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Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening

Paddy Ssentongo, Christine Hehnly, Patricia Birungi and 10 more

JAMA Network Open · 2021 · Meta-analysis

doi:10.1001/jamanetworkopen.2021.20736

Abstract

Question. What are the pooled prevalence of congenital cytomegalovirus infection and factors associated with the rates in high-income and low- and middle-income countries?

Findings. In this systematic review and meta-analysis including 77 studies from 36 countries comprising 515 646 infants younger than 3 weeks, the pooled overall prevalence of congenital cytomegalovirus was 0.67%. The infection burden was 3-fold greater in low- and middle-income countries than in high-income countries. Lower rates were reported in screening methods using blood compared with urine or saliva.

Meaning. The findings of this study suggest that low- and middle-income countries incur the greatest infection burden of congenital cytomegalovirus; a global effort to address congenital cytomegalovirus in regions with the greatest prevalence is needed to reduce disease incidence and morbidity.

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.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Human herpesvirus 5, cytomegalovirus (CMV), is a common cause of asymptomatic or mild illness in immunocompetent children and adults. However, congenital CMV (cCMV) infection can lead to permanent sequelae in 15% to 18% of births, including death in 1%, neurocognitive sequelae in 5% to 15%, and hearing loss in 12% of individuals with cCMV.,,,

Studies have suggested that cCMV infection is a disease of disparity, with increased incidence, prevalence, and severity in low-income populations.,,, However, most studies that have been used to generate estimates of the burden of cCMV infection are from high-income countries (HICs)., Thus, the burden of cCMV infection is likely higher than currently available studies suggest. Congenital CMV is likely underreported worldwide owing to the lack of available testing in low- and middle-income countries (LMICs) and lack of systematic testing in countries of all income levels.

Differentiation of congenital vs early postnatal CMV infections requires testing near the time of birth and also after 3 weeks., Symptomatic infants are more likely to undergo testing shortly after birth than asymptomatic infants. However, most infants with cCMV will be asymptomatic at birth, and the sequelae of congenital infection will not be evident until weeks, months, or even years later. By the time sequelae are noted, it is too late to accurately assess the association of cCMV with the child’s outcome.

These difficulties in accurately diagnosing cCMV in low-resource settings have led to estimating the burden of cCMV from prevalence estimates derived primarily in HICs. This factor, in addition to not accounting for differences in risk factors, such as maternal educational level, HIV exposure, and income distribution, contribute to underestimating the burden of infection., We sought to estimate the prevalence of cCMV with a meta-analysis of LMIC and HIC prevalence studies and estimate the influence that diagnostic methods as well as demographic and clinical factors have on cCMV prevalence.

Data Sources and Extraction

We searched the MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases for studies published between January 1, 1960, and March 1, 2021, using a combination of medical subject headings and key words in the title and abstract denoting birth prevalence of cCMV. We used terms CMV or cytomegalovirus combined with congenital, or newborn combined with epidemiology (eg, incidence, prevalence, burden, mortality) to search peer-reviewed publications. A full list of search terms is provided in the eMethods in the Supplement. The search was performed for all countries by their categorization in the July 2019 World Bank list. This study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

We also searched the references cited by the retrieved articles for additional material. We applied the following inclusion criteria: (1) original peer-reviewed studies, (2) identification of cCMV through universal screening, and (3) detection of CMV based on culture or polymerase chain reaction of urine, saliva, blood, serum, or dried blood spot samples collected within 3 weeks of birth. Studies not conducted in humans, case reports, letters to editor, case series, case-control studies, comparison studies, practice guidelines, meta-analyses, literature reviews, and commentaries were excluded. Studies that did not document CMV screening methods were also excluded. We did not impose any restrictions based on language of the articles or country. To further minimize selection bias and inflation of the prevalence estimates, we excluded studies that carried out targeted screening of CMV. These included studies conducted only in the HIV population, in neonates with abnormal results on hearing screening, and those admitted to the intensive care units. Some studies used the same population in several articles. For example, articles by the CMV and Hearing Multicenter Screening study group, had multiple overlapping populations. Therefore, we excluded articles with overlapping study populations.

Birth prevalence was defined as the number of infants with CMV infection divided by the total number of live-born infants tested for CMV in a defined population. Symptomatic cCMV infection was defined by each study, and definitions varied substantially across studies. The typical definition of the term symptomatic to describe clinical indications of CMV infection in newborns, known as cytomegalovirus inclusion disease, includes the presence of 1 or more of the following symptoms: petechiae, jaundice with associated hyperbilirubinemia, hepatosplenomegaly, thrombocytopenia, chorioretinitis, seizures, sensorineural hearing loss, microcephaly, intracranial calcifications, or fetal hydrops., The less-severe symptoms are usually transient in newborns. Many of the signs and symptoms listed are not specific to CMV or readily apparent, and hence symptomatic CMV often goes unrecognized in the absence of systematic attempts to identify it.

