{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:32:25Z","timestamp":1791815545177,"version":"4.3.4"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"am","delay-in-days":334,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"AFP"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014461","name":"Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014461","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006775","name":"GE Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011444","name":"GS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011444","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010905","name":"Illumina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010905","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Placenta"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.placenta.2019.04.005","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T11:01:47Z","timestamp":1556190107000},"page":"25-31","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"special_numbering":"C","title":["The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome"],"prefix":"10.1016","volume":"81","author":[{"given":"Alice E.","family":"Hughes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Sovio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gaccioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Stephen","family":"Charnock-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon C.S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.placenta.2019.04.005_bib1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/pd.2505","article-title":"Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndrome","volume":"30","author":"Huang","year":"2010","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib2","doi-asserted-by":"crossref","first-page":"S725","DOI":"10.1016\/j.ajog.2017.12.002","article-title":"Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers","volume":"218","author":"Gaccioli","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib3","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.ajog.2004.06.052","article-title":"First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (The FASTER Trial)","volume":"191","author":"Dugoff","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/01.AOG.0000172419.37410.eb","article-title":"Quad screen as a predictor of adverse pregnancy outcome","volume":"106","author":"Dugoff","year":"2005","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/01.AOG.0000191302.79560.d8","article-title":"Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome","volume":"107","author":"Smith","year":"2006","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib6","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1210\/jcem.87.4.8430","article-title":"Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth","volume":"87","author":"Smith","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.placenta.2019.04.005_bib7","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/pd.4141","article-title":"Association between first-trimester maternal serum pregnancy-associated plasma protein-A and obstetric complications","volume":"33","author":"D'Antonio","year":"2013","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/uog.5165","article-title":"First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses","volume":"31","author":"Spencer","year":"2008","journal-title":"Ultrasound Obstet. Gynecol. Off. J. Int. Soc. Ultrasound Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/uog.5163","article-title":"First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery","volume":"31","author":"Spencer","year":"2008","journal-title":"Ultrasound Obstet. Gynecol. Off. J. Int. Soc. Ultrasound Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/pd.1890","article-title":"Low levels of maternal serum PAPP-A in the first trimester and the risk of pre-eclampsia","volume":"28","author":"Spencer","year":"2008","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib11","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/uog.14899","article-title":"Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19-24 weeks, Ultrasound Obstet","volume":"46","author":"Lesmes","year":"2015","journal-title":"Gynecol. Off. J. Int. Soc. Ultrasound Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/0029-7844(96)00310-9","article-title":"The association between maternal serum alpha-fetoprotein and preterm birth, small for gestational age infants, preeclampsia, and placental complications","volume":"88","author":"Waller","year":"1996","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib13","first-page":"277","article-title":"Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome(1)","volume":"97","author":"Krause","year":"2001","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib14","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1242\/dev.00997","article-title":"Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development","volume":"131","author":"Conover","year":"2004","journal-title":"Development"},{"key":"10.1016\/j.placenta.2019.04.005_bib15","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1172\/JCI118277","article-title":"Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy","volume":"96","author":"Brownbill","year":"1995","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.placenta.2019.04.005_bib16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0028-2243(89)90058-0","article-title":"Maternal serum AFP levels in the first trimester of pregnancy","volume":"30","author":"Olajide","year":"1989","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"10.1016\/j.placenta.2019.04.005_bib17","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/pd.708","article-title":"Maternal weight correction of maternal serum PAPP-A and free\u202f?-hCG MoM when screening for trisomy 21 in the first trimester of pregnancy","volume":"23","author":"Spencer","year":"2003","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib18","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1136\/jcp.2005.034280","article-title":"Weight correction of MoM values: which method?","volume":"59","author":"Reynolds","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"10.1016\/j.placenta.2019.04.005_bib19","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":"10.1016\/j.placenta.2019.04.005_bib20","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1161\/HYPERTENSIONAHA.116.08620","article-title":"Prediction of preeclampsia using the soluble fms-like tyrosine kinase 1 to placental growth factor ratio: a prospective cohort study of unselected nulliparous women","volume":"69","author":"Sovio","year":"2017","journal-title":"Hypertens."