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Neonatal herpes simplex virus infection: Management and prevention

Gail J Demmler-Harrison, MD
Section Editors
Sheldon L Kaplan, MD
Leonard E Weisman, MD
Deputy Editor
Carrie Armsby, MD, MPH


Neonatal infection with herpes simplex virus (HSV) occurs in 1 out of every 3200 to 10,000 live births, causes serious morbidity and mortality, and leaves many survivors with permanent sequelae [1-4]. Despite this seemingly low prevalence, neonatal HSV accounts for 0.2 percent of neonatal hospitalizations and 0.6 percent of in-hospital neonatal deaths in the United States, and is associated with substantial healthcare resource utilization [5-8].

The management and prevention of neonatal HSV infection will be reviewed here. The clinical features and diagnosis of neonatal HSV infection and non-neonatal herpes simplex virus infection are discussed separately:

(See "Neonatal herpes simplex virus infection: Clinical features and diagnosis".)

(See "Genital herpes simplex virus infection and pregnancy".)

(See "Herpetic gingivostomatitis in young children".)


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Literature review current through: Sep 2016. | This topic last updated: Feb 16, 2016.
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  1. Brown ZA, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003; 289:203.
  2. Flagg EW, Weinstock H. Incidence of neonatal herpes simplex virus infections in the United States, 2006. Pediatrics 2011; 127:e1.
  3. Roberts S. Herpes simplex virus: incidence of neonatal herpes simplex virus, maternal screening, management during pregnancy, and HIV. Curr Opin Obstet Gynecol 2009; 21:124.
  4. Mahnert N, Roberts SW, Laibl VR, et al. The incidence of neonatal herpes infection. Am J Obstet Gynecol 2007; 196:e55.
  5. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev 2004; 17:1.
  6. Caviness AC, Demmler GJ, Swint JM, Cantor SB. Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates. Arch Pediatr Adolesc Med 2008; 162:665.
  7. Davis KL, Shah SS, Frank G, Eppes SC. Why are young infants tested for herpes simplex virus? Pediatr Emerg Care 2008; 24:673.
  8. Ambroggio L, Lorch SA, Mohamad Z, et al. Congenital anomalies and resource utilization in neonates infected with herpes simplex virus. Sex Transm Dis 2009; 36:680.
  9. Nagamori T, Koyano S, Asai Y, et al. Sequential changes in pathophysiology of systemic inflammatory response in a disseminated neonatal herpes simplex virus (HSV) infection. J Clin Virol 2012; 53:265.
  10. Egawa H, Inomata Y, Nakayama S, et al. Fulminant hepatic failure secondary to herpes simplex virus infection in a neonate: A case report of successful treatment with liver transplantation and perioperative acyclovir. Liver Transpl Surg 1998; 4:513.
  11. Maeba S, Hasegawa S, Shimomura M, et al. Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection. AJP Rep 2015; 5:e089.
  12. Yamada K, Yamamoto Y, Uchiyama A, et al. Successful treatment of neonatal herpes simplex-type 1 infection complicated by hemophagocytic lymphohistiocytosis and acute liver failure. Tohoku J Exp Med 2008; 214:1.
  13. American Academy of Pediatrics. Herpes simplex. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.432.
  14. Kimberlin DW, Lin CY, Jacobs RF, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 2001; 108:230.
  15. Whitley R, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 1991; 324:444.
  16. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  17. Jones CA, Walker KS, Badawi N. Antiviral agents for treatment of herpes simplex virus infection in neonates. Cochrane Database Syst Rev 2009; :CD004206.
  18. Whitley RJ, Nahmias AJ, Soong SJ, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 1980; 66:495.
  19. Kimberlin DW. Herpes simplex virus infections of the newborn. Semin Perinatol 2007; 31:19.
  20. Whitley RJ, Corey L, Arvin A, et al. Changing presentation of herpes simplex virus infection in neonates. J Infect Dis 1988; 158:109.
  21. Caviness AC, Demmler GJ, Almendarez Y, Selwyn BJ. The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates. J Pediatr 2008; 153:164.
  22. Long SS. In defense of empiric acyclovir therapy in certain neonates. J Pediatr 2008; 153:157.
  23. Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr 2008; 153:155.
