Oral acyclovir suppression and neurodevelopment after neonatal herpes

David W. Kimberlin, Richard J. Whitley, Wen Wan, Dwight A. Powell, Gregory Storch, Amina Ahmed, April Palmer, Pablo J. Sánchez, Richard F. Jacobs, John S. Bradley, Joan L. Robinson, Mark Shelton, Penelope H. Dennehy, Charles Leach, Mobeen Rathore, Nazha Abughali, Peter Wright, Lisa M. Frenkel, Rebecca C. Brady, Russell Van DykeLeonard B. Weiner, Judith Guzman-Cottrill, Carol A. McCarthy, Jill Griffin, Penelope Jester, Misty Parker, Fred D. Lakeman, Huichien Kuo, Choo Hyung Lee, Gretchen A. Cloud

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo- controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled - 45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P = 0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P = 0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.)

Original languageEnglish (US)
Pages (from-to)1284-1292
Number of pages9
JournalNew England Journal of Medicine
Volume365
Issue number14
DOIs
StatePublished - Oct 6 2011

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Acyclovir
Central Nervous System
Virus Diseases
Simplexvirus
Placebos
Newborn Infant
Skin
Mouth Diseases
National Institute of Allergy and Infectious Diseases (U.S.)
Recurrence
Eye Diseases
Body Surface Area
Child Development
Neutropenia
Skin Diseases
Mouth
Neonatal herpes
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kimberlin, D. W., Whitley, R. J., Wan, W., Powell, D. A., Storch, G., Ahmed, A., ... Cloud, G. A. (2011). Oral acyclovir suppression and neurodevelopment after neonatal herpes. New England Journal of Medicine, 365(14), 1284-1292. https://doi.org/10.1056/NEJMoa1003509

Oral acyclovir suppression and neurodevelopment after neonatal herpes. / Kimberlin, David W.; Whitley, Richard J.; Wan, Wen; Powell, Dwight A.; Storch, Gregory; Ahmed, Amina; Palmer, April; Sánchez, Pablo J.; Jacobs, Richard F.; Bradley, John S.; Robinson, Joan L.; Shelton, Mark; Dennehy, Penelope H.; Leach, Charles; Rathore, Mobeen; Abughali, Nazha; Wright, Peter; Frenkel, Lisa M.; Brady, Rebecca C.; Van Dyke, Russell; Weiner, Leonard B.; Guzman-Cottrill, Judith; McCarthy, Carol A.; Griffin, Jill; Jester, Penelope; Parker, Misty; Lakeman, Fred D.; Kuo, Huichien; Lee, Choo Hyung; Cloud, Gretchen A.

In: New England Journal of Medicine, Vol. 365, No. 14, 06.10.2011, p. 1284-1292.

Research output: Contribution to journalArticle

Kimberlin, DW, Whitley, RJ, Wan, W, Powell, DA, Storch, G, Ahmed, A, Palmer, A, Sánchez, PJ, Jacobs, RF, Bradley, JS, Robinson, JL, Shelton, M, Dennehy, PH, Leach, C, Rathore, M, Abughali, N, Wright, P, Frenkel, LM, Brady, RC, Van Dyke, R, Weiner, LB, Guzman-Cottrill, J, McCarthy, CA, Griffin, J, Jester, P, Parker, M, Lakeman, FD, Kuo, H, Lee, CH & Cloud, GA 2011, 'Oral acyclovir suppression and neurodevelopment after neonatal herpes', New England Journal of Medicine, vol. 365, no. 14, pp. 1284-1292. https://doi.org/10.1056/NEJMoa1003509
Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. New England Journal of Medicine. 2011 Oct 6;365(14):1284-1292. https://doi.org/10.1056/NEJMoa1003509
Kimberlin, David W. ; Whitley, Richard J. ; Wan, Wen ; Powell, Dwight A. ; Storch, Gregory ; Ahmed, Amina ; Palmer, April ; Sánchez, Pablo J. ; Jacobs, Richard F. ; Bradley, John S. ; Robinson, Joan L. ; Shelton, Mark ; Dennehy, Penelope H. ; Leach, Charles ; Rathore, Mobeen ; Abughali, Nazha ; Wright, Peter ; Frenkel, Lisa M. ; Brady, Rebecca C. ; Van Dyke, Russell ; Weiner, Leonard B. ; Guzman-Cottrill, Judith ; McCarthy, Carol A. ; Griffin, Jill ; Jester, Penelope ; Parker, Misty ; Lakeman, Fred D. ; Kuo, Huichien ; Lee, Choo Hyung ; Cloud, Gretchen A. / Oral acyclovir suppression and neurodevelopment after neonatal herpes. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 14. pp. 1284-1292.
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abstract = "BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo- controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled - 45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62{\%}) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P = 0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P = 0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.)",
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AU - Kimberlin, David W.

AU - Whitley, Richard J.

AU - Wan, Wen

AU - Powell, Dwight A.

AU - Storch, Gregory

AU - Ahmed, Amina

AU - Palmer, April

AU - Sánchez, Pablo J.

AU - Jacobs, Richard F.

AU - Bradley, John S.

AU - Robinson, Joan L.

AU - Shelton, Mark

AU - Dennehy, Penelope H.

AU - Leach, Charles

AU - Rathore, Mobeen

AU - Abughali, Nazha

AU - Wright, Peter

AU - Frenkel, Lisa M.

AU - Brady, Rebecca C.

AU - Van Dyke, Russell

AU - Weiner, Leonard B.

AU - Guzman-Cottrill, Judith

AU - McCarthy, Carol A.

AU - Griffin, Jill

AU - Jester, Penelope

AU - Parker, Misty

AU - Lakeman, Fred D.

AU - Kuo, Huichien

AU - Lee, Choo Hyung

AU - Cloud, Gretchen A.

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N2 - BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo- controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled - 45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P = 0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P = 0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.)

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