General discussion and future perspective

Abstract

CONCLUSIONS In this thesis, lymphatic maldevelopment as an explanation for the pathophysiology of increased nuchal translucency (NT) was studied. Previous research implicates that an altered or delayed lymphatic development can explain the pathophysiology for increased NT. It can explain both the local and temporary character of increased NT as the jugular lymphatic system undergoes a fi nalization of its development at the time the NT appears. We have shown that enlarged jugular lymphatic sacs (JLS) can be visualised with ultrasound in a signifi cant part of fetuses with a normal NT and concluded that the presence of small JLS in cases with normal NT is the result of a normal variation in development. We demonstrated a relation between enlarged JLS and altered jugular vein and ductus venosus Doppler fl ow velocities in fetuses with increased NT. Altered jugular vein and ductus venosus Doppler fl ow velocities were demonstrated both in fetuses with and without a cardiac defect. No relation was found between ductus venosus Doppler fl ow velocities and diff erent types of cardiac defects. We confi rmed the abnormal lymphatic endothelial diff erentiation in fetuses with nuchal edema, the morphological equivalent of increased NT. Furthermore, a possible explanation for the layer of smooth muscle cells which surround enlarged JLS was found. We have also demonstrated an aberrant lymphatic development in fetuses with a normal karyotype. This thesis provides further evidence for an abnormal lymphangiogenesis in fetuses with increased NT. NT measurement in the fi rst-trimester of pregnancy has become a widely used screening method for chromosomal abnormalities. 1 Besides aneuploidy, increased NT is associated with a variety of structural defects and genetic syndromes. 2 A part of the fetuses with enlarged NT present with a normal outcome. 3 The pathogenetic mechanism causing increased NT is, however , not completely understood. Several mechanisms have been suggested such as lymphatic maldevelopment, altered extracellular matrix composition and cardiac failure. 4 It was suggested that cardiac failure could play a role in the development of increased NT due to the altered ductus venosus Doppler fl ow velocities and cardiac defects, a frequent fi nding in fetuses with increased NT. 5-10 It was hypothesized that a cardiac defect could result in haemo-dynamic changes by an impaired cardiac function. 5;9 This might result in a lower velocity of the ductus venosus and subsequently enlargement of the NT. 5;9 In this thesis we evaluated if ductus …