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{{Herpes simplex}}
{{Herpes simplex}}
{{CMG}}, {{AE}} {{CZ}}; [[Lakshmi Gopalakrishnan, M.B.B.S.]]
{{CMG}}; {{AE}} {{CZ}}, [[Lakshmi Gopalakrishnan, M.B.B.S.]]


==Overview==
==Overview==
[[Infant|Neonatal]] HSV disease is a rare but serious condition, usually as a consequence of [[vertical transmission]] of the virus from the mother to the newborn child, although an estimated 10% of cases may be acquired [[postnatal|postnatally]] from a parent, caretaker, or sibling. From 1/3,000 to 1/20,000 of live births are infected with neonatal herpes. Approximately 22% of pregnant women have had a previous exposure HSV-2, and a further 2% or more women acquire the virus during pregnancy.<ref name="pmid16199646">{{cite journal |author=Brown ZA, Gardella C, Wald A, Morrow RA, Corey L |title=Genital herpes complicating pregnancy |journal=Obstet Gynecol |volume=106 |issue=4 |pages=845–56 |year=2005 |pmid=16199646 |doi=10.1097/01.AOG.0000180779.35572.3a}}</ref> Particularly among young adults, genital herpes infections are increasing caused by HSV-1.<ref name="pmid17197885">{{cite journal |author=Baker DA |title=Consequences of herpes simplex virus in pregnancy and their prevention |journal=Curr. Opin. Infect. Dis. |volume=20 |issue=1 |pages=73–6 |year=2007 |pmid=17197885 |doi=10.1097/QCO.0b013e328013cb19}}</ref>  
[[Infant|Neonatal]] [[HSV]] disease is a rare but serious condition, usually as a consequence of [[vertical transmission]] of the [[virus]] from the mother to the newborn child, although an estimated 10% of cases may be acquired [[postnatal|postnatally]] from a parent, caretaker, or sibling. Between 1 in 3,000 and 1 in 20,000 live births are infected with neonatal herpes. Approximately 22% of pregnant women have had a previous exposure [[HSV-2]], and a further 2% or more women acquire the virus during pregnancy.<ref name="pmid16199646">{{cite journal |author=Brown ZA, Gardella C, Wald A, Morrow RA, Corey L |title=Genital herpes complicating pregnancy |journal=Obstet Gynecol |volume=106 |issue=4 |pages=845–56 |year=2005 |pmid=16199646 |doi=10.1097/01.AOG.0000180779.35572.3a}}</ref> Particularly among young adults, genital herpes infections are increasing caused by [[HSV-1]].<ref name="pmid17197885">{{cite journal |author=Baker DA |title=Consequences of herpes simplex virus in pregnancy and their prevention |journal=Curr. Opin. Infect. Dis. |volume=20 |issue=1 |pages=73–6 |year=2007 |pmid=17197885 |doi=10.1097/QCO.0b013e328013cb19}}</ref>
==Pathophysiology==
===Risk of Transmission===
The risk of transmission is 30-57% in cases of primary infection acquisition by the mother in the [[Pregnancy#physiology|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 presence of significant [[titer]] of protective maternal antibodies in the fetus from about the seventh month of pregnancy.<ref name="pmid12517231">{{cite journal |author=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L |title=Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant |journal=JAMA |volume=289 |issue=2 |pages=203–9 |year=2003 |pmid=12517231 |doi=}}</ref> However, [[Herpes simplex asymptomatic shedding|shedding]] of [[HSV-1]] from both primary genital infection and [[Herpes simplex recurrence|reactivation]] is associated with high transmission from mother to infant.<ref name="pmid12517231"/>  


==Epidemiology and Demographics==
==Epidemiology and Demographics==
====Developing Countries:====
====Developing Countries====
HSV-1 neonatal herpes is extremely rare in developing countries because primary exposure to HSV-1 (and therefore development of HSV-1 specific antibodies) usually occurs in childhood or adolescence, precluding a genital HSV-1 infection; HSV-2 infections are much more common in these countries.  
[[HSV-1]] neonatal herpes is extremely rare in developing countries because primary exposure to [[HSV-1]] (and therefore development of HSV-1 specific antibodies) usually occurs in childhood or adolescence, precluding a genital HSV-1 infection; [[HSV-2]] infections are much more common in these countries.  


