Varicella Infection in Pregnancy - Consequences for Foetus and Neonate

Dr. Sayenna A Uduman, Dr. Abdul Kareem Uduman
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Management: varicella in Pregnant women & their Newborn:
Pregnant women:
Prevention of maternal varicella through vaccination is key to the prevention of maternal and neonatal complications. Varicella exposed mothers should have their susceptibility test (IgG VZV antibody Elisa test). done as soon as possible. But Varicella vaccine should not be administered to pregnant women, because the possible effects on fetal development are unknown.
Should consider post exposure prophylaxis with intramuscular VariZIG (Varicella zoster antibody rich IgG) for mothers found to be sero-negative for varicella antibodies. VariZIG is a purified immune globulin preparation made from pooled human plasma containing high levels of anti-VZV antibodies (IgG). To decrease the risk of severe maternal complications of infection, IM variZig should be given as soon as possible. It is ideal to administer within 72 to 96 hours of exposure and may be useful if given up to 10 days post exposure. IM VariZIG has not been proven to prevent CVS or neonatal varicella infection, but it is given
If IM variZIG is not available, IVIG (intravenous polyclonal Immunoglobulins) or Intravenous varicella antibody rich products (Biotest Pharma GmbH) that are used in Europe, can prevent or modify the course of disease. . The recommended IVIG dose for post-exposure prophylaxis of varicella is 400 mg/kg, administered once intravenously. The immune globulin preparations are not effective treatment once disease is established. Dosing of post exposure immune and chemoprophylaxis is given in table 1.
Intravenous human zoster immunoglobulin: Contains 25 IU/ml solution (Biotest Pharma GmbH). Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the fetus and the neonate are to be expected. Immunoglobulin’s are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.
Dosing: 1 ml (25 IU) per kg body weight. For post-exposure prophylaxis, it should be administered as soon as possible and not later than 96 h after exposure.

Antiviral therapy:
Acyclovir may be indicated, especially for severe maternal disease or varicella pneumonia develops. Acyclovir is a category B drug and oral acyclovir should be prescribed for pregnant women if they present within 24 hours of the onset of the rash and if they are more than 20 weeks of gestation. Acyclovir can be used with caution in early pregnancy and the risks and benefits should be discussed. Some experts recommend oral acyclovir or valacyclovir for pregnant women, especially during the second and third trimesters.
Intravenous acyclovir is recommended to all pregnant women with severe complications of varicella, irrespective of when the rash developed.

Dosing of anti-viral in pregnant women: If VariZIG or IVIG are not available, experts recommend prophylaxis with acyclovir OR valacyclovir; beginning 7 to 10 days after exposure and continuing for 7 days for patients without evidence of immunity who have been exposed to varicella or herpes zoster.
Acyclovir: 20 mg/kg per dose, administered 4 times per day, with a maximum daily dose of 3200 mg) Valacyclovir: 20 mg/kg per dose, administered 3 times per day, with a maximum daily dose of 3000 mg)
A 7-day course of acyclovir or valacyclovir also may be given to adults without evidence of immunity if vaccine is contraindicated.
Varicella infected mothers should be referred to a Fetal Medicine and Infectious Disease Consultant 5 weeks after infection for discussion and detailed ultrasound examination. The risks versus benefit of amniocentesis to detect varicella DNA by PCR should be discussed. Amniocentesis should be planned only after the skin lesions have completely healed.

Newborns exposed to maternal varicella during the time of delivery:
• Infants should be given IM variZIG immediately after birth even if maternal variZIG was administered. IVIG is an alternative if variZIG is unavailable. These infants should be observed closely, because many will still develop chickenpox infection. however, their risk of severe infection will be decreased.

IM variZIG is indicated for post exposure prophylaxis for preterm born less than 28 weeks' gestation, or who have a birth weight 1000 g or less. Also, preterm infants born more than 28 weeks gestation to susceptible mothers, should receive IM variZIG because these mothers will not have passed protective antibody to their infants
Postnatally exposed healthy term infants are generally protected by maternally derived IgG antibody. Therefore, post exposure immunoprophylaxis is not generally indicated for full term born infants. However, some would give variZIG to babies in the first 2 weeks of life whose mothers are not varicella immune by serology testing.
IV acyclovir may be useful for the treatment of severe infection or potentially severe infection in any infant with chickenpox. Famciclovir is available for treatment of VZV infections in adults, but its efficacy and safety have not been established for children.
Isolation of exposed or varicella infected patients is of critical importance, especially on labor in delivery units, and in neonatal care units. Airborne and contact isolation procedures need to be instituted for babies born to mothers with acute varicella for the first 21 days of life and continued for 28 days if the baby received VariZIG. However, should a woman develop zoster during the period from 5 days before until 2 days after delivery, there is no additional risk to the newborn as there is no hematogenous spread of the virus.

Table 1: Dosing of IM Varicella Zoster Immune Globulin Based on Weight
Weight (kg) VariZIG (units) Volume (ml) to administer
>40 625 (5 vials) 6.0
30.1 - 40 500 (4 vials) 4.8
20.1 - 30 375 (3 vials) 3.6
10.1 - 20 250 (2 vials) 2.4
2.1 - 10 125 (1 vial) 1.2
<2 62.5 (0.5 vial) 0.6
Note: If VariZIG is not available, IVIG is given once intravenously at the dose of 400 mg/kg.



Post exposure immunoglobulin prophylaxis (ZIG and VariZIG) has been recommended over- decades for newborn and other varicella susceptible high risk patients including pregnant woman. Efficacy is increased if prophylaxis is given as soon as possible after exposure
Women who develop varicella in early pregnancy should be referred to a Fetal Medicine and Infectious Diseases specialist. VariZIG has no therapeutic benefit once chickenpox has developed and should therefore not be used in pregnant women who have already developed varicella vesicles.
Neonatal varicella resulting from maternal infection near the time of delivery or immediately postpartum exposure may result a devastating clinical outcome. Therefore, it is vital that the neonate receives variZIG immunoprophylaxis as soon as possible with or without acyclovir.

References
Varicella Infection in Pregnancy - Consequences for Foetus and Neonate Varicella Infection in Pregnancy - Consequences for Foetus and Neonate 09/05/2018
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