Cardiovascular development and function in relation to nuchal translucency.

The nuchal translucency (NT) is a translucent area in the neck region of the
fetus. The ultrasonographic measurement of NT is part of the first-trimester
screening for Down syndrome. Increased NT is highly associated with Down
syndrome and other chromosomal abnormalities, such as trisomy 13 en 18, but
also occurs in fetuses with a normal karyotype. These latter fetuses are known
to be at risk for a variety of structural abnormalities. A major part of these
anomalies are cardiac defects.
Increased nuchal translucency is mesenchymal edema and is accompanied by
distended jugular lymphatic sacs (JLS) in both human fetuses as in trisomy 16
mouse embryos. Trisomy 16 embryos are an accepted animal model for human
trisomy 21. A previous morphological study suggests that the cause for the
distension of the JLS and subsequent edema is a disturbed endothelial
differentiation. A disturbed endothelial differentiation provides an
interesting link with the cardiovascular anomalies associated with nuchal edema
as endothelial processing is indispensable for normal cardiovascular
development.

Cardiac decompensation is frequently mentioned as the underlying cause of the
fluid accumulation in the fetal neck. Fetuses with increased NT show abnormal
ductus venosus blood flow velocity. The ductus venosus is a shunt between the
umbilical vein and the fetal heart (atria) and therefore an important regulator
of the fetal circulation. It has been suggested that an abnormal ductus venosus
velocity might be the result of impaired atrial contraction and reduced
myocardial compliance and thus reflects cardiac decompensation. However,
fetuses with increased NT show abnormal ductus venosus blood flow velocities
regardless of having a cardiac defect Because of the conflicting evidence in
previous studies it is important to further investigate the possible
relationship of increased nuchal translucency and cardiac function.

An explanation of the complete spectrum of anomalies seen in fetuses with
increased NT could be a disturbed endothelial differentiation related to the
cardiovascular development. Cardiac defects form the severe end of the
spectrum. More data, both clinical and morphological,of the heart, the great
arteries and veins, especially the ductus venosus, of the fetus with nuchal
edema should be gathered. The aim of this study is to gain more insight in the
morphological and pathophysiological processes in the head-neck-thoracic region
of the developing fetus leading to increased NT and / or cardiac defects and
relate them to the clinical findings.

Three studies will be performed. The two morphological studies will be
performed in Leiden University Medical Center, Department Anatomy and
Embryology. The clinical study will be performed in Vrije University Medical
Center, Department of Fetal Medicine. The two morphological studies will
investigate cardiovascular development in relation to increased NT. There will
be used mousemodels as well as human material. For further comment page 14 and
further of the protocol.
The clinical study will investigate the cardiac function in fetuses with an
increased nuchal translucency. There will be performed three ultrasounds in the
first trimester of the pregnancy. The heart and cardiac vessels will be
investigated using various echographic technics. For further comment page 22
and further of the protocol.

Multiple studies have been perfomed to evaluate the possible negative effects
of ultrasound during the pregnancy. A meta-analysis of all epidemiological and
prospective studies showed no association between ultrasound during the
pregnancy and birth weight, childhood malignancies and neurological
maldevelopment.
Patients will visit the VU medical center four times. Four ultrasonographic
examinations will be made (three times between 11 and 14 weeks of gestation and
one time at 20 weeks of gestation).