Neonatal herpes simplex

Congenital herpesviral (herpes simplex) infection
Classification and external resources
ICD-10	P35.2
ICD-9	771.2, 054.xx

Neonatal herpes simplex is a rare but serious condition, usually caused by vertical transmission of herpes simplex virus from mother to newborn.

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%^[1] of cases.

Epidemiology

Neonatal HSV rates in the U.S. are estimated to be between 1 in 3,000 and 1 in 6,000 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.^[2] 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. This in part is due to the transfer of significant titer of protective maternal antibodies to the fetus from about the seventh month of pregnancy.^[3][4] However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant.^[3]

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 seroprevalance 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 recent 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.^[1] 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,^[3][5] However, with prompt application of antiviral therapy, the prognosis of neonatal HSV-1 infection is better than that for HSV-2.

Presentation

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

• SEM herpes is characterized by external lesions but no internal organ involvement. 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).^[7]

• DIS herpes affects internal organs, particularly 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 seizures, tremors, lethargy, and irritability, they feed poorly, have unstable temperatures, and their fontanelle (soft spot of the skull) may bulge.^[3]

CNS herpes is associated with highest morbidity, and 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 its attendant increases in mortality and morbidity.

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 a concurrent sepsis in approximately one quarter of cases that further clouds speedy diagnosis.

Treatment

Reductions in morbidity and mortality are due to the use of antiviral treatments such as vidarabine and acyclovir.^{[6][8][9][10]} 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.^[11] A recent large scale retrospective study found disseminated NHSV paitents least likely to get timely treatment, contributing to the high morbidity/mortality in that group.^[12]

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.^[13] The current practice is to deliver women with primary or first episode non primary infection via caesarean section, and those with recurrrent infection vaginally, even in the presence of lesions because of the low risk (1-3%) of vertical transmission associated with recurrent herpes.

Risk factors

Among the maternal risk factors for Neonatal HSV-1: White non-Hispanic race^[14], young maternal age (<25), primary infection in third trimester^[15] , first pregnancy, HSV (1&2) seronegative,^[3][16] discordant partner,^[17] gestation <38 weeks^[15], receptive oral sex in third trimester.^[18]

Neonatal HSV-2 maternal risk factors: Black race^[19], young maternal age (<21)^[3][15], discordant partner, primary or non primary first episode infection in third trimester^[20], four or more lifetime sexual partners^[19], lower level of education^[19], history of previous STD, history of pregnancy wastage, first viable pregnancy, gestation <38 weeks.^[3][15]

See also

• Herpes simplex

References

1. ^ ^{a b} 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. doi:10.1542/peds.2005-1778. PMID 16740836. http://pediatrics.aappublications.org/cgi/content/abstract/117/6/1955. 
2. ^ 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. 
3. ^ ^{a b c d e f g} 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. doi:10.1001/jama.289.2.203. PMID 12517231. http://jama.ama-assn.org/cgi/reprint/289/2/203. 
4. ^ Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S, Vontver LA, Corey L (May 1991). "Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor". N Engl J Med 324 (18): 1247–52. doi:10.1056/NEJM199105023241804. PMID 1849612. 
5. ^ 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. doi:10.1080/00016340601151949. PMID 17564578. http://www.informaworld.com/smpp/content~content=a777727985~db=all. 
6. ^ ^{a b} 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. 
7. ^ Prober CG (1997). Long SS, Pickering, LK Prober CG. ed. Herpes simplex virus. Churchhill Livingstone, New York.. p. 1138. 
8. ^ Kesson AM (2001). "Management of neonatal herpes simplex virus infection". Paediatr Drugs 3 (2): 81–90. doi:10.2165/00128072-200103020-00001. PMID 11269641. 
9. ^ "The Merck Manual, Neonatal Herpes Simplex Virus (HSV) Infection". http://www.merck.com/mmpe/sec19/ch279/ch279h.html. 
10. ^ Brocklehurst P, Kinghorn GA et al. (1998). "randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection". Br J Obstet Gynaecol 105 (3): 275–80. doi:10.1111/j.1471-0528.1998.tb10086.x. PMID 9532986. 
11. ^ Jacobs RF (1998). "Neonatal herpes simplex virus infections". Semin. Perinatol. 22 (1): 64–71. doi:10.1016/S0146-0005(98)80008-6. PMID 9523400. 
12. ^ Caviness AC, Demmler GJ, Selwyn BJ (May 2008). "Clinical and laboratory features of neonatal herpes simplex virus infection: a case-control study". Pediatr. Infect. Dis. J. 27 (5): 425–30. doi:10.1097/INF.0b013e3181646d95. PMID 18360301. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0891-3668&volume=27&issue=5&spage=425. 
13. ^ Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 16th ed., 2005
14. ^ Xu F, Markowitz LE, Gottlieb SL, Berman SM (January 2007). "Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States". Am. J. Obstet. Gynecol. 196 (1): 43.e1–6. doi:10.1016/j.ajog.2006.07.051. PMID 17240228. http://linkinghub.elsevier.com/retrieve/pii/S0002-9378(06)01156-2. 
15. ^ ^{a b c d} Whitley R (June 2004). "Neonatal herpes simplex virus infection". Curr. Opin. Infect. Dis. 17 (3): 243–6. doi:10.1097/00001432-200406000-00012. PMID 15166828. 
16. ^ Nahmias AJ (August 2004). "Neonatal HSV infection Part II: Obstetric considerations -- a tale of hospitals in two cities (Seattle and Atlanta, USA)". Herpes 11 (2): 41–4. PMID 15955267. http://openurl.ingenta.com/content/nlm?genre=article&issn=0969-7667&volume=11&issue=2&spage=41&aulast=Nahmias. 
17. ^ Baker DA (December 2005). "Risk factors for herpes simplex virus transmission to pregnant women: a couples study". Am. J. Obstet. Gynecol. 193 (6): 1887–8. doi:10.1016/j.ajog.2005.08.007. PMID 16325587. http://linkinghub.elsevier.com/retrieve/pii/S0002-9378(05)01225-1. 
18. ^ Nahmias AJ (August 2004). "Neonatal HSV infection Part I: continuing challenges". Herpes 11 (2): 33–7. PMID 15955265. http://www.ihmf.org/journal/download/112Nahmias(33)vol1133.pdf. 
19. ^ ^{a b c} Mertz GJ (December 1993). "Epidemiology of genital herpes infections". Infect. Dis. Clin. North Am. 7 (4): 825–39. PMID 8106731. 
20. ^ Gardella C, Brown ZA, Wald A, et al. (August 2005). "Poor correlation between genital lesions and detection of herpes simplex virus in women in labor". Obstetrics and gynecology 106 (2): 268–74. doi:10.1097/01.AOG.0000171102.07831.74. PMID 16055574.