Carrier Screening in the Genomic Era: 9-gene Panel and Noninvasive Prenatal Testing Integration in Indonesia

Background: Genetic carrier screening and noninvasive prenatal testing (NIPT) have transformed prenatal care by enabling early detection of hereditary and chromosomal disorders. However, data from ethnically diverse Southeast Asian population remain scarce, particularly from Indonesia, which represents one of the most genetically heterogeneous regions globally. This study evaluated the clinical utility and feasibility of combining a nine-gene carrier screening panel with NIPT in a real-world, multiethnic Indonesian cohort. Methodology: In this retrospective analysis, 243 pregnant women who underwent prenatal screening between January and March 2025 were assessed. The carrier screening targeted pathogenic variants in nine clinically relevant genes, while concurrent NIPT analyzed cell-free fetal DNA (cfDNA) for chromosomal abnormalities. Maternal demographics, gestational characteristics, and ethnicity were recorded, and clinical variables – including age, parity, body mass index, gestational age, and cfDNA fraction – were statistically correlated with carrier status. Results: Carrier screening identified 26 positive cases, yielding an overall carrier frequency of 10.7%. The most frequent variants were linked to alpha-thalassemia (HBA1/HBA2; 42.3%), followed by HBB, SLC25A13, and G6PD (each 11.5%). Ethnicity-stratified analysis revealed marked variability, with the highest carrier frequencies among Tionghoa (38.5%), Javanese (19.2%), and Batak (15.4%) population. NIPT detected chromosomal abnormalities in 3.7% of pregnancies, predominantly trisomy 21. No statistically significant associations were identified between carrier status and maternal clinical parameters, supporting the genetic – rather than phenotypic – basis of carrier risk. Conclusions: Integrating targeted carrier screening with NIPT offers a comprehensive and feasible strategy for prenatal genetic evaluation in resource-limited settings. This combined approach enables ethnicity-informed risk assessment, enhances reproductive counseling, and advances the implementation of precision prenatal care in Indonesia and similar population.