Increased nuchal translucency in fetuses with a normal karyotype—diagnosis and management

Abstract

The use of nuchal translucency (NT) in 1992 by Nicolaides et al was a major breakthrough in screening for chromosomal aneuploidies at the end of the first trimester. However, pathological conditions other than chromosomal aneuploidies are also associated with increased NT, which can also be detected in normal fetuses. This study sought to evaluate the causes of this ultrasound sign in a group of patients from Iasi, Romania.During the decade-long study period, there were 71 certified cases involving increased NT; the patients in these cases underwent diagnostic amniocentesis and karyotyping.In most of the examined cases (55 cases, 78%), there was no aneuploidy. The remaining cases involved trisomy 21 (T21) (18%), trisomy 18 (T18) (2%), or triploidy (2%). In most cases, the indication for amniocentesis was increased NT alone (81%), whereas the remaining cases also involved advanced maternal age (5.5%), abnormal serologic markers (10%), or other ultrasound signs (3.5%) (2 cases—cardiac anomalies and fetal hydrops). A favorable pregnancy outcome at term was achieved in 40 cases (56% from total, 72% from euploid pregnancies); kidney anomalies or nonlethal cardiac conditions were observed in 12 cases (17%), 6 of which involved complications associated with premature onset of labor, and miscarriages occurred in 6 cases. Three cases were lost at follow-up.Although it is common practice to assume that increased NT is an indication for amniocentesis, both literature results and our study findings indicate that the majority of cases with increased NT involve no aneuploidy and result in a favorable outcome if no other anomaly is present. Better evidence-based management of such cases could be promoted by conducting larger, multicenter studies, and following cases for longer periods.

Prenatal Diagnosis of Fetuses With Increased Nuchal Translucency by Genome Sequencing Analysis

“…Detection of fetuses with increased nuchal translucency (NT) in routine first-trimester ultrasound screening has been widely used as a sensitive indication for fetal chromosomal abnormalities and/or fetal structural anomalies, such as congenital heart disorders or neurodevelopmental anomalies detected in later gestations (Leung et al, 2011; Huang et al, 2014; Socolov et al, 2017; Sinajon et al, 2019). Fetuses with increased NT and structural malformations are frequently contributed by genetic abnormalities and have poor prognoses.…”

The Fetal Phenotype of Noonan Syndrome Caused by Severe, Cancer-Related PTPN11 Variants

“…Prenatal screening with ultrasound allows the evaluation of gross fetal abnormalities and nuchal translucency thickness [ 8 ]. At present, NT measurement is primarily used to detect chromosomal aneuploidies [ 8 ], although there are many reasons for increased NT, including various genetic syndromes, cardiac anomalies, and other structural anomalies [ 9 ].…”

Clinical experience with multiplex ligation-dependent probe amplification for microdeletion syndromes in prenatal diagnosis: 7522 pregnant Korean women

“…Conventional cytogenetics has been the gold standard in prenatal diagnosis for detecting chromosomal abnormalities. At the light microscope level, the genome-wide numerical and structural anomalies can be examined and the resolution of chromosomal abnormalities of 5–10 Mb can be obtained [9, 10]. Indications for such prenatal diagnoses include advanced maternal age, increased risk for fetal trisomy identified by maternal serum screening, and fetal abnormalities (e.g., increased NT) detected through USG.…”

“…The conventional cytogenetic test using G-band karyotyping has been the method of choice for prenatal diagnosis, accurately detecting chromosomal abnormalities larger than 5 Mb [9, 10]. However, it is inefficient for detecting the sub-microscopic deletions and duplications that are often associated with malformations and mental retardation.…”