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.