Neonatal herpes

Last updated
Neonatal herpes simplex
Other namesNeonatal herpes
Herpes neonatal Herpes simplex b.jpg
A cutaneo-mucous form of herpes simplex in a neonate
Specialty Pediatrics   OOjs UI icon edit-ltr-progressive.svg
Usual onsetCongenital
Causes Herpes simplex virus infection
Frequency1 in 10,000 births [1]

Neonatal herpes simplex, or simply neonatal herpes, is a herpes infection in a newborn baby, caused by the herpes simplex virus (HSV). It occurs mostly as a result of vertical transmission of the HSV from an affected mother to her baby. [2] Types include skin, eye, and mouth herpes (SEM), disseminated herpes (DIS), and central nervous system herpes (CNS). [3] Depending on the type, symptoms vary from a fever to small blisters, irritability, low body temperature, lethargy, breathing difficulty, and a large abdomen due to ascites or large liver. [3] There may be red streaming eyes or no symptoms. [3]

Contents

The cause is HSV 1 and 2. [2] It can infect the unborn baby, but more often passes to the baby during childbirth. [4] Onset is typically in the first six weeks after birth. [3] The baby is at greater risk of being affected if the mother contracts HSV in later pregnancy. [2] In such scenarios a prolonged rupture of membranes or childbirth trauma may increase the risk further. [2]

Globally, it is estimated to affect one in 10,000 births. [1] Around 1 in every 3,500 babies in the United States contract the infection. [5]

Signs and symptoms

Neonatal herpes manifests itself in three forms: skin, eye, and mouth herpes (SEM, sometimes referred to as "localized"); disseminated herpes (DIS); and central nervous system herpes (CNS). [6]

CNS herpes is associated with higher morbidity, while DIS herpes has a higher mortality rate. These categories are not mutually exclusive and there is often overlap of two or more types. SEM herpes has the best prognosis of the three, however if left untreated it may progress to disseminated or CNS herpes with attendant increases in mortality and morbidity.[ citation needed ]

Death from neonatal HSV disease in the U.S. is currently decreasing; the current death rate is about 25%, down from as high as 85% in untreated cases just a few decades ago. Other complications from neonatal herpes include prematurity, with approximately 50% of cases having a gestation of 38 weeks or less, and concurrent sepsis in approximately one-quarter of cases that further clouds speedy diagnosis.[ citation needed ]

Cause

The cause is HSV 1 and 2. [2] It can infect the unborn baby, but more often passes to the baby during childbirth. [4] Onset is typically in the first six weeks after birth. [3] The baby is at greater risk of being affected if the mother contracts HSV in later pregnancy. [2] In such scenarios a prolonged rupture of membranes may increase the risk further. [2] Sites of injury such as forceps or scalp electrodes may provide a portal of entry for HSV. [4]

Risk factors

Maternal risk factors for neonatal HSV-1 include: White non-Hispanic race, [9] young maternal age (<25), primary infection in third trimester, [10] first pregnancy, HSV (1&2) seronegativity, [8] [11] a discordant partner, [12] gestation <38 weeks, [10] and receptive oral sex in the third trimester. [13]

Neonatal HSV-2 maternal risk factors: Black race, [14] young maternal age (<21), [8] [10] a discordant partner, primary or non-primary first episode infection in the third trimester, [15] four or more lifetime sexual partners, [14] lower level of education, [14] history of previous STD, history of pregnancy wastage, first viable pregnancy, and gestation <38 weeks. [8] [10]

Transmission

The majority of cases (85%) occur during birth when the baby comes in contact with infected genital secretions in the birth canal, most common with mothers that have newly been exposed to the virus (mothers that had the virus before pregnancy have a lower risk of transmission). An estimated 5% are infected in utero, and approximately 10% of cases are acquired postnatally. Detection and prevention is difficult because transmission is asymptomatic in 60–98% of cases. [16]

Post-natal transmission incidences can happen from a source other than the mother, such as an Orthodox Jewish mohel with herpetic gingivostomatitis who performs oral suction on a circumcision wound without using a prophylactic barrier to prevent contact between the baby's penis and the mohel's mouth. [17] [18] [19]

