{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:10:39Z","timestamp":1777497039746,"version":"3.51.4"},"reference-count":56,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pregnancy-associated plasma protein-A2 (PAPP-A2) is a recently discovered protease that cleaves a subset of insulin-like growth factor binding proteins (IGFBP). The molecular function suggests its involvement in the IGF system that is vital for fetal growth and development. Our objectives were to establish first trimester median curves of PAPP-A2, PAPP-A and hCG\u03b2 for singleton normal pregnancies and to investigate whether an altered level of one or more of the biomarkers is associated with small-for-gestational-age (SGA) neonates before and after stratification according to maternal hypertension and\/or proteinuria.<\/jats:p><jats:p>This was a case-control study based on 985 pregnant women delivering normal-weighted neonates and 170 pregnant women delivering SGA neonates. PAPP-A2 was measured by ELISA. PAPP-A and hCG\u03b2 were measured by an automatic analyzer. Median curves from 8+1 to 14+0 were established and all concentration values were converted to multiples of the median (MoM) values.<\/jats:p><jats:p>Before stratification the SGA cases had unaffected PAPP-A2 MoM and hCG\u03b2 MoM levels but lower PAPP-A MoM compared with normal controls. After stratification the SGA normotensive subgroup had lower PAPP-A2 MoM and PAPP-A MoM levels than the normal normotensive subgroup. Severe preeclamptic women delivering SGA neonates had higher PAPP-A2 MoM compared to the normotensive women delivering SGA neonates.<\/jats:p><jats:p>Pregnant women delivering SGA neonates did not have altered levels of PAPP-A2 or hCG\u03b2 but had lower PAPP-A level in the first trimester compared with pregnant women delivering normal-weighted neonates. Pregnancies complicated with severe preeclampsia and SGA may be associated with high PAPP-A2 level.<\/jats:p>","DOI":"10.1515\/cclm-2015-0230","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T17:01:06Z","timestamp":1431450066000},"source":"Crossref","is-referenced-by-count":12,"title":["First trimester PAPP-A2, PAPP-A and hCG\u03b2 in small-for-gestational-age pregnancies"],"prefix":"10.1515","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-560X","authenticated-orcid":false,"given":"Young Bae","family":"Hansen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vibeke","family":"Myrh\u00f8j","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn Stener","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Oxvig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steen","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref611","first-page":"191","article-title":"First - trimester maternal serum PAPP free - beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications : a population - based screening study ( the FASTER Trial","author":"Dugoff","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"ref201","first-page":"69","article-title":"Can pregnancy - associated plasma protein predict the outcome of pregnancy in women with threatened abortion and confirmed fetal viability","author":"Ruge","year":"1990","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref81","first-page":"264","article-title":"First - trimester ADAM as markers for intrauterine fetal growth restriction through their roles in the insulin - like growth factor system","volume":"12","author":"Cowans","year":"2007"},{"key":"ref281","first-page":"191","article-title":"First - trimester maternal serum PAPP free - beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications : a population - based screening study ( the FASTER Trial","author":"Dugoff","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"ref431","first-page":"152","article-title":"CA Pregnancy - associated plasma protein tissue expression and biological consequences of gene knockout in mice","author":"Conover","year":"2011","journal-title":"Endocrinology"},{"key":"ref161","first-page":"161","article-title":"Fetal size and dating charts recommended for clinical obstetric practice Ultrasound","volume":"17","author":"Loughna","year":"2009"},{"key":"ref21","first-page":"335","article-title":"Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin - like growth factor gene","author":"Woods","year":"1996","journal-title":"Engl J Med"},{"key":"ref241","first-page":"10","article-title":"The influence of fetal sex in screening for trisomy by fetal nuchal translucency maternal serum free beta - hCG and at weeks of gestation","volume":"20","author":"Spencer","year":"2000"},{"key":"ref331","first-page":"276","article-title":"Pregnancy - associated plasma protein a novel insulin - like growth factor - binding protein proteinase","author":"Overgaard","year":"2001","journal-title":"J Biol Chem"},{"key":"ref01","first-page":"276","article-title":"Pregnancy - associated plasma protein a novel insulin - like growth factor - binding protein proteinase","author":"Overgaard","year":"2001","journal-title":"J Biol Chem"},{"key":"ref631","article-title":"First trimester maternal serum PAPP