Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)

Leruez-Ville, Marianne; Chatzakis, Christos; Lilleri, Daniele; Blazquez-Gamero, Daniel; Alarcon, Ana; Bourgon, Nicolas; Foulon, Ina; Fourgeaud, Jacques; Gonce, Anna; Jones, Christine E.; Klapper, Paul; Krom, André; Lazzarotto, Tiziana; Lyall, Hermione; Paixao, Paulo; Papaevangelou, Vassiliki; Puchhammer, Elisabeth; Sourvinos, George; Vallely, Pamela; Ville, Yves; Vossen, Ann

doi:10.1016/j.lanepe.2024.100892

Cited by 5 publications

(1 citation statement)

References 73 publications

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“…Cytomegalovirus (CMV) is the most common congenital infection and the leading cause of childhood hearing loss, cognitive deficits, and visual impairment, with an estimated prevalence of 0.2-5% worldwide [1][2][3][4]. Congenital CMV infection (cCMV) can occur after maternal primary infection (MPI) or non-primary maternal infection (MNPI) [5,6]. Only 10 to 15 percent of the infected infants are born with clinical, laboratory, or imaging manifestations such as intrauterine growth retardation, microcephaly, intracranial calcifications, jaundice, hepatosplenomegaly, thrombocytopenia, and petechiae [4].…”

Section: Introductionmentioning

confidence: 99%

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

Izquierdo,

Guerra,

Reyes

et al. 2024

Viruses

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Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. Methods: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. Results: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22–0.84), with significantly higher rates (2.1%, 95% CI 0.58–5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31–4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23–37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). Conclusions: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

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Section: Introductionmentioning

confidence: 99%

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

Izquierdo,

Guerra,

Reyes

et al. 2024

Viruses

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In utero treatment of congenital cytomegalovirus infection with valganciclovir: an observational study on safety and effectiveness

Bourgon,

Lopez,

Fourgeaud

et al. 2024

Journal of Antimicrobial Chemotherapy

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Background The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease. Objectives We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir. Methods Retrospective cohort study of pregnant women and their symptomatic infected fetuses taking valganciclovir, 3 × 450 mg per day. All fetuses presented at least one prenatal feature on ultrasound. We assessed fetal/neonatal and maternal safety, as well as neonatal efficacy of treatment. The main outcome was neutropenia. Secondary outcomes included other haematological side effects, symptoms at birth and neonatal CMV-PCR was positive. Results Seventeen women with singleton pregnancies received valganciclovir from a median (IQR) of 27.1 (26.0–30.3) to 11.6 (6.5–12.9) weeks of gestation. No neonatal neutropenia was reported. One pregnancy was terminated for severe features. Three newborns (18%) were asymptomatic at birth, including one with negative CMV-PCR from blood and saliva. CMV-PCR was positive for 12/13 symptomatic newborns, with a median (IQR) log10 viral load of 3.36 (3.30–4.20), 4.03 (1.75–4.27) and 3.04 (0.00–3.40) log10 copies/mL in blood, urine and saliva, respectively. Conclusions Tertiary prevention by valganciclovir appears to be well tolerated for both fetus and mother. However, more extensive trials accompanied by long-term follow-up are needed.

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Cranial Ultrasound Findings in Infants With Congenital Cytomegalovirus Infection in a Universal Newborn Screening Study in Minnesota

Kruc,

Osterholm,

Holm

et al. 2024

Journal of the Pediatric Infectious Diseases Society

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Background Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016 – December 2022. Methods Newborns with cCMV infection (confirmed by urine CMV PCR following a positive screening saliva and/or dried blood spot result) underwent diagnostic evaluation, including cranial ultrasound (cUS), laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines. Results Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (n=10 infants) aligned with cUS cCMV-disease defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2 to 1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; p<0.0001). Conclusions Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although insufficient to define symptomatic disease, incidental findings were more common in infants with other manifestations of cCMV infection.

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Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)

Cited by 5 publications

References 73 publications

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

In utero treatment of congenital cytomegalovirus infection with valganciclovir: an observational study on safety and effectiveness

Cranial Ultrasound Findings in Infants With Congenital Cytomegalovirus Infection in a Universal Newborn Screening Study in Minnesota

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