====Developed Countries:====
====Developed Countries====
*In industrialized nations the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades as a result of better hygiene, less over-crowding, and smaller family size. The resulting increase in the number of young women entering the sexually active/child bearing years as HSV-1 seronegative, has been a harbinger of increased HSV-1 genital herpes, and as a result, increased HSV-1 neonatal herpes in developed nations.   
*In industrialized nations the adolescent [[HSV-1]] seroprevalance has been dropping steadily for the last 5 decades as a result of better hygiene, less over-crowding, and smaller family size. The resulting increase in the number of young women entering the sexually active/child bearing years as [[HSV-1]] [[seronegative]], has been a harbinger of increased HSV-1 genital herpes, and as a result, increased HSV-1 neonatal herpes in developed nations.   


*A recent three year study in Canada revealed neonatal HSV infections in 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases of neonatal herpes, and 98.7% of transmission was asymptomatic.<ref name=Kropp>{{cite journal  
*A recent three year study in Canada revealed neonatal [[HSV]] infections in 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases of neonatal herpes, and 98.7% of transmission was asymptomatic.<ref name=Kropp>{{cite journal  
| author=Kropp RY., Wong T, et al | title=Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study | journal=Pediatrics  | year=2006 | pages=1955-1962 | volume=117 | issue=61 | id=PMID 16740836 |  |doi= |url=http://pediatrics.aappublications.org/cgi/content/abstract/117/6/1955
| author=Kropp RY., Wong T, et al | title=Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study | journal=Pediatrics  | year=2006 | pages=1955-1962 | volume=117 | issue=61 | id=PMID 16740836 |  |doi= |url=http://pediatrics.aappublications.org/cgi/content/abstract/117/6/1955
}}</ref>  
}}</ref>  


*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.<ref name=ZA_Brown>{{cite journal  
*[[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]].<ref name=ZA_Brown>{{cite journal  
| author=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L | title=Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant | journal=JAMA  | year=2003 | pages=203-209 | volume=289 | issue=2 | id=PMID 12517231 |  |doi= |url=http://jama.ama-assn.org/cgi/reprint/289/2/203
| author=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L | title=Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant | journal=JAMA  | year=2003 | pages=203-209 | volume=289 | issue=2 | id=PMID 12517231 |  |doi= |url=http://jama.ama-assn.org/cgi/reprint/289/2/203
}}</ref><ref name=EL_Brown>{{cite journal  
}}</ref><ref name=EL_Brown>{{cite journal  
Line 31: Line 34:
}}</ref>
}}</ref>


==Risk of Transmission==
==Complications==
The risk of transmission is 30-57% in cases of primary infection acquisition by the mother in the [[Pregnancy#physiology|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 presence of significant titer of protective maternal antibodies in the fetus from about the seventh month of pregnancy.<ref name="pmid12517231">{{cite journal |author=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L |title=Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant |journal=JAMA |volume=289 |issue=2 |pages=203–9 |year=2003 |pmid=12517231 |doi=}}</ref> However, [[Herpes simplex asymptomatic shedding|shedding]] of HSV-1 from both primary genital infection and [[Herpes simplex recurrence|reactivation]] is associated with high transmission from mother to infant.<ref name="pmid12517231"/>
*Untreated, SEM herpes may spread to the internal organs and cause DIS or [[CNS]] herpes, resulting in increased mortality and morbidity.  


