Congenital Rubella Syndrome

Rubella is a mild, self-limiting viral infection except for one serious complication: an epidemic in Australia in the 1940s provided evidence that intrauterine exposure to rubella in early pregnancy can have profound consequences for the fetus.

Congenital rubella syndrome (CRS) is an entirely preventable disease.

• An effective immunisation scheme has made this condition very uncommon in the UK. Many of the women in the UK who deliver a baby with the syndrome did not grow up here¹ and so missed the routine immunisation programme. A campaign to vaccinate women arriving from abroad may have benefit.²
• Before the rubella vaccine was introduced, there were an estimated 200-300 cases of CRS per year in the UK. This fell to 21 with 43 terminations of pregnancy (TOP) for rubella contact between 1990-1995 and 17 cases with 17 TOPs between 1996-2000.
• Recent UK data suggests that 97% of pregnant women receive rubella susceptibility screening as part of their routine antenatal care.³ Susceptibility varies according to parity (nullips 2% versus parous women 1.2%) and ethnicity (women originating from the Mediterranean 4%, South Asian or Black women 5%, women from the Far East 8%). However, as immunisation is contra-indicated during pregnancy, susceptibility testing followed by immunisation after delivery only offers protection for future pregnancies. In 1995, data suggested an overall risk of rubella infection during pregnancy in susceptible women of about 2 in 1000 pregnancies.⁴
• Rubella vaccine is a live attenuated vaccine and so should not be given in pregnancy as theoretically the risk is as for the wild disease. However, it has been done inadvertently on a number of occasions and, where TOP has been declined, there is no documented case of CRS attributable to the vaccine.^5,6

In the mother

• Rubella has an incubation period of 18-21 days.
• There is a macular rash, posterior auricular lymphadenopathy and arthralgia affecting mostly the wrist and joints of the hand.
• There is very little malaise in children but adults tend to feel more unwell.
• It may cause first trimester miscarriage.
• 20-50% of all rubella infections are subclinical. Reinfection is possible but the immune response is modified and the risk to the foetus is low.

In the baby

• Transient:
  • Intrauterine growth retardation
  • Thrombocytopenia purpura (25% -"blueberry skin")
  • Haemolytic anaemia
  • Hepatosplenomegaly
  • Jaundice (common)
  • Radiolucent bone disease (20%)
  • Meningoencephalitis (25%) +/- neurological sequelae
• Developmental:
  • Sensorineural deafness (80%, variable, unilateral or bilateral) - rubella is commonest cause of congenital deafness in the developed world
  • Mental retardation (55%)
  • Insulin-dependent diabetes (20%, immune-mediated, but often delayed to adolescence or adulthood)
  • "Late-onset" disease at 3-12 months with rash, diarrhoea, pneumonitis and high mortality
• Permanent:
  • Congenital heart disease (commonly patent ductus arteriosus or peripheral pulmonary artery stenosis)
  • Eye defects including cataracts, congenital glaucoma, pigmentary retinopathy (50% - so-called "salt & pepper"), severe myopia, microphthalmia
  • Microcephaly

In a study from 1982, rubella defects occurred in:⁷

• All infants infected before the 11th week (principally congenital heart disease and deafness).
• In 35% of those infected at 13-16 weeks (deafness alone).
• None of the 63 children infected after 16 weeks.

There are a number of viruses that can cause a rubella-like rash and, so when an accurate diagnosis is imperative, as in early pregnancy, laboratory investigations must be undertaken.

