Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction

OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR).

METHODS: This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB ( 95th centile or UtA-PI > 95th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF  95th centile and UtA-PI > 95th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32).

CONCLUSIONS: Low maternal serum PlGF level ( 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.