Dataset Information

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.

SUBMITTER: Ssentongo P

PROVIDER: S-EPMC8383138 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMost infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated.MethodsTo confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used.ResultsA total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy.ConclusionWithout universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.

Project description:Importance: Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China.Objective: To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system.Design, setting, and participants: A decision tree for a simulated cohort population of 15?000?000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions: (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years).Main outcomes and measures: Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US dollars.Results: Incidence of cCMVi among newborns was reported to be approximately 0.7% in China. Targeted screening was less costly but also less effective than universal screening, identifying 41% of cases needing antiviral treatment and preventing nearly half of less severe or profound hearing loss. To avoid 1 CMV-related severe or profound hearing loss, 13 and 16 newborns need to be treated by targeted and universal screening, respectively. The ICERs of targeted and universal screening vs no screening were $79 and $2087 per quality-adjusted life-year gained, respectively, at the discounted rate of 3.5%. Both screening options were cost-effective for the Chinese health care system based on the willingness-to-pay threshold of 3?×?gross domestic product per capita. The sensitivity analysis showed that the prevalence of cCMVi, as well as diagnosis and treatment costs, were key factors that may be associated with decision-making.Conclusions and relevance: To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.