- Overview of Neonatal Infections
- Neonatal Sepsis
- Neonatal Hospital-Acquired Infection
- Neonatal Pneumonia
- Neonatal Bacterial Meningitis
- Neonatal Listeriosis
- Neonatal Conjunctivitis
- Neonatal Herpes Simplex Virus (HSV) Infection
- Neonatal Hepatitis B Virus (HBV) Infection
- Congenital and Perinatal Cytomegalovirus Infection (CMV)
- Congenital Rubella
- Congenital Syphilis
- Congenital Toxoplasmosis
- Perinatal Tuberculosis (TB)
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, polymerase chain reaction testing, immunofluorescence, or electron microscopy. Treatment is with high-dose parenteral acyclovir and supportive care.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, polymerase chain reaction testing, immunofluorescence, or electron microscopy. Treatment is with high-dose parenteral acyclovir and supportive care.
(See also Herpes Simplex Virus [HSV] Infections in adults and Overview of Neonatal Infections.)
Neonatal HSV infection has high mortality and significant morbidity. Incidence in the United States is as high as approximately 1 in 2000 live births (1). HSV type 2 causes more cases than HSV type 1.
HSV is usually transmitted during delivery through an infected maternal genital tract or contact with infectious vaginal fluid. 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.
General reference
1. Committee on Infectious Diseases, American Academy of Pediatrics: Herpes Simplex in Red Book: 2024–2027 Report of the Committee on Infectious Diseases, ed. 33, edited by Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, and Sawyer MH. Itasca, American Academy of Pediatrics, 2024.
Symptoms and Signs of Neonatal HSV Infection
Clinical manifestations generally occur between the first and third weeks of life but rarely may not appear until as late as the fourth week. Neonates may present with local or disseminated disease.
Skin vesicles are common with either type, occurring in approximately 70% of neonates overall. Neonates with no skin vesicles usually have eye lesions, oral lesions, or central nervous system (CNS) infection. 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 (1).
This close-up of a neonate's mouth shows a large red ulcer under the upper lip caused by HSV-1.
DR P. MARAZZI/SCIENCE PHOTO LIBRARY
This neonate with advanced HIV infection also has disseminated HSV-2 infection with lesions covering the entire body.
DR M.A. ANSARY/SCIENCE PHOTO LIBRARY
Clusters of vesicles on an erythematous base are characteristic and may be present on almost any part of the body.
By permission of the publisher. From Demmler G: Congenital and perinatal infections. In Atlas of Infectious Diseases: Pediatric Infectious Diseases. Edited by CM Wilfert. Philadelphia, Current Medicine, 1998.
This close-up of a neonate's mouth shows a large red ulcer under the upper lip caused by HSV-1.
DR P. MARAZZI/SCIENCE PHOTO LIBRARY
This neonate with advanced HIV infection also has disseminated HSV-2 infection with lesions covering the entire body.
DR M.A. ANSARY/SCIENCE PHOTO LIBRARY
Clusters of vesicles on an erythematous base are characteristic and may be present on almost any part of the body.
By permission of the publisher. From Demmler G: Congenital and perinatal infections. In Atlas of Infectious Diseases: Pediatric Infectious Diseases. Edited by CM Wilfert. Philadelphia, Current Medicine, 1998.
Localized disease
Neonates with localized disease can be divided into 2 groups. One group has encephalitis manifested by neurologic findings, cerebrospinal fluid 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.
Symptoms and signs reference
1. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev. 2004;17(1):1-13. doi:10.1128/CMR.17.1.1-13.2004
Diagnosis of Neonatal HSV Infection
HSV culture or polymerase chain reaction (PCR) testing
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 cerebrospinal fluid 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.
All infants with HSV disease should have an ophthalmologic examination and neuroimaging.
Treatment of Neonatal HSV Infection
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 acyclovir for 21 days. After this regimen, infants with any form of HSV disease are given oral Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. Infants with disseminated and/or CNS disease are given acyclovir for 21 days. After this regimen, infants with any form of HSV disease are given oralacyclovir for 6 months; this long-term regimen improves neurodevelopmental outcomes at 1 year of age but may cause neutropenia.
Vigorous supportive therapy is required, including appropriate IV fluids, nutritional support, respiratory support, correction of clotting abnormalities, and control of seizures.
For localized disease (skin, mouth, or conjunctivae), treatment is acyclovir for 14 days.
Herpetic keratoconjunctivitis requires concomitant topical therapy with a medication such as trifluridine or ganciclovir (see Herpetic keratoconjunctivitis requires concomitant topical therapy with a medication such as trifluridine or ganciclovir (seetreatment of herpetic keratoconjunctivitis).
Prognosis for Neonatal HSV Infection
The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 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 significantly increases the percentage of children who develop normally. Even in infants who have been treated, however, neurologic and developmental sequelae are seen in 13% of those with disseminated disease and in 40 to 70% of those with CNS disease (The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 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 significantly increases the percentage of children who develop normally. Even in infants who have been treated, however, neurologic and developmental sequelae are seen in 13% of those with disseminated disease and in 40 to 70% of those with CNS disease (1, 2).
Death is uncommon in neonates with local disease limited to the skin, eyes, or mouth. However, without treatment, many of these neonates progress to disseminated disease or CNS disease that may be unrecognized.
Prognosis references
1. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev. 2004;17(1):1-13. doi:10.1128/CMR.17.1.1-13.2004
2. Malm G. Neonatal herpes simplex virus infection. Semin Fetal Neonatal Med. 2009;14(4):204-208. doi:10.1016/j.siny.2009.01.005
Prevention of Neonatal HSV Infection
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.
To prevent neonatal herpes infection, pregnant patients with a history of genital herpes should be offered suppressive viral therapy at or beyond 36 weeks gestation (1). Cesarean delivery is recommended for pregnant patients with active genital herpes simplex lesions or prodromal symptoms at the time of delivery.
Neonates born to people with active genital lesions at the time of vaginal delivery should be evaluated and tested for HSV infection (2).
Prevention references
1. Management of Genital Herpes in Pregnancy: ACOG Practice Bulletin, Number 220. Obstet Gynecol. 2020;135(5):e193-e202. doi:10.1097/AOG.0000000000003840
2. Kimberlin DW, Baley J, Committee on infectious diseases, Committee on fetus and newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635-646. doi:10.1542/peds.2012-3216
Key Points
Neonatal herpes infection may be localized to the skin, eyes, or mouth, the central nervous system, 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 cerebrospinal fluid, blood, or lesions are essential to optimize outcomes.
Give parenteral acyclovir for both localized and disseminated disease.Give parenteral acyclovir for both localized and disseminated disease.
Perform cesarean delivery if the mother has active genital herpes lesions or prodromal symptoms present at term.
