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===Laboratory Findings===
===Laboratory Findings===
The diagnosis of congenital varicella syndrome is based on a documented history of varicella infection during the pregnancy and the presence of fetal manifestations on ultrasound.<ref name="pmid2175786">{{cite journal| author=Scharf A, Scherr O, Enders G, Helftenbein E| title=Virus detection in the fetal tissue of a premature delivery with a congenital varicella syndrome. A case report. | journal=J Perinat Med | year= 1990 | volume= 18 | issue= 4 | pages= 317-22 | pmid=2175786 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2175786  }} </ref><br>
The diagnosis of congenital varicella syndrome is based on a documented history of varicella infection during the pregnancy and the presence of fetal manifestations on [[ultrasound]].<ref name="pmid2175786">{{cite journal| author=Scharf A, Scherr O, Enders G, Helftenbein E| title=Virus detection in the fetal tissue of a premature delivery with a congenital varicella syndrome. A case report. | journal=J Perinat Med | year= 1990 | volume= 18 | issue= 4 | pages= 317-22 | pmid=2175786 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2175786  }} </ref><br>
{| border="1"
{| border="1"
|-
|-
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!'''History'''
!'''History'''
|
|
*Positive history for varicella infection during the period of gestation                                                                                                               
*Positive history for [[varicella]] infection during the [[period of gestation]]                                                                                                                
|-
|-
!'''Fetus / Neonatal Findings'''
!'''Fetus / Neonatal Findings'''
Line 238: Line 238:
!'''Proof of Intrauterine Varicella infection'''
!'''Proof of Intrauterine Varicella infection'''
|  
|  
*Positive PCR for VZV DNA
*Positive [[PCR]] for [[VZV]] [[DNA]]
*Persistence of IgG antibodies at 7 months of age
*Persistence of [[IgG]] [[antibodies]] at 7 months of age
|}
|}
<small>Table adopted from Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections<ref name="SauerbreiWutzler2006">{{cite journal|last1=Sauerbrei|first1=A.|last2=Wutzler|first2=P.|title=Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections|journal=Medical Microbiology and Immunology|volume=196|issue=2|year=2006|pages=95–102|issn=0300-8584|doi=10.1007/s00430-006-0032-z}}</ref></small><br>
<small>Table adopted from Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections<ref name="SauerbreiWutzler2006">{{cite journal|last1=Sauerbrei|first1=A.|last2=Wutzler|first2=P.|title=Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections|journal=Medical Microbiology and Immunology|volume=196|issue=2|year=2006|pages=95–102|issn=0300-8584|doi=10.1007/s00430-006-0032-z}}</ref></small><br>


