Title of Guideline (must include the word “Guideline” (not protocol, policy, procedure etc)

Guideline for the management of Chickenpox in Pregnancy and the postnatal period

Contact Name and Job Title (author) Directorate & Speciality

Dr Corah Ohadike, ST7 Obstetrics and Gynaecology Obstetrics

Implementation date

March 2013

Version

Four

Supersedes

Three

Date of submission

March 2013

Date on which guideline must be reviewed (this should March 2018 be one to three years) Explicit definition of patient group to which it applies All pregnant women who have contact (e.g. inclusion and exclusion criteria, diagnosis) with or develop chickenpox in pregnancy or the postnatal period Abstract This guideline describes the management of chickenpox in pregnancy and the postnatal period. It also covers management of the exposed neonate. Maternal, fetal and neonatal risks are discussed. Key Words Chickenpox, Shingles, Varicella, Pregnancy VZIG, aciclovir Statement of the evidence base of the guideline – has 2 the guideline been peer reviewed by colleagues? Evidence base: (1-5) 1a meta analysis of randomised controlled trials 1b at least one randomised controlled trial 2a at least one well-designed controlled study without randomisation 2b at least one other type of well-designed quasi-experimental study 3 well –designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practise based on the clinical experience of the guideline developer Consultation Process 1

Consultant virologist- Professor Irving;

Neonatologist; Nottingham maternity services guideline development group Maternity services staff; General practitioners; Accident and emergency staff

Target audience

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

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Chicken Pox in Pregnancy Introduction Chickenpox, primary varicella zoster virus (VZV) infection, is usually a mild, self-limiting disease of childhood. VZV is a DNA virus of the herpes family. Transmission occurs by respiratory droplets and direct personal contact with vesicular fluid (Tyring, 1992). In the UK, approximately 93% of adults have detectable antibodies to varicella so most pregnant women are immune (Nardone, et al. 2007). However, pregnant women who were born and raised in tropical and sub-tropical areas are at increased risk of varicella infection because a much lower proportion will have had chickenpox in childhood (Talukder et al, 2007). In many tropical countries 60% of the adult population is seropositive for VZV (Lee, 1998). The morbidity and mortality is more severe in adults than children. There are certain associated risk factors which include: pre-existing lung disease, smoking and immunocompromise. Pregnancy is also associated with more severe disease (Immunisation Against Infectious Disease, DOH). VZV infection incidence in pregnancy is quoted at 3 in 1000 or the estimated occurrence of Varicella in pregnancy is 2000 cases per year in England (Miller et al, 1993). Primary infection and reactivation VZV, a highly contagious virus, is transmitted in respiratory droplets, usually from a patient with chickenpox and less frequently from the rash of a patient with shingles. The primary infection manifests after an incubation period of 10-21 days. It is characterised by fever, malaise and a pruritic rash that develops into crops of maculopapules, which become vesicular and then crust over before healing. The disease is infectious 48 hours before the rash appears and until the vesicles crust over (Tyring, 1992). Following recovery, the virus remains latent in the sensory root ganglia but can reactivate later in life to cause a vesicular erythematous rash in a dermatomal distribution called herpes zoster or shingles (Shrim et al, 2012). Maternal shingles does not appear to cause fetal problems (Enders and Miller, 1994).

