Neonatal Herpes Simplex Virus Infections


Methods of Infection

  • In utero/congenital (5%)
    • Rare
    • Congenital abnormalities as birth-similar to other congenital infections
    • Triad of findings
      • Cutaneous: scarring, active lesions, hypo- and hyperpigmentation, erythematous macular exanthem
      • Ophthalmologic: microopthalmia, retinal dysplasia, optic atrophy, chorioretinitis
      • Neurological: microcephaly, encephalomalacia, hydranencephaly, intracranial calcification
  • Intrapartum (85%)
    • Mother must be shedding virus at time of delivery
  • Postnatal (10%)
    • Almost always HSV-1


3 types of infection from intrapartum (and postnatal) exposure

  • SEM
  • CNS
  • Disseminated



  • Frequency estimates range from 8-60/100,000
  • Estimated 1500 new cases in the US annually
  • Equivalent to neonatal HIV incidence before antiretroviral use in pregnancy
  • Higher than congenital syphilis, toxoplasmosis, and rubella in years these weren’t epidemics
  • Most maternal HSV infections—asymptomatic with cervical viral shedding
    • High shedding/low infection rate: protective transplacental antibodies


Increased risk of transmission

  • Acquisition during prenancy, particularly near delivery (vs. reactivation)
  • Seronegative mother (protective maternal Abs if seroconvert prior to delivery)
  • HSV isolated from maternal genital tract before delivery
  • Use of fetal scalp monitors
  • Cervical HSV infection
  • Prolonged rupture of membranes
  • Vaginal delivery (although there are reports from C-sections)
    • C-sections recommended for women with active lesions at delivery


SEM - infection contained to Skin, Eyes, and Mouth/mucosa

  • 45% of cases
  • Present days 10-12
  • Vesicular lesions on skin, eyes and mouth
  • No involvement of CNS or visceral organ



  • 30% of cases
  • Present days 16-19
  • Sx: lethargy, poor feeding, seizures, temperature instability, bulging fontanelle,  ± cutaneous lesions
  • CSF: pleocytosis, HSV DNA will confirm diagnosis (may be neg early in disease)
  • Morbidity HSV2 > HSV1
    • Developmental delay
    • Epilepsy
    • Blindness
    • Cognitive disability
  • Early acyclovir improves outcomes and survival



  • 25% of cases
  • Present days 10-12
  • Highest fatality rate (death in 30%)
    • Usually related to coagulopathy, liver dysfunction, and pulmonary involvement
  • Multiple organ system involvement
    • Encephalitis in 60-75%
  • Clinically looks like bacterial sepsis (indistinguishable on exam)
  • 20% never develop cutaneous vesicles


Differential diagnosis (CNS and disseminated)

  • HSV infection
  • Bacterial sepsis
  • Enterovirus infection
  • Congenital CMV, rubella, or toxoplasmosis
  • Neonatal VZV infections



  • Mom:    PCR for viral DNA, direct fluorescent antibody study, isolation in
                 culture, type-specific serology
  • Baby - Highly suspicious of infection
    • Swab conjunctiva, mouth, axilla, and any suspicious lesions AFTER 24 hrs to show infection rather than colonization
    • If positive start acyclovir and do close examination to determine extent
  • Baby - CNS or disseminated
    • HSV DNA PCR assay, viral PCR on blood, serum, and CSF
    • PCR especially beneficial in neonates without overt sx


Important to have a high index of suspicion:

60-80% women with HSV+ baby have no evidence of genital HSV infection, no history of HSV infection, and no sexual partner with HSV history!

Consider especially in infants with fever, negative bacterial cultures and no improvement at 48-72 hours after starting antibiotics for rule out sepsis


Before starting acyclovir therapy:

Obtain HSV cultures of: skin vesicles, oropharynx, conjunctivae, urine, blood, stool/rectum, CSF and CSF for viral PCR



  • IV acyclovir (20 mg/kg/dose Q8 hrs)
  • Side Effect:  neutropenia but without adverse clinical outcomes
  • Treatment at end of pregnancy to prevent recurrences
    • SEM:
      • Systemic treatment to avoid progression
      • High dose IV acyclovir Q8hr for 14 days
    • CNS disease:
      • High dose acyclovir Q8hr for 21 days
      • With CNS involvement recheck CSF PCR after treatment course
      • If still positive continue IV acyclovir until negative
    • Disseminated disease:
      • High dose acyclovir Q8hr for 21 days



  • SEM
    • Rate of normal development 24 mo after infection: 100% (up from 62% before acyclovir)
    • Possible recurrent cutaneous outbreaks in childhood — antivirals to reduce frequency
  • CNS disease
    • Rate of normal development 24 mo after infection: 31% (up from rare before acyclovir)
    • Mortality 6% (down from 50% with introduction of acyclovir treatment)
  • Disseminated disease
    • Rate of normal development 24 mo after infection: 83% (up from rare before acyclovir)
    • Mortality 31% (down from 85% with introduction of acyclovir treatment)



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  4. Thompson C, Whitley R. Neonatal Herpes simplex virus infections: where are we now? Advances in Experimental Medicine and Biology 2011. 697:221.
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