Multimodal genomic testing in prenatal diagnosis: incremental diagnostic contribution of chromosomal microarray and exome sequencing, real-world NIPT confirmation rates and pregnancy outcomes in 120 consecutive amniocenteses from northeastern Türkiye

Abstract Background Most evidence on chromosomal microarray analysis (CMA) and exome sequencing (ES) in prenatal diagnosis comes from high-volume centres. We evaluated the incremental diagnostic contribution of additional testing modalities, non-invasive prenatal testing (NIPT) confirmation rates and pregnancy outcomes at a regional centre in Türkiye. Methods Retrospective cohort of 120 consecutive amniocenteses (March 2022–June 2025). The pathway was retrospectively observed, not uniformly implemented: the intended first-tier panel (quantitative fluorescent PCR, G-banded chromosome analysis, CMA) was completed in 94 pregnancies (78.3%), CMA in 101 (84.2%); ES ( n = 13) and targeted testing ( n = 25) were selective. Findings were classified before analysis as fetal disease-causing or incidental/non-diagnostic. Cumulative yields use the whole cohort as denominator. Results Abnormal findings occurred in 36 of 120 pregnancies (30.0%): 27 (22.5%) disease-causing and 9 (7.5%) incidental/non-diagnostic — 3 heterozygous pathogenic or likely pathogenic variants in autosomal recessive genes (2.5%) and 6 variants of uncertain significance (VUS; 5.0%). Disease-causing yield rose from 16.7% to 22.5%: seven of the 27 diagnoses were first identified by CMA, ES or targeted testing, a cohort-specific contribution, not a diagnostic yield, as these modalities were not applied uniformly. Abnormal ultrasonography was associated with an abnormal genetic finding (31/83 vs. 5/37; unadjusted OR 3.82, 95% CI 1.35–10.82); not significant for disease-causing findings alone. Within this referral stream, confirmation of 14 high-risk NIPT referrals was 6/6 for trisomies 21 and 18, 0/4 for sex chromosome and rare autosomal aneuploidies and 1/4 for copy-number variants; these should not be read as population-level positive predictive values. Outcome, sought only after an abnormal finding, was documented in 30 of 36; 22 were terminated (trisomy 18, 4/4; isolated VUS, 1/6). Conclusions CMA, ES and targeted testing added diagnoses in a non-uniformly applied pathway (complete first-tier panel in 78.3%). The findings reinforce the importance of diagnostic confirmation of high-risk NIPT results before irreversible clinical decisions, particularly for less common targets, which were frequently not confirmed in this referral series. Termination frequencies varied across diagnostic categories; these descriptive differences should be considered in the context of the underlying fetal phenotype, diagnostic certainty, and parental preferences when counselling is provided.