Prediction of small for gestational age infants in healthy nulliparous women using clinical and ultrasound risk factors combined with early pregnancy biomarkers

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dc.contributor.author McCowan, Lesley M. E.
dc.contributor.author Thompson, John M. D.
dc.contributor.author Taylor, Rennae S.
dc.contributor.author Baker, Philip N.
dc.contributor.author North, Robyn A.
dc.contributor.author Poston, Lucilla
dc.contributor.author Roberts, Claire T.
dc.contributor.author Simpson, Nigel A. B.
dc.contributor.author Walker, James J.
dc.contributor.author Myers, Jenny
dc.contributor.author Kenny, Louise C.
dc.date.accessioned 2017-01-25T11:21:19Z
dc.date.available 2017-01-25T11:21:19Z
dc.date.issued 2017-01-09
dc.identifier.citation McCowan, L. M. E., Thompson, J. M. D., Taylor, R. S., Baker, P. N., North, R. A., Poston, L., Roberts, C. T., Simpson, N. A. B., Walker, J. J., Myers, J., Kenny, L. C. and On behalf of the, S. c. (2017) 'Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers', PLOS ONE, 12(1), pp. e0169311. doi:10.1371/journal.pone.0169311 en
dc.identifier.volume 12 en
dc.identifier.issued 1 en
dc.identifier.startpage e0169311-1 en
dc.identifier.endpage e0169311-15 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/3515
dc.identifier.doi 10.1371/journal.pone.0169311
dc.description.abstract Objective: Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks’ with ultrasound parameters at 20±1 weeks’ gestation. Methods: Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. Results: 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks’ clinical variables, 15±1 weeks’ clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks’ were: 0.63 (0.59–0.67), 0.64 (0.60–0.68) and 0.69 (0.66–0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57–0.66), 0.61 (0.56–0.66) and 0.68 (0.64–0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70–0.82), 0.80 (0.75–0.86) and 0.84 (0.78–0.89) with minimal change in the Training datasets. Conclusion: Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry. en
dc.description.sponsorship The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council (04/198); Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Australian SCOPE study was funded by the Premier’s Science and Research Fund, South Australian Government. The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (GT084) and University of Manchester Proof of Concept Funding (University of Manchester); Guy’s and St. Thomas’ Charity (King’s College London) and Tommy’s charity; King’s College London and University of Manchester); and Cerebra UK (University of Leeds). The biomarker study was funded by an unrestricted research grant from Alere Inc, San Diego, CA (www.alere.com), to the universities in the SCOPE consortium; Science Foundation Ireland (SFI Program Grant for INFANT (12/RC/2272)); National Health and Medical Research Council (NHMRC Senior Research Fellowship GNT1020749) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2017 McCowan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Biomarkers en
dc.subject Hypertensive disorders in pregnancy en
dc.subject Pregnancy en
dc.subject Infants en
dc.subject Placental growth factor en
dc.subject Preeclampsia en
dc.subject Forecasting en
dc.subject Hypertension en
dc.title Prediction of small for gestational age infants in healthy nulliparous women using clinical and ultrasound risk factors combined with early pregnancy biomarkers en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Louise Kenny, Obstetrics & Gynaecology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: l.kenny@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-01-25T10:08:38Z
dc.description.version Published Version en
dc.internal.rssid 381000657
dc.contributor.funder Health Research Council of New Zealand en
dc.contributor.funder Health Research Board en
dc.contributor.funder Biotechnology and Biological Sciences Research Council en
dc.contributor.funder University of Manchester en
dc.contributor.funder Guy's and St Thomas' Charity en
dc.contributor.funder Tommy's Baby Charity en
dc.contributor.funder Kings College London en
dc.contributor.funder Cerebra en
dc.contributor.funder University of Leeds en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder National Health and Medical Research Council en
dc.contributor.funder Evelyn Bond Fund, New Zealand en
dc.contributor.funder Auckland District Health Board Charitable Trust, New Zealand en
dc.contributor.funder Foundation for Research, Science and Technology, New Zealand en
dc.contributor.funder Premier’s Science and Research Fund, Australia en
dc.contributor.funder Government of South Australia en
dc.contributor.funder National Health Service, United Kingdom en
dc.contributor.funder Alere Inc, United States en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Plos One en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress l.kenny@ucc.ie en


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© 2017 McCowan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as © 2017 McCowan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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