Interpretation
These data agree with previous studies reporting an increased risk of
adverse pregnancy outcome for mildly increased NT (NT
95th-99thpercentile)4;21-22. Bardi et al. reported that 21.3%
of fetuses with an NT between the 95th and the
99th percentile had congenital abnormalities, either
genetic or structural.
The reported prevalence of healthy live-born children varied between
83%4 and 78.2%22, similar to our
study (74.96% of fetuses were born alive and healthy). A long term
follow up is crucial in terms of reporting adverse postnatal outcome, in
fact, in our cohort a high number of unfavourable diagnoses such as
genetic syndromes and neurodevelopmental delay were made between 6
months and 2 years of age.
The incidence of chromosomal abnormalities and genetic
syndromes varied in previous studies. Kagan et al. in
20066 reported a prevalence of 7.1% for NT between
95th and 99th percentile, but the
only genetic investigation performed was however standard karyotype. In
a study by Tekesin et al.22 the incidence of abnormal
fetal karyotype was 18.2% in a selected high risk population with NT
between 95th and 99th percentile. In
our study group, which mainly included a low risk population, fetuses
with these conditions accounted for 13.49% of cases.
Furthermore, according to recent studies23-24, the use
of CGH-arrays in fetuses with NT>3.5 mm can reveal
approximately 5% copy number variants (CNVs) with pathogenetic or
uncertain significance. Despite the level of anxiety that variants of
unknown significance (VOUS) could bring, it is now mandatory that
couples who are offered karyotyping are at least informed on the
existence of this genetic test.
The most common malformations reported in our population
were cardiac defects (40.35% of all malformations detected). This
result is consistent with the incidence reported in a meta-analysis by
Sotiriadis et al.10 where 45% of fetuses with cardiac
malformation showed an NT >95thpercentile, but only in 20% of them NT was above 99thpercentile. Therefore, the majority of fetuses with cardiac defects
showed an NT between 95th and 99thpercentile. Similar percentages (34.1%-41.57%) can be observed in more
recent studies21-22. These data suggest that an
NT>95th percentile could be the proper
cut off to offer fetal echocardiography.
With regards to neurodevelopmental delay , Hellmuth et
al. in 201725 found no increased risk in a cohort of
children with NT between 95th and 99th percentile at first trimester
scan, with a mean follow up of 4.4 years. The present study confirms the
reported results, showing that the incidence of those disorders is
1.95% in our population, not significantly different from the general
population.
A critical point in the management of pregnancies with NT between
95th and 99th percentile is the
level of investigations that should be offered to couples. At the
moment, international guidelines do not include
NT>95th percentile among the cases that
should benefit from further examinations than the routine ones. Souka et
al. in 20053 proposed a specific management for
fetuses with NT between 95th and
99th percentile which included a detailed ultrasound
at 20 weeks with examination of fetal heart, preferably performed by a
fetal echocardiography specialist. This protocol was also recommended by
De Domenico et al.9. Moreover, both authors stated
that fetal karyotype should be performed based on patients-specific risk
for chromosomal anomalies. Based on the high prevalence of chromosomal
anomalies and genetic syndromes in our cohort, we suggest that fetal
karyotyping should be offered also in case of NT between
95th and 99th percentile.