rcog RCOG - Advice on Chicken Pox
Individual recommendations have been graded according to the level of evidence on which they are based using the scheme endorsed by the NHS Executive: Grade A: randomised controlled trials Grade B: other robust experimental or observational studies Grade C: more limited evidence but the advice relies on expert opinion and has the endorsement of respected authorities Background
The individual recommendations in this guideline are based on the scheme endorsed by the NHS Executive.1
Varicella zoster (VZ) is a DNA virus of the herpes family that is highly contagious and transmitted by respiratory droplets and close personal contact. The primary infection is characterised by fever, malaise and a pruritic rash which develops into crops of maculopapules which become vesicular and crust over before healing. The incubation period is 10-20 days and the disease is infectious 48 hours before the rash appears and lasts until the vesicles crust over. Chickenpox (or primary VZ infection) is a common disease of childhood when it causes a mild infection, such that over 85% of the adult population is seropositive for VZ IgG antibody. Contact with chickenpox in pregnancy is common, but infection occurs in only one in 2000 pregnancies.2,3 A higher proportion of adults from tropical and sub-tropical areas are susceptible to VZ infection.4
Following the primary infection, the virus remains dormant but can be re-activated to cause a vesicular erythematous skin rash in a dermatomal distribution known as Herpes Zoster (HZ). HZ in pregnancy does not usually result in intrauterine infection, although there is a case report of congenital Varicella Syndrome in an immunocompromised woman with disseminated HZ. 5 Primary VZ infection in pregnancy can be associated with an adverse outcome in three possible ways:
1. Maternal VZ infection : Primary VZ infection can be more severe in adults and particularly in pregnancy. Pneumonia occurs in approximately 10% of cases. Mechanical ventilation may be required and mortality rates of up to 6% have been reported. Between 1985 and 1993, seven indirect maternal deaths and one late maternal death were reported in the UK in association with maternal Varicella pneumonia.6
2. Congenital Varicella Syndrome is secondary to primary VZ infection occurring before 20 weeks’ gestation. The Syndrome includes one or more of the following:
skin scarring in a dermatomal distribution;
eye defects (microphthalmia, chorioretinitis, cataracts);
hypoplasia of the limbs;
and neurological abnormalities (microcephaly, cortical atrophy, mental retardation and dysfunction of bowel and bladder sphincters).The risk is estimated to be approximately 2% and does not occur if the primary maternal infection occurs after 20 weeks’ gestation.7-9 The risk of spontaneous miscarriage after first trimester Varicella infection is not increased.10 The prenatal diagnosis of congenital Varicella Syndrome is essentially by ultrasound. Polyhydramnios, hyperechogenic foci in the liver and hydrops fetalis have been described. 11 Ultrasonography carried out five weeks after the primary infection may demonstrate structural changes. Cordocentesis and amniocentesis for VZ antibodies are of limited value.12
3. Varicella infection of the newborn : Transplacental passage of the virus appears to increase as gestation advances. Up to 50% of fetuses are infected when maternal infection occurs one to four weeks before delivery and one third of these babies develop clinical Varicella despite high titres of passively acquired maternal antibody.13 This infection can be lethal in 20%-30% of infants if the maternal infection occurs four days before delivery and up to two days postpartum.14 Babies with no clinical evidence of Varicella infection at birth can develop HZ in infancy, consistent with primary infection in-utero.
Immunisation
Live attenuated Varicella vaccine has been shown to be safe and effective in preventing chickenpox in adults,15 but it is not yet licensed for general use in the UK. 16 There may be a case for immunisation of all susceptible women prior to pregnancy17 and also for immunising health care workers in contact with pregnant women. (This guideline will be reviewed when an appropriate vaccine becomes available.) Pending availability of live attenuated Varicella vaccine for primary prevention, passive immunisation is the only available strategy in cases of exposure in a susceptible pregnant woman. There is only limited evidence that passive immunisation with VZ IgG prevents or reduces the severity of maternal infection13,18 or congenital Varicella Syndrome.8 As the IgG is a blood product obtained from human volunteers with high titers its use is associated with the usual expense and risks. It must be given as soon as possible, preferably within 72 hours of contact with the infectious person, although there is some evidence of benefit up to 10 days after exposure.
