Increased nuchal translucency with normal karyotype and genomic microarray analysis: A multicenter observational study

Objective: To define the residual risk of morbidity-related outcome in fetuses with nuchal translucency (NT) of 3.5 mm or more after normal genetic testing and mid-trimester anomaly scan. Methods: A total of 114 fetuses with isolated NT of 3.5 mm or more, normal karyotype, and array-based comparative genomic hybridization (array-CGH) were included and divided in three groups: NT 3.5–4.5 mm, NT 4.5–6 mm, and NT greater than 6 mm. RASopathy testing and ultrasound follow up were performed in all fetuses. We evaluated: (1) incidence of genetic disorders; (2) incidence of structural abnormalities; (3) pregnancy outcome; (4) long-term pediatric outcome before (point 1) and after (point 2) a normal RASopathy testing and mid-trimester anomaly scan. Results: After normal karyotype and array-CGH the residual risk of morbidity-related outcome was 24.64% for NT 3.5–4.5 mm, 25% for NT 4.5–6 mm and 76.47% for NT more than 6 mm. After a normal RASopathy testing and mid-trimester anomaly scan the residual risks decreased to 7.14%, 8.69%, and 33.3% in the three groups, respectively. Conclusion: In fetuses with an NT of 3.5 mm or more and both normal karyotype and array-CGH, the rate of morbidity-related outcome depends on NT size. A normal RASopathy testing and mid-trimester ultrasound are reassuring but the residual risk of morbidity-related outcome is increased compared with the general population, particularly if NT is greater than 6 mm.