MJA 2001; 174: 288-292
Recommendations 1A -
Recommendations 1B -
Recommendations 2 -
Recommendations 3 -
Recommendations 4 -
More articles on Obstetrics & gynaecology and women's health
- Zoster immunoglobulin (ZIG) should be offered to pregnant,
varicella-seronegative women with significant exposure to
varicella-zoster virus (VZV) (chickenpox) infection.
- Oral aciclovir prophylaxis should be considered for susceptible
pregnant women exposed to VZV who did not receive ZIG or have risk
factors for severe disease.
- Intravenous aciclovir should be given to pregnant women who develop
complicated varicella at any stage of pregnancy.
- Counselling on the risk of congenital varicella syndrome is
recommended for pregnant women who develop chickenpox.
- ZIG should be given to a baby whose mother develops chickenpox up to 7
days before delivery or up to 28 days after delivery.
- Intravenous aciclovir should be given to babies presenting unwell
with chickenpox, whether or not they received ZIG.
- Breastfeeding of babies infected with or exposed to VZV is
- A mother with chickenpox or zoster does not need to be isolated from
her own baby.
- If siblings at home have chickenpox, a newborn baby should be given
ZIG if its mother is seronegative.
- The newborn baby does not need to be isolated from its siblings with
chickenpox, whether or not the baby was given ZIG.
- After significant nursery exposure to VZV, ZIG should be given to
seronegative babies and to all babies born before 28 weeks'
Varicella-zoster virus (VZV) (chickenpox) infection can cause
severe morbidity in the pregnant woman, the fetus, and the newborn
The implications of primary VZV infection in pregnancy for the mother
and for the fetus vary with the period of gestation. For the mother, the
risk of adverse effects is greatest in the third trimester, whereas
for the fetus the risk is greatest in the first and second trimesters.
A. Maternal risk||
In normal adults, the mortality and morbidity of primary VZV
infection is greater than in children. Only about 2% of all cases occur
in adulthood, but they account for 25% of all VZV-related
deaths.1 Pneumonitis is 25 times more
common in adults.1,2|
A 1995 Australian study assessed VZV seronegativity in women
presenting to antenatal clinics and found 22% of women aged 14-19
years, 14% of those aged 20-24 years, 5% of those aged 25-29 years and 2%
of those aged 30 years and over had not had previous exposure and were
therefore susceptible to VZV infection.3
Anecdotally, chickenpox infection in pregnancy is more severe than
in non-pregnant adults, but there is scant supporting
evidence.4 A survey of 164 000
pregnancies in the United Kingdom described 98 women with
chickenpox, of whom seven developed severe illness and two
died.5 The UK confidential inquiry
into maternal deaths from 1985 to 1997 reported only seven deaths
associated with VZV in pregnancy, all of which occurred in the second
half of pregnancy. Other reports have also suggested increased
severity of illness in the second half of pregnancy.6
Zoster immunoglobulin (ZIG), given prophylactically at the time
of exposure, is known to prevent or reduce the severity of
Aciclovir, an antiviral agent, shortens the duration of
illness in young adults if administered during the incubation period
or within 24 hours of the onset of the rash.10,11 When administered
prophylactically (7 to 9 days after family exposure) it may be up to 84%
protective against infection and able to modify the illness in the
remaining family members.12
Although aciclovir is not licensed for use in pregnancy (because of
concerns about adverse fetal effects), there have been no reports of
adverse effects among hundreds of cases over several years of
Management algorithms (Boxes 1 and 2) have been devised for varicella
exposure in pregnancy.
Zoster immunoglobulin (ZIG) (Box 3)
- All pregnant women who have significant exposure to VZV
infection (defined as "living in the same household as a person
with active chickenpox or herpes zoster or face-to-face contact with
a person with chickenpox or uncovered zoster for at least 5
minutes"), who have no history of chickenpox and who are
seronegative (or serological testing is not readily available),
should be offered ZIG.4-6
- ZIG should be administered within 72 hours of
exposure for maximal effect, although it may provide some benefit up
to 96 hours after exposure for immunocompromised
- ZIG is ineffective, and should not be given, once clinical
illness is established.15 (E4)
Aciclovir (Box 3)
There is no high level evidence on the use of aciclovir in
pregnancy. Based on consensus view, we recommend:
- Consideration should be given to using oral aciclovir
prophylaxis for susceptible pregnant women with significant
exposure (defined above) who have not received ZIG, or who have any
underlying risk factors, such as chronic lung disease, cigarette
smoking,16 systemic corticosteroid
immunity,18 or are in the second half of
pregnancy (Box 3). (E4)
- Intravenous aciclovir should be given for varicella
pneumonitis or other complications at any stage of
pregnancy.4,6,19 These complications
include respiratory symptoms, neurological symptoms,
haemorrhagic rash and/or continued fever or appearance of new
lesions after 6 days.4 (E4)
- Extrapolation from data in children suggests that patients
receiving systemic corticosteroid therapy or those with underlying
immunodeficiency should be treated with intravenous aciclovir at
the earliest sign of chickenpox.18,20,21 (E4)
Management of delivery of the baby
- There is no evidence that ending the pregnancy speeds
maternal recovery. Expedited delivery should only be considered for
fetal compromise or if the gravid uterus is thought to be critically
impairing maternal ventilation.
