review and meta-analysis.","volume":"44","author":"Wu","year":"2025","journal-title":"Hypertens Pregnancy"},{"key":"key20260409080154_r12","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1515\/cclm-2023-0221","article-title":"Recommendation for the design of stability studies on clinical specimens.","volume":"61","author":"Gomez-Rioja","year":"2023","journal-title":"Clin Chem Lab Med"},{"key":"key20260409080154_r13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/0004563220911993","article-title":"Verification of placental growth factor and soluble-fms-like tyrosine kinase 1 assay performance in late pregnancy and their diagnostic test accuracy in women with reduced fetal movement.","volume":"57","author":"Armstrong-Buisseret","year":"2020","journal-title":"Ann Clin Biochem"},{"key":"key20260409080154_r14","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/pd.2894","article-title":"Stability of first trimester placental growth factor in serum and whole blood.","volume":"31","author":"Cowans","year":"2011","journal-title":"Prenat Diagn"},{"key":"key20260409080154_r15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1080\/00365513.2024.2340037","article-title":"Stability of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1).","volume":"84","author":"Lian","year":"2024","journal-title":"Scand J Clin Lab Invest"},{"key":"key20260409080154_r16","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1515\/cclm-2019-0586","article-title":"A protocol for testing the stability of biochemical analytes. Technical document.","volume":"57","author":"G\u00f3mez-Rioja","year":"2019","journal-title":"Clin Chem Lab Med"},{"key":"key20260409080154_r17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.placenta.2019.08.001","article-title":"Stability of placental growth factor, soluble fms-like tyrosine kinase 1, and soluble fms-like tyrosine kinase 1 e15a in human serum and plasma.","volume":"86","author":"Rowson","year":"2019","journal-title":"Placenta"},{"key":"key20260409080154_r18","doi-asserted-by":"crossref","DOI":"10.11613\/BM.2024.030704","article-title":"Short-and long-term stability of synovial fluid calprotectin.","volume":"34","author":"\u010ci\u010dak","year":"2024","journal-title":"Biochem Med (Zagreb)"},{"key":"key20260409080154_r19","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1515\/cclm-2015-0067","article-title":"Defining analytical performance specifications: Consensus Statement from the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine.","volume":"53","author":"Sandberg","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"key20260409080154_r20","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1515\/cclm-2019-0649","article-title":"Biological variation of two serum markers for preeclampsia prediction.","volume":"58","author":"Braga","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"key20260409080154_r21","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.clinbiochem.2010.02.010","article-title":"Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia.","volume":"43","author":"Schiettecatte","year":"2010","journal-title":"Clin Biochem"},{"key":"key20260409080154_r22","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/jalm\/jfab135","article-title":"Analytical Performance and Quality Indicators of Fully Automated Immunoassays for sFlt-1 and PlGF.","volume":"7","author":"Higgins","year":"2022","journal-title":"J Appl Lab Med"},{"key":"key20260409080154_r23","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.3109\/14767051003678242","article-title":"Effect of long-term storage on placental growth factor and fms-like tyrosine kinase 1 measurements in samples from pregnant women.","volume":"23","author":"Law","year":"2010","journal-title":"J Matern Fetal Neonatal Med."},{"key":"key20260409080154_r24","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1053\/j.ajkd.2013.09.013","article-title":"Urine stability studies for novel biomarkers of acute kidney injury.","volume":"63","author":"Parikh","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"key20260409080154_r25","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.preghy.2018.03.011","article-title":"Urinary sFlt-1 and PlGF levels are strongly correlated to serum sFlt-1\/PlGF ratio and serum PlGF in women with preeclampsia.","volume":"12","author":"Hebert-Schuster","year":"2018","journal-title":"Pregnancy Hypertens"},{"key":"key20260409080154_r26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejogrb.2024.05.002","article-title":"Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1\/creatinine ratio improves the prediction value.","volume":"298","author":"Mart\u00edn-Palumbo","year":"2024","journal-title":"Eur J Obstet Gynecol Reprod Biol"}],"container-title":["Biochemia medica"],"original-title":[],"link":[{"URL":"https:\/\/www.biochemia-medica.com\/assets\/images\/upload\/xml_tif\/bm-36-2-020701.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:58:32Z","timestamp":1782395912000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.biochemia-medica.com\/en\/journal\/36\/2\/10.11613\/BM.2026.020701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6,24]]},"published-print":{"date-parts":[[2026,6,15]]}},"URL":"https:\/\/doi.org\/10.11613\/bm.2026.020701","relation":{},"ISSN":["1846-7482","1330-0962"],"issn-type":[{"value":"1846-7482","type":"electronic"},{"value":"1330-0962","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,15]]}}}