Abstract
Background
Severe early-onset fetal growth restriction (FGR) predisposes to fetal death, neonatal
death, neonatal morbidity and neurodisability. The use of placental biomarkers has
been proposed for risk stratification in pre-eclampsia, but they could be equally
useful in fetal growth restriction in aiding management.
Objective
To determine the efficacy of angiogenic biomarkers at predicting adverse pregnancy
outcome in severe early-onset fetal growth restriction.
Study design
This is a secondary analysis of the multicentre, placebo-controlled STRIDER UK randomised
controlled trial of singleton pregnancies with severe early-onset fetal growth restriction.
Women with FGR pregnancies between 22+0 and 29+6 weeks of gestation were randomly assigned to receive either sildenafil 25 mg three
times daily or placebo until 32+0 weeks’ gestation or delivery. We developed prediction models based upon maternal
demographics (age, parity, blood pressure, preeclampsia, gestational hypertension),
fetal biometric (estimated fetal weight) and Doppler measurements (Middle Cerebral
Artery (MCA), Umbilical Artery (UA)) and maternal angiogenic biomarkers [placental
growth factor (PlGF), soluble endoglin (sEng), soluble fms-like tyrosine kinase 1
(sFlt-1) and sFlt-1:PlGF ratio) using both univariate and multivariate analysis.
Results
A complete data set was available for 105 of 135 randomised women. Multivariate regression
analysis identified estimated fetal weight (EFW) and sFlt-1:PlGF as independent predictors
of livebirth (EFW OR: 1.01 (1.008, 1.021); p < 0.001 and lower sFlt-1:PlGF ratio OR:
0.53 (0.284, 0.994); p = 0.048) and overall survival (EFW OR: 1.01 (1.006, 1.015);
p < 0.001 and lower sFlt-1/PlGF ratio OR: 0.51 (0.286, 0.904); p = 0.021). EFW was
a consistent predictor for all outcomes other than gestation at delivery. sFlt-1:PlGF
ratio was a consistent predictor for all outcomes other than neonatal morbidity.
Conclusions
In severe early-onset FGR pregnancies livebirth and overall survival can be predicted
using a model involving EFW and sFlt-1:PlGF ratio. This model require validation in
a larger cohort but may allow informed decision making about pregnancy management,
especially in previable cases.
Keywords
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Article info
Publication history
Published online: August 16, 2019
Accepted:
August 15,
2019
Received in revised form:
August 11,
2019
Received:
February 12,
2019
Identification
Copyright
© 2019 Published by Elsevier B.V.
