{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T18:13:29Z","timestamp":1775067209155,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003123","name":"Fetal Medicine Foundation","doi-asserted-by":"publisher","award":["Charity No: 1037116"],"award-info":[{"award-number":["Charity No: 1037116"]}],"id":[{"id":"10.13039\/501100003123","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>First, to describe the distribution of biomarkers of impaired placentation in small\u2010for\u2010gestational\u2010age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth\u2010related neonatal morbidity of a high soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101)\/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt\u20101\/PlGF ratio or low PlGF with that of the competing\u2010risks model for SGA in predicting growth\u2010related neonatal morbidity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective observational study of women attending for a routine hospital visit at 35\u2009+\u20090 to 36\u2009+\u20096\u2009weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt\u20101. The primary outcome was delivery within 4\u2009weeks after assessment and at &lt;\u200942\u2009weeks' gestation of a SGA neonate with birth weight &lt;\u200910<jats:sup>th<\/jats:sup> or &lt;\u20093<jats:sup>rd<\/jats:sup> percentile, combined with neonatal unit (NNU) admission for \u2265\u200948\u2009h or a composite of major neonatal morbidity. The detection rates in screening by PlGF &lt;\u200910<jats:sup>th<\/jats:sup> percentile, sFlt\u20101\/PlGF ratio &gt;\u200990<jats:sup>th<\/jats:sup> percentile, sFlt\u20101\/PlGF ratio &gt;\u200938 and the competing\u2010risks model for SGA, using combinations of maternal risk factors and <jats:italic>Z<\/jats:italic>\u2010scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt\u20101, were estimated. The detection rates by the different methods of screening were compared using McNemar's test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the study population of 29\u2009035 women, prediction of growth\u2010related neonatal morbidity at term provided by the competing\u2010risks model was superior to that of screening by low PlGF concentration or a high sFlt\u20101\/PlGF concentration ratio. For example, at a screen\u2010positive rate (SPR) of 13.1%, as defined by the sFlt\u20101\/PlGF ratio &gt;\u200938, the competing\u2010risks model using maternal risk factors and EFW predicted 77.5% (95%\u2009CI, 71.7\u201383.3%) of SGA &lt;\u200910<jats:sup>th<\/jats:sup> percentile and 89.3% (95%\u2009CI, 83.7\u201394.8%) of SGA &lt;\u20093<jats:sup>rd<\/jats:sup> percentile with NNU admission for \u2265\u200948\u2009h delivered within 4\u2009weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95%\u2009CI, 56.5\u201386.4%) and 90.0% (95%\u2009CI, 76.9\u2013100%). These were significantly higher than the respective values of 41.0% (95%\u2009CI, 34.2\u201347.8%) (<jats:italic>P\u2009&lt;\u2009<\/jats:italic>0.0001), 48.8% (95%\u2009CI, 39.9\u201357.7%) (<jats:italic>P\u2009&lt;\u2009<\/jats:italic>0.0001), 37.1% (95%\u2009CI, 21.1\u201353.2%) (<jats:italic>P\u2009=<\/jats:italic>\u20090.003) and 55.0% (95%\u2009CI, 33.2\u201376.8%) (<jats:italic>P\u2009=<\/jats:italic>\u20090.035) achieved by the application of the sFlt\u20101\/PlGF ratio &gt;\u200938. At a SPR of 10.0%, as defined by PlGF &lt;\u200910<jats:sup>th<\/jats:sup> percentile, the competing\u2010risks model using maternal factors and EFW predicted 71.5% (95%\u2009CI, 65.2\u201377.8%) of SGA &lt;\u200910<jats:sup>th<\/jats:sup> percentile and 84.3% (95%\u2009CI, 77.8\u201390.8%) of SGA &lt;\u20093<jats:sup>rd<\/jats:sup> percentile with NNU admission for \u2265\u200948\u2009h delivered within 4\u2009weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95%\u2009CI, 53.1\u201383.9%) and 85.0% (95%\u2009CI, 69.4\u2013100%). These were significantly higher than the respective values of 36.5% (95%\u2009CI, 29.8\u201343.2%) (<jats:italic>P\u2009&lt;\u2009<\/jats:italic>0.0001), 46.3% (95%\u2009CI, 37.4\u201355.2%) (<jats:italic>P\u2009&lt;\u2009<\/jats:italic>0.0001), 37.1% (95%\u2009CI, 21.1\u201353.2%) (<jats:italic>P\u2009=<\/jats:italic>\u20090.003) and 55.0% (95%\u2009CI, 33.2\u201376.8%) (<jats:italic>P\u2009=<\/jats:italic>\u20090.021) achieved by the application of PlGF &lt;\u200910<jats:sup>th<\/jats:sup> percentile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>At 36\u2009weeks' gestation, the prediction of growth\u2010related neonatal morbidity by the competing\u2010risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt\u20101\/PlGF ratio or low PlGF. \u00a9 2023 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.27533","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T20:04:32Z","timestamp":1699992272000},"page":"457-465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of angiogenic factors in prediction of growth\u2010related neonatal morbidity at term and comparison with competing\u2010risks model"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-1435","authenticated-orcid":false,"given":"I.","family":"Papastefanou","sequence":"first","affiliation":[{"name":"Department of Women and Children's Health School of Life Course and Population Sciences, Faculty of Life Sciences &amp; Medicine, King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Nobile Recalde","sequence":"additional","affiliation":[{"name":"Fetal Medicine Research Institute King's College Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Silva Souza","sequence":"additional","affiliation":[{"name":"Fetal Medicine Research Institute King's College Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-6072","authenticated-orcid":false,"given":"A.","family":"Syngelaki","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health School of Life Course and Population Sciences, Faculty of Life Sciences &amp; Medicine, King's College London  London UK"},{"name":"Fetal Medicine Research Institute King's College Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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