Congenital Rubella Syndrome

Rubella is a mild, self-limiting viral infection except for one serious complication. After an epidemic in Australia in the early 1940s it became apparent that if rubella is contracted in early pregnancy it can have profound consequences for the fetus.

Congenital rubella syndrome (CRS) is a 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 were not brought up here¹ and so missed immunisation. A campaign to vaccine women arrived from abroad may have benefit.²
• Before rubella vaccine there were an estimated 200 to 300 cases of CRS per year in the UK. This fell to 21 with 43 terminations of pregnancy for rubella contact between 1990 and 1995 and 17 cases with 17 TOPs between 1996 and 2000.
• 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 TOP has been declined but there is no documented case of CRS from the vaccine^3,4

In the Mother

• Rubella has an incubation period of 18 to 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, 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 is common
  • Radiolucent bone disease (20%)
  • Meningoencephalitis (25%) which may have 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)
  • Some develop a "late-onset" disease at 3-12 months with rash, diarrhoea, and pneumonitis, which has a high mortality.
• Permanent:
  • Congenital heart disease is commonly patent ductus arteriosus or peripheral pulmonary artery stenosis
  • Eye defects include cataracts, congenital glaucoma, pigmentary retinopathy (50% - so-called "salt & pepper"), severe myopia, microophthalmia
  • Microcephaly.

In a study from 1982:⁵

• Rubella defects occurred in all infants infected before the 11th week (principally congenital heart disease and deafness)
• In 35% of those infected at 13-16 weeks (deafness alone).
• No defects attributable to rubella were found in 63 children infected after 16 weeks.

There are a number of viruses that can cause a rash like rubella 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.

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.⁶
• 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.⁷

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 per month as maternal IgG does - which has disappeared by 6 months)
• PCR is a very sensitive test for the virus.⁸ PCR positive rubella virus, infants may continue excreting the virus for a year in pharyngeal secretions and urine⁶

• Mental handicap, hearing or visual defects, alone or in combination will probably require special schooling but for those with hearing or visual problems but moderate or normal intelligence input should begin as early as possible.
• 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 care⁹ but this is too late for the current pregnancy. Checking rubella immunity must be part of preconception counselling.
• Elimination of both rubella and CRS through universal immunization of infants and young children, surveillance, and ensuring immunity in women of childbearing age.
• Mathematical models show that poor uptake in preschool children 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.¹⁰

Issues to be discussed with parents are covered much more fully in health promotion for young children. Important points to make are:¹¹

• 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

There is also a mischievous suggestion that the MMR vaccine was derived from a cell line from an aborted fetus¹² and so it should be boycotted for ethical reasons. This is nonsensical. It would be of no value to the aborted fetus and there are no longer any original cells in the vaccine. It would increase the risk of rubella infection in pregnancy and consequently the number of TOPs or babies born with CRS.

• Sir Norman Gregg was an Australian ophthalmologist (and former member of the Davis Tennis Cup team) 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, Prof. 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.