The clinical utility of non-invasive prenatal testing in pregnancies with ultrasound anomalies

ObjectivesThis study aims to evaluate the application of non-invasive prenatal testing (NIPT) as an alternative to invasive diagnostic testing in pregnancies with abnormal ultrasound findings.MethodsA retrospective analysis was performed of 251 single and multiple pregnancies at high risk for fetal chromosomal abnormalities based on ultrasonographic examination, where NIPT was performed as first-tier test, by massively parallel sequencing of cell-free DNA in maternal plasma, allowing genome-wide detection of whole chromosome and partial autosomal aneuploidies.ResultsNIPT was performed at a median gestational age of 20 weeks, indicated by the presence of multiple congenital anomalies (n = 13), isolated structural anomalies (n = 57), increased nuchal translucency ≥3.5 mm (n = 58), softmarkers (n = 73), growth restriction (n = 40), and other anomalies (n = 10). NIPT results were normal in 224 (89.2%), inconclusive in 1 (0.4%) and abnormal in 26 pregnancies (10.4%). The majority of genetic aberrations detected were common whole chromosome aneuploidies: Trisomy 21 (n = 13), Trisomy 18 (n = 6), and Trisomy 13 (n = 3). There were 4 other abnormal NIPT results, of which one was highly suspect for confined placental mosaicism and one was of maternal origin. If NIPT results were normal, ultrasonographic follow-up or newborn examinations indicated diagnostic genetic testing in 33 pregnancies (14.7% of 224). Clinically relevant genetic aberrations were revealed in 7 cases (3.1% of 224), of which 2 were whole chromosome aneuploidies: Trisomy 13, and monosomy X. As sex chromosomes are currently not included in the analysis, the last cannot be considered a false negative result. Other discrepant findings were subchromosomal (<20 Mb, n = 2) and monogenic aberrations (n = 3).ConclusionsNIPT should not be recommended for the genetic evaluation of the etiology of ultrasound anomalies, as both resolution and sensitivity, or negative predictive value, are inferior to those of conventional karyotyping and microarray analysis.