Table 1 -Characteristics of studies reporting on the detection of structural anomalies in low risk and unselected populations using first trimester ultrasound. Notes: (i). In studies where both TA and TV ultrasound were used, the number in parentheses adjacent to the ultrasound modality refers to the percentage of the study population which received this screening test (when available). (ii). In studies where aneuploid fetuses were included, the percentage of the study population confirmed by karyotyping as aneuploid was indicated in parentheses (where available). (iii). The subgroup analysis column identifies the group(s) in which the respective study's data was analyzed. * Highlights studies where TV ultrasound was only performed in situations where visualization with TA ultrasound was deemed suboptimal. **Cardiac exam performed at time of first trimester scan, but cardiac malformations excluded from study analysis. ***For the purposes of this review, only the cohort of known euploid fetuses was included in analysis (as insufficient data was provided on the entire cohort reported in the study). GroupYear N Gestation (weeks) Population Health-Care Setting Aneuploid Included? Index Test Anatomy Checklist Cardiac Exam Done? Subgroup for data Analysis Achiron (62) 1991 800 9-13 Mixed indications: vaginal bleeding, dating and early anomaly screening Unclear Yes TV/TA Basic Yes 2 Hernadi (37) 1997 3991 11-14 Unselected Unclear Yes (0.2%) TV Basic No 1 Bilardo (25) (Low risk) 1998 1543 10-14 Consecutive, Singleton pregnancies, Normal NT (<3.0mm),

IntroductionIn the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy.Material and MethodsTo gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values.ResultsThe WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour.ConclusionOur study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB.