168 Non invasive prenatal testing and ultrasound fetal sex discrepancy: what are we missing?

Abstract

Non invasive prenatal testing (NIPT) for fetal sex chromosomes has a sensitivity of 99%. However, discordant fetal sex results on NIPT and anatomical ultrasound (US) have been reported at a rate of 0.0-0.9%. These results are commonly attributed to sampling errors, a vanishing twin, placental mosaicism, or disorders of sexual differentiation. The aim of this study was to identify additional genetic causes of this discordance. This was a retrospective observational study from 8/2015 -1/2020. A database was queried to identify discordance between fetal sex reported on NIPT and the observed genital phenotype on US. Pregnancies with anomalies and ongoing multifetal gestations were excluded. The NIPT brand, fetal fraction, invasive testing results, and pregnancy outcomes were reviewed. Twenty seven cases of discordance were identified, representing 0.2% of patients. NIPT was normal in 24 cases, and 45X was predicted in 3. Cases were classified into 5 categories (Table 1). Invasive testing was performed in 13 cases, with abnormal genotypes identified in 7 cases, including abnormal karyotypes in all 3 cases with NIPT consistent with 45X and male genitalia (Table 2). In 5 cases, the patient chose pregnancy termination. In cases with normal NIPT and discordant genitalia, invasive testing identified abnormal genotypes in 4 cases, with karyotype consistent with US in the remaining 6 cases. In 14 cases without invasive testing, 7 had normal anatomy at birth, with genitalia consistent with US. Five of these cases were likely secondary to “vanishing twin” based on early US demonstrating an additional non-viable gestation. In 2 cases without invasive testing, ambiguous genitalia was noted at birth, with presumptive diagnoses of partial androgen insensitivity. In most pregnancies with normal NIPT results and phenotypically normal appearing but discordant genitalia, the genotype is consistent with phenotype. However, some have genetic abnormalities. All pregnancies with discordant NIPT/US results should be offered invasive testing to inform counseling and pregnancy management.View Large Image Figure ViewerDownload Hi-res image Download (PPT)