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Virology
Vol. 17 No 2 | Winter 2015
Feature
Rubella and varicella in pregnancy
Dr Caitlin Keighley
MBBS, BMed Sc, DRANZCOG
Prof Gwendolyn Gilbert
MBBS, FRACP, FRCPath


This article is 5 years old and may no longer reflect current clinical practice.

As vaccination coverage varies in different countries and global travel increases, awareness of vaccine-preventable diseases continues to be important. In 2011–12, there were 36 cases of rubella and one notified case of congenital rubella syndrome in Australia.1 Over the same period, there were 805 hospitalisations for chickenpox. Rubella and varicella are both highly contagious and can have severe consequences in the antenatal and perinatal setting. An excellent resource is the Australian Society of Infectious Diseases (ASID) Perinatal Guidelines.2

Rubella

Worldwide, outbreaks of rubella have been described, with 29 cases in Vietnam in January already reported this year.3 4 Most infections are clinically apparent; after an incubation of 14–23 days, a cephalocaudal rash occurs in 75 per cent of cases and lasts two to seven days. Subclinical infections may be more common with secondary infection or vaccine failure.5 Less than five per cent of pregnant women are not immune at antenatal screening, although the protective antibody level is debatable.6 A small proportion of women are affected by reinfection and congenital rubella syndrome in this context has been reported.7 8 Antibody levels decrease over time and this may be particularly so in those vaccinated with the Cendehill strain prior to 1986.9 The WHO-recommended cut off for evidence of immunity is a rubella- specific IgG level above 10 IU/mL, and our immunisation guidelines recommend re-immunising if standard assays do not demonstrate evidence of current immunity.10

Diagnosis of maternal infection

Rubella testing in pregnancy should only be performed where there is a history of a rubella-like illness (fever, rash, arthralgia) or contact with confirmed rubella.11 12 In the first trimester, a pregnant woman should undergo testing even if she previously had a positive rubella IgG. If contact occurs in the second or third trimester, further testing is not necessary. A diagnosis is suggested by either antibody seroconversion or a four- fold rise in the IgG titre. Serology should be collected as soon as possible after contact or the onset of rash and repeated 10–14 days later. The diagnosis can be confirmed via nucleic acid testing or culture (on nasal specimens, blood and urine), but neither is widely available. As with all serology, false positive results and cross-reactivity occur and so caution is advised in counselling the mother on this basis alone.13

Management of suspected infection

The risk of fetal infection is low in maternal re-infection; less than five per cent overall and rare after 12 weeks gestation. There is no specific therapy for the mother, as rubella specific immunoglobulin is not effective as post-exposure prophylaxis and normal human immunoglobulin is not indicated.14 15

In primary maternal infection, the risk of fetal infection varies with gestation. The highest risk is in the first trimester with organogenesis, when the rate is 80–90 per cent with a similar risk of congenital defects.13 At 13–16 weeks gestation the risk of fetal infection is around 50 per cent, with around one-third complicated by congenital defects, primarily deafness.16 Thereafter, congenital defects are rare.17 18

Termination should be considered in the first trimester of pregnancy. Fetal testing may be performed via rubella polymerase chain reaction (PCR), rubella culture and fetal IgM on chorionic villus sampling or amniocentesis in the second trimester, at least six weeks after maternal infection. Although the specificity of PCR is excellent, there can be difficulties with interpretation, as PCR may be positive from contamination of the specimen with maternal tissue, and false negative fetal IgM is common until late in pregnancy.19

The infant at risk of rubella infection

Congenital rubella syndrome can be devastating, with deafness, cataracts, micropthalmia and heart defects (patent ductus arteriosus). After birth, the infant  may continue to shed rubella virus for  many months and, so, should be looked after only by individuals who have evidence of immunity to rubella. The infant should undergo testing for rubella via serology (IgM), PCR and culture of urine and throat specimens (if available).

Clinical features of congenital rubella syndrome can include:

  • sensorineural hearing loss (60–75 per cent);
  • opthalmological (10–25 per cent) – cataracts, micropthalmos, retinopathy, glaucoma, strabismus, cloudy cornea;
  • CNS (10–25 per cent) – developmental delay, mental retardation, microcephaly;
  • CVS (10–20 per cent) – patent ductus arteriosus, pulmonary artery stenosis, pulmonary stenosis; and/or
  • growth retardation, haematological

and gastrointestinal abnormalities, pneumonitis and osteitis.