'''Diagnosis of primary infection in the mother :''' In pregnant women diagnosis of a primary infection requires a combination of clinical manifestations and series of diagnostic tests. The tests are performed on the samples from the vesicular skin lesions and include the following:  
'''Diagnosis of primary infection in the mother :''' In pregnant women diagnosis of a primary infection requires a combination of clinical manifestations and series of diagnostic tests. The tests are performed on the samples from the vesicular skin lesions and include the following:  
*Culture for VZV, but takes 10 to 12 days to obtain the results.
*[[Culture]] for [[VZV]], but takes 10 to 12 days to obtain the results.
*Direct fluroscent antigen staining with monoclonal antibodies detects the VZV glycoproteins in the cells.
*Direct fluroscent [[antigen]] staining with [[monoclonal]] [[antibodies]] detects the [[VZV]] glycoproteins in the cells.
*PCR for the VZV  
*[[PCR]] for [[VZV]] [[DNA]]
*Serological tests are not useful for the dectection of primary infection in the mother as it takes time for the IgG antibodies to be produced aganist VZV.
*[[Serological]] tests are not useful for the dectection of primary infection in the [[mother]] as it takes time for the [[IgG]] antibodies to be produced aganist [[VZV]].
'''Prenatal Diagnosis'''
'''Prenatal Diagnosis'''
*Sequential ultrasound of the fetus is helpful to establish the presence of varicella infection and assess the severity of intrauterine infection.<ref name="pmid10215075">{{cite journal| author=Hartung J, Enders G, Chaoui R, Arents A, Tennstedt C, Bollmann R| title=Prenatal diagnosis of congenital varicella syndrome and detection of varicella-zoster virus in the fetus: a case report. | journal=Prenat Diagn | year= 1999 | volume= 19 | issue= 2 | pages= 163-6 | pmid=10215075 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10215075  }} </ref><ref name="pmid16601342">{{cite journal| author=Meyberg-Solomayer GC, Fehm T, Muller-Hansen I, Enders G, Poets C, Wallwiener D et al.| title=Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome. | journal=Fetal Diagn Ther | year= 2006 | volume= 21 | issue= 3 | pages= 296-301 | pmid=16601342 | doi=10.1159/000091360 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16601342  }} </ref>
*Sequential [[ultrasound]] of the [[fetus]] is helpful to establish the presence of [[varicella]] infection and assess the severity of intrauterine infection.<ref name="pmid10215075">{{cite journal| author=Hartung J, Enders G, Chaoui R, Arents A, Tennstedt C, Bollmann R| title=Prenatal diagnosis of congenital varicella syndrome and detection of varicella-zoster virus in the fetus: a case report. | journal=Prenat Diagn | year= 1999 | volume= 19 | issue= 2 | pages= 163-6 | pmid=10215075 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10215075  }} </ref><ref name="pmid16601342">{{cite journal| author=Meyberg-Solomayer GC, Fehm T, Muller-Hansen I, Enders G, Poets C, Wallwiener D et al.| title=Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome. | journal=Fetal Diagn Ther | year= 2006 | volume= 21 | issue= 3 | pages= 296-301 | pmid=16601342 | doi=10.1159/000091360 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16601342  }} </ref>
*Amniocentesis should be performed 4 weeks after the primary infection in the mother, positive amniotic PCR for VZV can establish the presence of infection but does not provide evidence regarding the presence of infection or the severity of infection in the fetus. There is no established evidence to recommend amniocentesis for the diagnosis and is not performed on regular basis.<ref name="pmid9369842">{{cite journal| author=Mouly F, Mirlesse V, Méritet JF, Rozenberg F, Poissonier MH, Lebon P et al.| title=Prenatal diagnosis of fetal varicella-zoster virus infection with polymerase chain reaction of amniotic fluid in 107 cases. | journal=Am J Obstet Gynecol | year= 1997 | volume= 177 | issue= 4 | pages= 894-8 | pmid=9369842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9369842  }} </ref>
*[[Amniocentesis]] should be performed 4 weeks after the primary infection in the mother, positive [[amniotic fluid]] [[PCR]] for [[VZV]] can establish the presence of infection in the amniotic fluid but does not provide evidence regarding the presence of infection or the severity of infection in the [[fetus]]. There is no established evidence to recommend amniocentesis for the diagnosis and is not performed on regular basis.<ref name="pmid9369842">{{cite journal| author=Mouly F, Mirlesse V, Méritet JF, Rozenberg F, Poissonier MH, Lebon P et al.| title=Prenatal diagnosis of fetal varicella-zoster virus infection with polymerase chain reaction of amniotic fluid in 107 cases. | journal=Am J Obstet Gynecol | year= 1997 | volume= 177 | issue= 4 | pages= 894-8 | pmid=9369842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9369842  }} </ref>
*Presence of VZV IgM antibodies in fetal blood.
*Presence of VZV IgM antibodies in fetal blood.


