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Clinical, ultrasound and molecular biomarkers for early prediction of large for gestational age infants in nulliparous women: An international prospective cohort study.

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posted on 2017-10-31, 15:45 authored by Matias C. Vieira, Lesley M. E. McCowan, Alexandra Gillett, Lucilla Poston, Elaine Fyfe, Gustaaf A. Dekker, Philip N. Baker, James J. Walker, Louise C. Kenny, Dharmintra Pasupathy, SCOPE Consortium
OBJECTIVE: To develop a prediction model for term infants born large for gestational age (LGA) by customised birthweight centiles. METHODS: International prospective cohort of nulliparous women with singleton pregnancy recruited to the Screening for Pregnancy Endpoints (SCOPE) study. LGA was defined as birthweight above the 90th customised centile, including adjustment for parity, ethnicity, maternal height and weight, fetal gender and gestational age. Clinical risk factors, ultrasound parameters and biomarkers at 14-16 or 19-21 weeks were combined into a prediction model for LGA infants at term using stepwise logistic regression in a training dataset. Prediction performance was assessed in a validation dataset using area under the Receiver Operating Characteristics curve (AUC) and detection rate at fixed false positive rates. RESULTS: The prevalence of LGA at term was 8.8% (n = 491/5628). Clinical and ultrasound factors selected in the prediction model for LGA infants were maternal birthweight, gestational weight gain between 14-16 and 19-21 weeks, and fetal abdominal circumference, head circumference and uterine artery Doppler resistance index at 19-21 weeks (AUC 0.67; 95%CI 0.63-0.71). Sensitivity of this model was 24% and 49% for a fixed false positive rate of 10% and 25%, respectively. The addition of biomarkers resulted in selection of random glucose, LDL-cholesterol, vascular endothelial growth factor receptor-1 (VEGFR1) and neutrophil gelatinase-associated lipocalin (NGAL), but with minimal improvement in model performance (AUC 0.69; 95%CI 0.65-0.73). Sensitivity of the full model was 26% and 50% for a fixed false positive rate of 10% and 25%, respectively. CONCLUSION: Prediction of LGA infants at term has limited diagnostic performance before 22 weeks but may have a role in contingency screening in later pregnancy.


The Australian SCOPE study was supported by the Premier’s Science and Research Fund, South Australian Government, and a NHMRC project grant (GNT519225). 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 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). Biomarker measurement was funded by an unrestricted research grant from Alere Inc, San Diego, CA. MCV is supported by a Science Without Borders Fellowship from CAPES (BEX: 9571/13-2). LCK is supported by a Science Foundation Ireland Program Grant for INFANT (12/RC/2272). DP and LP are supported by Tommy’s Charity, UK. Open access for this article was funded by King’s College London (Open Scholarship Fund).



PLoS One, 2017, 12(6): e0178484

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Data Availability: The SCOPE study which commenced recruitment in 2004 did not seek specific consent from participants for sharing their data publicly. However, the SCOPE Consortium Scientific Advisory Board is happy to receive and consider applications from interested parties who can email the chairperson, Professor Louise Kenny, at . Applicants will be asked to complete a Research Application Form specifying details for their planned study which will then be reviewed by the SCOPE Scientific Advisory Board. The SCOPE Consortium is keen to promote collaboration among researchers and to see our unique SCOPE database and pregnancy biobank used in studies which meet our ethics and consenting process. Therefore, we are a member of the MotherChild Link Registry,



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