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Neonatal Herpes Simplex Virus (HSV) Infection

By Mary T. Caserta, MD, Professor of Pediatrics, Division of Infectious Diseases; Attending Physician, University of Rochester School of Medicine and Dentistry; Golisano Children’s Hospital at Strong, University of Rochester Medical Center

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Neonatal herpes simplex virus infection is usually transmitted during delivery. A typical sign is vesicular eruption, which may be accompanied by or progress to disseminated disease. Diagnosis is by viral culture, PCR, immunofluorescence, or electron microscopy. Treatment is with high-dose parenteral acyclovir and supportive care.

Neonatal herpes simplex virus (HSV) infection has high mortality and significant morbidity. Incidence estimates range from 1/3,000 to 1/20,000 births. HSV type 2 causes more cases than HSV type 1.

HSV is usually transmitted during delivery through an infected maternal genital tract. Transplacental transmission of virus and hospital-acquired spread from one neonate to another by hospital personnel or family may account for some cases. Mothers of neonates with HSV infection tend to have newly acquired genital infection, but many have not had symptoms at the time of delivery.

Symptoms and Signs

Manifestations generally occur between the 1st and 3rd wk of life but rarely may not appear until as late as the 4th wk. Neonates may present with local or disseminated disease. Skin vesicles are common with either type, occurring in about 70% overall. Neonates with no skin vesicles usually present with localized CNS disease. In neonates with isolated skin or mucosal disease, progressive or more serious forms of disease frequently follow within 7 to 10 days if left untreated.

Localized disease

Neonates with localized disease can be divided into 2 groups. One group has encephalitis manifested by neurologic findings, CSF pleocytosis, and elevated protein concentration, with or without concomitant involvement of the skin, eyes, and mouth. The other group has only skin, eye, and mouth involvement and no evidence of CNS or organ disease.

Disseminated disease

Neonates with disseminated disease and visceral organ involvement have hepatitis, pneumonitis, disseminated intravascular coagulation, or a combination, with or without encephalitis or skin disease.

Other signs, which can occur singly or in combination, include temperature instability, lethargy, hypotonia, respiratory distress, apnea, and seizures.


  • HSV culture or PCR

  • Sometimes immunofluorescent testing of lesions or electron microscopy

Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. The nasopharynx, eyes, rectum, blood, and CSF should also be tested. In some neonates with encephalitis, virus is present only in the CNS. Diagnosis of neonatal HSV also can be made by immunofluorescence of lesion scrapings, particularly with use of monoclonal antibodies; and electron microscopy.

If no diagnostic virology facilities are available, a Tzanck test of the lesion base may show characteristic multinucleated giant cells and intranuclear inclusions, but this test is less sensitive than culture, and false-positives can occur.


The mortality rate of untreated disseminated disease is 85%; among neonates with untreated encephalitis, it is about 50%. Without treatment, at least 65% of survivors of disseminated disease or encephalitis have severe neurologic sequelae. Appropriate treatment, including parenteral acyclovir, decreases the mortality rate in CNS and disseminated disease by 50% and increases the percentage of children who develop normally from about 35% to 50 to 80%.

Death is uncommon in neonates with local disease limited to the skin, eyes, or mouth. However, without treatment, many of these neonates will progress to disseminated disease or CNS disease that may be unrecognized.


  • Parenteral acyclovir

  • Supportive therapy

Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. Infants with disseminated and/or CNS disease are given 20 mg/kg IV q 8 h for 21 days. After this regimen, infants with CNS disease are given oral acyclovir 300 mg/m2 tid for 6 mo; this long-term regimen improves neurodevelopmental outcomes at 1 yr of age but may cause neutropenia.

Vigorous supportive therapy is required, including appropriate IV fluids, alimentation, respiratory support, correction of clotting abnormalities, and control of seizures.

For localized disease (skin, mouth, or conjunctivae), treatment is acyclovir 20 mg/kg IV q 8 h for 14 days. Herpetic keratoconjunctivitis requires concomitant topical therapy with a drug such as trifluridine, iododeoxyuridine, or vidarabine (see Treatment).


Efforts to prevent neonatal transmission have not been very effective. Universal screening has not been recommended or shown to be effective, and most maternal infections with risk of transmission are asymptomatic. However, women with genital lesions at term should have testing and serology to diagnose HSV and determine the risk of transmission as well as to direct the care of the exposed but asymptomatic neonate. Cesarean delivery for women known to have a high risk of transmission (eg, active genital lesions present at term) has been shown to decrease transmission and is recommended even if the membranes have ruptured. Also, fetal scalp monitors should not be used during labor on infants whose mothers have suspected active genital herpes. Asymptomatic neonates born to women with active genital lesions at the time of delivery should be evaluated and tested for HSV infection. Additional information is available from the American Academy of Pediatrics (1).

Giving oral acyclovir or valacyclovir during in the last few weeks of pregnancy to women with a history of genital HSV may prevent recurrences at the time of delivery and decrease the need for cesarean delivery.

Prevention references

Key Points

  • Neonatal herpes may be localized to the skin, eyes, or mouth, the CNS, or may be disseminated.

  • Encephalitis and disseminated disease have a high mortality rate, and neurologic sequelae are common among survivors.

  • In suspected cases, presumptive therapy and rapid diagnosis by HSV PCR of CSF, blood, or lesions are essential to optimize outcomes.

  • Give parenteral acyclovir for both localized and disseminated disease.

  • Do cesarean delivery if the mother has active genital herpes lesions present at term.

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