Objective Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency.Methods Mouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26 eYfp ), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2 À/À ) or in utero inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied. Flow cytometry was performed to measure specific LEC populations.Results Cranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling in utero resulted in a significantly higher amount of precursor-LECs at the expense of mature LECs and caused nuchal edema.Conclusions Neural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema.

Objective To assess whether cardiac failure, because of cardiac defects, and abnormal jugular lymphatic development are involved in nuchal edema (NE) -the morphological equivalent of increased nuchal translucency -in various euploid mutant mouse models.

Abnormal DV-FVWs are not justified by alterations in ductus venosus morphology. DV-FVWs most probably reflect intracardiac pressure. © 2016 John Wiley & Sons, Ltd.

Kok Th, van der Jagt EJ, Haagsma EB, Bijleveld CMA, Jansen PLM, Boeve WJ. The value of Doppler ultrasound in cirrhosis and portal hypertension. Scand J Gasteroenterol 1999;34 Suppl 230:82-8. Background: Cirrhosis and portal hypertension affect the flow profile of the liver vasculature. In these conditions Doppler ultrasound can provide important information on the hemodynamics of the portal venous system, the hepatic artery and the hepatic veins. Methods: The value of Doppler ultrasound in the assessment of the patient with cirrhosis and portal hypertension was determined by reviewing the literature. Results: Portal venous blood flow becomes reversed with advanced portal hypertension. Reversed flow is also demonstrated in patients with veno-occlusive disease and portosystemic shunts. Despite general agreement that portal flow velocity is decreased in cirrhotic patients, the absolute values of portal flow velocity in both healthy subjects and cirrhotic patients vary considerably. Errors in Doppler measurements, observer variability and collateral pathways contribute to these variations. Furthermore, portal blood flow is influenced by numerous factors such as changes in the body position, phase of respiration, timing of meals, exercise and cardiac output. Finally, portal flow may be unaltered due to a combination of high inflow from the splanchnic organs and increased resistance within the liver. High resistive index of the hepatic artery is seen in patients with end-stage liver disease, particularly in children with severe cirrhosis secondary to biliary atresia. However, hepatic artery flow remains normal in most patients. Abnormal hepatic vein flow profiles are seen in patients with cirrhosis, but dampening or flattening of the flow profile has a multifactorial origin (Budd-Chiari, metastases, ascites) and can be observed in healthy subjects. Conclusions: Although many factors may affect the accuracy of volume flow and velocity measurements and the flow profile of the liver vasculature may change in different situations, Doppler ultrasound is useful in the assessment of the patient with cirrhosis and portal hypertension.

Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Ductus venosus flow velocity waveforms most probably reflect intracardiac pressure.