Congenital Cytomegalovirus

Luck, Suzanne; Wieringa, Jantien W; Blázquez‐Gamero, Daniel; Henneke, Philipp; Schuster, Katharina; Butler, Karina; Capretti, Maria Grazia; Cilleruelo, María José; Curtis, Nigel; Garofoli, Francesca; Heath, Paul T; Iosifidis, Εlias; Klein, Nigel; Lombardi, G; Lyall, Hermione; Nieminen, Tea; Pajkrt, Dasja; Papaevangelou, Vassiliki; Posfay‐Barbe, Klara M.; Puhakka, Laura; Roilides, Emmanuel; Rojo, Pablo; Saavedra-Lozano, Jesús; Shah, Teshri; Sharland, Mike; Saxén, Harri; Vossen, Ann C.T.M.

doi:10.1097/inf.0000000000001763

Cited by 230 publications

(214 citation statements)

References 56 publications

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“…Testing is recommended for those who have any condition that might be indicative of intrauterine CMV infection (2). Traditionally, viral isolation and culture from urine or saliva was the standard for diagnosing cCMV infection (53).…”

Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

“…It should be noted that if the diagnosis is made after the first 2-3 weeks of life (2,9), infection may have been postnatally acquired and attributable to infected breast milk from a seropositive mother (56), rather than cCMV. In this instance, congenital infection must be confirmed by detection of CMV from a sample taken at birth.…”

Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

“…Stored DBS can be used to diagnose cCMV retrospectively (2). In some countries (e.g., Germany), the use of DBS for retrospective diagnosis or screening of newborns is hampered by the destruction of samples after 3 months (62) due to data protection requirements.…”

Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

“…Currently, valganciclovir treatment is recommended based on severity or number of symptoms. A European expert consensus statement recommends that treatment with oral valganciclovir (intravenous ganciclovir under certain circumstances) is only for those with: evidence of central nervous system disease; evidence of life-threatening disease, severe single-organ disease or multi-organ involvement; "moderate" cCMV disease once discussed on a case-by-case basis with a clinician with experience of managing infants with cCMV (2). The informal International Congenital Cytomegalovirus Recommendations Group recommend oral valganciclovir treatment for those neonates with "moderately" to "severely" symptomatic cCMV disease (9).…”

Section: What Are the Gaps In Our Understanding?mentioning

confidence: 99%

“…Maternal primary and non-primary infection (exogenous reinfection with a different strain or endogenous viral reactivation) of cytomegalovirus (CMV) during pregnancy can result in in utero transmission to the fetus (1). Infants can be categorized as symptomatic or asymptomatic based on clinical symptoms/signs (Table 1) (2). Approximately 11% of live-born infants born with congenital CMV (cCMV) have abnormal clinical findings at birth (symptomatic) (3).…”

Section: Introductionmentioning

confidence: 99%

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Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

et al. 2020

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Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education.

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Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

Section: Diagnosis and Screening Of Neonatal Infectionmentioning

confidence: 99%

Section: What Are the Gaps In Our Understanding?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

et al. 2020

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Risk Factors for Hearing Loss at Birth in Newborns With Congenital Cytomegalovirus Infection

Cuyper

Acke

Keymeulen

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceWith a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus (cCMV) infection is a major cause of congenital nonhereditary sensorineural hearing loss. Despite the large amount of research on cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss.ObjectiveTo identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth.Design, Setting, and ParticipantsThis cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded.Main Outcomes and MeasuresPrimary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors. Binary logistic regression was performed to identify independent risk factors for congenital hearing loss in newborns with cCMV. Effect sizes were measured using Hedges g, odds ratio, or Cramer V.ResultsOf the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection. A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss. The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7; 95% CI, 1.9-23.9), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6; 95% CI, 1.5-14.1), and seroconversion in the first trimester (aOR, 3.1; 95% CI, 1.1-9.3). Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss (median [IQR] viral load, 447.0 [39.3-2345.8] copies per milliliter of sample [copies/mL] vs 1349.5 [234.3-14 393.0] copies/mL; median difference, −397.0 [95% CI, −5058.0 to 174.0] copies/mL).Conclusions and RelevanceFindings of this cross-sectional study suggest that newborns with cCMV infection and petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Clinicians may use these risk factors to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. Moreover, linking clinical features to hearing loss may provide new insights into the pathogenesis of cCMV-related hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.

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Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection

De Cuyper,

Acke,

Keymeulen

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportanceCongenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking.ObjectiveTo identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss.Design, Setting, and ParticipantsThis multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023.Main Outcomes and MeasuresPrimary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g).ResultsOf the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss.Conclusions and RelevanceFindings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

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Congenital Cytomegalovirus

Cited by 230 publications

References 56 publications

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts

Risk Factors for Hearing Loss at Birth in Newborns With Congenital Cytomegalovirus Infection

Risk Factors for Natural Hearing Evolution in Newborns With Congenital Cytomegalovirus Infection

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