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Maternal, Fetal and Neonatal Risks of Varicella in Pregnancy Maternal risks In susceptible pregnant women, chickenpox causes more severe disease. Varicella pneumonia occurs in 9% of cases (Heuchan and Isaacs, 2001; Mohsen and McKendrick, 2003). Risk factors include infection after 20 weeks gestation as T-cell function starts to decline, past history of smoking, pre-existing chronic lung disease, immunocompromise, and the presence of greater than 100 lesions (Harger et al, 2002). Mortality in pregnant women is increased, compared with non pregnant adults, primarily due to respiratory disease. Mortality rates are highest from the second trimester to beginning of the third trimester, 7 out of 9 deaths that occurred in England in 1985-1998 were between 27-32 weeks. (Enders and Miller, 2000). Fetal risks The risk of damage to fetus and newborn is dependent on gestational age at the time of maternal primary infection.  Varicella contracted in the first 13 weeks of pregnancy results in fetal Varicella syndrome (FVS) in less than 1% of cases.  The risk of FVS rises to 2% with infections acquired between week 13 and week 20 of gestation (Enders et al, 1994). The skin, musculoskeletal system and central nervous system are the main systems targeted in FVS with reported clinical features including skin scarring, limb hypoplasia, cortical atrophy, chorioretinitis and cataract. FVS does not occur after maternal shingles (Enders and Miller, 1994). Prenatal diagnosis is possible using detailed ultrasound for findings such as limb deformity, microcephaly, hydrocephalus, ventriculomegaly, porencephaly, soft tissue calcification, chest wall malformations, intestinal and hepatic echogenic foci, polyhydramnios, fetal hydrops, intrauterine growth restriction or fetal demise. Congenital cataract and micropthalmos are the most common ocular lesions but these are not easily detected on ultrasound scan (Degani, 2006).  Infections occurring as late as week 25 may still be complicated by FVS.  Maternal Varicella occurring at very late stages of pregnancy, usually within 7 days of childbirth, may result in 17-50% of cases in disseminated neonatal varicella (Miller et

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al, 1989). Peripartum and postnatal risks There is a risk of developing neonatal varicella if maternal infection occurs 7 days before or within 2 days after delivery. This is because the development and transfer of protective antibodies will not have had time to occur and the neonatal immune system is relatively immature. Mortality is up to 30% without treatment (Meyers, 1974). Infants born to VZV seronegative mothers are also at risk of disseminated Varicella if they become exposed to the virus within the first 7 days of life (Enders et al, 1994).

Management of the pregnant woman At Booking visit Enquire about a previous history of chickenpox. If there is no such history, women must be advised to avoid contact with chickenpox during pregnancy and to immediately inform health professionals of a potential exposure. Women must be advised to inform a health professional of any subsequent exposure to chicken-pox or shingles as soon as possible.

Pregnant woman who reports a contact with chickenpox (or shingles) A careful history must be taken to confirm the significance of the contact and the susceptibility of the pregnant woman to VZV. A. Assessing the significance of a VZV contact: For a contact to be regarded as significant the 3 criteria below must be met: 1. The type of VZV in the index case should be one of the following: - Chickenpox - Disseminated zoster - Immunocompetent individual with exposed zoster (e.g. Ophthalmic) - Immunocompromised patient with localised zoster on any part of the body (virus shedding presumed to be greater).

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2. The index case should be infectious at the time of exposure: - Patients with chickenpox and disseminated shingles are infectious from 48 hours before the rash appears until cropping has ceased and all lesions have crusted over. - Patients with localized shingles are infectious from the day of onset of the rash until crusting. 3. There should be close contact with the index case: - Maternal/neonatal contact. - Continuous house-hold contact. - Contact in the same room, including large open wards, for 15 minutes or more. - Face to face contact, for example while having a conversation. B. Assessing maternal immunity: If the pregnant woman have a history of chickenpox no ntervention is required. If there is no clear history of past chickenpox (i.e. negative or uncertain) then a serum sample should be tested for the presence of VZV IgG. Telephone the Queens Medical Centre (QMC) on 0115 9249924 ext 67690 or 63524 (QMC) and ask to speak to the duty virologist before sending the serum sample. All requests for VZV IgG should include the following information to enable the results to be timely reported with the correct interpretation: Full demographic details Gestational age Date and nature of VZV contact – must be a significant contact (see above) Name and telephone number of clinician/ midwife to whom the result may be telephoned by virology Women should be told that the results will usually be available on the same day. They should which professional will contact them with the results, this is usually the person who requested the test,