We extracted information on the studies’ characteristics and their participants, methods used to diagnose CMV, country-specific potential predictors of cCMV (HIV status, income level), and methodologic quality. Three of us (P.B., M.A.R., and J.S.) initially independently screened the titles and abstracts of articles and obtained the full-text articles and performed data extraction on those meeting the inclusion criteria. Three of us (P.B., M.A.R., and J.S.) jointly reviewed a random subset of articles to ensure selection accuracy. Disagreements about the included articles were resolved by 2 of us (P.S. and C.H.). A detailed account of the inclusion/exclusion process is shown in eFigure 1 in the Supplement.

Two of us (P.S. and C.H.) independently assessed the quality of the articles included in our analysis. Assessment of methodologic quality was conducted using the Newcastle-Ottawa Quality Assessment Scale, a validated tool for assessing cross-sectional, case-control, and cohort studies. Scores of 8 to the maximum score of 9 were defined as high quality; scores of 5 to 7 were defined as intermediate quality, and scores of 1 to 4 were considered low quality. Studies were included regardless of the risk of bias and quality scores, but metaregression analysis was conducted to ascertain the outcome of their inclusion.

Race or ethnicity was classified by the investigators of each study included in the meta-analysis. Options were defined by participants. Race or ethnicity was assessed because it is associated with the incidence of cCMV.

Statistical Analysis

We adopted a narrative approach describing the number of studies, study settings, and diagnostic criteria for cCMV. Descriptive statistics are reported as proportions of a population and as medians (interquartile range).

We applied random-effects models to estimate the prevalence of cCMV and their respective 95% CIs, and we reported the pooled prevalence as a percentage of the screened newborn infants. To pool the study estimates, we used a generalized linear mixed-effects model with the logit link. We estimated all parameters via maximizing the pseudolikelihood. The generalized linear mixed-effects model method is not affected by the potential problems of back-transformation of Freeman-Tukey double arcsine transformation of single proportions., Individual and pooled estimates are displayed using forest plots. Between-study variation was assessed using I2, which describes the percentage of total variation across studies that is due to heterogeneity rather than chance, expressed as percentage (low [25%], moderate [50%], and high [75%]). We report the pooled estimates as percentages.

We conducted random-effects metaregression analysis to investigate the sources of heterogeneity. We examined the associations of each of the explanatory variables included in the metaregression in association with the prevalence of cCMV. These variables included study-level maternal median or mean age, the proportion with HIV/AIDS exposure, maternal CMV seroprevalence (IgG or IgM antibodies), the proportion born premature, the proportion of males, and the proportion of Black individuals for studies conducted in the US or Canada. We also explored the association of socioeconomic status (defined by country-specific income level as described by the World Bank; low and middle income [≤$12 535] vs high income [≥$12 536], eFigure 2 in the Supplement), and population-level HIV prevalence. Differences in prevalence were also estimated by the biological specimen used for screening of CMV (blood, saliva, or urine). We regressed the estimates as a function of the study year to explore the prevalence trend.

To evaluate possible publication bias, we visually inspected the funnel plot for asymmetry by plotting the study effect size against SEs of the effect size and performed the Egger linear regression test and Begg rank correlation test. The Duval and Tweedie trim and fill procedure was used to adjust for the publication bias. An influence and outlier study sensitivity analysis was undertaken to estimate the association of each study with the overall pooled estimate. The metaprop, escalc, and rma functions from the R packages meta and metafor were used for the analysis. All statistical analyses were performed with R software, version 3.6.2 (R Foundation). The significance level was set at P <.05, and all P values were 2-tailed.

Results

The initial literature search yielded 1322 articles (eFigure 1 in the Supplement); of these, we excluded 223 duplicates. After a review of titles and abstracts, we excluded 942 articles if they (1) were conducted in animals; (2) were case series, case-controls, or reviews; (3) were long-term outcomes or sequelae studies; or (4) solely compared the sensitivity of cCMV testing methods. We fully examined a total of 157 full-text articles and excluded 80 articles because (1) the study focused on a specific subpopulation (targeted screening), such as neonates with clinical signs of cCMV or a nonrepresentative demographic cohort; (2) there were overlapping study populations; and (3) the article was a systematic review. A total of 77 articles were included in this meta-analysis. The final studies were from 36 countries (eFigure 3 in the Supplement) on 5 continents and are categorized by World Health Organization regions as follows: Africa, 6 countries (6 studies),,,,,; Americas–Latin, 5 countries (9 studies),,,,,,,,; Americas–US and Canada, 2 countries (18 studies),,,,,,,,,,,,,,,,,; Eastern Mediterranean, 1 country (3 studies),,; Europe, 16 countries (24 studies),,,,,,,,,,,,,,,,,,,,,,,; Southeast Asia, 2 countries (3 studies),,; and Western Pacific, 4 countries (14 studies).,,,,,,,,,,,,, The present analysis included a total sample of 515 646 infants. The number of neonates included in individual studies ranged widely (minimum 117 to maximum 73 239), with a median of 2032 infants (interquartile range, 741-10 328). Details of each study included in the meta-analysis are provided in eTable 1 in the Supplement.