Recommendations
All recommendations are Grade C.
1. Management of a Woman with Suspected Varicella Contact in Pregnancy
1.1 It is very important to elucidate the contact history with particular respect to the certainty of the infection, the infectiousness (vesicular rash or development of rash within 48 hours of contact) and the degree of exposure (household face-to-face for five minutes or indoors contact for more than one hour).
1.2 If the pregnant woman has a previous history of Varicella it is reasonable to assume that she is immune to primary VZ infection. However, if there is any doubt then the VZ IgG titre should be checked.
1.3 If the pregnant woman has had a significant contact and no previous history of Varicella, then check for VZ IgG in the serum. At least 85% of women will be positive and can be reassured. The virology laboratory may be able to use serum stored from booking antenatal bloods thus saving time.
1.4 If the pregnant woman is not immune to VZ and the infection occurs before 20 weeks’ gestation, then she should be given VZ IgG as soon as possible after contact.
1.5 Detection of IgM in maternal serum indicates primary VZ infection. If she develops primary VZ or shows serological evidence of sero-conversion in the first 20 weeks of pregnancy, then she has a 2% risk of congenital Varicella infection and will need to be informed of the implications.
1.6 Referral to a specialist centre for detailed ultrasound examination at 16-20 weeks’ gestation or five weeks after infection, whichever is the sooner, should be considered.
1.7 Neonatal ophthalmic examination should be organised at birth.
1.8 If there is no previous history of Varicella and the contact occurs after 20 weeks, there is no risk of congenital Varicella infection, but the risk of maternal Varicella pneumonia remains. In these circumstances the administration of VZ IgG should be considered, although the evidence to support its use is not strong.
2. Management of a Pregnant Woman who Presents with Chickenpox
2.1 The pregnant woman with Varicella should be isolated from all other pregnant women and neonates.
2.2 If the pregnant woman is in the second half of the pregnancy and is seen less than 24 hours after the development of the Varicella rash, then the administration of acyclovir may be expected to reduce the severity and duration of the illness (there are theoretical concerns about teratogenesis when acyclovir is used in the first trimester).
2.3 Where maternal infection occurs five days before or two days after delivery there is a 20%-30% risk of Varicella of the newborn. Thus where relevant and practical delivery should be delayed until 5-7 days after the onset of maternal illness to allow for passive transfer of antibodies.
2.4 If delivery occurs within five days of maternal infection, or if the mother develops primary Varicella infection within two days of giving birth, then the neonate should be given VZ IgG as soon as possible.
2.5 If neonatal infection occurs then this should be treated with acyclovir.
2.6 Hospitalisation and consultation with a specialist in infectious diseases is indicated if any respiratory symptoms occur in the infected woman, or if the lesions are dense and haemorrhagic, or if new lesions continue to develop six days after the onset.
2.7 Varicella pneumonia is an indication for treatment with intravenous acyclovir. In certain circumstances it may be necessary to consider mechanical ventilation. In the third trimester of pregnancy this may be facilitated by delivery, but elective delivery at this time will be associated with a high risk of neonatal Varicella.
3. Other Recommendations
3.1 On occasion a sibling has Varicella around the time mother and newborn baby are due for discharge from hospital. If the mother is immune to Varicella the risk to the newborn is minimal. However, if she is not immune both the newborn and the mother should be given VZ IgG.
3.2 All reasonable steps should be taken to isolate individuals, including health care professionals, with VZ infection, from pregnant women attending hospitals or general practitioner surgeries.
3.3 Staff who are thought (or known by previous testing) to be "not immune" should avoid contact with varicella patients. However, those who are exposed, should be tested for varicella antibodies, and if found to be susceptible should be warned they may develop varicella. The incubation period is between two and three weeks.
