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

38 Pages Posted: 1 Feb 2021

See all articles by Paddy Ssentongo

Paddy Ssentongo

Pennsylvania State University - Center for Neural Engineering

Christine Hehnly

Pennsylvania State University - Institute of Personalized Medicine

Patricia Birungi

Pennsylvania State University - College of Human and Health Development

Mikayla A. Roach

Pennsylvania State University - College of Engineering

Jada Spady

Pennsylvania State University - College of Agricultural Sciences

Claudio Fronterre

Lancaster University - Centre for Health Informatics, Computing, and Statistics

Ming Wang

Pennsylvania State University - Department of Public Health Sciences

Laura E. Murray-Kolb

Pennsylvania State University - Department of Nutritional Sciences

Laila Al-Shaar

Pennsylvania State University - Department of Public Health Sciences

Vernon M. Chinchilli

Pennsylvania State University - Department of Public Health Sciences

James R. Broach

Pennsylvania State University - Institute for Personalized Medicine

Jessica E. Ericson

Pennsylvania State University - Division of Pediatric Infectious Disease

Steven J. Schiff

Pennsylvania State University - Centers for Neural Engineering and Infectious Disease Dynamics

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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

Suggested Citation

Ssentongo, Paddy and Hehnly, Christine and Birungi, Patricia and Roach, Mikayla A. and Spady, Jada and Fronterre, Claudio and Wang, Ming and Murray-Kolb, Laura E. and Al-Shaar, Laila and Chinchilli, Vernon M. and Broach, James R. and Ericson, Jessica E. and Schiff, Steven J., Global and Regional Congenital Cytomegalovirus (CMV) Epidemiology and Burden: Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=3777198 or http://dx.doi.org/10.2139/ssrn.3777198

Paddy Ssentongo

Pennsylvania State University - Center for Neural Engineering ( email )

212 Earth and Engineering Sciences Building
University Park, PA 16802
United States

Christine Hehnly

Pennsylvania State University - Institute of Personalized Medicine ( email )

University Park
State College, PA 16802
United States

Patricia Birungi

Pennsylvania State University - College of Human and Health Development

University Park
State College, PA 16802
United States

Mikayla A. Roach

Pennsylvania State University - College of Engineering ( email )

University Park
State College, PA 16802
United States

Jada Spady

Pennsylvania State University - College of Agricultural Sciences ( email )

PA
United States

Claudio Fronterre

Lancaster University - Centre for Health Informatics, Computing, and Statistics ( email )

Lancaster
United Kingdom

Ming Wang

Pennsylvania State University - Department of Public Health Sciences

University Park
State College, PA 16802
United States

Laura E. Murray-Kolb

Pennsylvania State University - Department of Nutritional Sciences ( email )

University Park
State College, PA 16802
United States

Laila Al-Shaar

Pennsylvania State University - Department of Public Health Sciences ( email )

University Park
State College, PA 16802
United States

Vernon M. Chinchilli

Pennsylvania State University - Department of Public Health Sciences ( email )

University Park
State College, PA 16802
United States

James R. Broach

Pennsylvania State University - Institute for Personalized Medicine ( email )

University Park
State College, PA 16802
United States

Jessica E. Ericson

Pennsylvania State University - Division of Pediatric Infectious Disease ( email )

Hershey, PA
United States

Steven J. Schiff (Contact Author)

Pennsylvania State University - Centers for Neural Engineering and Infectious Disease Dynamics

University Park
State College, PA 16802
United States