Abstract
OBJECTIVES: To develop predictive models for fetal growth restriction (FGR) with and without the inclusion of OxNNet-derived first-trimester placental volume (FTPV), thereby evaluating the contribution of FTPV to these models and the extent to which FTPV percentile is associated with subsequent FGR. METHODS: This study utilized data from the First-trimester Placental Ultrasound (FirstPLUS) study, a longitudinal observational cohort study conducted at King's College Hospital NHS Foundation Trust, London, UK, between March and November 2022. Participants underwent routine ultrasound assessment between 11 + 2 and 14 + 1 weeks' gestation, in addition to three-dimensional placental sonography. The OxNNet toolkit was used for automated placental segmentation and volume calculation. Multivariable logistic regression models were developed to predict FGR, incorporating maternal factors, first-trimester biomarkers (serum pregnancy-associated plasma protein-A, mean arterial blood pressure and uterine artery pulsatility index) and FTPV. RESULTS: The final cohort comprised 3500 pregnancies, of which 250 (7.1%) developed FGR. Low FTPV was found to be a risk factor for FGR, with an odds ratio of 1.736 (95% CI, 1.499-2.015) per unit decrease in FTPV Z-score. Incorporating FTPV into the predictive model based on maternal factors and biomarkers significantly increased the area under the receiver-operating-characteristics curve (AUC) for predicting all cases of FGR, from 0.78 (95% CI, 0.75-0.81) to 0.79 (95% CI, 0.76-0.82) (P = 0.005). Subgroup analysis of normotensive and hypertensive cases demonstrated a statistically significant effect size for the prediction of FGR by FTPV Z-score in both groups. The addition of FTPV to the model based on maternal factors and biomarkers for the prediction of normotensive FGR increased the AUC from 0.77 (95% CI, 0.74-0.80) to 0.78 (95% CI, 0.75-0.81) (P = 0.01). For preterm FGR, the AUC was 0.85 (95% CI, 0.78-0.92) with FTPV and 0.85 (95% CI, 0.79-0.92) without (P = 0.93); the absence of a significant difference may be due to a lack of power. CONCLUSIONS: FTPV Z-score is a predictor of FGR. Integrating FTPV into predictive models significantly enhanced the discriminative ability for all cases of FGR, as well as for the subgroup of normotensive FGR. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.