beta - hCG and ADAM in prediction of small - for - gestational - age fetuses","volume":"12","author":"Pihl","year":"2008"},{"key":"ref301","article-title":"First trimester maternal serum PAPP beta - hCG and ADAM in prediction of small - for - gestational - age fetuses","volume":"12","author":"Pihl","year":"2008"},{"key":"ref101","first-page":"152","article-title":"CA Pregnancy - associated plasma protein tissue expression and biological consequences of gene knockout in mice","author":"Conover","year":"2011","journal-title":"Endocrinology"},{"key":"ref571","first-page":"10","article-title":"The influence of fetal sex in screening for trisomy by fetal nuchal translucency maternal serum free beta - hCG and at weeks of gestation","volume":"20","author":"Spencer","year":"2000"},{"key":"ref601","first-page":"15","article-title":"First - trimester biochemical markers of aneuploidy and the prediction of small - for - gestational age fetuses Ultrasound","volume":"31","author":"Spencer","year":"2008","journal-title":"Obstet Gynecol"},{"key":"ref341","first-page":"351","article-title":"is increased in severe early onset pre - eclampsia and upregulated with hypoxia Fertil","volume":"26","author":"Macintire","year":"2014"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1177\/1933719113512532","article-title":"First - trimester levels of pregnancy - associated plasma protein in the maternal circulation are elevated in pregnancies that subsequently develop preeclampsia","volume":"21","author":"Crosley","year":"2014","journal-title":"Reprod Sci"},{"key":"ref471","first-page":"150","article-title":"Severe preeclampsia - related changes in gene expression at the maternal - fetal interface include sialic acid - binding immunoglobulin - like lectin pappalysin","author":"Winn","year":"2009","journal-title":"Endocrinology"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1093\/molehr\/gat047","article-title":"robust immunoassay for pregnancy - associated plasma protein based on analysis of circulating antigen : establishment of normal ranges in pregnancy","volume":"19","author":"Kl\u00f8verpris","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"ref361","first-page":"345","article-title":"growth - deficiency phenotype in heterozygous mice carrying an insulin - like growth factor II gene disrupted by targeting","author":"DeChiara","year":"1990","journal-title":"Nature"},{"key":"ref61","first-page":"13","article-title":"Screening for trisomies by maternal age fetal nuchal translucency fetal heart rate free beta - hCG and pregnancy - associated plasma protein","volume":"21","author":"Kagan KO","year":"2008","journal-title":"Hum Reprod"},{"key":"ref371","first-page":"95","article-title":"Involvement of pregnancy - 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trimester screening for trisomy by free beta - human chorionic gonadotropin and pregnancy - associated plasma protein impact of maternal and pregnancy characteristics Ultrasound","volume":"31","author":"Kagan KO","year":"2008","journal-title":"Obstet Gynecol"},{"key":"ref271","first-page":"15","article-title":"First - trimester biochemical markers of aneuploidy and the prediction of small - for - gestational age fetuses Ultrasound","volume":"31","author":"Spencer","year":"2008","journal-title":"Obstet Gynecol"},{"key":"ref651","first-page":"71","article-title":"Localization of pregnancy - associated plasma protein and colocalization of pregnancy - associated plasma protein - A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta","author":"Bonno","year":"1994","journal-title":"Lab Invest"},{"key":"ref321","first-page":"71","article-title":"Localization of pregnancy - associated plasma protein and colocalization of pregnancy - associated plasma protein - A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta","author":"Bonno","year":"1994","journal-title":"Lab Invest"},{"key":"ref411","first-page":"264","article-title":"First - trimester ADAM as markers for intrauterine fetal growth restriction through their roles in the insulin - like growth factor system","volume":"12","author":"Cowans","year":"2007"},{"key":"ref441","article-title":"Christians de DR SH Pregnancy associated plasma protein affects bone size and shape and contributes to natural variation in postnatal growth in mice One","author":"Zwaan","year":"2013"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1177\/1933719113512532","article-title":"First - trimester levels of pregnancy - associated plasma protein in the maternal circulation are elevated in pregnancies that subsequently develop preeclampsia","volume":"21","author":"Crosley","year":"2014","journal-title":"Reprod Sci"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/molehr\/gan054","article-title":"Increased levels of pregnancy - associated plasma protein in the serum of pre - eclamptic patients","volume":"14","author":"Nishizawa","year":"2008","journal-title":"Mol Hum Reprod"},{"key":"ref641","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1093\/molehr\/gat047","article-title":"robust immunoassay for pregnancy - associated plasma protein based