Consistent with the expected publication bias, source articles from HICs (54 [70%]) were encountered more frequently than those from LMICs (23 [30%]). The median methodologic quality of studies in HICs was similar to that of LMICs. The estimated pooled overall prevalence of cCMV was 0.67% (95% CI, 0.54%-0.83%). Using the random-effects model, the prevalence of cCMV was significantly higher in LMICs (1.42%; 95% CI, 0.97%-2.08%) compared with HICs (0.48%; 95% CI, 0.40%-0.59%; P <.001 for subgroup differences) (Figure 1). Each subgroup's heterogeneity was high, as evidenced by the I2 value (>90% in each group). The definition of symptomatic cCMV varied by study. The most common cCMV clinical signs, laboratory test results, and imaging findings reported were sensorineural hearing loss, jaundice, hepatosplenomegaly, thrombocytopenia, and central nervous system involvement (microcephaly, intracranial calcifications, enlarged ventricles) (eTable 2 in the Supplement). Sixty studies reported the proportion of symptomatic cCMV. The pooled estimate was 10.85% (95% CI, 7.40%-15.65%). No significant differences were noted in the rates of symptomatic cCMV between LMICs (10.42%; 95% CI, 4.71%-21.49%) and HICs (11.0%; 95% CI, 7.10%-16.67%). Heterogeneity by income level was 60% (P <.001 for heterogeneity; 18 studies) for LMICs and 74% (P <.001 for heterogeneity; 42 studies) for HICs (P =.90 for subgroup differences) (Figure 2).

Detection of CMV DNA in blood and the sensitivity of CMV polymerase chain reaction in dried blood spot samples is highly variable, ranging from 30% to 90% depending on the technique used. Therefore, screening studies based on CMV polymerase chain reaction of dried blood spots will probably underestimate cCMV prevalence, but with improved methods, this form of testing may become more useful., To assess possible differences in the estimates due to the biological specimens used for screening for cCMV, we conducted subgroup analysis comparing studies that carried out screening using urine and/or saliva samples with those that used only blood or serum. There was a significant difference in the cCMV prevalence rates between the biological specimens used for screening: 0.79% (95% CI, 0.63%-1.00%) for urine or saliva vs 0.31% (95% CI, 0.22%- 0.46%) for blood or serum only (P <.001 for subgroup differences) (eFigure 3 in the Supplement).

A univariable random-effects metaregression model revealed LMICs (odds ratio [OR], 3.03; 95% CI, 2.05-4.47), higher maternal seroprevalence (OR, 1.19; 95% CI, 1.11-1.28) (Figure 3A), higher population-level HIV prevalence (OR, 1.22; 95% CI, 1.05-1.40), and younger maternal age (OR, 0.85; 95% CI, 0.78-0.92, older age was associated with lower cCMV rates) were significant factors associated with higher cCMV prevalence (Table). 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). When the analysis was restricted to studies conducted in the US and Canada, there was an association of Black individuals with a higher risk of cCMV prevalence compared with other races (OR, 1.13; 95% CI, 1.10-1.17; P <.01). Temporal trend analysis indicated that cCMV prevalence rate has remained constant for the past 60 years (R2 = 0.007; P =.48 for temporal trend) (Figure 3B).

Influence and outlier sensitivity analyses were performed for the birth prevalence of cCMV. In this analysis, 1 study was omitted and replaced 1 study at a time (leave-1-out method) from the meta-analysis, and we calculated the pooled data for the remaining studies. The pooled estimate remained close to the observed overall pooled estimate, indicating that no individual study had a large influence on the pooled estimate. The pooled point estimate ranged from 0.65 to 0.69 (eFigure 4 in the Supplement).

A symmetrical inverted funnel plot suggested the absence of publication bias (eFigure 5 in the Supplement). Similarly, neither the Begg rank correlation test (z = 0.83; P =.41) nor the Egger linear regression test (t = 0.05; df=75; P =.96) indicated publication bias. Nevertheless, the Duval and Tweedie trim and fill analysis was conducted to adjust for the potential small-study publication bias. Analyses suggested that the adjusted effect estimates would fall in the range of 0.57% to 0.87%, and no additional studies were added to the funnel plots (eFigure 6 in the Supplement). The median study quality score was 7 of 9 (range, 4-9).

Discussion

We report a comprehensive systematic review and meta-analysis of cCMV epidemiologic factors. More than 1300 titles were examined to identify 77 relevant peer-reviewed publications representing more than 500 000 neonates across 36 countries. The estimated birth prevalence of cCMV was 3-fold higher in LMICs than HICs. The higher maternal CMV seroprevalence, higher population-level HIV prevalence, and young maternal age were associated with cCMV rates. Screening methods for cCMV with urine and saliva samples provided higher prevalence rates than screening methods with blood or serum samples.