Diagnosis

Diagnosis is by blood tests and culture. [6] Swabs are generally taken from the mouth, nose, throat, eyes, and anus, for HSV culture an PCR. [4] Fluid from any blisters can be swabbed too. [4] Liver enzymes may be the first sign to be noted when suspecting neonatal HSV. [4] Other tests include a lumbar puncture and medical imaging of the brain; MRI, CT scan, ultrasound. [3] An assessment of the eyes may reveal eye disease. [3]

Differential diagnosis

Other skin conditions that may appear similar include erythema toxicum neonatorum, transient neonatal pustular melanosis, infantile acne, miliaria, infantile acropustulosis, and sucking blisters. [3] CNS disease may appear like bacterial or other viral meningitis's. [3] Conjunctivitis due to bacterial infection or other viruses can look like neonatal herpes eye disease. [3] Bacterial sepsis, viral hepatitis, and other infections including cytomegalovirus, toxoplasmosis, syphilis, rubella may mimic the disseminated type. [3]

Treatment

Reductions in morbidity and mortality are due to the use of antiviral treatments such as vidarabine and acyclovir. [20] [21] [22] [23] However, morbidity and mortality still remain high due to diagnosis of DIS and CNS herpes coming too late for effective antiviral administration; early diagnosis is difficult in the 20–40% of infected neonates that have no visible lesions. [24] A recent large-scale retrospective study found disseminated NHSV patients least likely to get timely treatment, contributing to the high morbidity/mortality in that group. [25]

Harrison's Principles of Internal Medicine recommends that pregnant women with active genital herpes lesions at the time of labor be delivered by caesarean section. Women whose herpes is not active can be managed with acyclovir. [26] The current practice is to deliver women with primary or first episode non-primary infection via caesarean section, and those with recurrent infection vaginally (even in the presence of lesions) because of the low risk (1–3%) of vertical transmission associated with recurrent herpes.[ citation needed ]

Epidemiology

Neonatal HSV rates in the U.S. are estimated to be between 1 in 3,000 and 1 in 20,000 live births. Approximately 22% of pregnant women in the U.S. have had previous exposure to HSV-2, and an additional 2% acquire the virus during pregnancy, mirroring the HSV-2 infection rate in the general population. [27] The risk of transmission to the newborn is 30–57% in cases where the mother acquired a primary infection in the third trimester of pregnancy. Risk of transmission by a mother with existing antibodies for both HSV-1 and HSV-2 has a much lower (1–3%) transmission rate. This in part is due to the transfer of a significant titer of protective maternal antibodies to the fetus from about the seventh month of pregnancy. [8] [28] However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant. [8]

HSV-1 neonatal herpes is extremely rare in developing countries because development of HSV-1 specific antibodies usually occurs in childhood or adolescence, precluding a later genital HSV-1 infection. HSV-2 infections are much more common in these countries. In industrialized nations, the adolescent HSV-1 seroprevalence has been dropping steadily for the last 5 decades. The resulting increase in the number of young women becoming sexually active while HSV-1 seronegative has contributed to increased HSV-1 genital herpes rates, and as a result, increased HSV-1 neonatal herpes in developed nations. A study in the United States from 2003 to 2014 using large administrative databases showed increasing trends in incidence of neonatal HSV from 7.9 to 10 cases per 100,000 live births and mortality of 6.5%. Babies of decreased gestational age and those of African American race had higher incidences of neonatal HSV. Another study from Canada showed similar results, with an incidence of 5.9 per 100,000 live births and a case fatality of 15.5%. [29] A three-year study in Canada (2000–2003) revealed a neonatal HSV incidence of 5.9 per 100,000 live births and a case fatality rate of 15.5%. HSV-1 was the cause of 62.5% of cases of neonatal herpes of known type, and 98.3% of transmission was asymptomatic. [16] Asymptomatic genital HSV-1 has been shown to be more infectious to the neonate, and is more likely to produce neonatal herpes than HSV-2. [8] [30] However, with prompt application of antiviral therapy, the prognosis of neonatal HSV-1 infection is better than that for HSV-2.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Varicella zoster virus</span> Herpes virus that causes chickenpox and shingles

Varicella zoster virus (VZV), also known as human herpesvirus 3 or Human alphaherpesvirus 3 (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles in adults but rarely in children. As a late complication of VZV infection, Ramsay Hunt syndrome type 2 may develop in rare cases. VZV infections are species-specific to humans. The virus can survive in external environments for a few hours.

<span class="mw-page-title-main">Shingles</span> Viral disease caused by the varicella zoster virus

Shingles, also known as herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.

