Sandbox: Reddy

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

Historical Perspective

• In 1947, the first case of congenital varicella syndrome was reported.

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 affecting the fetus in utero.
• The risk of abortion is high when the infection in the fetus occurs before 20 weeks of gestation.

Natural History, Prognosis and Complications

Prognosis

Prognosis of infants with congenital varicella syndrome is poor, early death is due to gastroesophageal reflux and recurrent aspiration pneumonia and respiratory failure.

Complications

• Fetal demise
• Intrauterine growth restriction
• Hydrops
• Limb deformities
• Microcephaly

Diagnosis

Physical Examination

Clinical manifestations suggestive of Congenital varicella syndrome include:

	Clinical Manifestations in congenital varicella syndrome
Skin	Cicatricial lesions Cutaneous defects Hypopigmentation
Eye	Chorioretinitis Cataracts Micropthalmia Anisocoria
Central Nervous System	Intrauterine encephalitis Cortical atrophy/porencephaly Seizures Mental retardation Autonomic instability
Musculoskeletal system	Limb hypoplasia Muscle hypoplasia
Gastrointestinal	Gastrointestinal reflux
Systemic Manifestations	Intrauterine growth retardation Developmental delay
Urinary Tract	Hydroureter Hydronephrosis

Laboratory Findings

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 of the scraped samples from the skin lesions can be done, but takes around 10 to 12 days for results.
• Direct fluroscent antigen staining with monoclonal antibodies detects the VZV glycoproteins in the cells from the skin lesion.
• PCR for the VZV
• Serological tests are not useful for the dectection of primary infection as it takes time for the IgG antibodies to be produced aganist VZV.

Prenatal Diagnosis

• Sequential ultrasound of the fetus is helpful to establish the presence of varicella infection and assess the severity of intrauterine infection.
• The features suggestive of intrauterine infection on ultrasound include presence of microcephaly, limb hypoplasia, liver calcifications.
• Amniocentesis should be performed 4weeks after the primary infection in the mother, positive amniotic PCR for VZV can establish the presence of infection but does not provide information regarding the infection status and severity in the fetus.

Imaging Studies

Ultrasound

• Sequential ultrasound in during the period of gestation helps in identifying fetal anomalies as a result of varicella infection.
• Features suggestive of congenital varicella syndrome include the following :
  • Cutaneous scars
  • Musculoskeletal deformities such as limb hypoplasia and contractures
  • Cerebral anomalies such as ventriculomegaly, microcephaly with polymicrogyria, and porencephaly
  • Ocular anomalies such as micropthalmia and congenital cataracts
  • Intestinal and hepatic echogenic foci suggestive of the presence of liver calcifications
  • Hydrops fetalis
  • Intrauterine growth restriction
  • Polyhydramnios

Prevention

Primary Prevention

• In all pregnant women documentation of varicella infection in the past and the pre-conceptional vaccination should be be documented.
• 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. These patients must be counseled regarding the risks of varicella infection as vaccination aganist VZV is contraindicated during the pregnancy.
• Vaccination is the best preventive measure, women who are seronegative should recieve two doses of the vaccine during the postpartum period 4 to 8 weeks apart, without any effect on breast feeding.
• Women can also 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 72-96hours of exposure. Passive immnuniaztion with immmunoglobulins decreases the risk of severe disease in the mother, but its efficacy in preventing the disease to the fetus is not established.