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or a designated deputy. Use of varicella zoster immunoglobulin (VZIG) to prevent severe chickenpox A seronegative pregnant woman with a significant contact should be offered VZIG, 1000mg IM (4 vials) as soon as possible and no later than 10 days post exposure. The rationale for the use of VZIG prophylaxis is to reduce the severity of maternal disease and minimize the risk of fetal infection in the first 20 weeks of pregnancy. VZIG is available from NUH Pharmacy (QMC) through the duty virologist/microbiologist. The VZIG MUST NOT be collected by anyone who is infectious. The VZIG can be administered in the community setting by either the practice nurse or midwife. Clinical chickenpox will still develop in a proportion of women given VZIG but it may be attenuated and/or delayed. Severe maternal varicella may rarely occur despite VZIG. Women who have had contact with chickenpox or shingles (regardless of whether or not they have received VZIG) should be asked to notify a healthcare professional if a rash develops. VZIG is NOT indicated in pregnant women who develop chickenpox. Management of the pregnant woman who develops chickenpox Most pregnant women with chickenpox should be managed in the community unless they are very sick. Diagnosis: The diagnosis of chickenpox is usually clinical (ie no laboratory tests required). However, if the rash is atypical and VZV disease is suspected, a vesicle swab should be obtained and sent to Virology in virus transport medium (VTM) requesting VZV DNA detection. Refrain from sending blood samples because serology has no role in confirming chickenpox or shingles diagnoses and hence sending blood samples is of little value. Anti-viral therapy: Aciclovir has been shown to reduce the duration of fever and 7

hasten the resolution of vesicles if commenced within 24 hours of onset of rash. Although it is not licensed in pregnancy, experience has shown that it is a very safe drug and no adverse fetal or neonatal effects have been reported with its use in pregnancy (Briggs, et al. 2005). It should be used with caution in first trimester due to insufficient evidence on its safety. The guidelines from the Royal College of Obstetricians and Gynaecologists (2007) restrict oral aciclovir to patients who: a. present in the first 24 hours of rash b. are more than 20 weeks pregnant. However, aciclovir treatment may still be considered in patients who are less than 20 weeks pregnant or whose onset of rash is more than 24 hours but still developing new lesions if there is a significant risk(s) of complications (Drugs and Therapeutics Bulletin, 2005). In each patient who develops chickenpox at less than 20 weeks gestation, the risk-benefit of aciclovir treatment should be assessed by an expert in the management of infections so that the patient can make an informed decision. The International Aciclovir pregnancy register performed a prospective study on 1129 patients of whom 729 had been given aciclovir and no adverse outcomes were reported. It is usual practice in many countries to treat pregnant women with antiviral therapy in all trimesters. (Tunbrige et al, 2008) In summary, aciclovir may be appropriate to give to the following groups of patients:  Any pregnant patient presenting within 24 hours of onset of rash  Patients who are still developing new crops of spots  Patients who are smokers  Patients who are on steroids  Patients with symptoms/signs of respiratory tract involvement Criteria for referral of pregnant women with chickenpox to hospital 1. If the patient develops any symptoms suggestive of complications. Pregnant women should be advised to report promptly any symptoms that suggest complications:  difficulty breathing

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 confusion/headache  a dense rash with or without mucosal lesions  the appearance of new lesions after 6 days  haemorrhagic rash or bleeding 2. If the pregnant woman is immunosuppressed, eg taking steroids or has taken steroids within the last 3 months 3. Consider referral to hospital if the risk of Varicella pneumonia is high, even in the absence of other complications eg if the pregnant woman is smoker, has chronic lung disease or has a dense rash – (Harger et al, 2002). Inpatient management of pregnant women:  Discuss all cases with the duty virologist  Admit to an infectious diseases ward  If admission to a maternity ward is unavoidable, women with Varicella should be isolated from other pregnant women  Commence intravenous aciclovir at 10 mg/kg three times a day for 5 days at least (monitor the renal function and maintain adequate hydration) A management plan is decided in consultation with the obstetrician, virologist and neonatologist (Nathwani et al, 1998). Beware of risk of VZV transmission to other pregnant women and/or immunocompromised inpatients. If possible, delivery should be delayed until 7 days after onset of maternal rash, to allow passive transfer of antibodies to neonates.

Management of the neonate exposed to chickenpox (or shingles) Neonates exposed to VZV should be referred to neonatologists. obstetricians, General Practitioners (GPs), midwives and health visitors should be aware of neonates who are at risk of severe Varicella who meet any of the following 3 criteria: 1. The mother develops chickenpox (not shingles) in the

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period 7 days before to 7 days after birth. 2. Infants with significant non-maternal exposure to VZV within the first 7 days of their life if their own or (their mother’s) VZV IgG is negative. 3. Infants of any age with significant exposure to VZV while still requiring care at Special Care Baby Unit/ Neonatal Unit if their VZV IgG is negative. Note that infants:  born before 28 weeks’ gestation or  weighing