B. Fetal risk||
Chickenpox in pregnancy may result in fetal varicella which is
usually benign and self-limiting.1 Occasionally, it produces a
characteristic pattern of abnormalities known as "congenital
varicella syndrome" (CVS).22,23 CVS very occasionally
follows maternal zoster infection.5 The risk of CVS after
first-trimester maternal chickenpox was estimated from
prospective studies as 2.2% (range, 0-9%; 95% CI,
0-4.6%).24-26 In a large prospective
European study, the incidence of CVS was 0.4% after maternal
chickenpox in the first 12 weeks of pregnancy, rising to 2% between
weeks 13 and 20.24 After 20 weeks the risk is
far lower, although isolated cases have been reported.3 The incidence of
CVS in Australia is 1 in 107 000 pregnancies.27 The congenital defects
are usually severe, causing cicatricial skin lesions, limb
hypoplasia or paresis, microcephaly and ophthalmic
lesions.22,24,28 It is hypothesised
that these lesions result from virus reactivation in utero or
disseminated zoster infection.2,29 Herpes zoster
(shingles) occurs in early childhood in about 1% of otherwise
asymptomatic infants exposed to maternal varicella during the
second or third trimester.24|
At present, there is no reliable marker of in-utero virus
reactivation or the predicted development of CVS. Serological tests
are an insensitive marker of fetal VZV infection and subsequent fetal
damage.24 The polymerase chain
reaction (PCR) has been used to detect VZV in amniotic fluid: a
negative PCR is associated with a favourable outcome, but a positive
PCR correlates poorly with the development of CVS.26 As
amniocentesis carries a risk of fetal loss, amniotic fluid PCR has a
While ZIG may prevent or modify the course of chickenpox in pregnancy,
it may not abolish the risk of fetal infection. Therefore, close
ultrasound monitoring for the development of fetal abnormalities
after maternal chickenpox or administration of ZIG in pregnancy is
- Counselling on the risk of congenital varicella syndrome is
recommended for women who develop chickenpox during pregnancy. (E4)
Maternal chickenpox in the peripartum period poses a risk of severe
neonatal varicella, with a mortality rate up to 30%.30,31 The
increased peripartum severity is attributed to a large
transplacental inoculum of virus in the absence of protective
maternal antibody. The timing of maternal infection in relation to
delivery determines the risk to the infant.31|
- Infection with onset more than seven days
before delivery ensures adequate transplacental passage of
specific anti-VZV antibody to protect the
- Infection with onset 7 days or less before delivery puts the infant at
risk of severe neonatal varicella. Passive immunisation of the baby
by giving ZIG immediately after delivery prevents or attenuates
neonatal varicella and is essential.7,33
Maternal varicella starting 1-2 days after delivery is also
associated with an increased risk of severe neonatal varicella from
transplacental spread of the virus.30 However, babies of
seronegative mothers exposed postnatally to varicella in the first
28 days after delivery apparently have increased risk of severe
illness compared with older infants.33 If the mother develops
chickenpox postnatally, her baby is evidently seronegative.
Therefore, ZIG is recommended for seronegative babies up to 28 days
old exposed to varicella.34,35
- ZIG is indicated for the baby if maternal varicella develops
up to 7 days before delivery or if the mother develops chickenpox up to
28 days after delivery.7,15,31-33 (E3)
- ZIG should be given to the baby as early as possible after
delivery or exposure, but must be within 72 hours.31,32 (E4)
- Maternal herpes zoster is not an indication for ZIG
administration to the baby. (E4)
- Clinical follow-up of infants receiving ZIG is essential
and they should be admitted to hospital if any rash develops, because
severe varicella can still occur despite passive
- Intravenous aciclovir should be administered (a) to babies
presenting with chickenpox who are unwell (eg, poor feeding,
tachypnoea), whether or not they received ZIG; (b) to any high risk
neonate who develops chickenpox and who inadvertently did not
receive ZIG prophylaxis or for whom it was delayed beyond 24 hours; and
(c) to immunocompromised neonates who develop chickenpox,
including those who are premature or being treated with
- Routine aciclovir prophylaxis in conjunction with ZIG is
not currently recommended in the neonatal population, due to lack of
- Breastfeeding of infected or exposed babies is encouraged.
