Utility of newborn screening cards for detecting CMV infection in cases of stillbirth

Howard, Jonathan; Hall, Beverly A.; Brennan, Lyndall Eve; Arbuckle, Susan; Craig, Maria E.; Graf, Nicole; Rawlinson, William D.

doi:10.1016/j.jcv.2008.12.013

Cited by 20 publications

(15 citation statements)

References 52 publications

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“…The extraction of CMV DNA from newborn screening cards was performed as previously reported 11 with few modifications 8 . Three disks of 3 mm diameter were prepared from newborn screening cards using a Wallac DBS Puncher (product number 1296‐071) (PerkinElmer, Turku, Finland).…”

Section: Methodsmentioning

confidence: 99%

“…For extraction of CMV DNA from urine samples, a MagNA Pure semi‐automated nucleic acid extraction machine (Roche Applied Science, Mannheim, Germany) was used. The samples were stored at − 20°C before polymerase chain reaction (PCR) testing for the presence of the CMV glycoprotein gene gp58, and for the major immediate gene 8 , 12 …”

Section: Methodsmentioning

confidence: 99%

“…Since initial results for 1999–2003 were reported, 6 newborn hearing screening has been introduced in most Australian states (Box 1), and therapeutic studies have been published 7 . New diagnostic techniques for cCMV infection allow for retrospective diagnosis of cCMV infection 8 , 9 . For this reason, we compare data from two 5‐year periods: 1999–2003 and 2004–2009.…”

Section: Boxmentioning

confidence: 99%

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Congenital cytomegalovirus — time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification

McMullan

Palasanthiran

Jones

et al. 2011

Medical Journal of Australia

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Objectives: To report on the burden of disease in Australian infants with congenital cytomegalovirus (cCMV) infection in the era of neonatal hearing screening and improved diagnostic techniques. Design, setting and participants: National data were collected from across Australia via the Australian Paediatric Surveillance Unit (APSU) with monthly reporting by > 1000 clinicians between January 1999 and February 2009. For each reported case, data on investigations and epidemiological and clinical features were analysed. Detailed clinical reviews were performed on 42 infants in two Sydney tertiary paediatric infectious diseases clinics. Results: There were 195 infants with cCMV identified, including 126 definite and 69 probable cases. Of these, 175 (90%) were symptomatic and only 15 were treated with antiviral agents. Identification was delayed beyond 60 days of age in 30 cases (15%). During the period of study, neonatal hearing screening was introduced for most Australian infants. Detection of hearing loss increased from 19% of cCMV cases in 1999–2003 to 31% in 2004–2009. Of 42 infants whose cases were reviewed in detail, 33 (79%) had symptomatic disease. DNA detection of CMV, using polymerase chain reaction testing of newborn screening cards, was useful in retrospective identification, and was strongly correlated with the presence of clinical sequelae (15/18; 83%). Conclusions: Congenital CMV is underdiagnosed, infrequently treated, and often manifests as isolated hearing loss. Delayed diagnoses both before and after the introduction of neonatal hearing screening represent missed treatment and management opportunities and are likely to lead to poorer, life‐long outcomes for these children. Retrospective analysis of newborn screening cards for CMV should be undertaken for infants with sensorineural hearing loss, to identify unrecognised cCMV.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Boxmentioning

confidence: 99%

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Congenital cytomegalovirus — time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification

McMullan

Palasanthiran

Jones

et al. 2011

Medical Journal of Australia

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“…For example, it is an important public health problem [1] whose incidence is similar to the combined incidence of all metabolic or endocrine disorders in the current US core screening panel [9,30]; there is a presymptomatic or early symptomatic stage [31]; the test would generally be acceptable to the population [32], and much is known of the natural history of the condition [22]. Furthermore, there is reason to believe that suitable screening technology, such as CMV DNA testing from dried blood spots (DBS), saliva, or urine, will be available soon [33–38]. On the other hand, potential harms may include increased parental stress or altered parent–child relationships from a false positive or true positive screening result (approximately three fourths of truly positive children never develop sequelae) [39], inappropriate antiviral treatment, or added costs from unnecessary medical visits or tests [40].…”

Section: Introductionmentioning

confidence: 99%

Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?

Cannon

Griffiths²,

Aston

et al. 2014

Reviews in Medical Virology

179

189

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SUMMARY Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions. Copyright © 2014 John Wiley & Sons, Ltd.

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“…A study from Australia [52] reported that 9% of blood samples taken from stillbirths by cardiac puncture were PCR positive for CMV. A recent study from Greece using PCR, showed significantly increased levels of CMV (16%) in the placentas of stillbirths compared to controls (3%) [53].…”

Section: Resultsmentioning

confidence: 99%

Effectiveness of interventions to screen and manage infections during pregnancy on reducing stillbirths: a review

et al. 2011

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BackgroundInfection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality.MethodsWe undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model.ResultsA total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55).ConclusionsThe clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.

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Utility of newborn screening cards for detecting CMV infection in cases of stillbirth

Cited by 20 publications

References 52 publications

Congenital cytomegalovirus — time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification

Congenital cytomegalovirus — time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification

Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?

Effectiveness of interventions to screen and manage infections during pregnancy on reducing stillbirths: a review

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