Dataset Information

Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study.

ABSTRACT:

Introduction

Most 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.

Methods

To 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.

Results

A 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.

Conclusion

Without 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.

SUBMITTER: Chiereghin A

PROVIDER: S-EPMC9298552 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceCongenital 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.ObjectiveTo estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system.Design, setting, and participantsA 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 measuresCost, 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.ResultsIncidence 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 relevanceTo 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.

Project description:ObjectiveTo develop and internally validate a noninvasive method for the prediction of congenital cytomegalovirus (CMV) infection after primary maternal CMV infection.MethodsWe conducted a secondary analysis of a multicenter randomized placebo-controlled trial of CMV hyperimmune globulin to prevent congenital infection. Women were eligible if they had primary CMV infection, defined as detectable plasma CMV-specific immunoglobulin (Ig)M and CMV-specific IgG with avidity less than 50% before 24 weeks of gestation or IgG seroconversion before 28 weeks, and were carrying a singleton fetus without ultrasonographic findings suggestive of CMV infection. Antibody assays were performed in a single reference laboratory. Congenital infection was defined as CMV detection in amniotic fluid, neonatal urine or saliva, or postmortem tissue. Using backward elimination, we developed logit models for prediction of congenital infection using factors known at randomization. The performance of the model was assessed using leave-one-out cross-validation (a method of internal validation).ResultsOf 399 women enrolled in the trial, 344 (86%) had informative data for this analysis. Congenital infection occurred in 68 pregnancies (20%). The best performing model included government-assisted insurance, IgM index 4.5 or higher, IgG avidity less than 32%, and whether CMV was detectable by polymerase chain reaction in maternal plasma at the time of randomization. Cross-validation showed an average area under the curve of 0.76 (95% CI 0.70-0.82), indicating moderate discriminatory ability. More parsimonious one-, two-, and three-factor models performed significantly less well than the four-factor model. Examples of prediction with the four-factor model: for a woman with government-assisted insurance, avidity less than 32%, IgM index 4.5 or higher, and detectable plasma CMV, probability of congenital infection was 0.69 (95% CI 0.53-0.82); for a woman with private insurance, avidity 32% or greater, IgM index less than 4.5, and undetectable plasma CMV, probability of infection was 0.03 (95% CI 0.02-0.07).ConclusionWe developed models to predict congenital CMV infection in the presence of primary maternal CMV infection and absence of ultrasonographic findings suggestive of congenital infection. These models may be useful for patient counseling and decision making.

Project description:BackgroundCongenital cytomegalovirus infection following maternal primary cytomegalovirus infection affects approximately 0.4% of newborns in the United States but may be hard to diagnose prenatally.ObjectiveTo evaluate the current sensitivity and specificity of amniocentesis in detecting congenital cytomegalovirus infection.Study designSecondary analysis of a multicenter randomized placebo-controlled trial designed to evaluate whether cytomegalovirus hyperimmune globulin reduces congenital cytomegalovirus infection in neonates of individuals diagnosed with primary cytomegalovirus infection before 24 weeks of gestation. At randomization, subjects had no clinical evidence of fetal infection. Eligible subjects were randomized to monthly infusions of cytomegalovirus hyperimmune globulin or placebo until delivery. Although not required by the trial protocol, amniocentesis following randomization was permitted. The fetuses and neonates were tested for the presence of cytomegalovirus at delivery. Comparisons were made between those with and without amniocentesis and between those with cytomegalovirus-positive and negative results, using chi-square or Fisher exact test for categorical variables and the Wilcoxon rank sum test or t test for continuous variables. A P value of <.05 was considered significant.ResultsFrom 2012 to 2018, 397 subjects were included, of whom 55 (14%) underwent amniocentesis. Cytomegalovirus results were available for 53 fetuses and neonates. Fourteen amniocenteses were positive (25%). Gestational age at amniocentesis was similar between those with and without cytomegalovirus present, as was the interval between maternal diagnosis and amniocentesis. The prevalence of fetal or neonatal infection was 26% (14/53). The neonates of all 12 subjects with a positive amniocentesis and available results had cytomegalovirus infection confirmed at delivery, as did 2 neonates from the group of 41 subjects with a negative amniocentesis, with a sensitivity of 86% (95% confidence interval, 57-98), specificity of 100% (95% confidence interval, 91-100), positive predictive value of 100% (95% confidence interval, 74-100), and negative predictive value of 95% (95% confidence interval, 83-99). Amniocentesis-positive pregnancies were delivered at an earlier gestational age (37.4 vs 39.6 weeks; P<.001) and had lower birthweights (2583±749 vs 3428±608 g, P=.004) than amniocentesis-negative pregnancies.ConclusionAmniocentesis results are an accurate predictor of congenital cytomegalovirus infection.

Project description:Congenital cytomegalovirus (CMV) infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. Here, we have assessed in a prospective study conducted on children in two French hospitals from 2016 to 2019, infection severity and olfactory performance after congenital CMV infection. Children with congenital CMV infection aged 3 to 10 years and healthy controls (CTL) matched for age and sex to CMV children symptomatic at birth (sCMV) were enrolled. Olfactory discrimination was assessed using mono-odorants and binary mixtures. Data were analyzed for 54 children with PCR-confirmed congenital CMV infection, including 34 sCMV (median [IQR] age, 6 [5-8] years; 19 [55.9%] male), and 20 CMV asymptomatic at birth (aCMV, median [IQR] age, 4 [3-6] years; 12 [60.0%] male). sCMV were compared to 34 CTL children. Olfactory scores in CMV-infected children were independent from vestibular deficit and hearing loss. The olfactory score was efficient to discriminate between CTL and sCMV for children > 6 years (area under the receiver-operating characteristic curve (AUC, 0.85; P = 0.0006), but not for children < 7 years. For children > 6 years, the proportion of children with total olfactory score < 4 differed between sCMV and CTL groups (91.2% and 18.7%, P < 0.001), but not between aCMV and age-matched healthy control groups. Conclusion: Congenital CMV infection is associated with reduced olfactory performance in children with infection symptoms at birth. Clinical trial registration: NCT02782988 (registration date: May 26, 2016). What is Known: •Congenital cytomegalovirus infection leads to olfactory bulb lesions in the fetus, yet little is known about its impact on olfaction after birth. •Depending on neonatal clinical presentation, children are either categorized as having a symptomatic or asymptomatic infection at birth. What is New: •Congenital cytomegalovirus infection is associated with reduced olfactory performance in children with infection symptoms at birth.

Project description:ImportanceCongenital 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.ObjectivesTo 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 sourcesMEDLINE/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 selectionStudies 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 synthesisPreferred 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 measuresBirth prevalence of cCMV ascertained through universal screening of infants younger than 3 weeks for CMV from urine, saliva, or blood samples.ResultsSeventy-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 relevanceIn 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.