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Synonyms and keywords: Fetal varicella syndrome, Congenital varicella-zoster syndrome, Varicella embryo-fetopathy, Varicella embryopathy, Varicella fetopathy, Fetal varicella-zoster syndrome

Overview

Congenital Varicella syndrome is a rare disease resulting from Varicella Zoster virus(VZV) infection during the period of gestation. Viremia during the primary infection can result in transplacental transmission of the infection to the developing fetus. 25% of women are estimated to have varicella infection during the pregnancy but the risk of developing congenital varicella syndrome is around 2%, therefore majority of the patients have normal newborns. Patients with primary infection before 20 weeks of gestation are at a higher risk of developing the severe form of infection, affecting the eyes, limbs, skin and the central nervous system. Diagnosis requires a documented history of primary infection in the mother and serial ultrasound demonstrating features suggestive of congenital varicella. There is no definitive treatment, termination of pregnancy in fetuses with severe features is recommended. Vaccination to prevent maternal varicella infection and proper counseling to avoid contact with infected people are important for the management options to reduce the incidence of congenital varicella syndrome.

Historical Perspective

Pathophysiology

Pathogenesis

Primary infection during the period of gestation:

  • Once a pregnant women has a primary varicella infection, transplacental transmission of the virus can take place as a result of the viremia affecting the fetus in utero. The resulting clinical manifestations are dependent on the gestational age of the fetus at the time of infection.[2]
  • An estimated of 25% fetuses are infected with varicella when the mother has a primary infection during the period of gestation, but only less than 2% of fetus develop congenital varicella syndrome.[3][4]
  • The risk of developing severe manifestations is high when the infection occurs before 20 weeks of gestation, which co-relate to the period of gestation when the innervation of the eyes and limbs occur.[5]
  • The risk of developing congenital varicella is (lower) 0.55% between weeks 0 and 12 and is higher (1.4%) between weeks 13 and 20.[6]
  • VZV is a neurotrophic virus and the pathogenesis of the wide variety of manifestations in the fetus is unclear, but it is proposed to be related to reactivation of the virus in the fetus, as it cannot mount a immune response aganist the infection.[7][8]
  • VZV virus is present in the sensory ganglia of the posterior roots of the spinal cord during the latent phase, reactivation of the virus in results in the destruction of the nervous tissue resulting in the characteristic cicatrical skin lesions, limb hypoplasia, bladder denervation, and bulbar palsy.[9]
  • The presence of diffuse calcifications in the liver, spleen, myocardium and brain support a mechanism of hematogenous spread.[10]

Epidemiology and Demographics

  • Congenital varicella syndrome is a rare disease and only 135 cases are reported in literature.

Causes

Congenital Varicella Syndrome is caused by Varicella zoster virus (VZV), a human alpha herpes virus.

Differentiating Congenital Varicella Syndrome From Other Diseases

The most important congenital infections, which can be transmitted vertically from mother to fetus are the TORCH infections. These infections have overlapping features and hence, must be differentiated from Congenital Varicella Syndrome:[11][12]

Congenital Infection Cardiac Findings Skin Findings Ocular Findings Hepatosplenomegaly Hydrocephalus Microcephaly Intracranial Calcifications Hearing deficits
Congenital Varicella Syndrome -
  • Cicatrical Skin Lesions
  • Skin Edema
  • Micropthalmus
  • Cataracts
 ✔ ✔ ✔
Toxoplasmosis ✔ ✔ ✔ Diffuse intracranial calcifications
Congenital Syphils ✔
Rubella ✔ ✔ ✔ ✔
Cytomegalovirus (CMV) ✔ ✔ ✔ Periventricular calcifications ✔
Herpes simplex virus (HSV) ✔ ✔ ✔ ✔
Parvovirus B19 ✔

Natural History, Prognosis and Complications

Natural History

VZV infection during pregnancy result in a normal newborn birth in majority of the patients, however, in a few patients it can result in congenital varicella syndrome, neonatal varicella and clinical zoster during infancy, the outcomes are dependent on the gestational age of fetus. Early gestational period infection via the transplacental route can result in congenital varicella syndrome resulting in a misscarriage, abortion or a newborn with features affecting the limbs, eyes, central nervous system, autonomic nervous system and present with features such as low birthweight, cutaneous scarring, limb hypoplasia, microcephaly, cortical atrophy, chorioretinitis and cataracts.[13][14]

