Risk stratification for early-onset fetal growth restriction in women with abnormal serum biomarkers: a retrospective cohort study

L Ormesher,E D Johnstone,L Warrander,S Thomas,J E Myers,Y Liu,G C S Smith,L Simcox

doi:10.1038/s41598-020-78631-5

Abstract

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21–24 week “placental screen” comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87–1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64–0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.

Highlights

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy
The aim of this study was to determine whether a 21–24 week “placental screen,” comprising ultrasound assessment of fetal biometry, placental biometry and uterine artery Doppler impedance, could identify the subgroup of women with AMSB who were at significant risk of developing early-onset fetal growth restriction (FGR)
Our study has confirmed the association between low plasma protein-A (PAPP-A), and increased βHCG/Inhibin/αFP, with SGA (24.5%) and FGR (10.3%) and demonstrated these markers to be useful incidental pregnancy risk factors when identified through combined aneuploidy screening

Summary

Introduction

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. Serial ultrasound assessment of fetal growth can detect both phenotypes of FGR and trigger iatrogenic delivery, but is resource intensive, if frequent serial scans are performed from 26 to 28 weeks. The aim of this study was to determine whether a 21–24 week “placental screen,” comprising ultrasound assessment of fetal biometry, placental biometry and uterine artery Doppler impedance, could identify the subgroup of women with AMSB who were at significant risk of developing early-onset FGR. We aimed to design a model with a high negative predictive value that could be used as a tool to rule-out early-onset FGR without compromising detection rates and direct ultrasound resources more appropriately

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