Others have attempted to estimate the prevalence of cCMV via systematic literature review, but these studies had limitations., The first systematic review of the global prevalence of cCMV was published in 2007. In this review, only 2 African countries and 1 country in the Southeast Asian region were included (Gambia and Ivory Coast from Africa and Thailand from Southeast Asia) and the risk factors were not systematically evaluated. In 2014, a systematic review of cCMV focusing on developing countries was published. Only 2 countries from Africa (Gambia and Ivory Coast) and 1 from Southeast Asia (India) were represented. This review did not evaluate the association of sociodemographic characteristics, maternal seroprevalence, fetal HIV exposure, maternal age, and race/ethnicity with the prevalence of cCMV. Since then, Africa and other LMICs have frequently published on congenital CMV (Figure 3B). Thus, an updated systematic review and meta-analysis is needed to accurately quantify the burden of cCMV to inform prevention, control, and mitigation strategies.

The large numbers of cCMV are a significant public health concern. Congenital CMV is the leading cause of nongenetic hearing loss, adding substantially to disability-adjusted life years. In addition, CMV is associated with neonatal sepsis,, a common cause of neonatal death in the developing world, and a disorder associated with significant sequelae, such as postinfectious hydrocephalus and other complications. The current guidelines for the treatment of moderate to severe symptomatic cCMV recommends 6 months of valganciclovir. However, the safety and cost of valganciclovir limit its use in LMICs. Therefore, children most likely to have cCMV also have the least access to treatment. In addition, children in LMICs are less likely to undergo routine developmental and hearing screening and to have access to interventions should they be found deficient in either of these domains. Therefore, cCMV in the LMICs remains an important unmet public health need.

Metaregression analysis revealed that a higher prevalence of HIV infection explained a significant variation in the heterogeneity of the prevalence estimates. HIV and CMV coinfection has been shown to have a synergistic interaction contributing to the higher morbidity and mortality rates in the first year of life of those infected, compared with infants without HIV exposure. It is postulated that interaction of HIV-1 and CMV at the maternal-fetal placental interface and exposure to in utero antiretroviral therapy may cause phenotypical and functional immunologic changes in fetuses exposed to HIV, enabling increased cCMV susceptibility and burden in this population. The increased rate of cCMV in neonates exposed to HIV may be due to more-frequent CMV reinfection or reactivation in their mothers, the waning of protective immunity, or a reduced transplacental transfer of protective antibodies.

Current mitigation strategies in LMICs are limited to hygienic precautions and behavioral modification among pregnant women to prevent primary infection or reinfection with a new CMV strain during pregnancy. These measures would not be expected to have substantial influences on congenital infections associated with reactivation of maternal CMV during pregnancy. We found that higher maternal seroprevalence is associated with an increased prevalence of cCMV, suggesting that nonprimary infection plays an important role in contributing to the burden of cCMV., Our results underscore the need for an effective vaccine and treatment strategies that can be administered in LMICs without undue risks of adverse events. Measures to facilitate universal neonatal screening to allow for early detection of sensorineural hearing loss and developmental delay are needed.,,,, A long-term neurodevelopmental delay study to assess the true impact of untreated cCMV in LMICs is needed.

Limitations

Several limitations of the study require consideration. Africa and Southeast Asia regions were represented by relatively fewer countries (n = 8). Therefore, interpolating these few countries' estimates to the entire region introduces the potential for substantial selection and detection biases. Within- and between-country disparities in cCMV in sub-Saharan Africa have been observed. However, we used a random-effects model to represent unmodeled errors that could not be accounted for with the regression models used in this report. The very small sample sizes in some countries are another limitation that introduce selection bias and uncertainty. Furthermore, inclusions of limited populations within individual countries introduce a potential bias reflected in substantial differences in cCMV-reported prevalence. Also, symptomatic prevalence ranged widely across studies that could be linked to selection bias, and symptomatic cCMV can vary based on genetic variation of the virus that was not factored into this analysis. In addition, CMV detection methods provide varying sensitivity and specificity that could bias the pooled estimates. These limitations should serve as a road map for future studies to better estimate the global health and economic burden of cCMV and maximize capacity building for resource allocation in regions of greatest need.

Conclusions

Congenital CMV is a major public health concern with the burden of infection estimated to be 3-fold greater in LMICs than HICs. It is necessary to better understand the economic burden of cCMV and provide more robust evaluations of health care interventions designed to reduce its incidence and impact. Nationally representative population-based studies, particularly in LMICs, are needed to assess the burden of cCMV in those regions. Region-specific prevention, diagnosis, and treatment options, and community-based education programs are needed to mitigate the incidence of cCMV and its sequelae, particularly in resource-poor settings.

