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. 2025 Jun 11:12:1609700.
doi: 10.3389/fmed.2025.1609700. eCollection 2025.

Global, regional, and national burden of orofacial clefts, 1990-2021: an analysis of data from the global burden of disease study 2021

Zhenghao Wang  1 , Weikun Qi  1 , Yiru Chen  1 , Feng Niu  1
Affiliations

Global, regional, and national burden of orofacial clefts, 1990-2021: an analysis of data from the global burden of disease study 2021

Zhenghao Wang et al. Front Med (Lausanne). .

Abstract

Background: Orofacial clefts (OFCs) are congenital craniofacial malformation caused by embryonic developmental abnormalities, characterized by incomplete fusion of the upper lip and/or palate, leading to feeding difficulties, speech impairments, and other functional challenges. OFCs represent the most prevalent congenital malformations of oral and maxillofacial region. We aim to characterize disease burden of OFCs across regions and countries, analyze temporal trends from 1990 to 2021, examine relationship with Socio-demographic Index (SDI), explore gender disparities and predict future epidemiological patterns.

Methods: Utilizing GBD 2021 database for 204 countries/regions, we analyzed age-standardized metrics including disability-adjusted life years (DALYs), prevalence, mortality, incidence, using tools like DisMod-MR 2.1 for Bayesian meta-regression. SDI, calculated from educational attainment, per capita income, and fertility rates (range 0-1), stratified nations into quintiles. Statistical analyses included SDI-burden correlations and future projections using Bayesian age-period-cohort (BAPC) modeling, implemented through R software.

Results: In 2021, there are a total of 4124006.8 cases of OFCs worldwide, with an age-standardized prevalence rate (ASPR) of 53.4 per 100,000 (95% UI: 43-64). The age-standardized incidence rate (ASIR) was 3.0 per 100,000 (95% UI: 2.2-3.9), while age-standardized deaths rate (ASDR) of 0 per 100,000 (95% UI: 0-0.1). Additionally, age-standardized DALYs rate was 5.8 per 100,000 (95% UI: 3.5-9.8). Regionally, low- to middle-SDI regions demonstrated the highest ASPR and ASIR, whereas low-SDI areas showed the most severe ASDR and DALYs rate. In contrast, high-SDI regions consistently exhibited the lowest burden across all metrics. At the subregional level, South Asia recorded the greatest ASPR, while Central Asia had the peak ASIR. Oceania displayed the highest ASDR and DALYs rate. Country-specific analysis identified Palestine with the maximum ASPR, Kazakhstan with the highest ASIR, Papua New Guinea with the greatest ASDR, and Afghanistan with the most elevated DALYs rate.

Conclusion: The global OFCs burden demonstrated consistent decline from 1990-2021, with persistent male predominance. Regional disparities correlate strongly with SDI, particularly affecting Central Asia, South Asia, and Africa populations.

Keywords: DALY (disability-adjusted life years); GBD (2021) database; cleft lip and palate; disease burden analysis; incidence; prevalence.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Trends in OFCs disability-adjusted life-years, OFCs prevalence, deaths, and incidence (1990–2021).
Figure 2
Figure 2
Association between SDI and disease burden indicators for OFCs in 21 regions.
Figure 3
Figure 3
Worldwide health impact of OFCs among both genders across 204 nations and regions. (A) Prevalence rate. (B) Incidence rate. (C) Death rate. (D) DALYs rate.
Figure 4
Figure 4
OFCs cases for both genders across 204 nations and regions. (A) Change prevalence cases. (B) Change incidence cases. (C) Change deaths cases. (D) Change DALYs.
Figure 5
Figure 5
Association between SDI and disease burden indicators for OFCs in 204 countries.
Figure 6
Figure 6
disease burden indicators for OFCs in males and females from 1990 to 2021.
Figure 7
Figure 7
Future forecasts of global burden of OFCs.
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References

    1. Merritt L. Part 1. Understanding the embryology and genetics of cleft lip and palate. Adv Neonatal Care. (2005) 5:64–71. doi: 10.1016/j.adnc.2004.12.006, PMID: - DOI - PubMed
    1. Nasreddine G, El Hajj J, Ghassibe-Sabbagh M. Orofacial clefts embryology, classification, epidemiology, and genetics. Mutat Res Mutat Res. (2021) 787:108373. doi: 10.1016/j.mrrev.2021.108373, PMID: - DOI - PubMed
    1. Munger RG, Tamura T, Johnston KE, Feldkamp ML, Pfister R, Cutler R, et al. Oral clefts and maternal biomarkers of folate-dependent one-carbon metabolism in Utah. Birt Defects Res A Clin Mol Teratol. (2011) 91:153–61. doi: 10.1002/bdra.20762, PMID: - DOI - PMC - PubMed
    1. Wang M, Yuan Y, Wang Z, Liu D, Wang Z, Sun F, et al. Prevalence of orofacial clefts among live births in China: a systematic review and meta-analysis. Birth Defects Res. (2017) 109:1011–9. doi: 10.1002/bdr2.1043, PMID: - DOI - PMC - PubMed
    1. Shi M, Wehby GL, Murray JC. Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects. Birth Defects Res Part C Embryo Today Rev. (2008) 84:16–29. doi: 10.1002/bdrc.20117, PMID: - DOI - PMC - PubMed

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