Prevalence of β‑Thalassemia Among Offspring of First‑Cousin Marriages in District Barkhan, Pakistan: An Extended Cross‑Sectional Study
DOI:
https://doi.org/10.61561/ssbgjms.v6i04.136Keywords:
β-thalassemia, First-cousin Marriage, Prevalence, Pakistan, Barkhan, Premarital Screening, Cascade Testing, ConsanguinityAbstract
Introduction: β-thalassemia is highly prevalent in Pakistan, where first-cousin unions are common. However, district-level data among offspring of consanguineous couples remains limited for Balochistan, including Barkhan.
Objective: To estimate the prevalence of β-thalassemia phenotypes among children (≤18 years) of first-cousin marriages in Barkhan and identify associated risk factors.
Methods: A 10-month observational cross-sectional study (September 2024–June 2025) was conducted using facility-based (District Headquarters Hospital, five Rural Health Centers, three laboratories) and community-based probability-proportional-to-size clusters (14 mobile camps). Diagnosis followed a standardized stepwise protocol: CBC/indices; HPLC or capillary electrophoresis; ferritin with iron-repletion and repeat testing for borderline HbA₂; and targeted HBB genotyping for discordant cases. The primary outcome was any β-thalassemia phenotype (trait, intermedia, or transfusion-dependent thalassemia [TDT]). Multivariable logistic regression identified independent predictors; sensitivity analyses addressed iron deficiency and genotype confirmation.
Result: Of 780 approached, 560 children had complete data (median age 10 years; 49% female; 70% rural). Overall prevalence was 12.5% (70/560; 95% CI 9.8–15.2), comprising trait (74.3%), intermedia (14.3%), and TDT (11.4%). Prevalence was higher in rural areas (13.3%) than in urban/semi-urban areas (10.7%). Independent predictors included lower parental education (AOR 1.74), rural residence (AOR 1.42), absence of premarital screening (AOR 1.69), family history (AOR 2.11), and lower awareness (per-point AOR 0.94). Among TDT cases, 50% had ferritin ≥2500 ng/mL, while HBsAg and anti-HCV positivity were 12.5% and 25%, respectively.
Conclusion: β-thalassemia prevalence among offspring of first-cousin unions in Barkhan is considerable. Strengthened premarital/antenatal screening, family cascade testing, community education, and improved transfusion/chelation services are critical for district-level control.
References
1. White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30(4):377–399. doi:10.1002/sim.4067.
2. Hosmer DW, Lemeshow S, Sturdivant RX. Applied Logistic Regression. 3rd ed. Hoboken (NJ): Wiley; 2013. doi:10.1002/9781118548387.
3. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The STROBE statement: Guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–1457. doi:10.1016/S0140-6736(07)61602-X.
4. Vichinsky EP. Changing patterns of thalassemia worldwide. Ann N Y Acad Sci. 2005;1054(1):18–24. doi:10.1196/annals.1345.003.
5. EQUATOR Network. STROBE: Strengthening the Reporting of Observational Studies in Epidemiology. Available from: https://www.equator-network.org/ (accessed 25 Aug 2025).
6. Sheridan E, Wright J, Small N, Corry PC, Oddie S, Whibley C, et al. Risk factors for congenital anomaly in a multiethnic birth cohort: An analysis of the Born in Bradford study. Lancet. 2013;382(9901):1350–1359. doi:10.1016/S0140-6736(13)61580-6.
7. Iqbal SA, Azhar Z, Leghari A, Wattoo JI, Shahid A, Raza H. Prevalence and trends of consanguineous marriages in Pakistan: Evidence from Pakistan demographic and health surveys, 1990–2018. PLoS One. 2022;17(1):e0262446. doi:10.1371/journal.pone.0262446.
8. Khan M, Qasim A. Evaluation of effect of iron deficiency anemia on HbA₂ levels. Pak Armed Forces Med J. 2023;73(Suppl-1):S115–S118. doi:10.51253/pafmj.v73iSUPPL-1.5991.