Prognosis

In fetuses with severe infection it results in abortion. Infants born with signs of congenital varicella syndrome the prognosis is poor and die during the first few months of life.[15][13] Infants with milder symptoms can have a normal development and good prognosis.[16][17]

Complications

Congenital varicella infection can result in the following complications:[18]

Diagnosis

History and Symptoms

Symptoms of primary infection in Mother :

Symptoms in the Neonate

Physical Examination

Clinical manifestations suggestive of Congenital varicella syndrome include:[23][24]

Clinical Manifestations in congenital varicella syndrome
Skin
  • Cicatricial lesions( Zig-Zag scarring in dermatomal distribution)[25]
  • Hypopigmentation
Eye
Central Nervous System
Musculoskeletal system
  • Limb hypoplasia
  • Muscle hypoplasia
Systemic Manifestations
Urinary Tract

Table adopted from varicella in fetus and newborn[29]

Laboratory Findings

The diagnosis of congenital varicella syndrome is based on a documented history of varicella infection during the pregnancy and the presence of fetal manifestations on ultrasound.[30]

Key findings for diagnosis of congenital varicella syndrome
History
Fetus / Neonatal Findings
  • Presence of characteristic cicatrical skin lesions, eye lesions, neurological deficits, limb abnormalities
Proof of Intrauterine Varicella infection

Table adopted from Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections[31]

Diagnosis of primary infection in the mother : In pregnant women diagnosis of a primary infection requires a combination of clinical manifestations and series of diagnostic tests. The tests are performed on the samples from the vesicular skin lesions and include the following:

Prenatal Diagnosis

  • Sequential ultrasound of the fetus is helpful to establish the presence of varicella infection and assess the severity of intrauterine infection.[32][33]
  • Amniocentesis should be performed 4 weeks after the primary infection in the mother, positive amniotic fluid PCR for VZV can establish the presence of infection in the amniotic fluid but does not provide evidence regarding the presence of infection or the severity of infection in the fetus. There is no established evidence to recommend amniocentesis for the diagnosis and is not performed on regular basis.[34]
  • Presence of VZV IgM antibodies in fetal blood.

Imaging Studies

Ultrasound

  • Sequential ultrasound in women with varicella infection during the period of gestation is the preffered diagnostic investigation to identify anomalies in the fetus. Ultrasound is usally done 4 weeks after the primary infection as earlier ultrasound might fail to detect anomalies. The findings suggestive of congenital varicella syndrome include limb deformities, microcephaly and hydrops.
  • The following is a list of features that can be present in the fetus with varicella fetopathy:[35][36]
    • Cutaneous scars
    • Musculoskeletal deformities such as limb hypoplasia and contractures
    • Intrauterine growth restriction
    • Ventriculomegaly, microcephaly with polymicrogyria, and porencephaly
    • Micropthalmia and congenital cataracts
    • Calcification in the brain, spleen and liver[10]
    • Features of Hydrops fetalis such as skin edema, hepatosplenomegaly
    • Colonic Atresia[37]
    • Polyhydramnios

MRI

Prenatal MRI is a useful investigation to assess the extent of CNS involvement and to confirm the findings of ultrasound.[38] Postnatal Diagnosis

  • Postnatal diagnosis of intrauterine varicella infection in the infant is by serological persistance of VZV IgG antibodies at 7 months of life.[39]

Treatment

Medical Therapy

  • In patients with established infection early in the period of gestation, regular follow up and ultrasound examination is recommended.[31]
  • Termination of pregnancy is indicated in cases with the presence of definitive signs of congenital varicella infection.
  • There is insufficient evidence regarding the prevention and treatment of congenital varicella syndrome with IgG immunoglobulins and acyclovir.[6]
  • Varicella infection doesnot progress postnatally, so treatment with acyclovir is not indicated.[40]
  • Isolation is recommended in patients with active skin lesions.

Surgical Therapy

There are no surgical therapies for treatment of congenital varicella syndrome.