on analysis of circulating antigen : establishment of normal ranges in pregnancy","volume":"19","author":"Kl\u00f8verpris","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"ref531","first-page":"69","article-title":"Can pregnancy - associated plasma protein predict the outcome of pregnancy in women with threatened abortion and confirmed fetal viability","author":"Ruge","year":"1990","journal-title":"Acta Obstet Gynecol Scand"},{"key":"ref261","first-page":"37","article-title":"Early fetal growth and free beta - hCG in relation to risk of delivering a small - for - gestational age infant Ultrasound","author":"Kirkegaard","year":"2011","journal-title":"Obstet Gynecol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1007\/s12079-015-0259-9","article-title":"The role of in the system location location location Signal Jan","volume":"25","author":"Oxvig","journal-title":"Cell"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1210\/jc.2012-2468","article-title":"Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction","author":"Whitehead","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref141","first-page":"150","article-title":"Severe preeclampsia - related changes in gene expression at the maternal - fetal interface include sialic acid - binding immunoglobulin - like lectin pappalysin","author":"Winn","year":"2009","journal-title":"Endocrinology"},{"key":"ref561","first-page":"493","article-title":"First - trimester screening for trisomy by free beta - human chorionic gonadotropin and pregnancy - associated plasma protein impact of maternal and pregnancy characteristics Ultrasound","volume":"31","author":"Kagan KO","year":"2008","journal-title":"Obstet Gynecol"},{"key":"ref391","first-page":"13","article-title":"Screening for trisomies by maternal age fetal nuchal translucency fetal heart rate free beta - hCG and pregnancy - associated plasma protein","volume":"21","author":"Kagan KO","year":"2008","journal-title":"Hum Reprod"},{"key":"ref41","first-page":"95","article-title":"Involvement of pregnancy - associated plasma protein in insulin - like growth factor binding protein proteolysis during pregnancy : a potential mechanism for increasing IGF bioavailability","volume":"20","author":"Yan","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref351","first-page":"335","article-title":"Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin - like growth factor gene","author":"Woods","year":"1996","journal-title":"Engl J Med"},{"key":"ref421","first-page":"949","article-title":"Prediction of pregnancy complications by first - trimester maternal serum PAPP free beta - hCG and with second - trimester uterine artery Doppler","volume":"25","author":"Spencer","year":"2005"},{"key":"ref291","first-page":"87","article-title":"AD Early pregnancy levels of pregnancy - associated plasma protein a and the risk of intrauterine growth restriction premature birth preeclampsia and stillbirth","author":"Smith","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1210\/jc.2012-2468","article-title":"Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction","author":"Whitehead","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1677\/joe.0.0840295","article-title":"- Das RE DR International Reference Preparation of Human Chorionic Gonadotrophin for Immunoassay : potency estimates in various bioassay and protein binding assay systems and International Reference Preparations of the alpha and beta subunits of human","author":"Storring","year":"1980","journal-title":"J Endocrinol"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/molehr\/gan054","article-title":"Increased levels of pregnancy - associated plasma protein in the serum of pre - eclamptic patients","volume":"14","author":"Nishizawa","year":"2008","journal-title":"Mol Hum Reprod"},{"key":"ref111","article-title":"Christians de DR SH Pregnancy associated plasma protein affects bone size and shape and contributes to natural variation in postnatal growth in mice One","author":"Zwaan","year":"2013"},{"key":"ref221","first-page":"13","article-title":"First - trimester risk calculation for trisomy comparison of the screening efficiency between locally developed programs and commercial software","volume":"21","author":"S\u00f8rensen","year":"2011","journal-title":"Clin Chem"},{"key":"ref591","first-page":"37","article-title":"Early fetal growth and free beta - hCG in relation to risk of delivering a small - for - gestational age infant Ultrasound","author":"Kirkegaard","year":"2011","journal-title":"Obstet Gynecol"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2015-0230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T23:49:06Z","timestamp":1619048946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2015-0230\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,1]]},"references-count":56,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1515\/cclm-2015-0230","relation":{},"ISSN":["1437-4331","1434-6621"],"issn-type":[{"value":"1437-4331","type":"electronic"},{"value":"1434-6621","type":"print"}],"subject":[],"published":{"date-parts":[[2016,1,1]]}}}