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. 2017 Jun 1;12(6):e0178484.
doi: 10.1371/journal.pone.0178484. eCollection 2017.

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

Matias C Vieira  1   2 , Lesley M E McCowan  3 , Alexandra Gillett  1 , Lucilla Poston  1   4 , Elaine Fyfe  3 , Gustaaf A Dekker  5 , Philip N Baker  6 , James J Walker  7 , Louise C Kenny  8 , Dharmintra Pasupathy  1   4 ; SCOPE Consortium
Affiliations

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

Matias C Vieira et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: LCK has a consultancy relationship with Alere. PNB and LCK are minority shareholders in Metabolomic Diagnostics, an SME who have licensed IP pertaining to the prediction of preeclampsia from UCC. In addition, PNB and LCK declare a US patent PCT/EP2010/070446 and LP declares patent PCT number GB01/04892. The Alere funding was used for sample retrieval and shipping, database sharing, and the time university employed researchers spent on the project. Alere developed the immunoassays and performed the biomarker measurements, but was blinded to clinical data and endpoints. In addition, Alere and other funders had no role in study design, data collection and analysis, and decision to publish or the data included in this publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in the guide for authors, http://www.PLOSone.org/static/editorial.action#competing). All other authors report no conflict of interest.

Figures

Fig 1
Fig 1. Study population.
Fig 2
Fig 2. Receiver operating characteristics curve for LGA prediction models in the validation dataset.
Model 1—clinical factors at 14–16 weeks; Model 2—clinical factors and candidate biomarkers at 14–16 weeks; Model 3—clinical factors and ultrasound at 14–16 and 19–21 weeks; Model 4—clinical factors, ultrasound and candidate biomarkers at 14–16 and 19–21 weeks; Model 5—full model including additional list of biomarkers.
See this image and copyright information in PMC

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