Global and Regional Congenital Cytomegalovirus (CMV) Epidemiology and Burden: Systematic Review and Meta-Analysis

Abstract

Background: Congenital cytomegalovirus (CMV) infection is the leading acquired cause of mental retardation, developmental delay and sensorineural deafness, yet a reliable assessment of the global disease burden is lacking. Therefore, we estimate the birth prevalence and annual new cases of congenital CMV (cCMV) worldwide. Methods: We performed a systematic literature review and meta-analysis to estimate the birth prevalence of cCMV by World Health Organization (WHO) region and World Bank income level using the MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases PROSPERO (CRD42021224431). A random-effects model predicted the global birth prevalence of symptomatic and asymptomatic cCMV infections. We conducted meta-regression analysis to evaluate the association of sociodemographic characteristics, maternal seroprevalence, fetal HIV exposure, maternal age, malnutrition, and race/ethnicity with the prevalence of cCMV. We estimated trends of the prevalence over time. Findings: 77 articles were included, representative of all WHO regions, and each income level. The pooled birth prevalence of cCMV was highest in Africa (3.71%; 95% CI 2.40% - 5.28%) compared to the United States and Canada (0.85%; 95% CI 0.64% - 1.09%, p<0.0001). The prevalence was higher in low- and middle-income countries (1.63% :95% CI 1.21%–2.11%) than in high-income countries (0.73%; 95% CI 0.61% - 0.87%,, p=0.003). On average, 2.7 million new cCMV cases occur each year worldwide. The greatest disease burden falls on African and South-East Asian regions, accounting for over 80% of new cases. High maternal CMV seroprevalence, HIV and malnutrition prevalence, lower socioeconomic status, high crude birth rate and younger average maternal age contributed to the higher annual case numbers in low- and middle-income countries than in high-income countries. Interpretation: Low- and middle-income countries incur the most significant disease burden, particularly those within the African and Southeast Asian regions. A global effort to address cCMV in regions with the greatest demand is imperative to reduce disease incidence, morbidity, and mortality. Funding: This work was supported by a U.S. National Institutes of Health (N.I.H) Director’s Transformative Award 1R01AI145057 (S.J.S.). Declaration of Interest: The authors declare no competing interests