The management of varicella-zoster virus exposure and infection in pregnancy and the newborn period

Abstract

• 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 encouraged.
  
• 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' gestation.

1. Management of VZV infection in pregnancy

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 chickenpox.^7-9

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 monitoring.¹³

Management algorithms (Boxes 1 and 2) have been devised for varicella exposure in pregnancy.

• 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 (E3)

• 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 subjects.¹⁴ (E3)

• 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 treatment,¹⁷ impaired 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.

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 limited role.

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 recommended.

• Counselling on the risk of congenital varicella syndrome is recommended for women who develop chickenpox during pregnancy. (E4)

2. Management of babies of mothers with perinatal chickenpox

• Infection with onset more than seven days before delivery ensures adequate transplacental passage of specific anti-VZV antibody to protect the infant.³²

• 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 immunisation.^35,36 (E4)

• 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 corticosteroids.^18,21 (E4)

• Routine aciclovir prophylaxis in conjunction with ZIG is not currently recommended in the neonatal population, due to lack of evidence. (E4)

• Breastfeeding of infected or exposed babies is encouraged. (E4)

• 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)

3. Management of neonates exposed to VZV infection on the postnatal wards or at home

If the mother has had chickenpox, the risk from siblings is negligible. If not, the baby should be given ZIG, which will minimise the risk.^34,35

• 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' gestation.^15,37 (E3)

• 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.

4. Management of VZV exposure within the neonatal unit

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 defined as:^10,15

• patient sharing the same open ward as a person with chickenpox or zoster;

• 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 g^11,37,38 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 crusted.¹⁵ (E3)

• Quarantine of contacts should be from days 7-21 after exposure, and from days 7-28 after exposure if they received ZIG.¹⁵ (E3)

• 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)

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Authors' details

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.
Correspondence: Professor D Isaacs, Department of Immunology and Infectious Diseases, The Children's Hospital at Westmead, PO Box 4001, Westmead, NSW 2145.
davidiATchw.edu.au

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