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Does Screening for Congenital Cytomegalovirus at Birth Improve

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Does Screening for Congenital Cytomegalovirus at Birth Improve Review Does screening for congenital cytomegalovirus at birth improve longer term hearing outcomes? Cathie Hilditch,1,2 Bianca Liersch,3 Nicola Spurrier,4,5 Emily J Callander,6 Celia Cooper,7 Amy K Keir1,2,8 ► Additional material is ABStract What is already known on this topic? published online only. To view Currently, the diagnosis of congenital cytomegalovirus please visit the journal online (cCMV) infection in most highly resourced countries (http:// dx. doi. org/ 10. 1136/ Congenital cytomegalovirus (cCMV) is the is based on clinical suspicion alone. This means only ► archdischild- 2017- 314404). largest non-genetic cause of sensorineural a small proportion of cCMV infections are diagnosed. 1Healthy Mothers, Babies hearing loss (SNHL) in children. Identification, through either universal or targeted and Children Theme, South cCMV-related SNHL is progressive in more than screening of asymptomatic newborns with cCMV, who ► Australian Health and Medical 50% of cases, and affected infants are likely to Research Institute, North would previously have gone undiagnosed, would allow pass their newborn hearing screen. Adelaide, South Australia, for potential early treatment with antiviral therapy, Australia ongoing audiological surveillance and early intervention 2Robinson Research Institute and the Adelaide Medical if sensorineural hearing loss (SNHL) is identified. This School, University of Adelaide, paper systematically reviews published papers examining North Adelaide, South Australia, the potential benefits of targeted and universal screening What this study adds? Australia 3 for newborn infants with cCMV. We found that the Children’s Audiology Service, ► Identification, through either universal or Women’s and Children’s Health treatment of these infants with antiviral therapy remains Network, North Adelaide, South controversial, and clinical trials are currently underway targeted screening of asymptomatic newborns Australia, Australia to provide further answers. The potential benefit of with cCMV, who would previously have gone 4South Australian Department earlier identification and intervention (eg, amplification undiagnosed. of Health and Ageing, Adelaide, and speech therapy) of children at risk of later-onset ► This would allow for potential early treatment South Australia, Australia with antiviral therapy if other symptoms are 5Department of Paediatrics and SNHL identified through universal screening is, however, Child Health, Flinders University clearer. identified, ongoing audiological surveillance of South Australia, Adelaide, and early intervention if SNHL develops. South Australia, Australia 6Australian Institute of Tropical Health and Medicin, James INTRODUCTION Cook University, Townsville, Definitions Queensland, Australia Congenital cytomegalovirus (cCMV) is the 7 most common intrauterine infection in highly The definition of symptomatic cCMV infection Department of Infectious 6 Diseases, Women’s and resourced countries, occurring in 0.4%–0.64% of varies in the literature. For the purposes of this Children’s Hospital, North all births.1 2 The true incidence of the disease is review, children are classified as symptomatic if Adelaide, South Australia, likely to be higher, as up to 90% of infected infants they have acute signs present at birth. These signs Australia include petechiae, jaundice, hepatosplenomegaly, 8Department of Neonatal are asymptomatic at birth. Up to 10%–25% of all Medicine, Women’s and childhood sensorineural hearing loss (SNHL) is microcephaly (head circumference <2nd centile Children’s Hospital, North attributed to cCMV infection, making cytomegalo- or 2 SD below the mean), SNHL, small for gesta- Adelaide, South Australia, virus (CMV) the largest non-genetic cause of SNHL tional age (birth weight <10th centile), chorioret- Australia in children.3 cCMV-related SNHL is progressive in initis and seizures. Targeted screening is defined as more than 50% of cases.1 Identification, through screening limited to those children having failed Correspondence to their newborn hearing screen. Dr Amy K Keir, Department of either universal or targeted screening of asymptom- Neonatal Medicine, Women’s atic newborns with cCMV, who would previously and Children’s Hospital, North have gone undiagnosed, would allow for potential Search strategy Adelaide, SA, 5006; early treatment with antiviral therapy, ongoing MEDLINE via Ovid (1946 to 3 June 2017), Embase amy. keir@ adelaide. edu. au audiological surveillance and early intervention if via Ovid (1974 to 11 July 2017) and the Mater- Received 31 October 2017 SNHL is identified. Early identification of hearing nity and Infant Care Database (1971 to June 2017) Revised 