A mohel is a Jewish man trained in the practice of brit milah, the "covenant of male circumcision". Women who are trained in the practice are referred to as a mohelet.

<span class="mw-page-title-main">Herpetic whitlow</span> Fingertip skin lesion due to infection by the herpes virus

A herpetic whitlow is a herpes lesion (whitlow), typically on a finger or thumb, caused by the herpes simplex virus (HSV). Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals.

<span class="mw-page-title-main">Vertically transmitted infection</span> Infection caused by pathogens that use mother-to-children transmission

A vertically transmitted infection is an infection caused by pathogenic bacteria or viruses that use mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother has a pre-existing disease or becomes infected during pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infections. Vertical transmission is important for the mathematical modelling of infectious diseases, especially for diseases of animals with large litter sizes, as it causes a wave of new infectious individuals.

<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

<span class="mw-page-title-main">Herpetic gingivostomatitis</span> Inflammation of the mouth, lips, and gums, often due to herpes infection

Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.

<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.

<span class="mw-page-title-main">Genital herpes</span> Infection by herpes simplex viruses of the genitals

Genital herpes is a herpes infection of the genitals caused by the herpes simplex virus (HSV). Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

<span class="mw-page-title-main">Genital ulcer</span> Ulcer located on the genital area

A genital ulcer is an open sore located on the genital area, which includes the vulva, penis, perianal region, or anus. Genital ulcers are most commonly caused by infectious agents. However, this is not always the case, as a genital ulcer may have noninfectious causes as well.

The central nervous system (CNS) controls most of the functions of the body and mind. It comprises the brain, spinal cord and the nerve fibers that branch off to all parts of the body. The CNS viral diseases are caused by viruses that attack the CNS. Existing and emerging viral CNS infections are major sources of human morbidity and mortality.

<span class="mw-page-title-main">Herpes</span> Viral disease caused by herpes simplex viruses

Herpes simplex, often known simply as herpes, is a viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are oral herpes and genital herpes, though other forms also exist.

<span class="mw-page-title-main">Herpes meningitis</span> Medical condition

Herpes meningitis is inflammation of the meninges, the protective tissues surrounding the spinal cord and brain, due to infection from viruses of the Herpesviridae family - the most common amongst adults is HSV-2. Symptoms are self-limiting over 2 weeks with severe headache, nausea, vomiting, neck-stiffness, and photophobia. Herpes meningitis can cause Mollaret's meningitis, a form of recurrent meningitis. Lumbar puncture with cerebrospinal fluid results demonstrating aseptic meningitis pattern is necessary for diagnosis and polymerase chain reaction is used to detect viral presence. Although symptoms are self-limiting, treatment with antiviral medication may be recommended to prevent progression to Herpes Meningoencephalitis.

<span class="mw-page-title-main">Herpes simplex encephalitis</span> Encephalitis associated with herpes simplex virus

Herpes simplex encephalitis (HSE), or simply herpes encephalitis, is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, and some studies suggest an incidence rate of 5.9 cases per 100,000 live births.

<span class="mw-page-title-main">Cold sore</span> Herpes simplex virus infection of the lip

A cold sore is a type of herpes infection caused by the herpes simplex virus that affects primarily the lip. Symptoms typically include a burning pain followed by small blisters or sores. The first attack may also be accompanied by fever, sore throat, and enlarged lymph nodes. The rash usually heals within ten days, but the virus remains dormant in the trigeminal ganglion. The virus may periodically reactivate to create another outbreak of sores in the mouth or lip.

The epidemiology of herpes simplex is of substantial epidemiologic and public health interest. Worldwide, the rate of infection with herpes simplex virus—counting both HSV-1 and HSV-2—is around 90%. Although many people infected with HSV develop labial or genital lesions, the majority are either undiagnosed or display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical herpes.

<span class="mw-page-title-main">Neonatal meningitis</span> Medical condition

Neonatal meningitis is a serious medical condition in infants that is rapidly fatal if untreated. Meningitis, an inflammation of the meninges, the protective membranes of the central nervous system, is more common in the neonatal period than any other time in life, and is an important cause of morbidity and mortality globally. Mortality is roughly half in developing countries and ranges from 8%-12.5% in developed countries.

<span class="mw-page-title-main">Herpes simplex keratitis</span> Medical condition

Herpetic simplex keratitis is a form of keratitis caused by recurrent herpes simplex virus (HSV) infection in the cornea.

