health professionals remain aware of the potentially devastating
effects on the developing fetus.
Outcomes: Rubella vaccination has been effective in virtually
eliminating congenital rubella syndrome in Canada.
searched for articles published between 1985 and 2007.
described in the report of the Canadian Task Force on Preventive
Sponsor: The Society of Obstetricians and Gynaecologists of
1. Since the effects of congenital rubella syndrome vary with the
gestational age at the time of infection, accurate gestational dating
should be established, as it is critical to counselling. (II-3A)
2. The diagnosis of primary maternal infection should be made by
serological testing. (II-2A)
3. In a pregnant woman who is exposed to rubella or who develops
signs or symptoms of rubella, serological testing should be
performed to determine immune status and risk of congenital
rubella syndrome (III-A)
4. Rubella immunization should not be administered in pregnancy but
may be safely given post partum. (III-B)
5. Women who have been inadvertently vaccinated in early
pregnancy or who become pregnant immediately following
vaccination can be reassured that there have been no cases of
congenital rubella syndrome documented in theses situations. (III-B)
6. Women wishing to conceive should be counselled and encouraged
to have their antibody status determined and undergo rubella
vaccination if needed. (I-A)
ubella, also called German measles, is a disease of child-
America since the introduction of routine childhood rubella
vaccination. In the absence of pregnancy, it is usually clini-
cally manifested as a mild self-limited infection.
tating effects on the developing fetus. It has been directly
responsible for inestimable wastage and for severe congeni-
This document will review some of the
tions are evaluated using the evidence criteria of the
Canadian Task Force on Preventive Health Care (Table 1).
The rubella vaccination program introduced in 1969 has
been very effective.
Rubella and the CRS have largely been
However, cases of CRS continue to
remains a concern.
l FEBRUARY JOGC FÉVRIER 2008
This guideline was prepared and reviewed by the Clinical Practice
Obstetrics Committee, reviewed by the Infectious Disease
Committee, and approved by Executive and Council of the Society
of Obstetricians and Gynaecologists of Canada.
Lorraine Dontigny, MD, FRCSC, Montréal (Québec)
Marc-Yvon Arsenault, MD, MSc, FRCSC, Montréal (Québec)
Marie-Jocelyne Martel MD, FRCSC, Saskatoon SK
Anne Biringer, MD, CCFP, FCFP, Toronto ON
Johanne Cormier, RN, Lasalle QC
Martina Delaney, MD, FRCSC, St. John’s NL
Tom Gleason, MD, FRCSC, Edmonton AB
Dean Leduc, MD, CCFP, Orleans ON
Marie-Jocelyne Martel, MD, FRCSC, (Chair) Saskatoon SK
Debbie Penava, MD, FRCSC, London ON
Joshua Polsky, MD, FRCSC, Windsor ON
Anne Roggensack, MD, FRCSC, Toronto ON
Carol Rowntree, MD, CCFP, Sundre AB
Ann Kathleen Wilson, BHSc, RM, Ilderton ON
No. 203, February 2008
1969, rubella epidemics occurred at irregular three- to
ten-year intervals. After 1970, the incidence of rubella
declined markedly and has stayed at a mean endemic rate of
4/100 000 population per year. This is an average of 1000
cases reported/year, range 237 to 2450.
Rubella virus con-
women are immune. Some segments of the population are
not immunized against rubella because they are missed,
refuse immunization, or come from countries where rubella
vaccination is not part of the routine immunization program.
Large rubella outbreaks occurred in Canada in the 1990s.
policies in the 1970s and 1980s, and current international
In 2005, 220 cases of rubella were
these cases were in members of a religious community in
which many members had not been vaccinated or had not
accepted the full range of vaccines routinely recom-
This is a reminder that rubella is not only a disease
Canada, and pregnant women born in Canada may be at risk
In a non-pregnant woman, rubella is usually an infection of
minor impact characterized by a mild, self-limited disease
associated with a characteristic rash.
from 7 days before to 5–7 days after rash onset.
viduals may experience mild prodromal symptoms such as
low-grade fever, conjunctivitis, sore throat, coryza, head-
aches or malaise, and tender lymphadenopathy. These
prodromal symptoms will usually last one to five days
before the onset of the scarletiniform rash, which may be
The rash characteristically begins on the
resolve within three days in the same order in which it
appeared (face first and then body).
