Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

Yamaguchi, Akira; Oh‐ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nobuaki; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, T; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

doi:10.1136/bmjopen-2016-013810

Cited by 46 publications

(54 citation statements)

References 29 publications

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“…a Sex from one case could not be determined from CMV-negative group. The 5.8% prevalence of congenital CMV infection found in our study from an urban birth cohort in Indonesia is higher compared to other newborn screening studies in Finland (0.2%) (Puhakka et al, 2018), Japan (0.3%) (Yamaguchi et al, 2017), Iran (0.5%) (Karimian et al, 2016), Panama (0.6%) (Estripeaut et al, 2007), China (0.7%) (Wang et al, 2017), Brazil (1.1%) (Mussi-Pinhata et al, 2009), India (2.1%) (Dar et al, 2008), and Nigeria (3.8%) (Olusanya et al, 2015), but similar to those observed in a peri-urban birth cohort in Gambia (5.4%) (van der Sande et al, 2007) and in a highrisk population in China (6.1%) (Zhang et al, 2007). Although maternal CMV immune status was not assessed in our study, an earlier report on healthy female blood donors has documented a 97.7% CMV seroprevalence in metropolitan Jakarta (Noviar et al, 2017).…”

Section: Discussioncontrasting

confidence: 84%

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia

Putri

Wiyatno

Dhenni

et al. 2019

International Journal of Infectious Diseases

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Objectives:Little is known about the birth prevalence and characteristics of congenital cytomegalovirus (CMV) infection in developing countries. To determine the prevalence and characteristics of congenital CMV infection in Indonesia, we conducted a prospective study in an urban birth cohort of neonates at a national referral hospital in 2016À2017, Jakarta, Indonesia. Methods: Consecutively born neonates were screened for the presence of CMV by using pan-herpesvirus nested-PCR and Sanger sequencing in saliva and/or urine specimens. Both the neonatal clinical findings as well as maternal characteristics were also evaluated. Results: From a total of 411 newborns screened, congenital CMV infection was confirmed in 5.8% of the neonates. These CMV-positive newborns were more likely to have ventriculomegaly and thrombocytopenia compared to CMV-negative neonates. Notably, 67% CMV-positive neonates in our study had clinical findings that required medical intervention, from which only nine presented with symptoms suggestive of congenital CMV infection. Furthermore, congenital CMV infected babies were almost four times more likely to be born to mothers that had placenta previa and placental abruption. Conclusions: Our work highlights the high prevalence of congenital CMV infection in neonates born in one of the biggest referral hospitals in metropolitan Jakarta, Indonesia.

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Section: Discussioncontrasting

confidence: 84%

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia

Putri

Wiyatno

Dhenni

et al. 2019

International Journal of Infectious Diseases

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“…Blood collection is inconvenient and painful for neonates, while urine and BM samples are collected more easily; therefore, urine and BM CMV‐DNA tests are recommended for primary screening of neonates with a CMV infection. Moreover, CMV intermittently releases toxins, and CMV samples not in the toxin‐releasing state will not conform to the clinical diagnosis; therefore, repeated, continuous, and multiple tests are suggested to improve the detection rate of CMV infection …”

Section: Discussionmentioning

confidence: 99%

High prevalence of breastmilk‐acquired cytomegalovirus infection in jaundiced infants

Hou¹,

Liu²,

Fan³

et al. 2020

Clinical Laboratory Analysis

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Background Our objective was to evaluate the prevalence and different diagnostic methods of breastmilk (BM)‐acquired cytomegalovirus (CMV) infection in a pathologically jaundiced cohort. Methods A total of 400 infants confirmed with pathological jaundice at The People's Hospital of Qingyang City were screened for BM‐acquired CMV infection between February 2018 and February 2019. A total of 300 infants were finally enrolled in our study. CMV infection was confirmed by detecting both CMV‐DNA in various samples using FQ‐PCR and CMV‐IgM with chemiluminescence. Clinical and other laboratory data were collected from these infants during their hospitalization or regular visits. Results Ninety‐eight (32.67%) subjects were confirmed to be BM CMV‐DNA–positive, and 18 (18.37%) were diagnosed with a BM‐acquired CMV infection. All 18 (100%) infants with a BM‐acquired CMV infection were CMV‐DNA–positive in urine, while 5 (27.78%) cases and 11 (61.11%) cases were confirmed in plasma and peripheral blood mononuclear cells (PBMCs), respectively. Only 6 (33.33%) infants were CMV‐IgM–positive. Birthweight, direct bilirubin, aspartate aminotransferase, and the viral load in BM of the BM‐acquired CMV group were higher than those in the non‐infected group (P < .05). Low birthweight and viral load in BM were risk factors for BM‐acquired CMV infection. Detecting CMV‐DNA in urine samples exhibited better performance than the other methods for screening BM‐acquired CMV infections. Conclusions Our study found a high prevalence of BM‐acquired CMV infection in jaundiced infants, and detecting CMV‐DNA in a urine sample was the most sensitive method for disease screening.

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“…Congenital CMV (cCMV) infection increases a child's risk for long-term health problems including hearing loss, and newborn screening for cCMV has been advocated [32]. The mean CMV DNA copy number in newborns with cCMV was 1790 copies/µ L and it was much higher in those newborns that had both sensorineural hearing loss and cCMV [33]. Using a prior cartridge and instrument-based heater design, we have shown feasibility of CMV amplification in a DMF system using saliva samples [34].…”

Section: S Per Cycle)mentioning

confidence: 99%

Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients

Sista

Nuffer

et al. 2020

Diagnostics

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“Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is an excellent example of clinical care that is not yet customized to the needs of children, especially newborns. Cumulative blood loss resulting from clinical testing does not typically impact critically ill adult patients, but can quickly escalate in children, leading to iatrogenic anemia and related comorbidities. Moreover, the tests prioritized for rapid, near-patient testing in adults are not always the most clinically relevant tests for children or newborns. This report describes the development of a digital microfluidic testing platform and associated clinical assays purposely curated to address current shortcomings in pediatric laboratory testing by using microliter volumes (<50 µL) of samples. The automated platform consists of a small instrument and single-use cartridges, which contain all reagents necessary to prepare the sample and perform the assay. Electrowetting technology is used to precisely manipulate nanoliter-sized droplets of samples and reagents inside the cartridge. To date, we have automated three disparate types of assays (biochemical assays, immunoassays, and molecular assays) on the platform and have developed over two dozen unique tests, each with important clinical application to newborns and pediatric patients. Cell lysis, plasma preparation, magnetic bead washing, thermocycling, incubation, and many other essential functions were all performed on the cartridge without any user intervention. The resulting assays demonstrate performance comparable to standard clinical laboratory assays and are economical due to the reduced hands-on effort required for each assay and lower overall reagent consumption. These capabilities allow a wide range of assays to be run simultaneously on the same cartridge using significantly reduced sample volumes with results in minutes.

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Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

Cited by 46 publications

References 29 publications

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia

High prevalence of breastmilk‐acquired cytomegalovirus infection in jaundiced infants

Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients

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