{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:32:39Z","timestamp":1788294759896,"version":"build-2803163510"},"reference-count":21,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["Antenatal, Maternal and Child Health theme"],"award-info":[{"award-number":["Antenatal, Maternal and Child Health theme"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Clinical Research Network, East of England","award":["Reproductive Health"],"award-info":[{"award-number":["Reproductive Health"]}]},{"name":"NIHR Cambridge Clinical Research Facility","award":["CRF 538"],"award-info":[{"award-number":["CRF 538"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00004\/07"],"award-info":[{"award-number":["MC_UU_00004\/07"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215524\/Z\/19\/Z"],"award-info":[{"award-number":["215524\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016545","name":"Roche Diagnostics","doi-asserted-by":"publisher","award":["Collaborative Research Agreement"],"award-info":[{"award-number":["Collaborative Research Agreement"]}],"id":[{"id":"10.13039\/100016545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,7,24]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Current UK guidelines recommend measurement of symphyseal fundal height and measurement of maternal blood pressure and urinalysis, with the aim of detecting women at increased risk of fetal growth restriction (FGR) and pre-eclampsia. Between 2008 and 2013, we conducted a prospective cohort study recruiting 4512 nulliparous women at the Rosie Hospital, Cambridge, where we performed serial ultrasonic imaging and serial blood sampling and generated a novel screening test for pre-eclampsia and FGR. The method involved measuring the ratio of two placental biomarkers (soluble fms-like tyrosine kinase receptor-1 and placenta growth factor) at ~36 weeks of gestational age (wkGA) and combining the result with maternal characteristics and ultrasonic imaging. Women who screened positive had a ~50%\u2009risk of a composite outcome, consisting of pre-eclampsia\u00b1delivery of a baby with a birth weight &lt;3rd percentile for sex and gestational age\u00b1perinatal morbidity or death. It is plausible that screening and intervention using this method might improve pregnancy outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Nulliparous women with an apparently normal singleton pregnancy will be recruited at their dating ultrasound scan. Blood will be obtained at this visit, at their anomaly scan (20 wkGA), and at two research appointments (28 wkGA and 36 wkGA) when research ultrasound scans will be performed. Blood for DNA will be obtained from the father of the baby where possible and the placenta will be sampled following birth. At 36 wkGA, women will be consented for participation in the randomised controlled trial (RCT) element of the study and their risk of term pre-eclampsia and FGR will be assessed using the novel approach. Women who screen high-risk will then be randomly allocated to either having the result revealed or masked. Women randomised to having the result revealed will be offered early delivery and\/or enhanced monitoring. Where the result is masked, there will be no communication between the research team and the participant, and she will continue to receive routine care at the Rosie Hospital. The primary outcome is a composite of pre-eclampsia, FGR and perinatal morbidity and mortality. The study will also generate data and biological samples to support future research in novel screening methods and disease mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study received ethical approval from the East of England Research Ethics Committee. All women provide written informed consent to participate in the cohort. Women provide a second written informed consent to participate in the RCT. The study results will be disseminated by presentation at international conferences and publication in peer reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN1218142\">ISRCTN1218142<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-122043","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:40:14Z","timestamp":1786110014000},"page":"e122043","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Prospective cohort study of unselected nulliparous women with a nested randomised controlled trial of screening using the sFLT1:PlGF ratio, ultrasound and maternal characteristics and intervention using enhanced monitoring and early delivery: study protocol for the POPS2 cohort and randomised controlled trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"isrctn1218142","registry":"10.18810\/isrctn"},{"clinical-trial-number":"isrctn01879376","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-0997","authenticated-orcid":false,"given":"Gordon C S","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Sutton-Cole","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Dyer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Sovio","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6718-7661","authenticated-orcid":false,"given":"Ian R","family":"White","sequence":"additional","affiliation":[{"name":"Clinical Trials & Methodology, University College London Faculty of Population Health Sciences, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4890","authenticated-orcid":false,"given":"D Stephen","family":"Charnock-Jones","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026080706400849000_16.8.e122043.1","unstructured":"WHO . 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