In the prenatal period, screening and diagnostic tests are performed regularly to check for abnormalities of the fetus. These should be as less invasive as possible but efficient, economical, reliable and should be available in early stages of pregnancy to allow proper counselling of the couple, manage all the emotional stress and be able to safely carry out any interventions [1], [2].

When fetal abnormalities are detected in the screening tests, it is important to carry out a genetic diagnostic study to try to understand if it's just an isolated finding or if can be associated with a genetic disorder [2], [3], [4].

In the past, prenatal genetic diagnosis has relied mostly on conventional G-banded karyotyping [5], which analyses all the chromosomal complement and detect numerical and structural aberrations larger than 5-10 Mb. However, this methodology involves cell culture, requires more time for reporting [6], [7] and do not detect submicroscopic rearrangements (microdeletions and microduplications), that represent a major cause for congenital anomalies and neurodevelopmental delay [8], [9].

Comparative genomic hybridization (aCGH) provides genome-wide coverage for detection of chromosomal unbalanced rearrangements and aneuploidies in a short period of time, with much higher resolution than karyotype [7], [10], [11]. It allows detection of submicroscopic changes also known as copy number variations (CNVs), which represents the variation in the number of copies of an individual's DNA segment when compared to a reference genome [12], [13], [14].

In 2013, the American College of Obstetricians and Gynecologists (ACOG) alongside Society for Maternal Fetal Medicine (SMFM) recommended that aCGH should supplement and, in some cases, replace karyotype. According to this, aCGH should be the gold standard test for cytogenetic analysis when ultrasound structural abnormalities are detected [15].

Currently, one great challenge in the interpretation of an aCGH result is the presence of variants of uncertain significance (VUS) once there is not enough knowledge in the literature if these CNVs could be or not causative of disease, and so may be either benign or pathogenic [16].

This study retrospectively evaluates the prevalence of abnormal CNVs detected by aCGH, in 772 prenatal samples in two tertiary hospitals, during a 9-years period. Furthermore, we evaluate the main clinical indications for aCGH test, correlate pathogenic/likely-pathogenic CNVs with clinical findings, analyze the prevalence of VUS as well as highlighting the clinical aCGH relevance in prenatal diagnosis.