In pregnancy, rubella is indistinguishable from parvovirus B19. Due to the wide differential and potential fetal risks, it is important to seek advice/follow HPA guidance on rash illness and exposure to rash illness during pregnancy.⁸

The other viruses in the TORCH group (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex) have the following common features:

• Preterm delivery
• Low birthweight
• Anaemia
• Thrombocytopaenia
• Hepatitis with jaundice and hepatosplenomegaly
• Microcephaly, mental handicap, seizures, and failure to thrive

If a pregnant woman is suspected of having rubella, the clinical diagnosis is very unreliable. Infection may be assumed if antibody tests show:

• Rubella specific IgM as IgM implies primary infection.
• A rise in IgG titre over 2 weeks.
• Reverse transcriptase PCR and sequencing for diagnosis and detection of rubella-specific IgG and IgM salivary antibody responses in oral fluid are now available.⁹
• In second trimester infection the risk to the fetus is low. Fetal viraemia can be detected by fetal blood sampling. Reliance on amniotic fluid may give false assurance.¹⁰

Criteria for postnatal diagnosis in the baby:

• Isolation of rubella virus (from amniotic fluid, throat, or urine).
• Demonstration of rubella-specific IgM (does not cross the placenta).
• Unexpected persistence of rubella IgG (does not drop at 2-fold dilution/month as maternal IgG does - which is cleared by 6 months).
• PCR is a very sensitive test for the virus.^11,12 Congenitally infected infants may continue excreting the virus for up to a year in pharyngeal secretions and urine.⁹

• The need for special educational provision will depend on the presence/combination of mental handicap, hearing and visual defects. These should be assessed at the earliest opportunity.
• Cochlear implants are showing some success.
• Cardiac surgery may be required.

Prognosis depends upon the severity of the lesions, the combinations of defects present and the quality of the input to the child.

Prevention is based on a programme of immunisation:

• Prevention of CRS through immunization of adolescent/women of childbearing age.
• Checking rubella antibody status is part of antenatal care⁴ but this is too late for the current pregnancy. Checking rubella immunity should occur as part of preconception counselling.
• Elimination of both rubella and CRS should be possible via:
  • Universal immunization of infants and young children.
  • Disease surveillance.
  • Ensuring immunity in women of childbearing age, prior to conception.
• Mathematical models show that poor uptake in preschool children (as occurred over the years of the MMR controversy) actually increases the proportion of older susceptible individuals. Therefore, a high vaccine uptake is essential.
• Because the clinical diagnosis is so unreliable, a history of having had the disease is not a reason to forgo immunisation.
• The current live attenuated vaccine, human diploid RA 27/3 is 95% effective, and is available in monovalent, divalent (with either measles or mumps), and trivalent (MMR) form. Other vaccine strains are available in China and Japan.
• Post-exposure immunoglobulin does not prevent infection, but as it may reduce symptoms, and therefore the level of viraemia, it is offered to infected pregnant women determined to proceed to term.

CRS is a disease that could be eradicated by a comprehensive programme of immunisation but there are impediments to achieving this aim. There is no animal reservoir of rubella.

• A first dose of MMR is said to provide immunity in 90% of cases, rising to nearly 100% with a second dose.
• There are a small number who will fail to seroconvert, who have genuine reasons for not having the vaccine such as serious adverse reactions or who lose immunity before conception.
• Hence it is important to have a high uptake of MMR vaccine to provide adequate herd immunity.
• Totally unfounded fears about the safety of MMR vaccine have led to a fall in uptake amongst children to around 80% nationally and 70% in London. In Scotland the numbers may have fallen below the level for herd immunity.¹³

Issues to be discussed with parents are covered much more fully in our record on health promotion for young children. Important points to make are:¹⁴

• The MMR vaccine has been very extensively studied and it has an excellent safety record with absolutely no suggestion of any association with autism.
• Even boys must have the vaccine or they may give rubella to susceptible pregnant women.

• Sir Norman Gregg was an Australian ophthalmologist who first identified the link between maternal rubella in early pregnancy and congenital cataracts in infants in 1941.
• It was not until 1947, when the Australian mathematician, Professor Oliver Lancaster demonstrated the association statistically, that he was believed by the outside world.
• The rubella virus was isolated in 1961, and following a world-wide outbreak in 1964-65 (20,000 cases of congenital cataract in the USA alone), vaccines were developed, the first licensed in 1969 - the shortest time period from virus identification to vaccine ever.
• The current RA 27/3 vaccine was introduced in 1979.