One-Tube Genomics in Prenatal Care for Low- and Middle-Income Countries: A Systematic Review of Integrated cfDNA-Based Aneuploidy, CNV, Monogenic Fetal Testing and Maternal Carrier Screening from a Single Maternal Sample

Objective To synthesise clinical, technical and health-system evidence on “one-tube genomics”, defined as using a single maternal cfDNA sample to deliver aneuploidy NIPT, genome-wide CNV analysis, monogenic fetal testing and maternal carrier screening in low- and middle-income countries (LMICs). Methods A PRISMA-guided systematic review was conducted in PubMed/MEDLINE, Embase, Scopus, Web of Science and PMC from inception to May 2025. We included human studies evaluating cfDNA-based aneuploidy, CNV, monogenic or carrier screening, or population genomics relevant to prenatal care in LMIC or mixed-income settings. Two reviewers independently screened records, assessed full texts and extracted data. Risk of bias was appraised using the Newcastle–Ottawa Scale and ROBIS where appropriate. Heterogeneity precluded meta-analysis; findings were synthesised narratively across predefined thematic domains. Results Of 1,326 records identified, 25 studies met inclusion criteria. Large cohorts confirmed high accuracy of cfDNA for common aneuploidies and selected genome-wide CNVs. Monogenic and haemoglobinopathy-focused cfDNA approaches showed strong analytic validity but were limited to specialised centres. Population-scale NIPT and exome datasets from Vietnam and neighbouring regions provided detailed recessive variant spectra. Implementation and ethical papers highlighted counselling needs, data-governance challenges and emerging issues around incidental maternal findings. Conclusion Current evidence supports the technical feasibility and potential health-system advantages of one-tube genomics in LMICs, but integrated workflows remain largely unrealised. Prospective LMIC implementation studies, harmonised reporting standards and robust ethical frameworks are now critical to move from fragmented testing towards truly integrated prenatal genomics.