Polyarthritis and polyarthralgia are potential sequelae,
(60–70%) about one week after the rash.
Rubella in Pregnancy
FEBRUARY JOGC FÉVRIER 2008
Quality of Evidence Assessment*
Classification of Recommendations†
Evidence obtained from at least one properly randomized
II-1: Evidence from well-designed controlled trials without
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
A. There is good evidence to recommend the clinical preventive
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
D. There is fair evidence to recommend against the clinical
E. There is good evidence to recommend against the clinical
There is insufficient evidence (in quantity or quality) to make
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
congenital rubella syndrome
chorionic villus sampling
enzyme linked immunoassay
fetal growth restriction
measles, mumps, rubella
polymerase chain reaction
arthritis rarely develops. Other manifestations, although
rare, include tenosynovitis, carpal tunnel syndrome,
CONGENITAL RUBELLA SYNDROME
CRS represents the neonatal manifestations of antenatal
infection with the rubella virus. The infection affects many
The risk of CRS abnormalities varies
Therefore, counselling regarding the risk to
individualized. Transplacental vertical infection by the
rubella virus can have catastrophic effects on the develop-
ing fetus, resulting in spontaneous abortion, fetal infection,
stillbirth, or fetal growth restriction.
Many children born
later in life. Pneumonitis, diabetes mellitus, thyroid
dysfunctions, and progressive panencephalitis are other late
expressions of CRS.
The most common congenital defects and late manifesta-
Fetal infection is acquired hematogenously, and the rate of
transmission varies with the gestational age at which mater-
nal infection occurs. After infecting the placenta, the rubella
virus spreads through the vascular system of the developing
fetus, causing cytopathic damage to blood vessels and
ischemia in developing organs.
When maternal infection/exposure occurs in the first tri-
in the late second trimester and increasing again in the third
trimester from 35% at 27–30 weeks’ gestation to nearly
100% beyond 36 weeks’ gestation.
The risk of congenital
tion occurs before 11 weeks of gestation, 33% at 11–12
weeks, 11% at 13–14 weeks, 24% at 15–16 weeks, and 0%
after 16 weeks.
Therefore, the risk of congenital defects after maternal
tion. Little, if any, risk of CRS is associated with infection
beyond 20 weeks, and FGR seems to be the only sequela of
third trimester infection.
Periconceptual maternal infec-
Maternal immunity, either after vaccination or naturally
Present at birth
Audiologic anomalies (60–75%)
Cardiac defects (10–20%)
Patent ductus arteriosus
Ventricular septal defect
Growth hormone deficit
Ophthalmic defects (10–25%)
Pigmentary and congenital glaucoma
Central nervous system (10–25%)
Radiolucent bone disease
Characteristic purpura (Blueberry muffin appearance)
Therefore, CRS should always be
gestive of congenital infection.
It should be noted that no
occurred after 12 weeks of pregnancy.
1. Since the effects of congenital rubella syndrome vary with
the gestational age at the time of infection, accurate ges-
tational dating should be established, as it is critical to
DIAGNOSIS OF RUBELLA INFECTION
Diagnosis of Maternal Infection
Accurate diagnosis of acute primary rubella infection in
pregnancy is imperative and requires serologic testing, since
an important number of cases are subclinical. Serology by
ELISA to measure rubella-specific IgG and IgM is conve-
nient, sensitive, and accurate. The presence of a rubella
infection is diagnosed by:
A fourfold rise in rubella IgG antibody titre between
A positive serologic test for rubella-specific IgM
A positive rubella culture (isolation of rubella virus in a
Serologic studies are best performed within 7 to 10 days
three weeks later. Viral cultures drawn from nasal, blood,
throat, urine, or cerebrospinal fluid maybe positive from
one week before to two weeks after the onset of the rash.
2. The diagnosis of primary maternal infection should be
made by serological testing. (II-2A)
Diagnosis of Fetal Infection
There are small series reporting the usefulness of
rubella-specific PCR on CVS for the prenatal diagnosis of
intrauterine rubella infection.