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    Cardoso ES, Jesus BL, Gomes LG, Sousa SM, Gadelha SR, Marin LJ. The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increases inclusion and detection rates. Rev Soc Bras Med Trop. 2015;48(2):206-207

    Not in our library10.1590/0037-8682-0200-2014

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    Yamamoto AY, Mussi-Pinhata MM, Isaac MdeL,. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediatr Infect Dis J. 2011;30(12):1043-1046

    Not in our library10.1097/inf.0b013e31822d9640

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    Noyola DE, Mejía-Elizondo AR, Canseco-Lima JM, Allende-Carrera R, Hernánsez-Salinas AE, Ramírez-Zacarías JL. Congenital cytomegalovirus infection in San Luis Potosi, Mexico. Pediatr Infect Dis J. 2003;22(1):89-90

    Not in our library10.1097/00006454-200301000-00022

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    Estripeaut D, Moreno Y, Ahumada SR, Martínez A, Racine J, Sáez-Llorens X. Seroprevalence of cytomegalovirus infection in puerperal women and its impact on their newborns. Presented at: Anales de pediatria; Barcelona, Spain; 2007.

    Not in our library10.1157/13098930

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    Yamamoto AY, Anastasio ART, Massuda ET,. Contribution of congenital cytomegalovirus infection to permanent hearing loss in a highly seropositive population: the Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study. Clin Infect Dis. 2020;70(7):1379-1384

    Not in our library10.1093/cid/ciz413

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    Yamamoto AY, Mussi-Pinhata MM, Pinto PC, Figueiredo LT, Jorge SM. Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus by the polymerase chain reaction technique. J Virol Methods. 2001;97(1-2):159-164

    Not in our library10.1016/s0166-0934(01)00347-0

  43. 43.

    Rico A, Dollard SC, Valencia D,. Epidemiology of cytomegalovirus Infection among mothers and infants in Colombia. J Med Virol. Published online January 21, 2021

    Not in our library10.1002/jmv.26815

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    Stagno S, Dworsky ME, Torres J, Mesa T, Hirsh T. Prevalence and importance of congenital cytomegalovirus infection in three different populations. J Pediatr. 1982;101(6):897-900

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    Not in our library10.1093/infdis/168.3.552

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    Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF. Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics. 1999;104(1, pt 1):55-60

    Not in our library10.1542/peds.104.1.55

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    Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ, Dollard SC. Use of screening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection. J Pediatr. 2010;157(2):191-197

    Not in our library10.1016/j.jpeds.2010.03.002

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    Boppana SB, Ross SA, Shimamura M,; National Institute on Deafness and Other Communication Disorders CHIMES Study. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med. 2011;364(22):2111-2118

    Not in our library10.1056/nejmoa1006561

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    Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection · 2021
    No notice
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    Stagno S, Pass RF, Cloud G,. Primary cytomegalovirus infection in pregnancy: incidence, transmission to fetus, and clinical outcome. JAMA. 1986;256(14):1904-1908

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    Birnbaum G, Lynch JI, Maribeth AM, Lonergan WM, Sever JL. Cytomegalovirus infections in newborn infants. J Pediatr. 1969;75(5):789-795

    Not in our library10.1016/s0022-3476(69)80301-x

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    Stagno S, Reynolds DW, Huang E-S, Thames SD, Smith RJ, Alford CA Jr. Congenital cytomegalovirus infection. N Engl J Med. 1977;296(22):1254-1258

    Not in our library10.1056/nejm197706022962203

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    Melish ME, Hanshaw JB. Congenital cytomegalovirus infection: progress of infants detected by routine screening. AJDC. 1973;126(2):190-194

    Not in our library10.1001/archpedi.1973.02110190168011

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    Larke RP, Wheatley E, Saigal S, Chernesky MA. Congenital cytomegalovirus infection in an urban Canadian community. J Infect Dis. 1980;142(5):647-653

    Not in our library10.1093/infdis/142.5.647

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    Yow MD, Williamson DW, Leeds LJ,. Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants. Am J Obstet Gynecol. 1988;158(5):1189-1195

    Not in our library10.1016/0002-9378(88)90252-9

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    Embil JA, Macdonald JM, Scott KE. Survey of a neonatal population for the prevalence of cytomegalovirus. Scand J Infect Dis. 1975;7(3):165-167

    Not in our library10.3109/inf.1975.7.issue-3.02

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    Hanshaw JB, Steinfeld HJ, White CJ. Fluorescent-antibody test for cytomegalovirus macroglobulin. N Engl J Med. 1968;279(11):566-570

    Not in our library10.1056/nejm196809122791102

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    Montgomery JR, Mason EO Jr, Williamson AP, Desmond MM, South MA. Prospective study of congenital cytomegalovirus infection. South Med J. 1980;73(5):590-593, 595

    Not in our library10.1097/00007611-198005000-00012

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    Hildebrandt RJ, Sever JL, Margileth AM, Callagan DA. Cytomegalovirus in the normal pregnant woman. Am J Obstet Gynecol. 1967;98(8):1125-1128

    Not in our library10.1016/0002-9378(67)90038-5

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    Karimian P, Yaghini O, Nasr Azadani H,. Prevalence, characteristics, and one-year follow-up of congenital cytomegalovirus infection in Isfahan City, Iran. Interdiscip Perspect Infect Dis. 2016;2016:7812106