Prevention

Primary Prevention

  • Documentation of previous varicella infection and vaccination status in all pregnant women at the first antenatal visit.[41]
  • If the pregnant women has no previous infection or is not vaccinated, VZV IgG antibody testing must be done to determine the maternal immune status. [42]
  • In pregnant women with positive IgG, pregnant women are reassured that the IgG antibodies would protect the baby.
  • In pregnant women with negative IgG, counseling regarding the risks of varicella infection and education regarding the measures to avoid contact with varicella are recommended as vaccination aganist VZV is contraindicated during the pregnancy.
  • Women who are seronegative should recieve two doses of the vaccine during the postpartum period 4 to 8 weeks apart with no effect on breast feeding.
  • Women can be vaccinated during the preconception period, but are adviced to avoid conceiving for a month after the last dose of the vaccine.

Secondary Prevention

  • In pregnant women with exposure to varicella, passive immunization with varicella zoster virus antibodies (VZV IgG) should be administered after 72-96 hours of exposure as postexposure prophylaxis. Passive immunization is not proven to reduce viremia therefore its role in preventing congenital varicella syndrome is not well established.
  • Only indication at present is to prevent maternal complications of varicella in pregnancy.[43]

References

  1. ↑ Laforet, Eugene G.; Lynch, Charles L. (1947). "Multiple Congenital Defects Following Maternal Varicella". New England Journal of Medicine. 236 (15): 534–537. doi:10.1056/NEJM194704102361504. ISSN 0028-4793.
  2. ↑ McKendry JB, Bailey JD (1973). "Congenital varicella associated with multiple defects". Can Med Assoc J. 108 (1): 66–8. PMC 1941110. PMID 4682642.
  3. ↑ Paryani, Sharon G.; Arvin, Ann M. (1986). "Intrauterine Infection with Varicella-Zoster Virus after Maternal Varicella". New England Journal of Medicine. 314 (24): 1542–1546. doi:10.1056/NEJM198606123142403. ISSN 0028-4793.
  4. ↑ Brice JE (1976). "Congenital varicella resulting from infection during second trimester of pregnancy". Arch Dis Child. 51 (6): 474–6. PMC 1546018. PMID 942245.
  5. ↑ Pastuszak, Anne L.; Levy, Maurice; Schick, Betsy; Zuber, Carol; Feldkamp, Marcia; Gladstone, Johnathan; Bar-Levy, Fanny; Jackson, Elaine; Donnenfeld, Alan; Meschino, Wendy; Koren, Gideon (1994). "Outcome after Maternal Varicella Infection in the First 20 Weeks of Pregnancy". New England Journal of Medicine. 330 (13): 901–905. doi:10.1056/NEJM199403313301305. ISSN 0028-4793.
  6. ↑ 6.0 6.1 Tan MP, Koren G (2006). "Chickenpox in pregnancy: revisited". Reprod Toxicol. 21 (4): 410–20. doi:10.1016/j.reprotox.2005.04.011. PMID 15979274.
  7. ↑ Higa K, Dan K, Manabe H (1987). "Varicella-zoster virus infections during pregnancy: hypothesis concerning the mechanisms of congenital malformations". Obstet Gynecol. 69 (2): 214–22. PMID 3027637.
  8. ↑ Grose C (1989). "Congenital varicella-zoster virus infection and the failure to establish virus-specific cell-mediated immunity". Mol Biol Med. 6 (5): 453–62. PMID 2560525.
  9. ↑ Nikkels AF, Delbecque K, Pierard GE, Wienkotter B, Schalasta G, Enders M (2005). "Distribution of varicella-zoster virus DNA and gene products in tissues of a first-trimester varicella-infected fetus". J Infect Dis. 191 (4): 540–5. doi:10.1086/426942. PMID 15655777.