11 April 2018 loss is associated with improved language develop- were searched for relevant articles. Full search strat- Accepted 12 April 2018 ment.4 Antiviral therapy has been shown to reduce egies and detailed results are availablein the online Published Online First supplementary data. A total of 124 articles, after 28 April 2018 hearing deterioration in symptomatic children with cCMV if started within the first month of birth.5 removal of duplicates, were found and screened Our review will address the structured clinical by title and abstract. Twenty-nine full-text articles question ‘In asymptomatic newborn infants in were subsequently reviewed, and six articles were highly resourced countries (P), does screening for included as relevant to the clinical question. These cCMV using saliva PCR testing (I) compared to are summarised in tables 1 and 2. To cite: Hilditch C, Liersch B, not screening (C) allow for earlier identification of Spurrier N, et al. infants with CMV-related SNHL and effective early Newborn screening for cCMV infection Arch Dis Child intervention/treatment?’. It will also assess cCMV To allow for better understanding of whether 2018;103:988–992. screening against the WHO screening criteria. cCMV may be an appropriate condition to screen 988 Hilditch C, et al. Arch Dis Child 2018;103:988–992. doi:10.1136/archdischild-2017-314404 Review Table 1 Universal screening Study type (level of Citation, country Study group evidence)* Outcome Key result Comments Leruez-Ville et al,19 11 740 neonates Prospective study (3). Prevalence of cCMV 51 newborns had a positive 9/44 (20%) of cCMV-positive infants France screened with CMV was 0.37% in this screening confirmed infected on were considered symptomatic. saliva PCR. population. subsequent samples. The four infants with hearing loss were Four of these infants with cCMV included in the larger group of nine were identified to have either symptomatic infants; however, the paper unilateral or bilateral hearing loss. does not indicate whether they had any other features of symptomatic cCMV. Barkai et al,20 9845 infants screened Prospective study (3). Prevalence of cCMV 56 infants had a positive saliva All 47 infants passed hearing testing Israel for cCMV by salivary was 0.49% in this assay. 47 of these cases were successfully prior to hospital discharge. PCR. population. confirmed by urine PCR and culture. One infant with a hearing loss was Two infants were diagnosed with detected on further testing done within hearing impairment (late onset in 23 weeks of age. Another infant was one case). diagnosed with unilateral SNHL at 3 months of age. CMV, cytomegalovirus; cCMW, congenital cytomegalovirus; SNHL, sensorineural hearing loss. for in all newborn infants, it will be assessed against the WHO infrastructures. Confirmation of the diagnosis of cCMV would criteria (box 1): need to be made and infants then assessed by a paediatrician or infectious diseases physician. Ongoing follow-up of symptom- Important health problem atic infants with cCMV is currently the responsibility of general cCMV is recognised as the most common preventable infective paediatricians, infectious disease physicians, audiologists and cause of SNHL in children and is the leading non-genetic cause allied health professionals. of SNHL. It is a significant public health problem.7 8 Asymptomatic newborns, identified solely through a universal cCMV screening programme, could either have normal or Accepted treatment or intervention for patients with recognised impaired hearing. The latter group would require paediatric, disease: antiviral therapy ear-nose-throat (ENT) surgical and audiological follow-up as Treatment of newborns with symptomatic cCMV with antiviral currently provided for infants with SNHL. In addition, they therapy has been shown to improve hearing and developmental would require closer monitoring of other aspects of develop- outcomes. There is evidence that the use of 6 weeks of ganci- ment during early childhood because of the increased risk of clovir improves or maintains hearing outcomes at 6 months subtle neurocognitive impairments associated with cCMV. if started within the first month of life.5 A subsequent study Asymptomatic newborns with normal hearing at birth but positive for CMV would also require initial medical review and demonstrated that 6 months of valganciclovir delivers more 7 sustained improvements in hearing and improves neurocognitive increased hearing surveillance. Approximately 50% of children 9 with SNHL due to cCMV will experience progressive hearing outcomes in newborns with cCMV. 7 In terms of evidence for treatment of infants with isolated loss. All children with cCMV should have their hearing tested SNHL and confirmed CMV and no other symptoms, there regularly in early childhood to ensure the early detection of have been no clinical
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