Overview
Definition:
Neonatal herpes simplex virus (HSV) infection is a serious, potentially life-threatening condition acquired by a neonate during pregnancy, delivery, or the postnatal period
It can manifest in localized forms (skin, eyes, mouth) or disseminated disease, often involving central nervous system (CNS) and/or vital organs.
Epidemiology:
The incidence of neonatal HSV infection in the US is estimated to be approximately 1 in 3,500 to 1 in 10,000 births
Maternal primary HSV infection near term is associated with the highest risk of transmission (up to 50%), whereas recurrent infections carry a lower risk (less than 1%).
Clinical Significance:
Untreated neonatal HSV infection has a high mortality rate, with disseminated disease and CNS involvement carrying the worst prognosis
Early diagnosis and prompt antiviral treatment are critical to reduce morbidity and mortality, and prevent long-term neurological sequelae.
Clinical Presentation
Symptoms:
Symptoms can be subtle or severe, often appearing between the 1st and 4th week of life, but can be delayed up to 6 weeks
Signs may include: Lethargy
Irritability
Poor feeding
Fever or hypothermia
Jaundice
Seizures
Vesicular rash (may be absent in disseminated or CNS disease)
Respiratory distress
Hepatomegaly and splenomegaly
Signs of disseminated intravascular coagulation (DIC).
Signs:
Physical examination findings can range from nonspecific signs of illness to specific vesicular lesions
Look for: Vesicular or pustular lesions on the skin, eyes, or mouth (pathognomonic but often absent)
Hepatosplenomegaly
Jaundice
Neurological signs: seizures, altered mental status, poor tone
Respiratory distress
Signs of sepsis.
Diagnostic Criteria:
Diagnosis is confirmed by detecting HSV DNA or virus in clinical specimens
Definitive diagnosis requires: Polymerase chain reaction (PCR) testing for HSV DNA in cerebrospinal fluid (CSF), blood, or lesion exudates
Viral culture of lesions, conjunctival swabs, or pharyngeal swabs
Serological testing is generally not useful for acute diagnosis in neonates.
Diagnostic Approach
History Taking:
Key history points include: Maternal history of genital herpes, particularly primary infection in late pregnancy
Antepartum, intrapartum, and postpartum events
Presence of maternal genital lesions at delivery
Neonatal symptoms and their onset
History of PROM or invasive fetal monitoring
A history of neonatal herpes, even if seemingly mild, warrants thorough investigation.
Physical Examination:
A comprehensive physical examination is crucial, focusing on: Skin for vesicular lesions
Eyes for conjunctivitis or keratitis
Oral mucosa for lesions
Neurological assessment for tone, reflexes, seizures, and mental status
Abdominal examination for hepatosplenomegaly
Cardiopulmonary assessment for distress.
Investigations:
Recommended investigations include: Blood for complete blood count (CBC) with differential, liver function tests (LFTs), electrolytes, urea, creatinine, coagulation profile (PT/INR, aPTT), and HSV PCR or culture
CSF for cell count, protein, glucose, Gram stain, bacterial culture, and HSV PCR (most sensitive test for CNS disease)
Swabs from any suspicious lesions (e.g., skin vesicles, conjunctiva, pharynx) for HSV PCR and viral culture
Chest X-ray if respiratory distress is present
Cranial ultrasound or MRI if CNS involvement is suspected.
Differential Diagnosis:
Differential diagnoses for neonatal sepsis and meningitis include: Bacterial sepsis (e.g., Group B Streptococcus, E
coli)
Other viral infections (e.g., enterovirus, cytomegalovirus)
Congenital syphilis
Neonatal meningitis due to other pathogens
Severe dehydration with metabolic derangement
Congenital malformations.
Management
Initial Management:
Immediate management for suspected neonatal HSV includes: Empiric broad-spectrum antibiotics to cover bacterial pathogens while awaiting cultures
Prompt initiation of antiviral therapy with intravenous acyclovir as soon as HSV is suspected, even before definitive diagnosis
Supportive care including fluid resuscitation, respiratory support, and management of seizures.