==Clinical Presentation==
*Death from neonatal HSV disease in the United States is currently decreasing; as many as 85% of [[HSV]]-infected neonates died a few decades ago, whereas the current death rate is about 25%. Reduction in mortality is due to the use of [[Antiviral Therapy|antiviral treatments]] such as [[vidarabine]] and [[acyclovir]].<ref name="pmid15685144">Kimberlin DW, Whitley RJ (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15685144 Neonatal herpes: what have we learned.] ''Semin Pediatr Infect Dis'' 16 (1):7-16. [http://dx.doi.org/10.1053/j.spid.2004.09.006 DOI:10.1053/j.spid.2004.09.006] PMID: [http://pubmed.gov/15685144 15685144]</ref><ref name="pmid11269641">Kesson AM (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11269641 Management of neonatal herpes simplex virus infection.] ''Paediatr Drugs'' 3 (2):81-90. PMID: [http://pubmed.gov/11269641 11269641]</ref>
 
*However, morbidity and mortality still remain high, as the diagnosis of DIS and CNS herpes often comes too late for effective antiviral administration. Early diagnosis is difficult because 20-40% of infected neonates that have no visible lesions.<ref name="pmid9523400">{{cite journal |author=Jacobs RF |title=Neonatal herpes simplex virus infections |journal=Semin. Perinatol. |volume=22 |issue=1 |pages=64–71 |year=1998 |pmid=9523400 |doi=}}</ref>
==Diagnosis==
===History and Symptoms===
*Neonatal herpes manifests itself in three forms: skin, eyes and mouth (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes.<ref name="pmid15685144"/>  
*Neonatal herpes manifests itself in three forms: skin, eyes and mouth (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes.<ref name="pmid15685144"/>  


:*SEM herpes is characterized by external lesions but no internal organ involvement, and has the best prognosis. Lesions are likely to appear on trauma sites such as the attachment site of fetal scalp electrodes, forceps or vacuum extractors that are used during delivery, in the margin of the eyes, the [[nasopharynx]], and in areas associated with trauma or surgery (including circumcision).<ref name="pmid12517231"/>  
:*SEM herpes is characterized by [[Lesions|external lesions]] but no internal organ involvement, and has the best prognosis. Lesions are likely to appear on trauma sites such as the attachment site of [[Electrodes|fetal scalp electrodes]], [[forceps]] or vacuum extractors that are used during delivery; in the margin of the eyes; the [[nasopharynx]]; and in areas associated with trauma or [[surgery]] (including circumcision).<ref name="pmid12517231"/>  


:*DIS herpes affects internal organs, especially the liver.
:*DIS herpes affects internal organs, especially the [[liver]].
 
:*CNS herpes is an infection of the nervous system and the brain that can lead to encephalitis. Infants with CNS herpes present with [[seizure]]s, [[tremor]]s, [[lethargy]], and irritability, they feed poorly, have unstable temperatures, and their [[fontanelle]] (soft spot of the skull) may bulge.<ref name="pmid12517231"/>  CNS herpes is associated with highest [[morbidity]], and DIS herpes has a higher [[mortality]] rate.


:*CNS herpes is an infection of the [[nervous system]] and the [[brain]] that can lead to [[encephalitis]]. Infants with CNS herpes present with [[seizure]]s, [[tremor]]s, [[lethargy]], and [[irritability]]. They feed poorly, have unstable temperatures, and their [[fontanelle]] (soft spot of the skull) may bulge.<ref name="pmid12517231"/>  CNS herpes is associated with highest [[morbidity]], and DIS herpes has a higher [[mortality]] rate. 
==Treatment==
==Treatment==
*Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a pediatric infectious disease specialist.  
===Medical Therapy===
 
*Infants exposed to [[HSV]] during birth, as documented by maternal virologic testing or presumed by observation of maternal [[lesions]], should be followed carefully in consultation with a pediatric infectious disease specialist.  
*Surveillance cultures of mucosal surfaces to detect HSV infection might be considered before the development of clinical signs of neonatal herpes.  
*Surveillance cultures of [[Mucosal|mucosal surfaces]] to detect [[HSV]] infection might be considered before the development of clinical signs of neonatal herpes.  
 
