Atypical karyotypic abnormalities not identified through NIPT: the value of identifying fetal anomalies at the first or second trimester scan?

Objectives: Using a population based database including >200,000 Danish pregnancies, we have previously shown that 23% of all phenotypically important chromosomal abnormalities would not be diagnosed using currently available NIPT techniques. The aim of the current study was to assess how many of those would likely have been diagnosed because of ultrasound findings at the first- or second trimester scan Methods: A retrospective population-based analysis of all singleton pregnancies booked for combined first trimester screening (cFTS) in Denmark 2007-2011. Data concerning cFTS, anomalies diagnosed in the first and second trimester, and prenatal and postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosome anomaly would have been detected by NIPT, and whether they were likely to affect phenotype Results: cFTS was completed in 193,638 pregnancies. 10,205 (5.3%) had a karyotype 1,122 (11.0%) were abnormal and 262 (23%) would have been missed by standard NIPT. At the first trimester scan, in thirty-five (13,4%) of these pregnancies a structural anomaly (n=14) or NT above 3.5 mm (n=21) as isolated finding was found. Forty-eight (18.3%) had spontaneous abortion (n=6) between the cFTS and the 2nd trim scan, or a structural anomaly (n=42) at the 2nd trim anomaly scan (