Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening: A Systematic Review and Meta-analysis

Abstract

Importance: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and the leading acquired cause of developmental disabilities and sensorineural deafness, yet a reliable assessment of the infection burden is lacking.

Objectives: To estimate the birth prevalence of cCMV in low- and middle-income countries (LMICs) and high-income countries (HICs), characterize the rate by screening methods, and delineate associated risk factors of the infection.

Data sources: MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases were searched from January 1, 1960, to March 1, 2021, and a total of 1322 studies were identified.

Study selection: Studies that provided data on the prevalence of cCMV derived from universal screening of infants younger than 3 weeks were included. Targeted screening studies were excluded.

Data extraction and synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Extraction was performed independently by 3 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Random-effects meta-analysis was undertaken. Metaregression was conducted to evaluate the association of sociodemographic characteristics, maternal seroprevalence, population-level HIV prevalence, and screening methods with the prevalence of cCMV.

Main outcomes and measures: Birth prevalence of cCMV ascertained through universal screening of infants younger than 3 weeks for CMV from urine, saliva, or blood samples.

Results: Seventy-seven studies comprising 515 646 infants met the inclusion criteria from countries representative of each World Bank income level. The estimated pooled overall prevalence of cCMV was 0.67% (95% CI, 0.54%-0.83%). The pooled birth prevalence of cCMV was 3-fold greater in LMICs (1.42%; 95% CI, 0.97%-2.08%; n = 23 studies) than in HICs (0.48%; 95% CI, 0.40%-0.59%, n = 54 studies). Screening methods with blood samples demonstrated lower rates of cCMV than urine or saliva samples (odds ratio [OR], 0.38; 95% CI, 0.23-0.66). Higher maternal CMV seroprevalence (OR, 1.19; 95% CI, 1.11-1.28), higher population-level HIV prevalence (OR, 1.22; 95% CI, 1.05-1.40), lower socioeconomic status (OR, 3.03; 95% CI, 2.05-4.47), and younger mean maternal age (OR, 0.85; 95% CI, 0.78-0.92, older age was associated with lower rates) were associated with higher rates of cCMV.

Conclusions and relevance: In this meta-analysis, LMICs appeared to incur the most significant infection burden. Lower rates of cCMV were reported by studies using only blood or serum as a screening method.

Figure 1.. Congenital Cytomegalovirus (CMV) Prevalence by World Bank Income Level in High-Income Countries (HICs) and Low- to Middle-Income Countries

Effect size values represent congenital CMV cases expressed as a percentage and their corresponding 95% CIs. Blue squares and their corresponding lines are the point estimates and 95% CIs. Diamonds represent the pooled estimate of each subgroup's prevalence (width denotes 95% CI). Heterogeneity by income level: low- to middle-income countries, I² = 96 (23 studies); high-income countries, I² = 92% (54 studies). Differences between subgroups were all significant at P < .001.

Figure 2.. Symptomatic Congenital Cytomegalovirus (CMV) Prevalence by World Bank Income Level in High-Income Countries and Low- to Middle-Income Countries

Effect size values represent congenital CMV cases expressed as a percentage and their corresponding 95% CIs. Blue squares and their corresponding lines are the point estimates and 95% CIs. Diamonds represent the pooled estimate of each subgroup's prevalence (width denotes 95% CI). Heterogeneity by income level: low- to middle-income countries (I² = 60%; heterogeneity P < .001; 18 studies); high-income countries (I² = 74%; heterogeneity P < .001; 42 studies); test for subgroup differences P = .90.

Figure 3.. Determinants and Temporal Trends of Congenital Cytomegalovirus (cCMV)

A, Maternal CMV seroprevalence is a significant determinant of congenital CMV. B, The prevalence of congenital CMV has remained consistent for the past 6 decades. Linear fit from linear regression model. Circles represent countries and are labeled by their International Organization for Standardization (ISO) code. The size of the circle is proportional to the sample size of each study and the colors represent the World Health Organization region. The ISO codes are defined in eTable 1 in the Supplement.