- A mother and/or her baby with active vesicles should be
isolated from other mothers and babies, but an infected mother does
not need to be isolated from her own baby. (E4)
The commonest neonatal exposure to VZV is when one or more siblings
develops chickenpox in the weeks after delivery. The risk of the
newborn developing severe disease from postnatal exposure is
considerably less than from transplacentally acquired varicella,
but some babies with postnatal exposure will develop severe
disease.34 The risk to the newborn
baby is determined primarily by the presence or absence of
transplacentally acquired maternal IgG antibody.
If the mother has had chickenpox, the risk from siblings is
negligible. If not, the baby should be given ZIG, which will minimise
- ZIG should be administered to a baby up to 28 days old exposed
to VZV if the mother is seronegative, her serostatus can not be
determined, or if the infant was born at or before 28 weeks'
- A newborn baby does not need to be isolated from its siblings
with chickenpox, whether or not the baby was given ZIG. (E4)
- Parents should be advised that medical attention should be
sought if any signs of chickenpox develop. (E4)
- Admit to hospital for aciclovir treatment if baby becomes
unwell (eg, poor feeding, tachypnoea). (E4)
- The role of prophylactic aciclovir is unproven.
VZV poses a particular threat in this setting, because babies born
prematurely are relatively deprived of the usual third-trimester
transfer of transplacental antibodies.37-39 Spread of VZV is
primarily by the respiratory route, so isolation in a separate room is
desirable for babies with pneumonitis, and essential if they require
artificial ventilation. Staff handwashing is important in reducing
spread of the virus.
VZV vaccines are now available in Australia, and immunisation of
susceptible staff is strongly recommended.35
A significant exposure in the neonatal unit or on the postnatal ward is
- patient sharing the same open ward as a person with chickenpox or
- face-to-face contact with a person with chickenpox or zoster for at
least 5 minutes; and
- contact for one hour or more with person (staff or patient) with
chickenpox lesions or who developed lesions up to 48 hours later.
All staff who have had significant exposure to an index case (see
above) and who do not have a history of previous chickenpox infection
or of VZV vaccination should have serological tests. If they are VZV
antibody negative, they should be removed from clinical duties from
days 7-21 after exposure (days 7-28 if they receive ZIG).
- Infants born after 28 weeks' gestation15 should only be
given ZIG if they have had significant exposure (defined above) and
serological tests show the mother to be seronegative. (E4)
- All infants born at or before 28 weeks' gestation or born
weighing under 1000 g11,37,38 with significant
exposure should be given ZIG regardless of the results of serological
testing of the mother. (E4)
- Quarantine of cases should continue until all lesions have
- Quarantine of contacts should be from days 7-21 after
exposure, and from days 7-28 after exposure if they received
- Although quarantine of cases and those considered to have
significant contact is recommended, this should not compromise
medical and nursing care of a sick infant. (E4)
- Infants with pneumonitis requiring ventilation must be
isolated. Where isolation facilities are unavailable, cases should
be transferred to a unit with isolation facilities. (E4)
- Aim to discharge all patients requiring quarantine from
hospital as soon as possible. (E4)
Background and evidence basis of recommendations
This position statement was circulated to all members
of the Australasian Subgroup in Paediatric Infectious Diseases (ASPID)
for comments. The comments were analysed by the authors, discussed with
colleagues, and subsequent versions incorporating the comments were re-circulated
to all ASPID members.
The recommendations of ASPID on the management of VZV exposure and infection
in pregnancy and the neonatal period are endorsed by the Royal Australian
and New Zealand College of Obstetricians and Gynaecologists.
The recommendations are based
on the following levels of evidence (simplified from the NHMRC's "Quality
of evidence ratings")40
||Systematic review or meta-analysis of
all relevant randomised controlled trials (RCTs)
||Well-designed cohort or case-control
||Consensus opinion of ASPID members
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Wales, 1967-85. BMJ 1988; 296: 673-676.
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infections in pregnancy and the newborn. A review prepared for the UK
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Study of Infection. J Infect 1998; 36 Suppl 1: 59-71.
Smego RA Jr, Asperilla MO. Use of acyclovir for varicella pneumonia
during pregnancy. Obstet Gynecol 1991; 78: 1112-1116.
Brunell PA, Ross A, Miller LH, Kuo B. Prevention of varicella by
zoster immune globulin. N Engl J Med 1996; 280: 1191-1194.
Gershon AA. Prevention and treatment of varicella zoster virus
infection. Pediatr Infect Dis J 1984; 3 (Suppl): 34-36.
