When should treatment be started for a newborn exposed to active Herpes Simplex Virus (HSV) infection at delivery?

Management of Newborns Exposed to Active HSV Infection at Delivery

Newborns exposed to active HSV infection at delivery should receive immediate evaluation and treatment with intravenous acyclovir (30-60 mg/kg/day divided into three doses) as soon as possible after birth, regardless of maternal HSV history. 1

Diagnostic Evaluation

The diagnostic workup for exposed newborns should include:

• Surface cultures/PCR from:
  • Mouth/nasopharynx
  • Eyes
  • Skin vesicles (if present)
  • Rectum/stool
  • Urine
• Blood for HSV PCR
• CSF for HSV PCR and analysis
• Liver function tests

Diagnostic testing should be performed immediately, but treatment should not be delayed while awaiting results 2, 1.

Treatment Protocol Based on Exposure Risk

High-Risk Exposure (Primary maternal infection)

• Start IV acyclovir (20 mg/kg/dose three times daily) immediately
• Continue treatment for 14-21 days depending on disease classification:
  • 14 days for skin, eye, and mouth disease
  • 21 days for CNS or disseminated disease 2, 1
• For CNS disease, repeat CSF HSV PCR at day 19-21 of treatment; continue treatment if still positive 2

Lower-Risk Exposure (Recurrent maternal infection)

• Careful observation with surface cultures
• Start treatment immediately if any clinical signs develop
• Consider empiric treatment while awaiting test results in symptomatic infants 1, 3

Disease Classification and Duration of Treatment

1. Disseminated disease (25% of cases):

   • Multiple organ involvement
   • 21 days of IV acyclovir
   • Mortality remains high despite treatment

2. CNS disease (35% of cases):

   • Localized to central nervous system
   • 21 days of IV acyclovir
   • Repeat CSF HSV PCR at treatment completion

3. Skin, Eye, and Mouth (SEM) disease (40% of cases):

   • 14 days of IV acyclovir
   • Monitor for recurrences during first 6 months 2, 1

Important Clinical Considerations

• Neonatal HSV can present with or without skin lesions - absence of vesicles does not rule out infection
• Only 60% of infants with CNS or disseminated disease have visible skin lesions 2
• Symptoms typically appear around 9-11 days of age, but can occur earlier
• Neurologic sequelae remain a risk even after successful treatment, particularly with CNS disease
• Even infants with localized skin/eye/mouth disease have a 2-6% risk of later neurologic sequelae 2

Follow-up Management

• Monitor for neutropenia during treatment (common side effect)
• Consider suppressive therapy with oral acyclovir after completion of IV treatment
• Long-term neurodevelopmental follow-up is essential, particularly for infants with CNS involvement

Prevention Strategies

• Maternal antiviral suppression with valacyclovir (500mg twice daily) or acyclovir (400mg three times daily) starting at 36 weeks gestation can reduce risk of active lesions at delivery 1
• Cesarean delivery is recommended for women with active genital lesions at the time of delivery 1
• Breastfeeding is generally safe unless the mother has cracked nipples with detectable HSV DNA 1

The most critical factor in improving outcomes is early recognition and prompt initiation of high-dose acyclovir therapy, as delays in treatment significantly increase morbidity and mortality.