Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns

Suresh B. Boppana, Shannon A. Ross, Masako Shimamura, April L. Palmer, Amina Ahmed, Marian G. Michaels, Pablo J. Sánchez, David I. Bernstein, Robert W. Tolan, Zdenek Novak, Nazma Chowdhury, William J. Britt, Karen B. Fowler

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives - real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth - have been developed. METHODS: In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS: A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS: Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.)

Original languageEnglish (US)
Pages (from-to)2111-2118
Number of pages8
JournalNew England Journal of Medicine
Volume364
Issue number22
DOIs
StatePublished - Jun 2 2011

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Cytomegalovirus
Saliva
Newborn Infant
Confidence Intervals
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Cytomegalovirus Infections
Parturition
Hearing Loss
Sensitivity and Specificity
National Institute on Deafness and Other Communication Disorders (U.S.)
Multicenter Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Boppana, S. B., Ross, S. A., Shimamura, M., Palmer, A. L., Ahmed, A., Michaels, M. G., ... Fowler, K. B. (2011). Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. New England Journal of Medicine, 364(22), 2111-2118. https://doi.org/10.1056/NEJMoa1006561

Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. / Boppana, Suresh B.; Ross, Shannon A.; Shimamura, Masako; Palmer, April L.; Ahmed, Amina; Michaels, Marian G.; Sánchez, Pablo J.; Bernstein, David I.; Tolan, Robert W.; Novak, Zdenek; Chowdhury, Nazma; Britt, William J.; Fowler, Karen B.

In: New England Journal of Medicine, Vol. 364, No. 22, 02.06.2011, p. 2111-2118.

Research output: Contribution to journalArticle

Boppana, SB, Ross, SA, Shimamura, M, Palmer, AL, Ahmed, A, Michaels, MG, Sánchez, PJ, Bernstein, DI, Tolan, RW, Novak, Z, Chowdhury, N, Britt, WJ & Fowler, KB 2011, 'Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns', New England Journal of Medicine, vol. 364, no. 22, pp. 2111-2118. https://doi.org/10.1056/NEJMoa1006561
Boppana SB, Ross SA, Shimamura M, Palmer AL, Ahmed A, Michaels MG et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. New England Journal of Medicine. 2011 Jun 2;364(22):2111-2118. https://doi.org/10.1056/NEJMoa1006561
Boppana, Suresh B. ; Ross, Shannon A. ; Shimamura, Masako ; Palmer, April L. ; Ahmed, Amina ; Michaels, Marian G. ; Sánchez, Pablo J. ; Bernstein, David I. ; Tolan, Robert W. ; Novak, Zdenek ; Chowdhury, Nazma ; Britt, William J. ; Fowler, Karen B. / Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. In: New England Journal of Medicine. 2011 ; Vol. 364, No. 22. pp. 2111-2118.
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abstract = "BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives - real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth - have been developed. METHODS: In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS: A total of 177 of 34,989 infants (0.5{\%}; 95{\%} confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5{\%}; 95{\%} CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100{\%} (95{\%} CI, 95.8 to 100) and 99.9{\%} (95{\%} CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4{\%} (95{\%} CI, 83.8 to 96.2) and 100{\%} (95{\%} CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4{\%}; 95{\%} CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4{\%} (95{\%} CI, 90.8 to 99.7) and 99.9{\%} (95{\%} CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2{\%} (95{\%} CI, 81.7 to 95.7) and 99.9{\%} (95{\%} CI, 99.9 to 100), respectively. CONCLUSIONS: Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.)",
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AU - Boppana, Suresh B.

AU - Ross, Shannon A.

AU - Shimamura, Masako

AU - Palmer, April L.

AU - Ahmed, Amina

AU - Michaels, Marian G.

AU - Sánchez, Pablo J.

AU - Bernstein, David I.

AU - Tolan, Robert W.

AU - Novak, Zdenek

AU - Chowdhury, Nazma

AU - Britt, William J.

AU - Fowler, Karen B.

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Y1 - 2011/6/2

N2 - BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives - real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth - have been developed. METHODS: In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS: A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS: Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.)

AB - BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives - real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth - have been developed. METHODS: In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS: A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS: Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.)

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