    Not in our library10.1155/2016/7812106

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    Fahimzad A, Afgeh SA, Eghbali E, Abdinia B, Shiva F, Rahbar M. Screening of congenital CMV infection in saliva of neonates by PCR: report of a pilot screening study in Iran. Clin Lab. 2013;59(9-10):1171-1174

    Not in our library10.7754/clin.lab.2013.120910

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    Noorbakhsh S, Farhadi M, Haghighi F, Minaeian S, Hasanabad MH. Neonatal screening for congenital cytomegalovirus infection in Tehran, Iran, using Guthrie cards. Iran J Microbiol. 2020;12(3):198-203

    Not in our library10.18502/ijm.v12i3.3236

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    Schlesinger Y, Halle D, Eidelman AI,. Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection. Arch Dis Child Fetal Neonatal Ed. 2003;88(5):F371-F374

    Not in our library10.1136/fn.88.5.f371

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    Barlinn R, Dudman SG, Trogstad L,. Maternal and congenital cytomegalovirus infections in a population-based pregnancy cohort study. APMIS. 2018;126(12):899-906

    Not in our library10.1111/apm.12899

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    Sahiner F, Cekmez F, Cetinkaya M,. Congenital cytomegalovirus infections and glycoprotein B genotypes in live-born infants: a prevalence study in Turkey. Infect Dis (Lond). 2015;47(7):465-471

    Not in our library10.3109/23744235.2015.1018316

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    Barbi M, Binda S, Caroppo S,. Multicity Italian study of congenital cytomegalovirus infection. Pediatr Infect Dis J. 2006;25(2):156-159

    Not in our library10.1097/01.inf.0000199261.98769.29

  68. 68.

    Barbi M, Binda S, Primache V, Clerici D; NEOCMV Group. Congenital cytomegalovirus infection in a northern Italian region. Eur J Epidemiol. 1998;14(8):791-796

    Not in our library10.1023/a:1007554726449

  69. 69.

    Barkai G, Ari-Even Roth D, Barzilai A,. Universal neonatal cytomegalovirus screening using saliva—report of clinical experience. J Clin Virol. 2014;60(4):361-366

    Not in our library10.1016/j.jcv.2014.04.024

  70. 70.

    de Vries JJ, Korver AM, Verkerk PH,. Congenital cytomegalovirus infection in the Netherlands: birth prevalence and risk factors. J Med Virol. 2011;83(10):1777-1782

    Not in our library10.1002/jmv.22181

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    Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. J Pediatr. 2008;153(1):84-88

    Not in our library10.1016/j.jpeds.2007.12.049

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    Barkai G, Barzilai A, Mendelson E, Tepperberg-Oikawa M, Roth DA, Kuint J. Newborn screening for congenital cytomegalovirus using real-time polymerase chain reaction in umbilical cord blood. Isr Med Assoc J. 2013;15(6):279-283.

    Not in our library

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    Waters A, Jennings K, Fitzpatrick E,. Incidence of congenital cytomegalovirus infection in Ireland: implications for screening and diagnosis. J Clin Virol. 2014;59(3):156-160

    Not in our library10.1016/j.jcv.2013.12.007

  74. 74.

    Halwachs-Baumann G, Genser B, Danda M,. Screening and diagnosis of congenital cytomegalovirus infection: a 5-y study. Scand J Infect Dis. 2000;32(2):137-142

    Not in our library10.1080/003655400750045222

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    Paradiž KR, Seme K, Puklavec E, Paro-Panjan D, Poljak M. Prevalence of congenital cytomegalovirus infection in Slovenia: a study on 2,841 newborns. J Med Virol. 2012;84(1):109-115

    Not in our library10.1002/jmv.22230

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    Arapović J, Rajič B, Pati S,. Cytomegalovirus seroprevalence and birth prevalence of congenital CMV infection in Bosnia and Herzegovina: a single-center experience. Pediatr Infect Dis J. 2020;39(2):140-144

    Not in our library10.1097/inf.0000000000002510

  77. 77.

    Paix ão P, Almeida S, Gouveia P, Vilarinho L, Vaz Osório R. Prevalence of human cytomegalovirus congenital infection in Portuguese newborns. Euro Surveill. 2009;14(9):13-15.

    Not in our library

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    Leruez-Ville M, Magny J-F, Couderc S,. Risk factors for congenital cytomegalovirus infection following primary and nonprimary maternal infection: a prospective neonatal screening study using polymerase chain reaction in saliva. Clin Infect Dis. 2017;65(3):398-404

    Not in our library10.1093/cid/cix337

  79. 79.

    Gaytant MA, Galama JM, Semmekrot BA,. The incidence of congenital cytomegalovirus infections in the Netherlands. J Med Virol. 2005;76(1):71-75

    Not in our library10.1002/jmv.20325

  80. 80.

    Engman M-L, Malm G, Engström L,. Congenital CMV infection: prevalence in newborns and the impact on hearing deficit. Scand J Infect Dis. 2008;40(11-12):935-942

    Not in our library10.1080/00365540802308431

  81. 81.

