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

dc.contributor.authorMcCowan, Lesley M. E.
dc.contributor.authorThompson, John M. D.
dc.contributor.authorTaylor, Rennae S.
dc.contributor.authorBaker, Philip N.
dc.contributor.authorNorth, Robyn A.
dc.contributor.authorPoston, Lucilla
dc.contributor.authorRoberts, Claire T.
dc.contributor.authorSimpson, Nigel A. B.
dc.contributor.authorWalker, James J.
dc.contributor.authorMyers, Jenny
dc.contributor.authorKenny, Louise C.
dc.contributor.funderHealth Research Council of New Zealanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderBiotechnology and Biological Sciences Research Councilen
dc.contributor.funderUniversity of Manchesteren
dc.contributor.funderGuy's and St Thomas' Charityen
dc.contributor.funderTommy's Baby Charityen
dc.contributor.funderKings College Londonen
dc.contributor.funderUniversity of Leedsen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderNational Health and Medical Research Councilen
dc.contributor.funderEvelyn Bond Fund, New Zealanden
dc.contributor.funderAuckland District Health Board Charitable Trust, New Zealanden
dc.contributor.funderFoundation for Research, Science and Technology, New Zealanden
dc.contributor.funderPremier’s Science and Research Fund, Australiaen
dc.contributor.funderGovernment of South Australiaen
dc.contributor.funderNational Health Service, United Kingdomen
dc.contributor.funderAlere Inc, United Statesen
dc.description.abstractObjective: 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.sponsorshipThe 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 (, 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationMcCowan, 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.0169311en
dc.identifier.journaltitlePlos Oneen
dc.publisherPublic Library of Scienceen
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.subjectHypertensive disorders in pregnancyen
dc.subjectPlacental growth factoren
dc.titlePrediction of small for gestational age infants in healthy nulliparous women using clinical and ultrasound risk factors combined with early pregnancy biomarkersen
dc.typeArticle (peer-reviewed)en
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