Trends in premarital hemoglobinopathy screening and genetic counseling outcomes: A serial cross-sectional analysis of Saudi National Registry Data (2016–2023)

Abstract: BACKGROUND: Thalassemia and sickle cell disease are the most prevalent inherited hemoglobinopathies in Saudi Arabia, imposing substantial clinical and economic burden. The Saudi mandatory premarital screening and genetic counseling program, established in 2004, represents a primary prevention strategy intended to reduce hemoglobinopathy transmission through carrier identification and reproductive counseling. Comprehensive national evaluation of program coverage, carrier detection rates, and genetic counseling outcomes across subnational strata remains limited. OBJECTIVES: To characterize program coverage trends, regional variation in hemoglobinopathy carrier prevalence, and genetic counseling outcomes among at-risk couples in Saudi Arabia from 2016 to 2023 and to assess program performance relative to national targets. MATERIALS AND METHODS: This serial cross-sectional analysis examined the secondary data from the Saudi Ministry of Health Premarital Screening Program National Registry (2016–2023), the 2022 National Hemoglobinopathy Registry, and Ministry of Health Annual Statistical Yearbooks. Carrier status was defined as heterozygous carriage of a beta-thalassemia or sickle cell mutation. At-risk couples were defined as couples in which both partners carried mutations conferring a ≥25% risk of an affected offspring. Descriptive statistics characterized coverage, carrier prevalence, and genetic counseling outcomes by year, region, and couple risk category; proportions are reported with Wilson 95% confidence intervals (CIs), and the Cochran-Armitage test for trend was used to assess the statistical significance of temporal changes in coverage and counseling outcomes. RESULTS: National program coverage reached 96.8% of registered marriages in 2023 (95% CI, 96.6%–96.9%), increasing from 88.2% in 2016 (95% CI, 88.0%–88.4%; Cochran-Armitage test for trend, P < 0.001). The national hemoglobinopathy carrier prevalence was 8.7% overall, with sickle cell trait (6.1%) predominating over beta-thalassemia trait (2.6%). The Eastern region recorded the highest combined carrier prevalence (18.4%), compared to 4.2% in the Northern region. At-risk couples (both partners carrying compatible mutations) represented 6.3% of all screened couples in 2023. Among at-risk couples receiving genetic counseling in 2023, 61.4% (95% CI, 59.9%–62.9%) elected to proceed with marriage, 22.8% (95% CI, 21.6%–24.1%) chose to postpone pending further evaluation, and 15.8% (95% CI, 14.7%–16.9%) mutually agreed not to proceed. Over 2016–2023, the proportion of at-risk couples electing to proceed declined from 72.1% (95% CI, 70.7%–73.5%) to 61.4%, while the proportion electing not to proceed increased from 9.3% (95% CI, 8.4%–10.3%) to 15.8%; both trends, together with the accompanying rise in postponement (18.6%–22.8%), were statistically significant (Cochran-Armitage test for trend, all P < 0.001). CONCLUSIONS: The Saudi premarital screening program has achieved near-universal coverage, and genetic counseling among at-risk couples is associated with a statistically significant shift toward postponing or declining marriage over time; actual reductions in affected birth rates were not measured in this analysis. Pronounced regional disparities in carrier prevalence, particularly in the Eastern and Southern regions, indicate priority areas for targeted screening outreach, counselor training, and culturally tailored community education. Continued program investment, aligned with Saudi Vision 2030’s preventive healthcare and chronic disease burden reduction priorities, is warranted to strengthen counseling effectiveness and work toward reducing hemoglobinopathy transmission.