*In addition, administration of [[acyclovir]] might be considered for infants born to women who acquired [[HSV]] near term because the risk for neonatal herpes is high for these infants.  
*In addition, administration of [[acyclovir]] might be considered for infants born to women who acquired HSV near term because the risk for neonatal herpes is high for these infants.  
*All infants who have neonatal herpes should be promptly evaluated and treated with [[acyclovir|systemic acyclovir]]. The recommended regimen for infants treated for known or suspected neonatal herpes is [[acyclovir]] 20 mg/kg IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the [[skin]] and [[mucous membranes]].
 
===Prevention===
*All infants who have neonatal herpes should be promptly evaluated and treated with '''[[acyclovir|systemic acyclovir]]'''. The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the skin and mucous membranes.
*Herpes simplex virus infection in the newborn "carries high mortality and morbidity rates from central nervous system involvement," according to [[Harrison's Principles of Internal Medicine]], which recommends that pregnant women with active genital herpes [[lesions]] at the time of [[Labor (childbirth)|labor]] be delivered by [[cesarean section]].  
 
==Complications==
*Untreated, SEM herpes may spread to the internal organs and cause DIS or CNS herpes resulting in increased mortality and morbidity.
 
*Death from neonatal HSV disease in the US is currently decreasing; as high as 85% of HSV infected neonates died a few decades ago whereas the current death rate is about 25%. Reduction in mortality is due to the use of antiviral treatments such as [[vidarabine]] and [[acyclovir]].<ref name="pmid15685144">Kimberlin DW, Whitley RJ (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15685144 Neonatal herpes: what have we learned.] ''Semin Pediatr Infect Dis'' 16 (1):7-16. [http://dx.doi.org/10.1053/j.spid.2004.09.006 DOI:10.1053/j.spid.2004.09.006] PMID: [http://pubmed.gov/15685144 15685144]</ref><ref name="pmid11269641">Kesson AM (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11269641 Management of neonatal herpes simplex virus infection.] ''Paediatr Drugs'' 3 (2):81-90. PMID: [http://pubmed.gov/11269641 11269641]</ref>
 
*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 20-40% of infected neonates that have no visible lesions.<ref name="pmid9523400">{{cite journal |author=Jacobs RF |title=Neonatal herpes simplex virus infections |journal=Semin. Perinatol. |volume=22 |issue=1 |pages=64–71 |year=1998 |pmid=9523400 |doi=}}</ref>
 
==Prevention==
*Herpes simplex virus infection in the newborn "carries high mortality and morbidity rates from central nervous system involvement," according to [[Harrison's Principles of Internal Medicine]], which recommends that pregnant women with active genital herpes lesions at the time of labor be delivered by [[cesarean section]].  


*Women whose herpes is not active can be managed with [[acyclovir]].<ref>Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 17th ed., 2008</ref>
*Women whose herpes is not active can be managed with [[acyclovir]].<ref>Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 17th ed., 2008</ref>
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==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}


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Latest revision as of 22:09, 29 July 2020

For patient information on herpes simplex neonatorum, click here

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Lakshmi Gopalakrishnan, M.B.B.S.

Overview

Neonatal HSV disease is a rare but serious condition, usually as a consequence of vertical transmission of the virus from the mother to the newborn child, although an estimated 10% of cases may be acquired postnatally from a parent, caretaker, or sibling. Between 1 in 3,000 and 1 in 20,000 live births are infected with neonatal herpes. Approximately 22% of pregnant women have had a previous exposure HSV-2, and a further 2% or more women acquire the virus during pregnancy.[1] Particularly among young adults, genital herpes infections are increasing caused by HSV-1.[2]

Pathophysiology

Risk of Transmission

The risk of transmission is 30-57% in cases of primary infection acquisition by the mother 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 presence of significant titer of protective maternal antibodies in the fetus from about the seventh month of pregnancy.[3] However, shedding of HSV-1 from both primary genital infection and reactivation is associated with high transmission from mother to infant.[3]

Epidemiology and Demographics

Developing Countries

HSV-1 neonatal herpes is extremely rare in developing countries because primary exposure to HSV-1 (and therefore development of HSV-1 specific antibodies) usually occurs in childhood or adolescence, precluding a genital HSV-1 infection; HSV-2 infections are much more common in these countries.

