Introduction: Preterm birth (PTB) and fetal growth restriction (FGR) are significant contributors to the worldwide burden of disease. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) are strongly associated with placental dysfunction but their utility with fetoplacental Dopplers for PTB in FGR remains unknown.

Aims: To assess the utility of PlGF, sFlt-1/PlGF ratio and their association with Umbilical Artery (UA) and Uterine Artery Pulsatility Index (UtA PI) in various combinations to predict PTB in FGR.

Methods: A prospective cohort study of pregnancies complicated by FGR. Maternal serum PlGF, sFlt-1/PlGF ratio, UA PI and UtA PI were measured at 4-weekly intervals from recruitment to delivery. Cox proportional hazards models and Harrell's concordance statistic were used to predict PTB.

Results: Of the 320 pregnancies-179(55.9%) were FGR and 141(44.1%) were appropriate for gestational age (AGA). Low PlGF <100 ng/L and elevated sFlt-1/PlGF ratio (>5.78 if <28 weeks and > 38 if ≥28 weeks) were strongly predictive for PTB and risk for medically indicated PTB in both FGR and AGA. In FGR, low PlGF was a better predictor of PTB than either sFlt-1/PlGF ratio or combination of both (Harrell's C 0.81, 0.79, 0.75 respectively). The predictive utility was highest when PlGF <100 ng/L, UA PI and UtA PI >95th centile was combined (Harrell's C 0.88) (Hazard Ratio 32.99 95%CI 10.74,101.32).

Discussion: Low maternal PlGF and abnormal UA PI and UtA PI (>95th centile) in combination have greatest predictive utility for PTB in FGR pregnancies and may help guide clinical management of these complex pregnancies.

Funding: National Health and Medical Research Council and Mater Foundation.