{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:52:14Z","timestamp":1777593134471,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["91614177"],"award-info":[{"award-number":["91614177"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union ERASMUS +","award":["ROIASI 02"],"award-info":[{"award-number":["ROIASI 02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Fetal growth restriction (FGR) affects about 3% to 8% of pregnancies, leading to higher perinatal mortality and morbidity. Current strategies for detecting fetal growth impairment are based on ultrasound inspections. However, antenatal detection rates are insufficient and critical in countries with substandard care. To overcome difficulties with detection and to better discriminate between high risk FGR and low risk small for gestational age (SGA) fetuses, we investigated the suitability of risk assessment based on the analysis of a recently developed proteome profile derived from maternal serum in different study groups. Maternal serum, collected at around 31 weeks of gestation, was analyzed in 30 FGR, 15 SGA, and 30 control (CTRL) pregnant women who delivered between 31 and 40 weeks of gestation. From the 75 pregnant women of this study, 2 were excluded because of deficient raw data and 2 patients could not be grouped due to indeterminate results. Consistency between proteome profile and sonography results was obtained for 59 patients (26 true positive and 33 true negative). Of the proteome profiling 12 contrarious grouped individuals, 3 were false negative and 9 were false positive cases with respect to ultrasound data. Both true positive and false positive grouping transfer the respective patients to closer surveillance and thorough pregnancy management. Accuracy of the test is considered high with an area-under-curve value of 0.88 in receiver-operator-characteristics analysis. Proteome profiling by affinity-mass spectrometry during pregnancy provides a reliable method for risk assessment of impaired development in fetuses and consumes just minute volumes of maternal peripheral blood. In addition to clinical testing proteome profiling by affinity-mass spectrometry may improve risk assessment, referring pregnant women to specialists early, thereby improving perinatal outcomes.<\/jats:p>","DOI":"10.3390\/jcm9051374","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"1374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Precision Diagnostics by Affinity-Mass Spectrometry: A Novel Approach for Fetal Growth Restriction Screening during Pregnancy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8220-9072","authenticated-orcid":false,"given":"Charles A.","family":"Okai","sequence":"first","affiliation":[{"name":"Proteome Center Rostock, University Medicine and Natural Science Faculty, University of Rostock, 18051 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Russ","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, University Medicine and Natural Science Faculty, University of Rostock, 18051 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manja","family":"W\u00f6lter","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, University Medicine and Natural Science Faculty, University of Rostock, 18051 Rostock, Germany"},{"name":"Department of Obstetrics and Gynecology, Medical Faculty, University of Rostock, Clinic S\u00fcdstadt, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Faculty, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Faculty, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"},{"name":"Department of Obstetrics and Gynecology, Medical Faculty, RWTH Aachen University, 52062 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-482X","authenticated-orcid":false,"given":"Michael O.","family":"Glocker","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, University Medicine and Natural Science Faculty, University of Rostock, 18051 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0784-1262","authenticated-orcid":false,"given":"Ulrich","family":"Pecks","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Faculty, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (2019). ACOG Practice Bulletin No. 204: Fetal Growth Restriction. Obstet. Gynecol., 133, e97\u2013e109.","DOI":"10.1097\/AOG.0000000000003070"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000357592","article-title":"Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol","volume":"36","author":"Figueras","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1055\/s-0043-118908","article-title":"Intrauterine Growth Restriction. Guideline of the German Society of Gynecology and Obstetrics (S2k-Level, AWMF Registry No. 015\/080, October 2016)","volume":"77","author":"Kehl","year":"2017","journal-title":"Geburtshilfe Und Frauenheilkd."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mazarico, E., Martinez-Cumplido, R., Diaz, M., Sebastiani, G., Ibanez, L., and Gomez-Roig, M.D. (2016). Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157194"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ajog.2010.08.055","article-title":"Intrauterine growth restriction: New concepts in antenatal surveillance, diagnosis, and management","volume":"204","author":"Figueras","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/S1701-2163(15)30587-9","article-title":"Customized charts and their role in identifying pregnancies at risk because of fetal growth restriction","volume":"36","author":"Gardosi","year":"2014","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jprot.2016.04.027","article-title":"Proteoform profiling of peripheral blood serum proteins from pregnant women provides a molecular IUGR signature","volume":"149","author":"Koy","year":"2016","journal-title":"J. Proteom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/ajo.12902","article-title":"Introduction of a customised growth chart protocol increased detection of small for gestational age pregnancies in a tertiary Melbourne hospital","volume":"59","author":"Jayawardena","year":"2019","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1746146","DOI":"10.1155\/2017\/1746146","article-title":"Care-Related and Maternal Risk Factors Associated with the Antenatal Nondetection of Intrauterine Growth Restriction: A Case-Control Study from Bremen, Germany","volume":"2017","author":"Ernst","year":"2017","journal-title":"Biomed Res. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e16069","DOI":"10.1097\/MD.0000000000016069","article-title":"Better prediction for FGR (fetal growth restriction) with the sFlt-1\/PIGF ratio: A case-control study","volume":"98","author":"Visan","year":"2019","journal-title":"Medicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1177\/1469066718820991","article-title":"Comparison of blood serum protein analysis by MALDI-MS from either conventional frozen samples or storage disc-deposited samples: A study with human serum from pregnant donors and from patients with intrauterine growth restriction","volume":"25","author":"Russ","year":"2019","journal-title":"Eur. J. Mass Spectrom."},{"key":"ref_12","first-page":"57","article-title":"Mass spectrometric profiling of cord blood serum proteomes to distinguish infants with intrauterine growth restriction from those who are small for gestational age and from control individuals","volume":"164","author":"Pecks","year":"2014","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_13","first-page":"1881","article-title":"A proteome signature for intrauterine growth restriction derived from multifactorial analysis of mass spectrometry-based cord blood serum profiling","volume":"33","author":"Koy","year":"2012","journal-title":"Electrophoresis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.jasms.2009.12.013","article-title":"Multifactorial analysis of affinity-mass spectrometry data from serum protein samples: A strategy to distinguish patients with preeclampsia from matching control individuals","volume":"21","author":"Pecks","year":"2010","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0002-9378(85)90298-4","article-title":"Estimation of fetal weight with the use of head, body, and femur measurements\u2014A prospective study","volume":"151","author":"Hadlock","year":"1985","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1515\/jpm.2011.135","article-title":"Maternal and fetal cord blood lipids in intrauterine growth restriction","volume":"40","author":"Pecks","year":"2012","journal-title":"J. Perinat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1800017","DOI":"10.1002\/prca.201800017","article-title":"Maternal Apolipoprotein B100 Serum Levels are Diminished in Pregnancies with Intrauterine Growth Restriction and Differentiate from Controls","volume":"12","author":"Okai","year":"2018","journal-title":"Proteom. Clin. Appl."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gauglitz, G., and Moore, D.S. (2014). Multiparametric Analysis of Mass Spectrometry-Based Proteome Profiling in Gestation-Related Diseases. Handbook of Spectroscopy, Wiley-VCH Verlag GmbH & Co. KGaA. [2nd ed.].","DOI":"10.1002\/9783527654703"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0014-5793(03)00097-8","article-title":"Detection of novel truncated forms of human serum amyloid A protein in human plasma","volume":"537","author":"Kiernan","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1002\/pmic.200402098","article-title":"Cryodetector mass spectrometry profiling of plasma samples for HELLP diagnosis: An exploratory study","volume":"5","author":"Koy","year":"2005","journal-title":"Proteomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1002\/pmic.200401234","article-title":"Plasma protein profiling: Unique and stable features of individuals","volume":"5","author":"Nelsestuen","year":"2005","journal-title":"Proteomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e4808","DOI":"10.1097\/MD.0000000000004808","article-title":"Early risk prognosis of free-flap transplant failure by quantitation of the macrophage colony-stimulating factor in patient plasma using 2-dimensional liquid-chromatography multiple reaction monitoring-mass spectrometry","volume":"95","author":"Yang","year":"2016","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"ref_24","unstructured":"Davis, P.J. (1975). Interpolation and Approximation, Courier Corporation."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0001-2998(78)80014-2","article-title":"Basic principles of ROC analysis","volume":"8","author":"Metz","year":"1978","journal-title":"Semin. Nucl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/00031305.1988.10475580","article-title":"Opening the box of a boxplot","volume":"42","author":"Benjamini","year":"1988","journal-title":"Am. Stat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1002\/sim.1228","article-title":"Estimation of the area under the ROC curve","volume":"21","author":"Faraggi","year":"2002","journal-title":"Stat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0167-5877(00)00115-X","article-title":"Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests","volume":"45","author":"Greiner","year":"2000","journal-title":"Prev. Vet. