Two Decades of the Saudi Mandatory Premarital Screening and Genetic Counseling Program (2004–2024): A Systematic Review and Meta-Analysis of Long-Term Outcomes

Background. Saudi Arabia implemented mandatory premarital screening and genetic counseling (PMSGC) for sickle cell disease and β-thalassaemia in February 2004. Over two decades the programme has screened more than eight million individuals, yet its cumulative outcomes have never been synthesized. We assessed the long-term impact of the PMSGC programme on at-risk marriage detection, marriage cancellation, regional heterogeneity, and hemoglobinopathy burden from 2004 to 2024. Methods.We conducted a systematic review and meta-analysis following PRISMA 2020. Six databases (PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL, Saudi Digital Library) were searched from January 2004 to December 2024 without language restrictions. Studies reporting outcomes of the Saudi PMSGC programme — prevalence, at-risk couples, marriage cancellation rates, knowledge/attitudes/practices, or cost — were eligible. Two reviewers screened and extracted data independently in Rayyan. Risk of bias was assessed with Joanna Briggs Institute checklists. Random-effects meta-analysis pooled proportions using the Freeman–Tukey double arcsine transformation. Meta-regression tested temporal trends and regional moderators. The review was registered with PROSPERO (CRD420261378326). Findings. Of 3,008 records identified from databases and 145 from other sources, 62 studies met inclusion criteria, with 47 contributing to the meta-analysis. The pooled prevalence of sickle cell trait was 45.4 per 1,000 (95% CI 42.5–48.4; I² = 99.7%; 10 studies, >9.6 million individuals), with marked regional gradient (Eastern Province 134 per 1,000 vs Northern regions 13–14 per 1,000; ~10-fold). Pooled β-thalassaemia trait prevalence was 21.0 per 1,000 (95% CI 17.4–24.8; I² = 99.9%). Marriage cancellation rate among at-risk couples rose from 9.2% in 2004 to 51.9% in 2009 (Era 1 pooled 24.9%, 95% CI 13.0–39.2), to 60.5% in 2010–2019 (95% CI 49.6–70.9), to 76.7% in 2020–2024 (95% CI 63.1–87.9). Meta-regression on year midpoint showed a significant positive trend (β = +3.28 percentage points per year, P < 0.001). Decision-tree cost analysis indicated approximately 73% healthcare cost reduction attributable to the programme for sickle cell disease (~US$29.7 million annual saving). Interpretation. The Saudi PMSGC programme has achieved substantial population-level impact on hemoglobinopathy prevention over two decades, with marriage cancellation rates rising eight-fold and persistent — though narrowing — regional heterogeneity. Gaps remain in expanding the screening panel (spinal muscular atrophy, cystic fibrosis, phenylketonuria), in cost-effectiveness evidence, and in standardized outcome reporting. These findings support Saudi Vision 2030 health transformation goals and inform regional neighbours considering similar programmes.