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PEDIATRICS Vol. 108 No. 2 August 2001, pp. 223-229

Natural History of Neonatal Herpes Simplex Virus Infections in the Acyclovir Era

Received Sep 1, 2000; accepted Dec 11, 2000.

David W. Kimberlin*, Chin-Yu Lin*, Richard F. JacobsDagger , Dwight A. Powell§, Lisa M. Frenkelparallel , William C. Gruber, Mobeen Rathore#, John S. Bradley**, Pamela S. DiazDagger Dagger , Mary Kumar§§, Ann M. Arvin||, Kathleen Gutierrez||, Mark Shelton¶¶, Leonard B. Weiner##, John W. Sleasman***, Teresa Murguía de SierraDagger Dagger Dagger , Seng-Jaw Soong*, Jan Kiell*, Fred D. Lakeman*, Richard J. Whitley*, and the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Groupa

From the * Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; Dagger  Department of Pediatrics, University of Arkansas, Little Rock, Arkansas; § Department of Pediatrics, Ohio State University, Columbus, Ohio; parallel  Department of Pediatrics, University of Washington, Seattle, Washington;  Department of Pediatrics, Vanderbilt University, Nashville, Tennessee; # Department of Pediatrics, University of Florida Health Science Center, Jacksonville, Florida; ** Department of Pediatrics, University of California San Diego, San Diego, California; Dagger Dagger  Chicago Department of Public Health, Chicago, Illinois; §§ Department of Pediatrics, Case Western Reserve, Cleveland, Ohio; || Department of Pediatrics, Stanford University, Stanford, California; ¶¶ Cook Children's Medical Center, Fort Worth, Texas; ## Department of Medicine, State University of New York, Syracuse, New York; *** Department of Pediatrics, University of Florida, Gainesville, Florida; and Dagger Dagger Dagger  Hospital Infantil de Mexico, Mexico City, Mexico.

Objective.  During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made.

Design/Methods.  Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported.

Results.  Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >= 10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy.

Conclusion.  Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.  Key words:  newborn, herpes simplex virus, acyclovir.




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