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1007\/s13361-010-0031-6","article-title":"Mass spectrometric characterization of protein structure details refines the proteome signature for invasive ductal breast carcinoma","volume":"22","author":"Koy","year":"2011","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1007\/s00216-009-3187-9","article-title":"Towards a proteome signature for invasive ductal breast carcinoma derived from label-free nanoscale LC-MS protein expression profiling of tumorous and glandular tissue","volume":"395","author":"Vissers","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1158\/1078-0432.CCR-18-3181","article-title":"MGMT Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide: A Pooled Analysis of Four Clinical Trials","volume":"25","author":"Hegi","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1373\/clinchem.2006.081802","article-title":"Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency","volume":"53","author":"Ho","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/CIRCULATIONAHA.111.054361","article-title":"Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia","volume":"125","author":"Rana","year":"2012","journal-title":"Circulation"},{"key":"ref_35","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":"ref_36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.preghy.2018.03.013","article-title":"Placental Growth Factor informed management of suspected pre-eclampsia or fetal growth restriction: The MAPPLE cohort study","volume":"14","author":"Sharp","year":"2018","journal-title":"Pregnancy Hypertens."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0140-6736(05)66379-9","article-title":"Compared to what? Finding controls for case-control studies","volume":"365","author":"Grimes","year":"2005","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/0021-9681(85)90039-6","article-title":"The \u201ccase-control\u201d study: Valid selection of subjects","volume":"38","author":"Miettinen","year":"1985","journal-title":"J. Chronic Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1097\/AOG.0b013e3181c2bde8","article-title":"Pregnancy and laboratory studies: A reference table for clinicians","volume":"114","author":"Greer","year":"2009","journal-title":"Obstet. Gynecol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1074\/mcp.M112.018192","article-title":"Longitudinal analysis of maternal plasma apolipoproteins in pregnancy: A targeted proteomics approach","volume":"12","author":"Tinnemore","year":"2013","journal-title":"Mol. Cell. Proteom. MCP"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1210\/jcem.85.12.7027","article-title":"Low density lipoprotein (LDL) subfractions during pregnancy: Accumulation of buoyant LDL with advancing gestation","volume":"85","author":"Winkler","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1161\/HYPERTENSIONAHA.113.01787","article-title":"New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1\/placental growth factor ratio as a diagnostic test for preeclampsia","volume":"63","author":"Verlohren","year":"2014","journal-title":"Hypertension"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3109\/14767058.2012.733747","article-title":"Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: A matched-pair analysis","volume":"26","author":"Reimer","year":"2013","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_44","first-page":"908","article-title":"Screening for fetal growth restriction: A mathematical model of the effect of time interval and ultrasound error","volume":"92","author":"Mongelli","year":"1998","journal-title":"Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1542\/peds.111.6.1253","article-title":"International Small for Gestational Age Advisory Board consensus development conference statement: Management of short children born small for gestational age, April 24\u2013October 1, 2001","volume":"111","author":"Lee","year":"2003","journal-title":"Pediatrics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.bpobgyn.2009.09.004","article-title":"Fetal growth screening by fundal height measurement","volume":"23","author":"Morse","year":"2009","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_47","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":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.placenta.2016.03.010","article-title":"Placental growth factor as a marker of fetal growth restriction caused by placental dysfunction","volume":"42","author":"Benton","year":"2016","journal-title":"Placenta"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Quezada, M.S., Rodriguez-Calvo, J., Villalain, C., Gomez-Arriaga, P.I., Galindo, A., and Herraiz, I. (2019). sFlt-1\/PlGF ratio and timing of delivery in early-onset fetal growth restriction with antegrade umbilical artery flow. Ultrasound Obstet. Gynecol.","DOI":"10.1002\/uog.21949"},{"key":"ref_50","first-page":"CD012245","article-title":"Biochemical tests of placental function versus ultrasound assessment of fetal size for stillbirth and small-for-gestational-age infants","volume":"5","author":"Heazell","year":"2019","journal-title":"Cochrane Database Syst. Rev."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:26:23Z","timestamp":1760174783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,7]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["jcm9051374"],"URL":"https:\/\/doi.org\/10.3390\/jcm9051374","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,7]]}}}