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

Abstract 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.