Reference charts for first-trimester placental volume derived using OxNNet

Objective:
To establish a comprehensive reference range for OxNNet-derived first-trimester placental volume (FTPV), based on values observed in healthy pregnancies.

Methods:
Data were obtained from the First Trimester Placental Ultrasound Study, an observational cohort study in which three-dimensional placental ultrasound imaging was performed between 11 + 2 and 14 + 1 weeks' gestation, alongside otherwise routine care. A subgroup of singleton pregnancies resulting in term live birth, without neonatal unit admission or major chromosomal or structural abnormality, were included. Exclusion criteria were fetal growth restriction, maternal diabetes mellitus, hypertensive disorders of pregnancy or other maternal medical conditions (e.g. chronic hypertension, antiphospholipid syndrome, systemic lupus erythematosus). Placental images were processed using the OxNNet toolkit, a software solution based on a fully convolutional neural network, for automated placental segmentation and volume calculation. Quantile regression and the lambda-mu-sigma (LMS) method were applied to model the distribution of FTPV, using both crown-rump length (CRL) and gestational age as predictors. Model fit was assessed using the Akaike information criterion (AIC), and centile curves were constructed for visual inspection.

Results:
The cohort comprised 2547 cases. The distribution of FTPV across gestational ages was positively skewed, with variation in the distribution at different gestational timepoints. In model comparisons, the LMS method yielded lower AIC values compared with quantile regression models. For predicting FTPV from CRL, the LMS model with the Sinh-Arcsinh distribution achieved the best performance, with the lowest AIC value. For gestational-age-based prediction, the LMS model with the Box-Cox Cole and Green original distribution achieved the lowest AIC value. The LMS models were selected to construct centile charts for FTPV based on both CRL and gestational age. Evaluation of the centile charts revealed strong agreement between predicted and observed centiles, with minimal deviations. Both models demonstrated excellent calibration, and the Z-scores derived using each of the models confirmed normal distribution.

Conclusions:
This study established reference ranges for FTPV based on both CRL and gestational age in healthy pregnancies. The LMS method provided the best model fit, demonstrating excellent calibration and minimal deviations between predicted and observed centiles. These findings should facilitate the exploration of FTPV as a potential biomarker for adverse pregnancy outcome and provide a foundation for future research into its clinical applications.