    Griffiths PD, Baboonian C, Rutter D, Peckham C. Congenital and maternal cytomegalovirus infections in a London population. Br J Obstet Gynaecol. 1991;98(2):135-140

    Not in our library10.1111/j.1471-0528.1991.tb13358.x

  82. 82.

    Ahlfors K, Ivarsson S-A, Harris S,. Congenital cytomegalovirus infection and disease in Sweden and the relative importance of primary and secondary maternal infections: preliminary findings from a prospective study. Scand J Infect Dis. 1984;16(2):129-137

    Not in our library10.3109/00365548409087131

  83. 83.

    Andersen HK, Brostrøm K, Hansen KB,. A prospective study on the incidence and significance of congenital cytomegalovirus infection. Acta Paediatr Scand. 1979;68(3):329-336

    Not in our library10.1111/j.1651-2227.1979.tb05015.x

  84. 84.

    Stern H, Tucker SM. Prospective study of cytomegalovirus infection in pregnancy. BMJ. 1973;2(5861):268-270

    Not in our library10.1136/bmj.2.5861.268

  85. 85.

    Peckham CS, Chin KS, Coleman JC, Henderson K, Hurley R, Preece PM. Cytomegalovirus infection in pregnancy: preliminary findings from a prospective study. Lancet. 1983;1(8338):1352-1355

    Not in our library10.1016/s0140-6736(83)92138-4

  86. 86.

    Leinikki P, Granström M-L, Santavuori P, Pettay O. Epidemiology of cytomegalovirus infections during pregnancy and infancy: a prospective study. Scand J Infect Dis. 1978;10(3):165-171

    Not in our library10.3109/inf.1978.10.issue-3.02

  87. 87.

    Dar L, Pati SK, Patro ARK,. Congenital cytomegalovirus infection in a highly seropositive semi-urban population in India. Pediatr Infect Dis J. 2008;27(9):841-843

    Not in our library10.1097/inf.0b013e3181723d55

  88. 88.

    Viswanathan R, Bafna S, Mergu R,. Direct saliva real-time polymerase chain reaction assay shows low birth prevalence of congenital cytomegalovirus infection in urban western India. Pediatr Infect Dis J. 2019;38(4):e65-e68

    Not in our library10.1097/inf.0000000000002094

  89. 89.

    Putri ND, Wiyatno A, Dhenni R,. Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia. Int J Infect Dis. 2019;86:31-39

    Not in our library10.1016/j.ijid.2019.06.009

  90. 90.

    Moteki H, Isaka Y, Inaba Y,. A rational approach to identifying newborns with hearing loss caused by congenital cytomegalovirus infection by dried blood spot screening. Acta Otolaryngol. 2018;138(8):708-712

    Not in our library10.1080/00016489.2018.1441545

  91. 91.

    Zhang X-W, Li F, Yu X-W, Shi X-W, Shi J, Zhang J-P. Physical and intellectual development in children with asymptomatic congenital cytomegalovirus infection: a longitudinal cohort study in Qinba mountain area, China. J Clin Virol. 2007;40(3):180-185

    Not in our library10.1016/j.jcv.2007.08.018

  92. 92.

    Tsai CH, Tsai FJ, Shih YT, Wu SF, Liu SC, Tseng YH. Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction. Acta Paediatr. 1996;85(10):1241-1243

    Not in our library10.1111/j.1651-2227.1996.tb18237.x

  93. 93.

    Sohn YM, Park KI, Lee C, Han DG, Lee WY. Congenital cytomegalovirus infection in Korean population with very high prevalence of maternal immunity. J Korean Med Sci. 1992;7(1):47-51

    Not in our library10.3346/jkms.1992.7.1.47

  94. 94.

    Wang S, Wang T, Zhang W,. Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China. Medicine (Baltimore). 2017;96(5):e6007

    Not in our library10.1097/md.0000000000006007

  95. 95.

    Yamada H, Tanimura K, Fukushima S,. A cohort study of the universal neonatal urine screening for congenital cytomegalovirus infection. J Infect Chemother. 2020;26(8):790-794

    Not in our library10.1016/j.jiac.2020.03.009

  96. 96.

    Koyano S, Inoue N, Oka A,; Japanese Congenital Cytomegalovirus Study Group. Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study. BMJ Open. 2011;1(1):e000118

    Not in our library10.1136/bmjopen-2011-000118

  97. 97.

    Numazaki K, Fujikawa T. Chronological changes of incidence and prognosis of children with asymptomatic congenital cytomegalovirus infection in Sapporo, Japan. BMC Infect Dis. 2004;4(1):22

    Not in our library10.1186/1471-2334-4-22

  98. 98.

    Endo T, Goto K, Ito K,. Detection of congenital cytomegalovirus infection using umbilical cord blood samples in a screening survey. J Med Virol. 2009;81(10):1773-1776

    Not in our library10.1002/jmv.21594

  99. 99.

    Uchida A, Tanimura K, Morizane M,. Clinical factors associated with congenital cytomegalovirus infection: a cohort study of pregnant women and newborns. Clinical Infectious Diseases.2020;71(11):2833-2839

    Not in our library10.1093/cid/ciz1156

  100. 100.

