Prenatal cytogenetic abnormalities, including trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and pathogenic copy number variants, remain significant contributors to fetal morbidity and long-term disability. Advances in genomic technologies—particularly non-invasive prenatal testing (NIPT)—have transformed prenatal screening strategies. However, their integration into population-based maternal health programs poses important public health and policy challenges.

This systematic review was conducted in accordance with PRISMA 2020 guidelines and included 92 eligible studies published between 2005 and 2026. Fifty-two studies provided sufficient data for comparative analysis of diagnostic performance across screening and diagnostic modalities, including first-trimester screening, NIPT, chromosomal microarray analysis (CMA), and invasive cytogenetic techniques.

NIPT demonstrated superior diagnostic performance compared with conventional biochemical screening, while chromosomal microarray analysis (CMA) substantially improved detection of clinically significant copy number variants beyond conventional karyotyping. Despite these advances, equitable implementation, genetic counselling and cost-effective integration into national maternal health programs remain important challenges. Despite improved diagnostic precision, biological limitations, variable positive predictive values in low-risk populations, and inequitable access remain important concerns.

Prenatal cytogenetic screening is transitioning toward a precision medicine framework. While genomic technologies substantially enhance detection accuracy and reduce unnecessary invasive procedures, their successful implementation requires cost-effective strategies, strengthened genetic counseling services, and equitable integration into national maternal health programs. Policymakers in low- and middle-income settings must balance technological advancement with accessibility to ensure responsible and population-centered prenatal care.