Methods
A multicenter retrospective observational study promoted by the Fetal
Medicine Unit of the Azienda Ospedaliero Universitaria Careggi
(Florence) with the collaboration of Piero Palagi Hospital (Florence).
All patients who underwent NT measurement in the first trimester between
January 2015 and December 2020 were included. Among them, all cases with
NT between 95th and 99th percentile
for gestational age were selected12. Exclusion
criteria were: maternal age under 18 years, monochorionic placentation,
multiple pregnancies, incomplete data or absent informed consent for the
study.
NT was measured according to the Fetal Medicine Foundation
guidelines18. All ultrasound examinations were
performed by a certified FMF sonographer. Cases with positive combined
test or NT≥3mm were offered genetic counselling, CVS or amniocentesis,
monthly detailed ultrasound and fetal echocardiography as per local
protocol. Information regarding maternal demographic characteristics,
genetic tests, ultrasound scans and other prenatal investigations (such
as fetal magnetic resonance imaging in selected cases), pregnancy
outcome and long-term postnatal outcome were obtained by reviewing
hospital records and patients’ interviews. Patients were asked to
provide copy of medical records in case of postnatal diagnosis of
neonatal disease.
We considered as unfavourable outcome: miscarriage or intrauterine fetal
death (IUFD), the presence of chromosomal abnormality/genetic syndrome,
major malformation or neurodevelopmental delay. Major malformations were
defined as those requiring chronic medical treatment or major surgery
and/or associated with mental or physical disability. Minor
malformations were not included in the unfavourable outcome. In all
cases of neurodevelopmental delay the diagnosis was made by an expert
clinician.
Postnatal outcomes were compared with general population’s data from the
EUROCAT (European Network of Population Based Registries for the
Epidemiological Surveillance of Congenital
Anomalies)19 register regarding chromosomal
abnormalities/genetic syndromes and major malformations. With regards to
neurodevelopmental delay, a recent review by Sotiriadis et
al.20 was used for comparison.
The study was approved by the local Ethic Committee (CEAVC n=17892) and
it was conducted in accordance with the standards of the Helsinki
Declaration.
Statistical analysis was performed using “Statistical Package for
Social Sciences” (SPSS Inc, version 21, Chicago, Il USA), and Microsoft
Office Excel package (Microsoft Corp., Redmond, WA, USA). Chi-square or
Fisher exact test were used to compare categorical variables and T Test
for continuous variables. A p-value of 0.05 was considered as
statistically significant. Odds ratio (OR) and 95% confidence intervals
(IC 95%) were also calculated.