  24. Long SS, Pool TE, Vodzak J, et al. Herpes simplex virus infection in young infants during 2 decades of empiric acyclovir therapy. Pediatr Infect Dis J 2011; 30:556.
  25. Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics 2011; 128:1153.
  26. Mejías A, Bustos R, Ardura MI, et al. Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis. J Perinatol 2009; 29:290.
  27. Kimura H, Futamura M, Kito H, et al. Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid. J Infect Dis 1991; 164:289.
  28. Troendle-Atkins J, Demmler GJ, Buffone GJ. Rapid diagnosis of herpes simplex virus encephalitis by using the polymerase chain reaction. J Pediatr 1993; 123:376.
  29. Gutierrez K, Pinsky B, Arvin AM. Herpes simplex viruses 1 and 2. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.1933.
  30. Melvin AJ, Mohan KM, Schiffer JT, et al. Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection. J Pediatr 2015; 166:827.
  31. Current Drug Shortages. US Food and Drug Administration. www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm314739.htm (Accessed on November 28, 2012).
  32. Shortage of intravenous acyclovir. Red Book Online Special Alert - November 28, 2012.
  33. Kimberlin DW. Ganciclovir may be used during intravenous acyclovir shortage. AAP News 2009; 30:10.
  34. Kimberlin DW, Whitley RJ, Wan W, et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med 2011; 365:1284.
  35. Fish DN, Vidaurri VA, Deeter RG. Stability of valacyclovir hydrochloride in extemporaneously prepared oral liquids. Am J Health Syst Pharm 1999; 56:1957.
  36. Bomgaars L, Thompson P, Berg S, et al. Valacyclovir and acyclovir pharmacokinetics in immunocompromised children. Pediatr Blood Cancer 2008; 51:504.
  37. Kimberlin DW, Jacobs RF, Weller S, et al. Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month through 11 years of age. Clin Infect Dis 2010; 50:221.
  38. Fonseca-Aten M, Messina AF, Jafri HS, Sánchez PJ. Herpes simplex virus encephalitis during suppressive therapy with acyclovir in a premature infant. Pediatrics 2005; 115:804.
  39. Kimberlin D, Powell D, Gruber W, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial. Pediatr Infect Dis J 1996; 15:247.
  40. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001; 108:223.
  41. Whitley R, Arvin A, Prober C, et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 1991; 324:450.
  42. Verma A, Dhawan A, Zuckerman M, et al. Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type I. J Pediatr Gastroenterol Nutr 2006; 42:282.
  43. Twagira M, Hadzic N, Smith M, et al. Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation. Eur J Pediatr 2004; 163:166.
  44. Westerberg BD, Atashband S, Kozak FK. A systematic review of the incidence of sensorineural hearing loss in neonates exposed to Herpes simplex virus (HSV). Int J Pediatr Otorhinolaryngol 2008; 72:931.
  45. Grose C. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection. Semin Pediatr Neurol 2012; 19:115.
  46. Landry ML, Mullangi P, Nee P, Klein BR. Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes. J Pediatr 2005; 146:836.
  47. American Academy of Pediatrics. Transmission of infectious agents via human milk. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th, Pickering LK. (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.128.
  48. Gutierrez KM, Whitley RJ, Arvin AM. Herpes simplex virus infections. In: Infectious Diseases of the Fetus and Newborn Infant, 7th ed, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.813.
  49. Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med 2009; 361:1376.
  50. Overall JC Jr. Empiric therapy with acyclovir for suspected neonatal herpes simplex infection. Pediatr Infect Dis J 1989; 8:808.
  51. Overall JC Jr. Herpes simplex virus infection of the fetus and newborn. Pediatr Ann 1994; 23:131.
  52. Prober CG, Corey L, Brown ZA, et al. The management of pregnancies complicated by genital infections with herpes simplex virus. Clin Infect Dis 1992; 15:1031.
  53. Scott LL. Perinatal herpes: current status and obstetric management strategies. Pediatr Infect Dis J 1995; 14:827.
  54. Kimberlin DW, Baley J, Committee on infectious diseases, Committee on fetus and newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics 2013; 131:e635.