Maternity Care Calendar and Guidelines: Screening for varicella immunity

Background
Varicella zoster is a highly contagious DNA virus of the herpes family that causes a primary illness (chickenpox), establishes a latent phase in the sensory nerve ganglia and can reactivate causing shingles or herpes zoster.[1] It is transmitted between hosts by oral secretions, airborne spread or direct contact with virus shed from characteristic skin lesions. The varicella virus has an incubation period ranging from 10-21 days and typically affects children under the age of 10.[2] Infectivity begins 1-2 days before the onset of the rash and persists until the last vesicle has crusted.[1, 2] Approximately 90% of household contacts will develop chickenpox. Antibody develops within a few days of infections and confers lifelong immunity. Chickenpox is more common in temperate climates and immigrants from subtropical regions may have a higher rate of susceptibility than the general population.[2]

Primary varicella zoster virus (VZV) infection in pregnancy can lead to untoward maternal, fetal and neonatal effects:

Primary VZV is more severe in adults than children, with increased rates of pneumonia, encephalitis and death. The case fatality rate is 10-30 times higher in adults than children.[1] Many authors report that varicella pneumonia is more severe during pregnancy[3, 4] with a considerable mortality (40% mortality rate in pregnant women prior to the advent of antiviral agents)[5]. However, this has not been substantiated by population-based studies.[1, 6] Oral acyclovir is felt to be safe in pregnancy and can be prescribed. If pneumonia develops, IV acyclovir may be used.[4, 7] If started within 24 hours, oral acyclovir is known to reduce the number of lesions and the duration of symptoms. [4]

Maternal infection in the first 20 weeks of pregnancy is associated with a 1-2% risk of congenital varicella syndrome -with the highest risk of vertical transmission between 13 and 20 weeks.[8-11] Congenital varicella syndrome is characterized by low birth weight, limb hypoplasia, opthalmologic abnormalities (cataracts, micropthalmia, chorioretinitis), neurologic abnormalities (microcephaly, mental retardation, cortical atrophy, bowel and bladder dysfunction) and dermatomal skin scarring.[8, 9, 11] Ultrasonography remains the preferred method of diagnosis of congenital varicella syndrome, although the sensitivity is unknown.[4] Invasive prenatal diagnosis is reassuring when test results are negative, but does not accurately predict the severity of infection when virus is detected by PCR in amniotic fluid, chorionic villi or fetal blood. [4]Treatment of maternal VZV infection with acyclovir has not been shown to prevent or reduce the incidence of congenital varicella syndrome. [4]

There was no significant increase in the rate of miscarriage in one study of 106 women with VZV infection in the first 20 weeks of pregnancy. [8]

When a pregnant woman is exposed to chickenpox, if her immunity is not already know, a past history of chickenpox should be elicited. If there is a definite history, it is reasonable to assume she is immune to VZV infection.[7] If there is any doubt about past infection, the serum should be tested for varicella zoster IgG. (80-90% of women without a history of chickenpox will be found to be immune.) Non-immune women should be given varicella zoster immune globulin (VZIG) as soon as possible.[5, 12] Although VIZG is usually administered within 96 hours of exposure, some authors advocate its use up to 10 days following exposure. [7, 13] The primary purpose of administering VZIG is the prevention of maternal infection. There is controversy in the literature as to whether VZIG prevents embryopathy. [5] In one observational study, where 97 pregnant women contracted varicella, despite VZIG administration, there were no cases of congenital varicella syndrome or zoster in infancy.[9] In another study of 106 women with VZV infection in the first 20 weeks of pregnancy, there was 1 infant born with severe congenital varicella syndrome in a women that received VZIG 4 days after exposure to chickenpox.[8] A cost-effectiveness analysis showed that management based on serotesting was preferable to universal administration of VZIG to all exposed pregnant women without a history of chickenpox. [14]

Maternal infection with VZV can also lead to herpes zoster in the infant (0.8%-1.7% of cases)[1, 6]

Infants born to mothers who develop chickenpox from between 5 days before to 2 days after delivery are at risk of developing severe neonatal varicella (15-30%).[1, 6, 15] If the mother contracts VZV during this time, protective antibody is not passed to the neonate and consequently, disease in the newborn is often severe and associated with a high mortality rate (20-30%).[4, 6] This risk is greatly reduced by administration of VZIG and all such neonates should receive it. [4, 9, 12, 15] Infants who develop VZV within the first 2 weeks of life should also be treated with acyclovir. [4]

Shingles in pregnancy are not associated with an increased risk of congenital defects.[16] Also maternal shingles in the perinatal period does not appear to be a concern, as the infants possess passive antibody and zoster is not associated with viremia.[7, 9, 16]

