Contribution of Breastfeeding to False-Positive Saliva Polymerase Chain Reaction for Newborn Congenital Cytomegalovirus Screening

Ross, Shannon A.; Michaels, Marian G.; Ahmed, Amina; Palmer, April; Sánchez, Pablo J.; Bernstein, David I.; Feja, Kristina N.; Stewart, Audra; Boppana, Suresh B.; Fowler, Karen B.

doi:10.1093/infdis/jiy057

Cited by 41 publications

(24 citation statements)

References 8 publications

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“…However, amounts of CMV DNA due to contamination with genital secretions or mother´s milk after breastfeeding should be smaller than CMV DNA levels resulting from cCMV infection. Consistently, participants with false positive saliva screening samples had significantly lower viral load levels than participants with confirmed congenital CMV infection (see above, [1,21,31]. The percentage of false positive screening results also differed largely between the studies varying from 7.5% to 41% of samples positive in the initial screen.…”

Section: Discussionmentioning

confidence: 71%

“…Contamination of neonatal saliva samples by CMV DNA present in genital secretions in the birth canal during delivery [10] or in the milk remaining from the last breast feeding [11,30] are possible reasons for that. Ross et al concluded that breastfeeding in the first weeks of life contributes to low but acceptable rates (0.03-0.14%) of false positive saliva PCR results [31]. However, amounts of CMV DNA due to contamination with genital secretions or mother´s milk after breastfeeding should be smaller than CMV DNA levels resulting from cCMV infection.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

et al. 2020

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The majority of congenital cytomegalovirus (cCMV) infections are asymptomatic at birth and therefore not diagnosed. Approximately 10-15% of these infants develop late-onset hearing loss and other developmental disorders. Implementation of a universal screening approach at birth may allow early initiation of symptomatic interventions due to a closer follow-up of infants at risk and offers the opportunity to consider treatment of late-onset disease. Realtime PCR assays for the detection of CMV DNA in buccal swab samples demonstrated feasibility and good clinical sensitivity in comparison to a rapid culture screening assay. Because most cCMV infections remain asymptomatic, a universal screening assay that stratifies CMV infected infants according to low and high risk of late-onset cCMV disease could limit the parental anxiety and reduce follow-up costs. We therefore developed and characterized a screening algorithm based on a highly-sensitive quantitative real-time PCR assay that is compatible with centralized testing of samples from universal screening and allows to determine CMV DNA load of saliva samples either as International Units (IU)/ml saliva or IU/10 5 cell equivalents. 18 of 34 saliva samples of newborns that tested positively by the screening algorithm were confirmed by detection of CMV DNA in blood and/or urine samples obtained during the first weeks of life. All screening samples that could not be confirmed had viral loads of <2.3x10 5 IU/ml saliva (median: 6.8x10 3) or 1.3x10 5 IU/10 5 cell equivalents (median: 4.0x10 2). The viral load of screening samples with confirmed cCMV infection ranged from 7.5x10 2 to 8.2x10 9 IU/ml saliva (median: 9.3x10 7) or 1.5x10 2 to 5.6x10 10 IU/10 5 cell equivalents (median: 3.5x10 6). Clinical follow-up of these newborns with confirmed cCMV infection should reveal whether the risk of late-onset cCMV disease correlates with CMV DNA load in early life saliva samples and whether a cutoff can

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

et al. 2020

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“…Concerns about false positive results with these samples have been raised because virus transmission during breastfeeding may occur. Several articles reported the excretion of this virus in the breast milk of healthy women [ 22 , 23 ]. To prevent these false-positive during screening programs an approach would be to instruct health professionals to collect the sample before the first breastfeeding, although this is not always possible.…”

Section: Discussionmentioning

confidence: 99%

Saliva pools for screening of human cytomegalovirus using real-time PCR

et al. 2020

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Human cytomegalovirus (HCMV) is the leading congenital infection agent in the world. The importance of screening this infection has been debated, as 10–15% of the asymptomatic newborns with HCMV at birth will present late sequelae. The aim of this study was to test the feasibility of using saliva pools from newborns in a screening program for congenital HCMV infection, in two Portuguese hospitals. The screening was based on the use of pools of 10 saliva samples for detection of viral DNA by real-time PCR. Whenever there was a positive pool, the samples were tested individually, and for each positive sample the result was confirmed with a urine sample collected in the first 2 weeks of life. The study involved 1492 newborns. One hundred and fifty pools were screened, with 14 positive results in saliva, but only 10 were confirmed in urine samples, giving a prevalence of congenital HCMV infection in both hospitals of 0.67% (CI95% 0.36 to 1.23%). Conclusion: The overall prevalence of congenital HCMV infection in both hospitals was 0.67%. The use of saliva pools proved to be effective for the screening of this congenital infection, allowing timely screening and confirmation in a large population, with associated cost reduction. What is Known:• Newborn screening for HCMV is desirable.• Saliva is a good and practical sample. What is New:• The feasibility of using saliva pools for a large-scale screening.• The cost reduction of this strategy.

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“…The use of saliva samples for detection of congenital CMV infection has been shown to be very sensitive (>97%) and specific (99%) in a prospective multicenter study (Boppana et al, 2011). Although CMV shedding in mothers' breastmilk could lead to falsepositive results when using saliva for detection of congenital infection, the false-positive rates has been shown to be very low, which ranged from 0.03% to 0.14% (Ross et al, 2018). In our study, the median time of saliva sample collection of the CMV-positive was 0 days (0À14 days) after birth.…”

Section: Discussionmentioning

confidence: 99%

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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Contribution of Breastfeeding to False-Positive Saliva Polymerase Chain Reaction for Newborn Congenital Cytomegalovirus Screening

Cited by 41 publications

References 8 publications

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay

Saliva pools for screening of human cytomegalovirus using real-time PCR

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

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