Late manifestations include epilepsy, tooth defects, insulin-dependent diabetes mellitus (50 times the rate in the general population), thyroid dysfunction and panencephalitis.20

In the absence of these features, but with a positive IgM (and/or PCR), the infant is infected, but asymptomatic. These infants should also be isolated from potentially pregnant female contacts, and in droplet and contact precautions while in hospital. Breastfeeding can be continued.

Varicella

Varicella infection is highly contagious and has an incubation period of 10–21 days. It is infectious from two days before the rash until lesions have crusted over. In adults, clinical findings strongly suggest the diagnosis and this is confirmed on nucleic acid testing and/or immunofluorescence. Serology is useful in establishing risk in the antepartum period and, if negative, immunisation should be offered postpartum. Fetal infection occurs in 10–15 per cent of cases of chickenpox, is usually transient and most commonly manifests as shingles in the infant.13 Chickenpox in the first half of pregnancy is complicated by fetal varicella syndrome in two to three per cent of pregnancies. Congenital varicella syndrome is characterised by microcephaly, low IQ, convulsions, dermatomal skin scarring and ipsilateral limb hypoplasia.

Exposure during pregnancy

Exposure to varicella during pregnancy is a common problem encountered in obstetric, general and infectious diseases practice, although it has become less so since the introduction of routine childhood immunisation. Women who have had significant exposure (living with someone with active chickenpox or herpes zoster, or face-to-face contact for at least five minutes) should be evaluated.21

If the mother has had chickenpox previously or she has been vaccinated, nothing further is needed. If her history is uncertain and serology is negative or unavailable within 96 hours of exposure, she should be given varicella zoster immunoglobulin (ZIG). ZIG is most effective within 48 hours, but is not effective after rash onset.22 After the 96-hour mark, post-exposure prophylaxis may be considered for women in the second half of pregnancy who also have underlying lung disease, are immunocompromised or who smoke. This is owing to an increased risk of varicella pneumonia in this subset of women.

Management during pregnancy

Oral acyclovir is effective if started less than 24 hours after the onset of chickenpox rash. Complicated chickenpox is characterised by respiratory, haemorrhagic or neurological complications, new lesions or persistent fever after six days. Complications or infection in immunocompromised women should be treated with intravenous acyclovir.

The infant at risk of varicella

Although fetal varicella syndrome (FVS) in the first trimester is rare, intrauterine diagnosis is often requested. Major abnormalities can usually be detected by serial ultrasound examination in the second trimester. If abnormalities are detected, the diagnosis can be confirmed by amniotic fluid PCR. In the absence of gross abnormalities, PCR performed at least six weeks after maternal infection has a high negative predictive value.23 A positive result indicates fetal infection, not necessarily damage. An ultrasound is required to assess the impact on the fetus, if any.

In the perinatal period, the risk of infection varies with the timing to delivery, as it can be acquired in utero or in transition through the birth canal. Chickenpox that occurs more than one week before delivery presents very little risk; very preterm <28 weeks or very low birthweight <1kg infants are treated with intravenous acyclovir nonetheless. If it occurs between two and 28 days after delivery, varicella immune globulin should be given to preterm and very low birthweight infants. The greatest risk is in the context of infection between seven days before and two days after delivery, in which instance varicella zoster immune globulin should be given immediately.

Term infants exposed to chickenpox require no specific action if their mothers are immune. In the absence of demonstrated immunity, ZIG should be given, ideally within 96 hours of exposure. They should then be isolated between days seven to 21 after exposure.