References
1. Mann T. Clinical Guidelines : Using clinical guidelines to improve patient care within the NHS, 1996. NHS Executive (Catalogue No 96CC0001).
2. Gershon, A A, Raker A, Steinburg S, Topf-Olstein B, Drusin L M. Antibody to varicella-zoster virus in parturient women and their offspring during the first year of the life. Pediatrics 1976, 58:692-6.
3. Sever J A, White L R. Intrauterine viral infections. Annu Rev Med 1969, 19:471-86.
4. Gershon A A. Chickenpox, measles and mumps. In : Infectious diseases of the fetus and newborn infant. Remington J S, Klein J O eds. 3rd Ed. Philadelphia W B Saunders, 1990:395-445.
5. Enders G, Miller E, Cradock-Watson J et al. Consequences of varicella and herpes zoster in pregnancy : prospective study of 1739 cases. Lancet 1994, 343:1548-51.
6. Reports on Confidential Enquiries into Maternal Deaths in the United Kingdom 1985-87, 1988-90 and 1991-93. London HMSO.
7. Preblud S R, Cochi S I, Orenstein W A. Varicella-zoster infection in pregnancy. N Engl J Med 1986, 315:1416-7.
8. Pastuszak A L, Levy M, Schick R N et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N Engl J Med 1994, 330:901-5.
9. Jones K L, Johnson K A, Chambers C D. Offspring of women infected with varicella during pregnancy : A prospective study. Teratology 1994, 49:29-32.
10. Siegel M, Fuerst H T, Peress N S. Comparative fetal mortality in maternal virus diseases. N Engl J Med 1966, 274:768-71.
11. Pretorius D H, Hayward I, Jones K L, Stamm E. Sonographic evaluation of pregnancies with maternal varicella infection. J Ultrasound Med 1992, 11:459-63.
12. Lecuru F, Taurelle R, Bernard J P et al. Varicella zoster virus infection during pregnancy: the limits of prenatal diagnosis. Euro J Obstet Gynecol Reprod Biol 1994, 56(1):6 7-8.
13. Miller E, Cradock-Watson J E, Ridehalgh M K S. Outcome in newborn babies given anti-varicella zoster immunoglobulin after perinatal maternal infection with varicella zoster virus. Lancet 1989, ii:371-3.
14. Zieger W, Friese K, Weigel M, Becker K P, Melchert F. Varicella infection at birth Z Geburtshilfe Perinatol 1994 Aug 198:4,134-7 (in German).
15. Gershon A A, Steinberg S P. The National Institute of Allergy and Infectious Disease Varicella Vaccine Collaborative Study Group. Live attenuated varicella : protection in healthy adults compared with leukaemic children. J Infect Dis 1990, 158:661-6.
16. Immunisation against Infectious Disease 1996. HMSO.
17. Seidman D S, Stevenson D K, Arvin A M. Varicella vaccine in pregnancy. Br Med J 1996, 313:701-2.
18. Enders G. Management of varicella zoster contact and infection in pregnancy using a standardised varicella-zoster ELISA test. Postgrad Med J 1985, 61(supp4):23-30.
Addendum
The Public Health Laboratory Service has drawn our attention to the extremely limited supply in England and Wales of anti-varicella-zoster immunoglobulin (VZIG). As you may be aware, the stocks are only held by the Public Health Laboratory Service (PHLS) and designated NHS microbiology laboratories. The PHLS is only authorised by the Department of Health to issue it for patients meeting the criteria as outlined in their guideline "Immunisation against Infectious Disease".
Our recommendation 3.1 suggests that non-immune postpartum women about to be discharged to a home in which another child has varicella should be given VZIG. As this is at variance with the Department of Health advice, it will not be possible to implement this recommendation. Similarly, the PHLS currently issues VZIG only for pregnant women who have been exposed in the first 20 weeks' gestation.
November 1997