},{"key":"10.1016\/j.placenta.2019.04.005_bib21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1471-2393-8-51","article-title":"Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study","volume":"8","author":"Pasupathy","year":"2008","journal-title":"BMC Pregnancy Childbirth"},{"key":"10.1016\/j.placenta.2019.04.005_bib22","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/S0140-6736(15)00131-2","article-title":"Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study","volume":"386","author":"Sovio","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.placenta.2019.04.005_bib23","series-title":"The English Indices of Deprivation 2007","author":"Noble","year":"2008"},{"key":"10.1016\/j.placenta.2019.04.005_bib24","series-title":"Antenatal Care for Uncomplicated Pregnancies","year":"2008"},{"key":"10.1016\/j.placenta.2019.04.005_bib25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/adc.73.1.17","article-title":"Cross sectional stature and weight reference curves for the UK, 1990","volume":"73","author":"Freeman","year":"1995","journal-title":"Arch. Dis. Child."},{"key":"10.1016\/j.placenta.2019.04.005_bib26","first-page":"1122","article-title":"Task force on hypertension in pregnancy, hypertension in pregnancy","volume":"122","author":"American College of Obstetricians and Gynecologists","year":"2013","journal-title":"Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib27","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.placenta.2016.10.011","article-title":"The pregnancy outcome prediction (POP) study: investigating the relationship between serial prenatal ultrasonography, biomarkers, placental phenotype and adverse pregnancy outcomes","volume":"59","author":"Gaccioli","year":"2017","journal-title":"Placenta"},{"key":"10.1016\/j.placenta.2019.04.005_bib28","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"10.1016\/j.placenta.2019.04.005_bib29","doi-asserted-by":"crossref","first-page":"h5527","DOI":"10.1136\/bmj.h5527","article-title":"STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies","volume":"351","author":"Bossuyt","year":"2015","journal-title":"BMJ"},{"key":"10.1016\/j.placenta.2019.04.005_bib30","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/sim.5727","article-title":"Testing for improvement in prediction model performance","volume":"32","author":"Pepe","year":"2013","journal-title":"Stat. Med."},{"key":"10.1016\/j.placenta.2019.04.005_bib31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1471-2393-8-33","article-title":"Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: systematic review and meta-analysis","volume":"8","author":"Morris","year":"2008","journal-title":"BMC Pregnancy Childbirth"},{"key":"10.1016\/j.placenta.2019.04.005_bib32","doi-asserted-by":"crossref","DOI":"10.1177\/0969141313486893","article-title":"Allowing for ethnic group in antenatal screening for Down's syndrome","volume":"20","author":"Bestwick","year":"2013","journal-title":"J. Med. Screen"},{"key":"10.1016\/j.placenta.2019.04.005_bib33","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/(SICI)1097-0223(199911)19:11<1065::AID-PD695>3.0.CO;2-R","article-title":"The influence of smoking on maternal serum PAPP-A and free beta hCG levels in the first trimester of pregnancy","volume":"19","author":"Spencer","year":"1999","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib34","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/pd.313","article-title":"Maternal smoking: age distribution, levels of alpha-fetoprotein and human chorionic gonadotrophin, and effect on detection of Down syndrome pregnancies in second-trimester screening","volume":"22","author":"Crossley","year":"2002","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib35","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1093\/humrep\/16.7.1501","article-title":"First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction","volume":"16","author":"Liao","year":"2001","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.placenta.2019.04.005_bib36","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/humrep\/deg153","article-title":"Maternal serum hCG and alpha-fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen-thawed embryos","volume":"18","author":"Hui","year":"2003","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.placenta.2019.04.005_bib37","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1001\/jama.292.18.2249","article-title":"First-trimester placentation and the risk of antepartum stillbirth","volume":"292","author":"Smith","year":"2004","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.placenta.2019.04.005_bib38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/pd.5001","article-title":"Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis","volume":"37","author":"Morris","year":"2017","journal-title":"Prenat. Diagn."},{"key":"10.1016\/j.placenta.2019.04.005_bib39","unstructured":"Investigation and Management of the Small-for-Gestational-Age Fetus, Royal College of Obstetricians and Gynaecologists, Guideline No. 31, 2002."},{"key":"10.1016\/j.placenta.2019.04.005_bib40","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.3109\/00016349.2010.493195","article-title":"Low maternal PAPP-A is associated with small-for-gestational age newborns and stillbirths","volume":"89","author":"Marttala","year":"2010","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"10.1016\/j.placenta.2019.04.005_bib41","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1056\/NEJMoa1704559","article-title":"Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia","volume":"377","author":"Rolnik","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.placenta.2019.04.005_bib42","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S2352-4642(18)30129-9","article-title":"Screening for fetal growth restriction using ultrasound and the sFLT1\/PlGF ratio in nulliparous women: a prospective cohort study","volume":"2","author":"Gaccioli","year":"2018","journal-title":"Lancet Child Adolesc. Heal."},{"key":"10.1016\/j.placenta.2019.04.005_bib43","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ajog.2015.06.013","article-title":"Prognostic models in obstetrics: available, but far from applicable","volume":"214","author":"Kleinrouweler","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.placenta.2019.04.005_bib44","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1002\/sim.7993","article-title":"Minimum sample size for developing a multivariable prediction model: Part I - continuous outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat. Med."},{"key":"10.1016\/j.placenta.2019.04.005_bib45","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/sim.7992","article-title":"Minimum sample size for developing a multivariable prediction model: PART II - binary and time-to-event outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat. Med."}],"container-title":["Placenta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0143400419300761?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0143400419300761?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:58:17Z","timestamp":1758909497000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0143400419300761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":45,"alternative-id":["S0143400419300761"],"URL":"https:\/\/doi.org\/10.1016\/j.placenta.2019.04.005","relation":{},"ISSN":["0143-4004"],"issn-type":[{"value":"0143-4004","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome","name":"articletitle","label":"Article Title"},{"value":"Placenta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.placenta.2019.04.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}