Developed Countries

  • In industrialized nations the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades as a result of better hygiene, less over-crowding, and smaller family size. The resulting increase in the number of young women entering the sexually active/child bearing years as HSV-1 seronegative, has been a harbinger of increased HSV-1 genital herpes, and as a result, increased HSV-1 neonatal herpes in developed nations.
  • A recent three year study in Canada revealed neonatal HSV infections in 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases of neonatal herpes, and 98.7% of transmission was asymptomatic.[4]
  • 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.[5][6]

Complications

  • Untreated, SEM herpes may spread to the internal organs and cause DIS or CNS herpes, resulting in increased mortality and morbidity.
  • Death from neonatal HSV disease in the United States is currently decreasing; as many as 85% of HSV-infected neonates died a few decades ago, whereas the current death rate is about 25%. Reduction in mortality is due to the use of antiviral treatments such as vidarabine and acyclovir.[7][8]
  • However, morbidity and mortality still remain high, as the diagnosis of DIS and CNS herpes often comes too late for effective antiviral administration. Early diagnosis is difficult because 20-40% of infected neonates that have no visible lesions.[9]

Diagnosis

History and Symptoms

  • Neonatal herpes manifests itself in three forms: skin, eyes and mouth (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes.[7]
  • SEM herpes is characterized by external lesions but no internal organ involvement, and has the best prognosis. Lesions are likely to appear on trauma sites such as the attachment site of fetal scalp electrodes, forceps or vacuum extractors that are used during delivery; in the margin of the eyes; the nasopharynx; and in areas associated with trauma or surgery (including circumcision).[3]
  • DIS herpes affects internal organs, especially the liver.

Treatment

Medical Therapy

  • Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a pediatric infectious disease specialist.
  • Surveillance cultures of mucosal surfaces to detect HSV infection might be considered before the development of clinical signs of neonatal herpes.
  • In addition, administration of acyclovir might be considered for infants born to women who acquired HSV near term because the risk for neonatal herpes is high for these infants.
  • All infants who have neonatal herpes should be promptly evaluated and treated with systemic acyclovir. The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the skin and mucous membranes.

Prevention

  • Women whose herpes is not active can be managed with acyclovir.[10]

References

  1. Brown ZA, Gardella C, Wald A, Morrow RA, Corey L (2005). "Genital herpes complicating pregnancy". Obstet Gynecol. 106 (4): 845–56. doi:10.1097/01.AOG.0000180779.35572.3a. PMID 16199646.
  2. Baker DA (2007). "Consequences of herpes simplex virus in pregnancy and their prevention". Curr. Opin. Infect. Dis. 20 (1): 73–6. doi:10.1097/QCO.0b013e328013cb19. PMID 17197885.
  3. 3.0 3.1 3.2 3.3 Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L (2003). "Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant". JAMA. 289 (2): 203–9. PMID 12517231.
  4. Kropp RY., Wong T; et al. (2006). "Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study". Pediatrics. 117 (61): 1955–1962. PMID 16740836.
  5. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L (2003). "Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant". JAMA. 289 (2): 203–209. PMID 12517231.
  6. Brown ZA, Gardella C, Malm G, Prober CG, Forsgren M, Krantz EM, Arvin AM, Yasukawa LL, Mohan K, Brown Z, Corey L, Wald A (2007). "Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes". Acta Obstet et Gynecol Scand. 86 (5): 523–529. PMID 17564578.
  7. 7.0 7.1 Kimberlin DW, Whitley RJ (2005) Neonatal herpes: what have we learned. Semin Pediatr Infect Dis 16 (1):7-16. DOI:10.1053/j.spid.2004.09.006 PMID: 15685144
  8. Kesson AM (2001) Management of neonatal herpes simplex virus infection. Paediatr Drugs 3 (2):81-90. PMID: 11269641
  9. Jacobs RF (1998). "Neonatal herpes simplex virus infections". Semin. Perinatol. 22 (1): 64–71. PMID 9523400.
  10. Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 17th ed., 2008

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