  10. ↑ 10.0 10.1 Rigsby CK, Donnelly LF (1997). "Fetal varicella syndrome: association with multiple hepatic calcifications and intestinal atresia". Pediatr Radiol. 27 (9): 779. doi:10.1007/s002470050229. PMID 9285750.
  11. ↑ Neu N, Duchon J, Zachariah P (2015). "TORCH infections". Clin Perinatol. 42 (1): 77–103, viii. doi:10.1016/j.clp.2014.11.001. PMID 25677998.
  12. ↑ Ajij M, Nangia S, Dubey BS (2014). "Congenital rubella syndrome with blueberry muffin lesions and extensive metaphysitis". J Clin Diagn Res. 8 (12): PD03–4. doi:10.7860/JCDR/2014/10271.5293. PMC 4316306. PMID 25654000.
  13. ↑ 13.0 13.1 Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M (1994). "Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases". Lancet. 343 (8912): 1548–51. PMID 7802767.
  14. ↑ Frey HM, Bialkin G, Gerson AA (1977). "Congenital varicella: case report of a serologically proved long-term survivor". Pediatrics. 59 (1): 110–2. PMID 402633.
  15. ↑ Sauerbrei A, Wutzler P (2000). "The congenital varicella syndrome". J Perinatol. 20 (8 Pt 1): 548–54. PMID 11190597.
  16. ↑ Kotchmar GS, Grose C, Brunell PA (1984). "Complete spectrum of the varicella congenital defects syndrome in 5-year-old child". Pediatr Infect Dis. 3 (2): 142–5. PMID 6328456.
  17. ↑ Schulze A, Dietzsch HJ (2000). "The natural history of varicella embryopathy: a 25-year follow-up". J Pediatr. 137 (6): 871–4. doi:10.1067/mpd.2000.109005. PMID 11113846.
  18. ↑ Savage MO, Moosa A, Gordon RR (1973). "Maternal varicella infection as a cause of fetal malformations". Lancet. 1 (7799): 352–4. PMID 4121940.
  19. ↑ Katz VL, Kuller JA, McMahon MJ, Warren MA, Wells SR (1995). "Varicella during pregnancy. Maternal and fetal effects". West J Med. 163 (5): 446–50. PMC 1303168. PMID 8533407.
  20. ↑ Sauerbrei A, Wutzler P (2007). "Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections". Med Microbiol Immunol. 196 (2): 95–102. doi:10.1007/s00430-006-0032-z. PMID 17180380.
  21. ↑ Andreou A, Basiakos H, Hatzikoumi I, Lazarides A (1995). "Fetal varicella syndrome with manifestations limited to the eye". Am J Perinatol. 12 (5): 347–8. doi:10.1055/s-2007-994493. PMID 8540940.
  22. ↑ Alexander I (1979). "Congenital varicella". Br Med J. 2 (6197): 1074. PMC 1596860. PMID 519294.
  23. ↑ Magliocco AM, Demetrick DJ, Sarnat HB, Hwang WS (1992). "Varicella embryopathy". Arch Pathol Lab Med. 116 (2): 181–6. PMID 1733414.
  24. ↑ Mendívil A, Mendívil MP, Cuartero V (1992). "Ocular manifestations of the congenital varicella-zoster syndrome". Ophthalmologica. 205 (4): 191–3. PMID 1336591.
  25. ↑ Lloyd KM (1990). "Skin lesions as the sole manifestation of the fetal varicella syndrome". Arch Dermatol. 126 (4): 546–7. PMID 2322006.
  26. ↑ Charles NC, Bennett TW, Margolis S (1977). "Ocular pathology of the congenital varicella syndrome". Arch Ophthalmol. 95 (11): 2034–7. PMID 411463.
  27. ↑ Cotlier E (1978). "Congenital varicella cataract". Am J Ophthalmol. 86 (5): 627–9. PMID 717518.
  28. ↑ Scheffer IE, Baraitser M, Brett EM (1991). "Severe microcephaly associated with congenital varicella infection". Dev Med Child Neurol. 33 (10): 916–20. PMID 1743417.