Bose B, Kerr M, Brookes E. Varicella zoster immunoglobulin to
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Lin TY, Huang YC, Ning HC, Hsueh C. Oral acyclovir prophylaxis
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varicella in otherwise healthy adolescents. The Collaborative
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Andrews EB, Yankasksas BC, Cordero JF, et al. Aciclovir in
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Immunisation Practices. MMWR Morb Mortal Wkly Rep 1996; 45
American Academy of Pediatrics. Varicella-zoster infection.
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Academy of Pediatrics, 2000: 624-638.
Grayson ML, Newton-John H. Smoking and varicella pneumonia. J
Infect 1988; 16: 312.
Rice P, Simmons K, Carr R, Banatvala J. Near fatal chickenpox
during prednisolone treatment. BMJ 1994; 309: 1069-1070.
Balfour HH. Intravenous acyclovir therapy for varicella in
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Haake DA, Zakowski PC, Haake DL, Bryson YJ. Early treatment with
acyclovir for varicella pneumonia in otherwise healthy adults.
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Feldman S, Hughes WT, Daniels CB. Varicella in children with
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Scharf A, Scerr O, Enders G, Helftenbein E. Virus detection in the
fetal tissue of a premature delivery with congenital varicella
syndrome. A case report. J Perinat Med 1990; 18: 317-322.
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varicella and herpes zoster in pregnancy: prospective study of 1739
cases. Lancet 1994; 343: 1548-1551.
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varicella zoster virus infection with polymerase chain reaction of
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for immunoprophylaxis in neonates exposed to varicella. Pediatr
Infect Dis J 1986; 56: 100-102.
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Reynolds L, Struik S, Nadel S. Neonatal varicella: varicella
zoster immunoglobulin (VZIG) does not prevent disease. Arch Dis
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Linder N, Waintraub I, Smetana Z, et al. Placental transfer and
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Pediatr 2000; 137: 85-89.
Conway SP, Dear PRF, Smith I. Immunoglobulin profile of the
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National Health and Medical Research Council. How to use the
evidence: assessment and application of scientific evidence.
(accessed February 2001).
King George V Hospital, Sydney, NSW.
Anne-Marie Heuchan, MB, MRCP, Fellow in Neonatal Medicine.
The Children's Hospital at Westmead, Sydney, NSW.
David Isaacs, MD, FRACP, FRCPCH, Paediatric Infectious
Diseases Physician; and Clinical Professor, University of Sydney.
Reprints will not be available from the authors.
Professor D Isaacs, Department of Immunology and Infectious
Diseases, The Children's Hospital at Westmead, PO Box 4001,
Westmead, NSW 2145.
1: Management of significant exposure* to varicella zoster virus (VZV) during pregnacy (Algorithm 1)
*Significant exposure is defined as living in the same household as a person with active chickenpox or herpes zoster or face-to-face contact with a person with chickenpox or zoster for at least 5 minutes.
Risk factors for severe maternal VZV infection are second half of pregnancy, underlying lung disease, immunocompromised, and smoker.
See Box 3 for dosage of zoster immunoglobulin (ZIG) and aciclovir.
Recommendations based on consensus view.
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|2: Management of chickenpox in pregnancy (Algorithm 2)
*Complications: respiratory symptoms, haemorrhagic rash, persistent fever >6 days, and new lesions developing >6 days.
At high risk are those women in the second half of pregnancy with underlying lung disease, who are immunocompromised, and who smoke.
See Box 3 for doses of aciclovir.
Recommendations based on consensus view.
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|3: Administration and dosage of zoster immunoglobulin
(ZIG) and aciclovir
- High-titre ZIG is available
from the Red Cross Blood Transfusion Service in Australia on a restricted
basis for the prevention of VZV infection in high-risk subjects. Each
vial contains 2mL (16% solution of gammaglobulin fraction of human plasma
from donors with high titre of varicella antibodies + thiomersal 0.01%
- The recommended dose is 2mL for children 0-5 years,
4mL for children 6-12 years and 6mL for adults.32
- Administration is by intramuscular injection, with
few adverse effects other than local discomfort reported. This can be
lessened if the ZIG is at room temperature when administered.
- ZIG should never be given intravenously.36
- Aciclovir appears to be a safe and relatively well
tolerated drug, although it may impair renal function if given to patients
who are not adequately hydrated.17 It is not licensed for use in pregnancy
but appears to be safe12 and its use is indicated in the high-risk situations
- The recommended intravenous dose for treating VZV
infection in adults and infants is 10-20mg/kg every 8 hours.
- The oral dose for adults is 800mg five times daily.
- The use of oral aciclovir in neonates is not recommended.
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