{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:44:12Z","timestamp":1793335452434,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the inter\u2010relationships between five first\u2010trimester biomarkers (pregnancy associated plasma protein A [PAPP\u2010A], alpha\u2010fetoprotein [AFP], beta human chorionic gonadotrophin [beta\u2010hCG], placenta growth factor [PlGF] and soluble fms\u2010like tyrosine kinase receptor\u20101 [sFlt\u20101]) and a range of adverse pregnancy outcomes (APOs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Prospective cohort study of nulliparous singleton pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Cambridge, UK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Population or Sample<\/jats:title>\n                    <jats:p>4056 pregnancy outcome prediction study participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The biomarker concentrations were measured in maternal serum at ~12\u2009weeks of gestation. Univariable analysis of APOs was performed using logistic regression. Multivariable analysis used best subsets logistic regression with cross\u2010validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Pre\u2010eclampsia (PE), small for gestational age (SGA), including severe SGA (birthweight &lt;3rd), fetal growth restriction (FGR), preterm birth (PTB, both induced and spontaneous [iPTB and sPTB, respectively]), pre\u2010viable loss and stillbirth, plus combinations of outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lower values of PAPP\u2010A, PlGF and sFlt\u20101 and higher values of AFP were associated with FGR (OR\u2009for\u20091 SD higher value 0.59 [95% CI 0.48\u20130.74], OR 0.56 [95% CI 0.44\u20130.70], OR 0.68 [95% CI 0.54\u20130.87] and OR 1.53 [95% CI 1.25\u20131.88]), severe SGA (OR\u00a00.59 [95% CI 0.49\u20130.72], OR 0.71 [95% CI 0.57\u20130.87], OR 0.74 [95% CI 0.60\u20130.91] and OR 1.41 [95% CI 1.17\u20131.71]), sPTB (OR\u2009 0.61 [95% CI 0.50\u20130.73], OR 0.79 [95% CI 0.66\u20130.96], OR 0.57 [95% CI 0.47\u20130.70] and OR 1.41 [95% CI 1.18\u20131.67]) and iPTB (OR\u2009 0.72 [95% CI 0.57\u20130.91], OR 0.62 [95% CI 0.49\u20130.78], OR 0.71 [95% CI 0.56\u20130.90] and OR 1.44 [95% CI 1.16\u20131.78]), respectively. When combinations of biomarkers were assessed, PAPP\u2010A and AFP were independently associated with severe SGA; PAPP\u2010A alone with PE\u2009+\u2009PTB; PlGF alone with severe PE; PlGF, beta\u2010hCG, AFP and PAPP\u2010A with the combination of PE and SGA; AFP and sFlt\u20101 with sPTB; and AFP and PlGF with iPTB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combinations of first\u2010trimester placental biomarkers are associated with APOs. However, the patterns vary for different types of APO, indicating heterogeneity in the underlying pathophysiological pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1471-0528.17691","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:29:54Z","timestamp":1697081394000},"page":"823-831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study"],"prefix":"10.1111","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-1105","authenticated-orcid":false,"given":"Ulla","family":"Sovio","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre University of Cambridge  Cambridge UK"},{"name":"Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research (CTR) University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-8921","authenticated-orcid":false,"given":"Francesca","family":"Gaccioli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre University of Cambridge  Cambridge UK"},{"name":"Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research (CTR) University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-4443","authenticated-orcid":false,"given":"Emma","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4890","authenticated-orcid":false,"given":"D. Stephen","family":"Charnock\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre University of Cambridge  Cambridge UK"},{"name":"Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research (CTR) University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-0997","authenticated-orcid":false,"given":"Gordon C. S.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre University of Cambridge  Cambridge UK"},{"name":"Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research (CTR) University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.12.002"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.102"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704559"},{"key":"e_1_2_12_5_1","volume-title":"Saving babies' lives version three: a care bundle for reducing perinatal mortality","author":"NHS","year":"2023"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.10.011"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2019.04.005"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.03.064"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08620"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(18)30129-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00131-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531779"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0049124104268644"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz274"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu140"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m441"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.08.009"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000265804.09161.0d"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031884"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313276"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251816"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0020731418786360"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-8-51"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001274"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.01.019"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2021.05.006"}],"container-title":["BJOG: An International Journal of Obstetrics &amp; Gynaecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.17691","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T21:55:12Z","timestamp":1712008512000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/1471-0528.17691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/1471-0528.17691"],"URL":"https:\/\/doi.org\/10.1111\/1471-0528.17691","archive":["Portico"],"relation":{},"ISSN":["1470-0328","1471-0528"],"issn-type":[{"value":"1470-0328","type":"print"},{"value":"1471-0528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]},"assertion":[{"value":"2023-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}