9. NHS England. Gene-editing therapy that could cure blood disorder thalassaemia for NHS patients. News release; 2024 Aug 8. Available from: https://www.england.nhs.uk/ (accessed 25 Aug 2025).
10. Bain BJ, Daniel Y, Henthorn J, de la Salle B, Hogan A, Roy NBA, et al. Significant haemoglobinopathies: A guideline for screening and diagnosis. A British Society for Haematology guideline. Br J Haematol. 2023;201(6):1047–1065. doi:10.1111/bjh.18794.
11. UK NEQAS Haematology. External Quality Assessment (EQA) programmes. Available from: https://ukneqas.org.uk/ (accessed 25 Aug 2025).
12. Temaj G, Pearce M, Mitchell R. The impact of consanguinity on human health and disease. Discover Genetics. 2022;2:4. doi:10.1007/s44162-022-00004-5.
13. Akhtar MW, Iqbal I, ul Haq A, Shoukat A, Bashir A, Zafar MI, et al. Thalassemia in Pakistan: Current status and the way forward. J Pak Med Assoc. 2022;72(5):1017–1024.
14. O’Brien RM. A caution regarding rules of thumb for variance inflation factors. Qual Quant. 2007;41(5):673–690. doi:10.1007/s11135-006-9018-6.
15. Ghafoor S, Ali M. Premarital screening for thalassemia in Pakistan: Opportunities and challenges. J Pak Med Assoc. 2024. [No DOI listed].
16. OpenEpi. OpenEpi: Open Source Epidemiologic Statistics for Public Health (Version 3.x). Available from: https://www.openepi.com/ (accessed 25 Aug 2025).
17. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29–36. doi:10.1148/radiology.143.1.7063747.
18. National Institute for Health and Care Excellence (NICE). Exagamglogene autotemcel (Casgevy) for transfusion-dependent beta-thalassaemia (TA1003). 2024 Sep 11. Available from: https://www.nice.org.uk/ (accessed 25 Aug 2025).
19. Khayat RM, Obeidat N, Bdour S, Al-Heresh R, Ababneh M, AlGhazawi M, et al. Consanguinity and the risk of congenital anomalies: A systematic review and meta-analysis. Cureus. 2024;16(3):e56392. doi:10.7759/cureus.56392.
20. Ahmed S, Zubair M, Dilshad SMR, Zaidi NUSS, Kalkan N, Khan MA, et al. Thalassemia patients from Baluchistan (Pakistan) infected with multiple hepatitis B or hepatitis C virus strains. Viruses. 2021;13(9):1801. doi:10.3390/v13091801.
21. Riaz M, Abbas M, Rasool G, Baig IS, Mahmood Z, Munir N, et al. Prevalence of transfusion-transmitted infections in multiple blood transfusion-dependent thalassaemic patients in Asia: A systematic review. Int J Immunopathol Pharmacol. 2022;36:03946320221096909. doi:10.1177/03946320221096909.
22. Farmakis D, Giakoumis A, Cannon L, Angastiniotis M, Eleftheriou A. The 2021 Thalassaemia International Federation guidelines for the management of transfusion-dependent thalassaemia and non-transfusion-dependent thalassaemia. HemaSphere. 2022;6(1):e676. doi:10.1097/HS9.0000000000000676.
23. Rasheed F, Khan SA, Khan ZU, Khan MA. Transfusion-transmitted infections in multi-transfused thalassemia patients in Pakistan. Transfus Apher Sci. 2021;60(5):103226. doi:10.1016/j.transci.2021.103226.
24. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration. PLoS Med. 2007;4(10):e297. doi:10.1371/journal.pmed.0040297.
25. Bain BJ. Haemoglobinopathy Diagnosis. 3rd ed. Chichester (UK): Wiley-Blackwell; 2020. doi:10.1002/9781119579977.
26. Rockhill B, Newman B, Weinberg C. Use and misuse of population attributable fractions. Am J Public Health. 1998;88(1):15–19. doi:10.2105/AJPH.88.1.15.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