References

  1. Australian Institute of Health and Welfare (2014) Immunisation and vaccine preventable disease. AIHW cat. no. AUS 178. Canberra, Australia.
  2. Australian Society of Infectious Diseases (ASID). Management of Perinatal Infections. ASID Inc [Internet]. 2014 Jul 22;1–92. Available from: www.asid.net.au/resources/ clinical-guidelines .
  3. Keighley CL, Saunderson RB, Kok J, Dwyer DE. Viral exanthems. Curr Opin Infect Dis. 2015 Apr;28(2):139-50.
  4. Vaccine-Preventable Outbreaks [Internet]. Council on Foreign Relations; [cited 2015 Apr 2]. Available from: www.cfr.org/interactives/GH_Vaccine_Map/#map .
  5. Gilbert G. Infectious Diseases in Pregnancy and Newborn Infant. Switzerland: Harwood Academic Publications; 1991.
  6. Sintchenko V, Field PR, Gilbert GL. Rubella antibody in antenatal clinic patients. Aust N Z J Med. 1999 Apr;29(2):284.
  7. Gilbert G. Infectious Diseases in Pregnancy and Newborn Infant. Switzerland: Harwood Academic Publications; 1991.
  8. LeBaron CW, Forghani B, Matter L, Reef SE, Beck C, Bi D, et al. Persistence of Rubella Antibodies after 2 Doses of Measles Mumps Rubella Vaccine. Journal of Infectious Diseases. 2009 Sep 15;200(6):888-99.
  9. Song N, Gao Z, Wood JG, Hueston L, Gilbert GL, MacIntyre CR, et al. Current epidemiology of rubella and congenital rubella syndrome in Australia: Progress towards elimination. Vaccine. 2012 Jun;30(27):4073-8.
  10. National Health and Medical Research Council (NHMRC), editor. The Australian Immunisation Handbook. 10th ed. Canberra; 2014.
  11. Australian Society of Infectious Diseases (ASID). Management of Perinatal Infections. ASID Inc [Internet]. 2014 Jul 22;1–92. Available from: www.asid.net.au/resources/clinical-guidelines .
  12. Best JM, O’Shea S, Tipples G, Davies N, Al-Khusaiby SM, Krause A, Hesketh LM, Jin L, Enders G. Lesson of the week: Interpretation of rubella serology in pregnancy—pitfalls and problems. British Medical Journal. 2002 Jul 20;325(7356):147.
  13. Best JM, O’Shea S, Tipples G, Davies N, Al- Khusaiby SM, Krause A, Hesketh LM, Jin L, Enders G. Lesson of the week: Interpretation of rubella serology in pregnancy—pitfalls and problems. British Medical Journal. 2002 Jul 20;325(7356):147.
  14. Best JM. Rubella. Seminars in Fetal and Neonatal Medicine. 2007 Jun;12(3):182- 92.
  15. Cradock-Watson JE, Ridehalgh MK, Anderson MJ, Pattison JR. Outcome of asymptomatic infection with rubella virus during pregnancy. J Hyg (Lond). 1981 Oct 1;87(2):147-54.
  16. Gilbert GL. 1: Infections in pregnant women.Med J Aust. 2002 Mar 4;176(5):229-36.
  17. Gilbert G. Infectious Diseases in Pregnancy and Newborn Infant. Switzerland: Harwood Academic Publications; 1991.
  18. Best JM. Rubella. Seminars in Fetal and Neonatal Medicine. 2007 Jun;12(3):182- 92.
  19. Mace M, Cointe D, Six C, Levy-Bruhl D, Parent du Chatelet I, Ingrand D, et al. Diagnostic Value of Reverse Transcription- PCR of Amniotic Fluid for Prenatal Diagnosis of Congenital Rubella Infection in Pregnant Women with Confirmed Primary Rubella Infection. Journal of Clinical Microbiology. 2004 Oct 7;42(10):4818-20.
  20. Best JM. Rubella. Seminars in Fetal and Neonatal Medicine. 2007 Jun;12(3):182- 92.
  21. Australian Society of Infectious Diseases (ASID). Management of Perinatal Infections. ASID Inc [Internet]. 2014 Jul 22;1–92. Available from: www.asid.net.au/resources/ clinical-guidelines .
  22. Gilbert GL. 1: Infections in pregnant women.Med J Aust. 2002 Mar 4;176(5):229-36.
  23. Sanchez MA, Bello-Munoz JC, Cebrecos I, Sanz TH, Martinez JS, Moratonas EC, et al. The prevalence of congenital varicella syndrome after a maternal infection, but before 20 weeks of pregnancy: a prospective cohort study. J Matern Fetal Neonatal Med. 2011 Feb;24(2):341-7.

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