<span class="mw-page-title-main">Pritelivir</span> Chemical compound

Pritelivir is a direct-acting antiviral drug in development for the treatment of herpes simplex virus infections (HSV). This is particularly important in immune compromised patients. It is currently in Phase III clinical development by the German biopharmaceutical company AiCuris Anti-infective Cures AG. US FDA granted fast track designation for pritelivir in 2017 and breakthrough therapy designation 2020.

<span class="mw-page-title-main">Neonatal infection</span> Human disease

Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.

References

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  2. 1 2 3 4 5 6 7 Hussein, Abir; Moss, Nicholas J.; Wald, Anne (2022). "55. Herpes simplex virus genital infection". In Jong, Elaine C.; Stevens, Dennis L. (eds.). Netter's Infectious Diseases (2nd ed.). Philadelphia: Elsevier. pp. 300–307. ISBN   978-0-323-71159-3.
  3. 1 2 3 4 5 6 7 8 9 10 11 Fernandes, Neil D.; Arya, Kapil; Ward, Rebecca (2023). "Congenital Herpes Simplex". StatPearls. StatPearls Publishing. PMID   29939674.
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  6. 1 2 Muller, William J.; Zheng, Xiaotian (May 2019). "Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections". Journal of Clinical Microbiology. 57 (5). doi:10.1128/JCM.01460-18. ISSN   0095-1137. PMC   6498033 . PMID   30602444.
  7. ↑ Prober, Charles G. (1997). "Herpes simplex virus". In Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (eds.). Principles and Practices of Pediatric Infectious Diseases (3rd rev. ed.). New York: Churchhill Livingstone. p. 1138.
  8. 1 2 3 4 5 6 7 Brown, Zane A.; Wald, Anna; Morrow, Rhoda Ashley; Selke, Stacy; Zeh, Judith; Corey, Lawrence (January 2003). "Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant". . 289 (2): 203–209. doi: 10.1001/jama.289.2.203 . PMID   12517231.
  9. ↑ Xu, Fujie; Markowitz, Lauri E.; Gottlieb, Sami L.; Berman, Stuart M. (1 January 2007). "Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States". American Journal of Obstetrics and Gynecology . 196 (1): 43.e1–6. doi: 10.1016/j.ajog.2006.07.051 . PMID   17240228.
  10. 1 2 3 4 Whitley, Richard (June 2004). "Neonatal herpes simplex virus infection". Current Opinion in Infectious Diseases . 17 (3): 243–246. doi:10.1097/00001432-200406000-00012. PMID   15166828. S2CID   8336377.
  11. ↑ Nahmias, Andre J. (August 2004). "Neonatal HSV infection Part II: Obstetric considerations -- a tale of hospitals in two cities (Seattle and Atlanta, USA)". Herpes. 11 (2): 41–44. PMID   15955267.
  12. ↑ Baker, David A. (December 2005). "Risk factors for herpes simplex virus transmission to pregnant women: A couples study". American Journal of Obstetrics and Gynecology . 193 (6): 1887–1888. doi:10.1016/j.ajog.2005.08.007. PMID   16325587.
  13. ↑ Nahmias, Andre J. (August 2004). "Neonatal HSV infection Part I: continuing challenges" (PDF). Herpes . 11 (2): 33–7. PMID   15955265. Archived from the original (PDF) on 2009-04-12. Retrieved 2009-05-20.
  14. 1 2 3 Mertz, Gregory J. (December 1993). "Epidemiology of genital herpes infections". Infectious Disease Clinics of North America . 7 (4): 825–839. doi:10.1016/S0891-5520(20)30561-4. PMID   8106731.
  15. ↑ Gardella, Carolyn; Brown, Zane A.; Wald, Anna; Morrow, Rhoda Ashley; Selke, Stacy; Krantz, Elizabeth; Corey, Lawrence; et al. (August 2005). "Poor correlation between genital lesions and detection of herpes simplex virus in women in labor". . 106 (2): 268–274. doi:10.1097/01.AOG.0000171102.07831.74. PMID   16055574. S2CID   23039017.
