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Significant reductions in blood flow and umbilical diameters were reported in pregnancies affected by intrauterine growth restriction (IUGR) from placental insufficiency. However, it is not known if IUGR umbilical blood vessels experience different hemodynamic wall shear stresses (WSS) compared to normal umbilical vessels. As WSS is known to influence vasoactivity and vascular growth and remodeling, which can regulate flow rates, it is important to study this parameter. In this study, we aim to characterize umbilical vascular WSS environment in normal and IUGR pregnancies, and evaluate correlation between WSS and vascular diameter, and gestational age. Twenty-two normal and 21 IUGR pregnancies were assessed via ultrasound between the 27th and 39th gestational week. IUGR was defined as estimated fetal weight and/or abdominal circumference below the 10th centile, with no improvement during the remainder of the pregnancy. Vascular diameter was determined by 3D ultrasound scans and image segmentation. Umbilical artery (UA) WSS was computed via computational flow simulations, while umbilical vein (UV) WSS was computed via the Poiseuille equation. Univariate multiple regression analysis was used to test for the differences between normal and IUGR cohort. UV volumetric flow rate, UA and UV diameters were significantly lower in IUGR fetuses, but flow velocities and WSS trends in UA and UV were very similar between normal and IUGR groups. In both groups, UV WSS showed a significant negative correlation with diameter, but UA WSS had no correlation with diameter, suggesting a constancy of WSS environment and the existence of WSS homeostasis in UA, but not in UV. Despite having reduced flow rate and vascular sizes, IUGR UAs had hemodynamic mechanical stress environments and trends that were similar to those in normal pregnancies. This suggested that endothelial dysfunction or abnormal mechanosensing was unlikely to be the cause of small vessels in IUGR umbilical cords. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction is a prevalent disease in pregnancy in which placental insufficiency leads to 5 to 10 times higher mortality and lifelong morbidities. The current detection rate is poor, and recently, ultrasound strain elastography (USEL) was proposed as a new diagnostic technique. Currently, placental USEL uses maternal subcutaneous fat as the reference layer, but this is not ideal as fat tissue stiffness can vary widely between subjects. Current USEL also uses manual palpation, and under different compression depths and rates, viscoelastic tissues such as placenta can yield different stiffness results. In the study described here, we strove to improve placental USEL by (i) using an external polymeric pad of known stiffness as the reference layer and (ii) adopting motorized control of the transducer during USEL to standardize palpation motion. Results indicated that motorized USEL reduced measurement variability by 67% compared with freehand USEL. Satisfactory and statistically significant correlations between USEL measurements and mechanical testing validation results were obtained for our new USEL protocol. Placental tissues were found to be non-linear and viscoelastic in nature and, thus, differed in stiffness at different compression rates and depths. Our study also revealed that there was a specific compression depth and rate during USEL that provided better correlation to mechanical testing, and should be considered in clinical placental USEL. [ABSTRACT FROM AUTHOR]

Background Intrauterine Growth Restriction (IUGR) is a disease where the placenta is unable to transfer enough nutrients to the fetus, limiting its growth, and resulting in high mortality and life-long morbidities. Current detection rates of IUGR are poor, resulting in limited disease management. Elastography is a promising non-invasive tool for the detection of IUGR, and works by detecting changes in the mechanical properties of the placenta. To date, however, it is not known whether IUGR placentas have different mechanical properties from normal ones, and thus investigating this is the first focus of the current study. The second focus is to evaluate and model the viscoelastic properties of the normal and IUGR placenta, so that it may be possible to improve elastography in the future by incorporating viscoelasticity. Methods Cyclic uniaxial mechanical compression testing was conducted on post-delivery human placenta samples. 18 samples from 5 normal placentae and 12 samples from 3 IUGR placentae were tested. Viscoelastic models were fitted to the resulting experimental data. Results Mechanical testing showed that IUGR placentae have reduced stiffness and viscosity compared to normal placentae. Linear viscoelastic models were unable to provide a good fit to the data, but non-linear viscoelastic solid (NVS) models could do so. The best performing model was a five parameters bi-exponential NVS model. Two of the five parameters appear to capture the differences between normal and diseased samples. Discussion Our results demonstrate that IUGR placentae have different mechanical properties from normal placentae, and a five parameter bi-exponential NVS model can effectively describe the mechanical properties of the placenta in health and disease. [ABSTRACT FROM AUTHOR]

The objective of the study is to investigate the effect of Nuchal Fold (NF) in predicting Fetal Growth Restriction (FGR) using machine learning (ML), to explain the model's results using model-agnostic interpretable techniques, and to compare the results with clinical guidelines. This study used second-trimester ultrasound biometry and Doppler velocimetry were used to construct six FGR (birthweight < 3rd centile) ML models. Interpretability analysis was conducted using Accumulated Local Effects (ALE) and Shapley Additive Explanations (SHAP). The results were compared with clinical guidelines based on the most optimal model. Support Vector Machine (SVM) exhibited the most consistent performance in FGR prediction. SHAP showed that the top contributors to identify FGR were Abdominal Circumference (AC), NF, Uterine RI (Ut RI), and Uterine PI (Ut PI). ALE showed that the cutoff values of Ut RI, Ut PI, and AC in differentiating FGR from normal were comparable with clinical guidelines (Errors between model and clinical; Ut RI: 15%, Ut PI: 8%, and AC: 11%). The cutoff value for NF to differentiate between healthy and FGR is 5.4 mm, where low NF may indicate FGR. The SVM model is the most stable in FGR prediction. ALE can be a potential tool to identify a cutoff value for novel parameters to differentiate between healthy and FGR. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) affects 5–10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation at the organ level alters microvascular shear stress, impairing angiogenesis. A computational model of placental vasculature predicted elevated placental micro-vascular shear stress in FGR placentae (0.2 Pa in severe FGR vs 0.05 Pa in normal placentae). Endothelial cells cultured under predicted FGR shear stresses migrated significantly slower and with greater persistence than in shear stresses predicted in normal placentae. These cell behaviors suggest a dominance of vessel elongation over branching. Taken together, these results suggest (1) poor vascular development increases vessel shear stress, (2) increased shear stress induces cell behaviors that impair capillary branching angiogenesis, and (3) impaired branching angiogenesis continues to drive elevated shear stress, jeopardizing further vascular formation. Inadequate vascular branching early in gestation could kick off this cyclic loop and continue to negatively impact placental angiogenesis throughout gestation. [ABSTRACT FROM AUTHOR]