Screening for Varicella Immunity in Pregnancy:
A number of authors have advocated a program of routine screening of women of childbearing years for varicella immunity and vaccination of non-immune women.[5, 17, 18] One cost-effectiveness analysis showed that selective serotesting of pregnant women without a prior history of varicella infection, with postpartum vaccination of seronegative women, would prevent nearly half the chickenpox cases in this cohort and is cost-saving[19]. However, others have found that routine antenatal varicella screening of history negative women was not cost effective unless it was part of a policy of universal screening of all history-negative adults, with immunization as appropriate.[20] Interestingly, one study found that relying on a strategy in which those with a reliable history of chickenpox would be considered immune and not sent for serologic testing, missed as many susceptible individuals as it identified (10/19 subjects).[21]

The varicella vaccine
"Varivax III" or "Varilrix" are live vaccines consisting of an attenuated strain of the varicella virus and is much less virulent than the wild type strain. However, because it is a live vaccine, the varicella vaccine is contraindicated in pregnancy due to concerns that its use in pregnancy may precipitate congenital varicella syndrome. To determine the effects of Varicella on the fetus a Varivax pregnancy registry was established to follow cases of accidental Varicella vaccine administration during pregnancy. To date, the varicella vaccine administered during pregnancy has not resulted in morbidity to the fetus.[6, 22] Studies also indicate that women vaccinated with the varicella vaccine should be advised to avoid becoming pregnant within an interval of 1-3 months.[6, 22]

Breastfeeding:
Although it is not clear at present whether the varicella vaccine virus is excreted in breast milk, varicella vaccination of mother or child is not contraindicated during breastfeeding. [1, 6, 23, 24] Varicella vaccine can be given to persons in households with newborns, [1] although there has been one case report of a pregnant woman contracting primary varicella infection from exposure to her children vaccinated with varicella vaccine.[25] Other references say the vaccination of non-immune nursing mothers is only appropriate if the risk of exposure the chickenpox is high.[26]

• fair evidence for the vaccination of susceptible adolescents (level II-2 evidence -prospective cohort studies) and adults (level II-1, II-2 evidence -controlled trials, prospective cohort studies) (Grade B Recommendation).

• for adults, 2 doses given 4-8 weeks apart appear more effective than a single dose based on immunogenicity data in subjects over 12 years old, although effectiveness data are needed to determine the optimal number of doses
• There is insufficient evidence documenting the safety of varicella zoster vaccine in pregnancy to recommend vaccination in susceptible pregnant women, although the risk is likely to be less than for naturally acquired varicella virus. There have been no clinical trials of varicella vaccine in pregnant women
• In the "Varivax in Pregnancy" Registry (women inadvertently vaccinated while pregnant) -of 16 women with birth outcomes, 14 had normal infants and 2 had spontaneous abortions.

U.S. Preventive Services Task Force (USPSTF)

The USPSTF has not completed a review of varicella in pregnancy or varicella immunization.

• ACOG recommends that non pregnant women of childbearing age should be asked about previous infection with varicella at the preconception visit and offered vaccination if no history of infection is elicited. They note that conception should ideally be delayed until 1 month after immunization is complete.
• The report discusses the controversy around antenatal screening of pregnant women who don't have a clear history of prior VZV infection.
• Non-immune pregnant women should be counseled to avoid exposure to chickenpox and women who are exposed should have their antibody status assessed and receive VZIG passive immunization as soon as possible. While VZIG is effective in reducing the severity of maternal varicella it "does not ameliorate or prevent fetal infection".
• Pregnant women who develop chickenpox should be treated with oral acyclovir

• Non-pregnant women of childbearing age who are susceptible to varicella should be immunized with 2 doses of either vaccine; those who are vaccinated should avoid pregnancy for 1 month after vaccination (III -B)
• Neither varicella vaccine should be used in pregnant women
• Postpartum susceptible women who are breastfeeding their newborn infants can be immunized with either vaccine
• Women who receive anti-Rho(D) IG should not be immunized with either vaccine for 3 months afterwards. (III-C)

• Ask about a prior infection with chickenpox.
• If no prior history of chickenpox, check immunity with varicella zoster IgG.
• If not immune if not pregnant, offer vaccine. (delay conception for 1 month following immunization.) If pregnant counsel re avoiding exposure and reporting exposures immediately, vaccinate postpartum.
  
  

• in bold font (CTFPHC gives grade B recommendation to vaccinating susceptible adults)
• it will be located under "clinical", ideally at the preconception visit (or alternatively in early pregnancy)