Assessment of first-trimester utero-placental vascular morphology by 3D power Doppler ultrasound image analysis using a skeletonization algorithm: the Rotterdam Periconception Cohort.

<bold>Study Question: </bold>Can three-dimensional (3D) Power Doppler (PD) ultrasound and a skeletonization algorithm be used to assess first-trimester development of the utero-placental vascular morphology?<bold>Summary Answer: </bold>The application of 3D PD ultrasonography and a skeletonization algorithm facilitates morphologic assessment of utero-placental vascular development in the first trimester and reveals less advanced vascular morphologic development in pregnancies with placenta-related complications than in pregnancies without placenta-related complications.<bold>What Is Known Already: </bold>Suboptimal development of the utero-placental vasculature is one of the main contributors to the periconceptional origin of placenta-related complications. The nature and attribution of aberrant vascular structure and branching patterns remain unclear, as validated markers monitoring first-trimester utero-placental vascular morphologic development are lacking.<bold>Study Design, Size, Duration: </bold>In this prospective observational cohort, 214 ongoing pregnancies were included before 10 weeks gestational age (GA) at a tertiary hospital between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception Cohort study.<bold>Participants/materials, Setting, Methods: </bold>By combining 3D PD ultrasonography and virtual reality, utero-placental vascular volume (uPVV) measurements were obtained at 7, 9 and 11 weeks GA. A skeletonization algorithm was applied to the uPVV measurements to generate the utero-placental vascular skeleton (uPVS), a network-like structure containing morphologic characteristics of the vasculature. Quantification of vascular morphology was performed by assigning a morphologic characteristic to each voxel in the uPVS (end-, vessel-, bifurcation- or crossing-point) and calculating total vascular network length. A Mann-Whitney U test was performed to investigate differences in morphologic development of the first-trimester utero-placental vasculature between pregnancies with and without placenta-related complications. Linear mixed models were used to estimate trajectories of the morphologic characteristics in the first trimester.<bold>Main Results and the Role Of Chance: </bold>All morphologic characteristics of the utero-placental vasculature increased significantly in the first trimester (P < 0.005). In pregnancies with placenta-related complications (n = 54), utero-placental vascular branching was significantly less advanced at 9 weeks GA (vessel points P = 0.040, bifurcation points P = 0.050, crossing points P = 0.020, total network length P = 0.023). Morphologic growth trajectories remained similar after adjustment for parity, conception mode, foetal sex and occurrence of placenta-related complications.<bold>Limitations, Reasons For Caution: </bold>The tertiary setting of this prospective observational study provides high internal, but possibly limited external, validity. Extrapolation of the study's findings should therefore be addressed with caution.<bold>Wider Implications Of the Findings: </bold>The uPVS enables assessment of morphologic development of the first-trimester utero-placental vasculature. Further investigation of this innovative methodology needs to determine its added value for the assessment of (patho-) physiological utero-placental vascular development.<bold>Study Funding/competing Interest(s): </bold>This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest.<bold>Trial Registration Number: </bold>Registered at the Dutch Trial Register (NTR6854). [ABSTRACT FROM AUTHOR]