Angiogenic factors for planning fetal surveillance in fetal growth restriction and small-for-gestational-age fetuses: A prospective observational study

Objective: The aim of this study was to assess the added value of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio for adjusting the periodicity of ultrasound examinations in early-onset fetal growth restriction (FGR) and small for gestational age (SGA).

Design: A prospective, observational study.

Setting: Tertiary referral hospital.

Population: One hundred and thirty-four single pregnancies with ultrasonographic estimated fetal weight (EFW) below the 10th centile between 20⁺⁰ and 31⁺⁶ weeks of gestation with antegrade umbilical artery flow.

Methods: The time from Doppler and sFlt-1/PlGF assessment to delivery was recorded and classified into four ranges: <1, <2, <3 and <4 weeks.

Main outcome measures: Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of sFlt-1/PlGF values to predict the time to delivery.

Results: In the SGA cohort, the NPV calculated for an sFlt-1/PlGF cut-off value of 38 was 100% for delivery before 3 weeks, and 98% for delivery before 4 weeks after diagnosis (95% CI 0.89-1.00). In the FGR cohort, the NPV calculated for an sFlt-1/PlGF cut-off value of 38 was 100% for delivery before 2 weeks after diagnosis (95% CI 0.92-1.00). By contrast, more than 50% of cases with an sFlt-1/PlGF value of >85 required an elective delivery before 1 week.

Conclusions: sFlt-1/PlGF values in early-onset SGA and FGR are predictive of the time to delivery and could be used for planning fetal surveillance, by reducing the frequency of ultrasound in cases with sFlt-1/PlGF < 38 and by providing closer follow-up in cases with sFlt-1/PlGF >85.

Tweetable abstract: sFlt-1/PlGF values in early-onset SGA/FGR could be used in addition to Doppler for planning fetal surveillance.