    Yamaguchi A, Oh-Ishi T, Arai T,. Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study. BMJ Open. 2017;7(1):e013810

    Not in our library10.1136/bmjopen-2016-013810

  101. 101.

    Torii Y, Yoshida S, Yanase Y,. Serological screening of immunoglobulin M and immunoglobulin G during pregnancy for predicting congenital cytomegalovirus infection. BMC Pregnancy Childbirth. 2019;19(1):205

    Not in our library10.1186/s12884-019-2360-1

  102. 102.

    Yamagishi Y, Miyagawa H, Wada K,. CMV DNA detection in dried blood spots for diagnosing congenital CMV infection in Japan. J Med Virol. 2006;78(7):923-925

    Not in our library10.1002/jmv.20642

  103. 103.

    Kamada M, Komori A, Chiba S, Nakao T. A prospective study of congenital cytomegalovirus infection in Japan. Scand J Infect Dis. 1983;15(3):227-232

    Not in our library10.3109/inf.1983.15.issue-3.01

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    Pellegrinelli L, Alberti L, Pariani E, Barbi M, Binda S. Diagnosing congenital cytomegalovirus infection: don’t get rid of dried blood spots. BMC Infect Dis. 2020;20(1):217

    Not in our library10.1186/s12879-020-4941-z

  105. 105.

    Viechtbauer W, Cheung MWL. Outlier and influence diagnostics for meta-analysis. Res Synth Methods. 2010;1(2):112-125

    Not in our library10.1002/jrsm.11

  106. 106.

    Lanzieri TM, Dollard SC, Bialek SR, Grosse SD. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis. 2014;22:44-48

    Not in our library10.1016/j.ijid.2013.12.010

  107. 107.

    Paulson JN, Williams BL, Hehnly C,. Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. Sci Transl Med. 2020;12(563):eaba0565

    Not in our library10.1126/scitranslmed.aba0565

  108. 108.

    Olusanya BO, Luxon LM, Wirz SL. Benefits and challenges of newborn hearing screening for developing countries. Int J Pediatr Otorhinolaryngol. 2004;68(3):287-305

    Not in our library10.1016/j.ijporl.2003.10.015

  109. 109.

    Falconer O, Newell M-L, Jones CE. The effect of human immunodeficiency virus and cytomegalovirus infection on infant responses to vaccines: a review. Front Immunol. 2018;9:328

    Not in our library10.3389/fimmu.2018.00328

  110. 110.

    Afran L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: a growing population with a vulnerable immune system?Clin Exp Immunol. 2014;176(1):11-22

    Not in our library10.1111/cei.12251

  111. 111.

    Barber V, Calvert A, Vandrevala T,. Prevention of acquisition of cytomegalovirus infection in pregnancy through hygiene-based behavioral interventions: a systematic review and gap analysis. Pediatr Infect Dis J. 2020;39(10):949-954

    Not in our library10.1097/inf.0000000000002763

  112. 112.

    Mack I, Burckhardt MA, Heininger U, Prüfer F, Schulzke S, Wellmann S. Symptomatic congenital cytomegalovirus infection in children of seropositive women. Front Pediatr. 2017;5:134

    Not in our library10.3389/fped.2017.00134

  113. 113.

    Coppola T, Mangold JF, Cantrell S, Permar SR. Impact of maternal immunity on congenital cytomegalovirus birth prevalence and infant outcomes: a systematic review. Vaccines (Basel). 2019;7(4):E129

    Not in our library10.3390/vaccines7040129

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    Short- and long-term impact of vaccination against cytomegalovirus: a modeling study · 2020
    Not checked
  115. 115.

    Adler SP, Finney JW, Manganello AM, Best AM. Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: a randomized controlled trial. Pediatr Infect Dis J. 1996;15(3):240-246

    Not in our library10.1097/00006454-199603000-00013

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    Prevention of Primary Cytomegalovirus Infection in Pregnancy · 2015
    Not checked
  117. 117.

    Vauloup-Fellous C, Picone O, Cordier A-G,. Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? results of a 3-year prospective study in a French hospital. J Clin Virol. 2009;46(suppl 4):S49-S53

    Not in our library10.1016/j.jcv.2009.09.003

  118. 118.

    Adler SP, Finney JW, Manganello AM, Best AM. Prevention of child-to-mother transmission of cytomegalovirus among pregnant women. J Pediatr. 2004;145(4):485-491

    Not in our library10.1016/j.jpeds.2004.05.041

  119. 119.

    Cannon MJ, Stowell JD, Clark R,. Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children. BMC Infect Dis. 2014;14(1):569

    Not in our library10.1186/s12879-014-0569-1

  120. 120.

    Dobbins GC, Patki A, Chen D,. Association of CMV genomic mutations with symptomatic infection and hearing loss in congenital CMV infection. BMC Infect Dis. 2019;19(1):1046

    Not in our library10.1186/s12879-019-4681-0

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