Complementary Diagnostic Roles of Non-Invasive Prenatal Testing, Chromosomal Microarray Analysis, and Karyotyping in...

Background/Objectives: Prenatal chromosomal assessment can benefit from the complementary use of non-invasive prenatal testing (NIPT), chromosomal microarray analysis (CMA), and karyotyping because each test provides different information. Methods: We retrospectively analyzed 14,011 fetus-specific amniotic fluid cases obtained through second-trimester amniocentesis between 2014 and 2023. The study included overlapping subgroups tested by NIPT and karyotyping (n = 1300), CMA and karyotyping (n = 444), or all three methods (n = 78). Results: Karyotyping identified fetal chromosomal abnormalities in 1288 cases (9.2%). Among 983 evaluable cases in the clinically selected NIPT-karyotyping subgroup referred for invasive diagnosis by amniocentesis, the positive predictive value was 88.8% for trisomy 21, 66.7% for trisomy 18, 21.4% for trisomy 13, and 37.0% for sex chromosome abnormalities. Because these estimates were derived from a highly selected referral cohort rather than an unselected prenatal screening population, the PPV and NPV values should be interpreted within this referral setting and should not be generalized to unselected prenatal screening populations. Low-risk or inconclusive NIPT results did not completely exclude fetal chromosomal abnormalities. CMA detected pathogenic or likely pathogenic copy-number findings in 17 of 397 cases with normal karyotypes and provided additional molecular information in selected cases with abnormal karyotypes. Conversely, karyotyping identified 11 abnormalities among 388 cases with only likely benign, benign, or normal CMA results, including 10 apparently balanced reciprocal translocations and one diploid-tetraploid mosaicism. Conclusions: These findings show that NIPT, CMA, and karyotyping provide complementary rather than interchangeable information. High-risk NIPT results should be confirmed by invasive diagnostic testing, while CMA and karyotyping should be selected according to the clinical indication and suspected type of abnormality.