Medical Management:
Intravenous acyclovir is the mainstay of treatment
Dosing recommendations for neonatal HSV are: Initial dose: 10-15 mg/kg per dose administered intravenously over 1 hour every 8 hours (240 mg/kg/day)
Duration of therapy: For localized disease (skin, eyes, mouth), typically 14 days
For CNS or disseminated disease, typically 21 days
Prolonged therapy may be considered for recurrent disease or complications
Doses should be adjusted for renal impairment.
Surgical Management:
Surgical intervention is generally not a primary treatment for neonatal HSV infection itself
However, surgical consultation may be required for complications such as: Management of skin lesions requiring debridement if superinfected or necrotic
Excision of localized abscesses if they form
Circumcision in neonates with maternal history of HSV might be considered to reduce risk, but evidence is mixed
current recommendations focus on maternal antiviral prophylaxis and careful delivery management.
Supportive Care:
Supportive care is critical and includes: Careful fluid and electrolyte management
Nutritional support, often via nasogastric or intravenous feeding
Respiratory support (e.g., oxygen, mechanical ventilation) as needed
Management of seizures with appropriate anticonvulsant medications
Monitoring of vital signs, urine output, and laboratory parameters.ophthalmic care for ocular lesions to prevent blindness.
Complications
Early Complications:
Early complications include: Disseminated intravascular coagulation (DIC)
Hepatic failure
Fulminant hepatitis
Pneumonitis
Myocarditis
Multiorgan failure
Seizures and status epilepticus
Hydrocephalus
Neonatal death.
Late Complications:
Long-term sequelae in survivors, particularly those with CNS involvement, can include: Developmental delay
Intellectual disability
Cerebral palsy
Seizure disorders
Visual impairment (retinitis, cortical visual impairment)
Hearing loss
Behavioral problems.
Prevention Strategies:
Prevention strategies focus on reducing transmission from mother to neonate: Antiviral prophylaxis (e.g., acyclovir) for pregnant women with recurrent genital herpes in the last month of pregnancy
Avoidance of invasive fetal monitoring if maternal lesions are present
Cesarean delivery for mothers with active genital lesions or prodromal symptoms at the time of labor
Education of pregnant women about HSV transmission and risks
Careful perinatal management and screening of pregnant women at high risk.
Prognosis
Factors Affecting Prognosis:
Prognostic factors include: Type of disease (localized < CNS < disseminated)
Age at onset of symptoms (earlier onset = worse prognosis)
Promptness of diagnosis and initiation of treatment
Presence of seizures
Neurological involvement
Maternal HSV status (primary vs
recurrent infection).
Outcomes:
Mortality rates vary significantly: Localized HSV (skin, eyes, mouth): 0-10%
CNS disease: 15-30%
Disseminated disease: 30-50% or higher
Survivors with CNS or disseminated disease have a high risk of significant long-term neurological deficits (up to 50-70%)
Localized disease survivors usually have a good prognosis with minimal long-term sequelae.
Follow Up:
Survivors require intensive long-term follow-up
This includes: Regular neurodevelopmental assessments
Audiology and ophthalmology evaluations
Monitoring for seizures and initiating anticonvulsant therapy if needed
Developmental therapy and early intervention services
Psychosocial support for families
Continued antiviral therapy may be considered in select cases with recurrent disease.
Key Points
Exam Focus:
Neonatal HSV is a critical diagnosis
Remember the high mortality and morbidity
Empiric acyclovir should be started immediately for any neonate with signs of sepsis or vesicular lesions, especially with maternal risk factors
PCR of CSF is the gold standard for CNS HSV
Dosing is crucial: 10-15 mg/kg IV q8h, duration 14-21 days based on disease type.
Clinical Pearls:
Vesicular lesions may be absent in up to 50% of neonates with disseminated or CNS HSV, so do not rule out HSV based on skin findings alone
Maternal history of primary HSV infection in late pregnancy is a major red flag
Always consider HSV in a neonate with unexplained lethargy, irritability, or seizures, even without typical rash
Careful ophthalmological assessment is vital to prevent blindness.
Common Mistakes:
Delaying acyclovir initiation until definitive diagnosis is confirmed
Underdosing acyclovir
Incorrect duration of therapy
Inadequate workup for CNS or disseminated disease
Failing to consider HSV in neonates with nonspecific signs of illness
Not adequately counseling families about long-term sequelae and follow-up.