Purpose: To evaluate the diagnostic yield of chromosomal microarray (CMA) in pregnancies with normal ultrasound.
Methods: This retrospective cohort analysis included all pregnancies with normal ultrasound undergoing CMA testing between the years 2010 and 2016. We calculated the rate of detection of clinically significant CMA findings in the whole cohort and according to various indications.
Results: Of 5541 CMA analyses, clinically significant findings were yielded in 78 cases (1.4%). Of these, 31 (39.7%) variants could have theoretically been detected by karyotyping (e.g., sized above 10 Mb), and 28 (35.9%) by noninvasive prenatal screening aimed at five common aneuploidies. Of the 47 submicroscopic findings detectable by CMA only, the majority (37 cases, 78.7%) represented known recurrent syndromes. Detection of clinically significant CMA findings in women with no indication for invasive testing was 0.76% (21/2752), which was significantly lower compared with 1.8% in advanced maternal age group (41/2336), 2.8% in abnormal biochemical serum screening (6/211), and 4.1% (10/242) in fetuses with sonographic soft markers.
Conclusion: Clinically significant CMA aberrations are detected in 1 of 71 pregnancies with normal ultrasound, and in 1 of 131 women with no indication for invasive testing. Thus, CMA might be recommended a first-tier test in pregnancies with normal ultrasound.
Keywords: chromosomal microarray analysis; karyotype; low-risk pregnancies; noninvasive prenatal screening; prenatal diagnosis.