  29. ↑ Smith, Candice K.; Arvin, Ann M. (2009). "Varicella in the fetus and newborn". Seminars in Fetal and Neonatal Medicine. 14 (4): 209–217. doi:10.1016/j.siny.2008.11.008. ISSN 1744-165X.
  30. ↑ Scharf A, Scherr O, Enders G, Helftenbein E (1990). "Virus detection in the fetal tissue of a premature delivery with a congenital varicella syndrome. A case report". J Perinat Med. 18 (4): 317–22. PMID 2175786.
  31. ↑ 31.0 31.1 Sauerbrei, A.; Wutzler, P. (2006). "Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections". Medical Microbiology and Immunology. 196 (2): 95–102. doi:10.1007/s00430-006-0032-z. ISSN 0300-8584.
  32. ↑ Hartung J, Enders G, Chaoui R, Arents A, Tennstedt C, Bollmann R (1999). "Prenatal diagnosis of congenital varicella syndrome and detection of varicella-zoster virus in the fetus: a case report". Prenat Diagn. 19 (2): 163–6. PMID 10215075.
  33. ↑ Meyberg-Solomayer GC, Fehm T, Muller-Hansen I, Enders G, Poets C, Wallwiener D; et al. (2006). "Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome". Fetal Diagn Ther. 21 (3): 296–301. doi:10.1159/000091360. PMID 16601342.
  34. ↑ Mouly F, Mirlesse V, Méritet JF, Rozenberg F, Poissonier MH, Lebon P; et al. (1997). "Prenatal diagnosis of fetal varicella-zoster virus infection with polymerase chain reaction of amniotic fluid in 107 cases". Am J Obstet Gynecol. 177 (4): 894–8. PMID 9369842.
  35. ↑ Pretorius DH, Hayward I, Jones KL, Stamm E (1992). "Sonographic evaluation of pregnancies with maternal varicella infection". J Ultrasound Med. 11 (9): 459–63. PMID 1337112.
  36. ↑ Hofmeyr GJ, Moolla S, Lawrie T (1996). "Prenatal sonographic diagnosis of congenital varicella infection--a case report". Prenat Diagn. 16 (12): 1148–51. doi:10.1002/(SICI)1097-0223(199612)16:12<1148::AID-PD7>3.0.CO;2-J. PMID 8994252.
  37. ↑ Hitchcock R, Birthistle K, Carrington D, Calvert SA, Holmes K (1995). "Colonic atresia and spinal cord atrophy associated with a case of fetal varicella syndrome". J Pediatr Surg. 30 (9): 1344–7. PMID 8523241.
  38. ↑ Verstraelen H, Vanzieleghem B, Defoort P, Vanhaesebrouck P, Temmerman M (2003). "Prenatal ultrasound and magnetic resonance imaging in fetal varicella syndrome: correlation with pathology findings". Prenat Diagn. 23 (9): 705–9. doi:10.1002/pd.669. PMID 12975778.
  39. ↑ Gershon AA, Raker R, Steinberg S, Topf-Olstein B, Drusin LM (1976). "Antibody to Varicella-Zoster virus in parturient women and their offspring during the first year of life". Pediatrics. 58 (5): 692–6. PMID 185578.
  40. ↑ Harish, Rekha; Jamwal, Ashu; Dang, Ketan (2009). "Congenital varicella syndrome/ vericella zoster virus VZV fetopathy". The Indian Journal of Pediatrics. 77 (1): 92–93. doi:10.1007/s12098-009-0259-y. ISSN 0019-5456.
  41. ↑ "Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP)".
  42. ↑ Shrim A, Koren G, Yudin MH, Farine D, Maternal Fetal Medicine Committee (2012). "Management of varicella infection (chickenpox) in pregnancy". J Obstet Gynaecol Can. 34 (3): 287–92. PMID 22385673.
  43. ↑ Cohen A, Moschopoulos P, Maschopoulos P, Stiehm RE, Koren G (2011). "Congenital varicella syndrome: the evidence for secondary prevention with varicella-zoster immune globulin". CMAJ. 183 (2): 204–8. doi:10.1503/cmaj.100615. PMC 3033924. PMID 21262937.
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