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Neonatal herpes simplex virus infection

Last updated: December 12, 2025

Summarytoggle arrow icon

Neonatal herpes simplex virus (HSV) infection is a potentially life-threatening infection caused by HSV-1 or HSV-2, most commonly transmitted from a birthing parent with active genital tract disease during delivery. Neonatal HSV infection can manifest as skin, eye, and mouth (SEM) disease; central nervous system (CNS) disease; and disseminated disease. SEM disease is characterized by vesicular lesions localized to the skin, eyes, and/or mouth; CNS disease manifests with meningoencephalitis; and disseminated disease is characterized by signs of neonatal sepsis and multiorgan involvement. Diagnosis is confirmed by detection of HSV via NAAT or viral culture from skin or mucosal surfaces, vesicles, cerebrospinal fluid, and/or blood. Immediate treatment with acyclovir is indicated for all forms of the disease. Asymptomatic neonates with exposure to HSV at delivery require additional monitoring, which includes assessment for signs of infection and diagnostic testing for HSV, regardless of the form of delivery (i.e., vaginal or cesarean). Prevention is critical and includes management of genital herpes in pregnancy and avoiding exposure of neonates to active lesions.

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Epidemiologytoggle arrow icon

  • US incidence: ∼ 1 case per 2,000 live births per year [1]
  • Worldwide incidence: ∼ 1 case per 10,000 live births per year [2]

Epidemiological data refers to the US, unless otherwise specified.

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Etiologytoggle arrow icon

  • Pathogen: HSV-2 or HSV-1 [1]
  • Transmission [1]
    • Occurs more commonly after primary infection in the birthing parent rather than recurrent infection [1]
    • Modes of transmission
      • Intrauterine (rare): contracted via ascending infection through intact or ruptured amniotic membranes [1]
      • Peripartum (most common): contracted during birth via contact with active genital tract disease [1]
      • Postnatal: contracted through close contact (e.g., oral secretions, skin lesions) with infected individuals such as caregivers and siblings [1]

In over 75% of cases, HSV infection occurs in neonates whose birthing parent has no history or clinical features of genital HSV. [1]

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Clinical featurestoggle arrow icon

Clinical features depend on when the infection occurs. Symptoms may manifest at birth or develop up to 6 weeks later. [1][3]

Congenital HSV [4][5]

Congenital HSV is rare and caused by intrauterine infection. Features include:

Peripartum or postpartum infection

Vesicular skin lesions occur in up to two-thirds of infants with HSV with CNS and/or disseminated disease but may not manifest concurrently with other symptoms. [1]

Consider HSV in infants up to 6 weeks of age with vesicular skin lesions, persistent fever with negative cultures, and/or symptoms of meningitis, encephalitis, or sepsis. [1]

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Diagnosistoggle arrow icon

Indications for diagnostic testing include neonates with suggestive clinical features and asymptomatic HSV-exposed neonates. See also "Approach to suspected neonatal bacterial infection" and "Management of the well-appearing febrile infant ≤ 60 days of age."

Neonatal HSV testing [1]

A positive serum NAAT cannot distinguish between disseminated disease, CNS disease, and SEM disease. Interpret findings in conjunction with clinical presentation. [1]

Additional diagnostic testing [1]

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Managementtoggle arrow icon

SEM disease caused by HSV has a good prognosis if detected and treated early. [3]

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Preventiontoggle arrow icon

Educate pregnant individuals and caregivers on how to reduce the risk of neonatal HSV infection. [1]

A mother with HSV can safely breastfeed if there are no lesions on the breasts and all active lesions are covered. [1]

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