47: Abnormal nuchal translucency with normal NIPT: What are we missing?

Noninvasive prenatal testing (NIPT) has high sensitivity and specificity for Trisomies 13/18/21 and sex chromosome abnormalities. While abnormal nuchal translucency (NT) is associated with these chromosomal abnormalities, it can reflect other genetic abnormalities. Our objective was to determine the proportion of genetic abnormalities that could be identified by NIPT in pregnancies with abnormal NT. From 2015-2016, pregnancies with NT ≥ 3.0mm identified on ultrasounds performed at our institution were identified. Recommended genetic testing included karyotype, microarray (MA), Noonan syndrome, and testing for other single gene disorders when indicated. Pregnancies without genetic testing were excluded. Trisomies 13/18/21, sex chromosome aneuploidy, and triploidy were considered “detectable” on NIPT. Comparisons of the proportion of genetic abnormalities detectable with NIPT vs. other genetic abnormalities were made based on NT values (3.0-3.4mm; 3.5-5.4mm; ≥ 5.5mm) and maternal age (≥ 35 vs. < 35). Chi-Square analysis and Fisher's exact test were used for statistical comparison. 87 patient met inclusion criteria. Genetic abnormalities were diagnosed in 42 cases (48.3%), with 29 (69.0%) detectable on NIPT and 13 (31.0%) not detectable. The 13 non-detectable abnormalities included Noonan syndrome (4), karytoype abnormalities involving other chromosomes (4), MA abnormalities (3), Millroy lymphedema (1) and Cornelia-de-Lange (1). Genetic test results based on NT and maternal age are seen in the Table. All four genetic abnormalities with NT 3.0-3.4mm were detectable with NIPT. In those with NT ≥ 3.5mm, however, 13 of 38 (34.2%) of abnormalities would be missed by NIPT. While NIPT would identify 20 of 22 abnormalities in women ≥ 35 (90.9%), it would identify only 9 of 20 (45.0%) of genetic abnormalities in younger women (p=.002). While NIPT may be reassuring in those with mildly abnormal NT, a significant proportion of abnormalities in those with NT ≥ 3.5mm would not be detected. This is particularly true in younger women, in whom NIPT would miss the majority of genetic abnormalities. Invasive testing should be strongly recommended when NT is abnormal, especially when NT is ≥ 3.5mm and in women under age 35.