  16. 1 2 Kropp, Rhonda Y.; Wong, Thomas; Cormier, Louise; Ringrose, Allison; Burton, Sandra; Embree, Joanne E.; Steben, Marc; et al. (June 2006). "Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study". . 117 (61): 1955–1962. doi:10.1542/peds.2005-1778. PMID   16740836. S2CID   9632498.
  17. ↑ "Baby Dies of Herpes in Ritual Circumcision by Orthodox Jews". ABC News .
  18. ↑ "Cases of herpes in baby boys linked to ultra-Orthodox Jewish circumcision ritual going up" . Independent.co.uk . 10 March 2017. Archived from the original on 2022-06-18.
  19. ↑ "4 NY babies get herpes from Jewish circumcision rite in past 6 months". The Times of Israel .
  20. ↑ Kimberlin, David W.; Whitley, Richard J. (2005). "Neonatal herpes: What have we learned". Seminars in Pediatric Infectious Diseases. 16 (1): 7–16. doi:10.1053/j.spid.2004.09.006. PMID   15685144.
  21. ↑ Kesson, Alison M. (2001). "Management of neonatal herpes simplex virus infection". Paediatric Drugs. 3 (2): 81–90. doi:10.2165/00128072-200103020-00001. PMID   11269641. S2CID   22544225.
  22. ↑ "Neonatal Herpes Simplex Virus (HSV) Infection - Pediatrics". Merck Manuals Professional Edition.
  23. ↑ Brocklehurst, Peter; Kinghorn, George R.; Carney, Orla; Helsen, K.; Ross, Emma; Ellis, E; Shen, R. N.; Cowan, Frances M.; Mindel, Adrian; et al. (1998). "A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection". British Journal of Obstetrics and Gynaecology . 105 (3): 275–280. doi:10.1111/j.1471-0528.1998.tb10086.x. PMID   9532986. S2CID   20915886.
  24. ↑ Jacobs, Richard F. (1998). "Neonatal herpes simplex virus infections". Seminars in Perinatology . 22 (1): 64–71. doi:10.1016/S0146-0005(98)80008-6. PMID   9523400.
  25. ↑ Caviness, A Chantal; Demmler, Gail J.; Selwyn, Beatrice J. (May 2008). "Clinical and Laboratory Features of Neonatal Herpes Simplex Virus Infection: A Case-Control Study". Pediatric Infectious Disease Journal . 27 (5): 425–430. doi:10.1097/INF.0b013e3181646d95. PMID   18360301. S2CID   13294240.
  26. ↑ Kasper, Dennis L.; Braunwald, Eugene; Fauci, Anthony S.; Hauser, Stephen L.; Longo, Dan L.; Jameson, J. Larry (2005). "Medical Disorders During Pregnancy". Harrison's Principles Of Internal Medicine (16th ed.). McGraw-Hill Medical Publishing Division.
  27. ↑ Brown, Zane A.; Gardella, Carolyn; Wald, Anna; Morrow, Rhoda Ashley; Corey, Lawrence (2005). "Genital herpes complicating pregnancy". Obstetrics and Gynecology. 106 (4): 845–856. doi:10.1097/01.AOG.0000180779.35572.3a. PMID   16199646. S2CID   8768010.
  28. ↑ Brown, Zane A.; Benedetti, Jacqueline; Ashley, Rhoda; Burchett, Sandra; Selke, Stacy; Berry, Sylvia; Vontver, Louis A.; Corey, Lawrence (May 1991). "Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor". New England Journal of Medicine . 324 (18): 1247–1252. doi: 10.1056/NEJM199105023241804 . PMID   1849612.
  29. ↑ Donda, Keyur; Sharma, Mayank; Amponsah, Jason K.; Bhatt, Parth; Chaudhari, Riddhi; Okaikoi, Michael; Dapaah-Siakwan, Fredrick (25 March 2019). "Trends in the incidence, mortality, and cost of neonatal herpes simplex virus hospitalizations in the United States from 2003 to 2014". Journal of Perinatology . 39 (5): 697–707. doi:10.1038/s41372-019-0352-7. PMID   30911082. S2CID   85494894.
  30. ↑ Brown, Elizabeth L.; Gardella, Carolyn; Malm, Gunilla; Prober, Charles G.; Forsgren, Marianne; Krantz, Elizabeth M.; Arvin, Ann M.; Yasukawa, Linda L.; Mohan, Kathleen; Brown, Zane; Corey, Lawrence; Wald, Anna (2007). "Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes". Acta Obstetricia et Gynecologica Scandinavica . 86 (5): 523–529. doi: 10.1080/00016340601151949 . PMID   17464578. S2CID   42137591.
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