Assessing the sensitivity of placental growth factor and soluble fms-like tyrosine kinase 1 at 36 weeks’ gestation to predict small-for-gestational-age infants or late-onset preeclampsia: a prospective nested case-control study

Abstract

BackgroundFetal growth restriction is a disorder of placental dysfunction with three to four-fold increased risk of stillbirth. Fetal growth restriction has pathophysiological features in common with preeclampsia. We hypothesised that angiogenesis-related factors in maternal plasma, known to predict preeclampsia, may also detect fetal growth restriction at 36 weeks’ gestation. We therefore set out to determine the diagnostic performance of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1:PlGF ratio, measured at 36 weeks’ gestation, in identifying women who subsequently give birth to small-for-gestational-age (SGA; birthweight <10th centile) infants. We also aimed to validate the predictive performance of the analytes for late-onset preeclampsia in a large independent, prospective cohort.MethodsA nested 1:2 case-control study was performed including 102 cases of SGA infants and a matched group of 207 controls; and 39 cases of preeclampsia. We determined the diagnostic performance of each angiogenesis-related factor, and of their ratio, to detect SGA infants or preeclampsia, for a predetermined 10% false positive rate.ResultsMedian plasma levels of PlGF at 36 weeks’ gestation were significantly lower in women who subsequently had SGA newborns (178.5 pg/ml) compared to normal birthweight controls (326.7 pg/ml, p < 0.0001). sFlt-1 was also higher among SGA cases, but this was not significant after women with concurrent preeclampsia were excluded. The sensitivity of PlGF to predict SGA infants was 28.8% for a 10% false positive rate. The sFlt-1:PlGF ratio demonstrated better sensitivity for preeclampsia than either analyte alone, detecting 69.2% of cases for a 10% false positive rate.ConclusionsPlasma PlGF at 36 weeks’ gestation is significantly lower in women who subsequently deliver a SGA infant. While the sensitivity and specificity of PlGF currently limit clinical translation, our findings support a blood-based biomarker approach to detect late-onset fetal growth restriction. Thirty-six week sFlt-1:PlGF ratio predicts 69.2% of preeclampsia cases, and could be a useful screening test to triage antenatal surveillance.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-1992-x) contains supplementary material, which is available to authorized users.

Role of sFlt-1 and PlGF in the screening of small-for-gestational age neonates during pregnancy: A systematic review

“…Therefore, it was conceivable that measuring these placental biomarkers in maternal blood could be used in the prediction of pre-eclampsia and fetal growth restriction. 6,9 The serum sFlt-1/PlGF ratio has already been used in improving the clinical management for preeclampsia. Pre-eclampsia is defined as the new onset of hypertension and proteinuria after 20 weeks of gestation.…”

Standard care informed by the result of a placental growth factor blood test versus standard care alone in women with reduced fetal movement at or after 36+0 weeks’ gestation: a pilot randomised controlled trial

“…Although most research utilising the sFlt-1/PlGF ratio in placental dysfunction has been targeted at preeclampsia [21], more recent work has been investigating the use of these biomarkers for detecting other pregnancy complications such as the identification of SGA babies [35][36][37], fetal compromise associated with RFM [18] and gestational hypertension and placental abruption [38]. It is likely that interest will increase in the use of biomarkers combined with other aspects of care for the management of RFM after results from the AFFIRM trial indicated that a care package for RFM did not significantly reduce the rate of stillbirth but increased the rate of obstetric intervention [39].…”

MicroRNAs 363 and 149 are differentially expressed in the maternal circulation preceding a diagnosis of preeclampsia

“…FLAG study design overview 38 . This study is part of the Fetal Longitudinal Assessment of Growth (FLAG) study Women carried out at the Mercy Hospital for Women, a tertiary maternity hospital in Melbourne with approximately 6000 births annually.…”