This technique has proved
Because CVS is done at 10 to 12 weeks of gesta-
samples, such as amniotic fluid taken at 14 to 16 weeks or
fetal blood obtained at 18 to 20 weeks of pregnancy.
Ultrasound diagnosis of CRS is extremely difficult. Biomet-
ric data can aid in the diagnosis of FGR but are not a good
tool for diagnosing CRS, given the nature of the malforma-
tions encountered. Any fetus presenting with FGR should
be evaluated for congenital viral infections, including
MANAGEMENT OF RUBELLA EXPOSURE/
The management of the exposed pregnant woman must be
individualized and depends when during gestation she was
exposed and on her state of immunity. Confirmation of
acute rubella infection in pregnant women is often difficult.
Clinical diagnosis is unreliable because a large proportion of
cases are subclinical and because clinical features can be
very similar to those of other illnesses. The Figure shows a
guide for the management of the exposed pregnant woman
or woman presenting with rubella-like symptoms in
If a pregnant woman develops signs or symptoms of a
rubella-like illness or has recently been exposed to rubella,
gestational age should be determined as well as her state of
1. Known immune
³ 12 weeks of gestation.
a. No further testing is necessary. CRS has not been
reported after maternal reinfection beyond 12 weeks’
2. Known immune
a. If these women demonstrate a significant rise in
rubella IgG antibody titre without detection of IgM
antibody, they should be informed that reinfection is
likely to have occurred.
Fetal risk for congenital
trimester has been estimated at 8% (95% CI
Appropriate counselling should be
3. Non-immune or immunity unknown.
a. Gestational age
£ 16 weeks.
i. Acute and convalescent IgG and IgM should be
obtained. (The diagnosis of recent rubella
infection should include serologic testing of acute
sera for both IgG and IgM antibody.) Acute
infection is diagnosed when IgM antibodies are
positive. When IgM antibodies are negative or
unavailable, testing of paired acute and
convalescent sera for IgG antibody should be
performed. During a rubella-like illness, the acute
specimen should be drawn as soon as possible,
followed by a convalescent specimen two to three
weeks later if the first IgM specimen was negative.
When there is a suspected exposure, the acute
specimen should be drawn immediately, followed
by a convalescent specimen 4 to 5 weeks later.
i. Instances of CRS between 16 and 20 weeks’
gestation are rare (< 1%) and may be manifested
by sensorineural deafness (often severe) in the
newborn. Appropriate counselling to the
non-immune pregnant woman should be
c. Gestational age
> 20 weeks.
i. A pregnant woman exposed to rubella or
presenting with rubella-like illness after
20 weeks of gestation should be reassured, since
no studies have documented CRS after
d. Diagnostic difficulty–late presentation with
unknown immune status.
i. A pregnant woman presenting 5 weeks or more
after exposure to a rash illness or 4 weeks or more
after onset of a rash presents a diagnostic
dilemma. If IgG antibodies are negative, the
patient is clearly susceptible to rubella and has no
evidence of a recent infection. If IgG are positive,
there is evidence of a previous infection. It is then
difficult to determine the date of infection and the
risk to the fetus, although a low level of antibody
suggests more remote infection. Testing for IgM
antibody or repeating the test for IgG antibody
levels to determine whether there is a significant
rise or decline may be considered.
3. In a pregnant woman who is exposed to rubella or who
develops signs or symptoms of rubella, serological test-
ing should be performed to determine immune status
and risk of congenital rubella syndrome. (III-A)
The treatment of acute rubella infection is supportive. The
prognosis is generally excellent for pregnant women with
There are no data supporting the use of immunoglobulin in
pregnant women with acute infection in order to diminish
the fetal response to disease. The Centers for Disease Con-
trol recommend limiting its use to women with known
rubella exposure who decline pregnancy termination.
SOGC CLINICAL PRACTICE GUIDELINES
Adapted from ACOG Education and Technical Bulletins 2002
The first live attenuated rubella vaccine was introduced in
1969. A single dose of this vaccine will result in measurable
antibody in almost 95% of susceptible persons. Antibody
levels persist for at least 18 years in more than 90% of the
Primary failure of the rubella vaccine
reinfections have resulted in only 8% risk of CRS in the first
trimester of pregnancy.
The rubella vaccine is usually well tolerated. Side effects to
adenopathy, and fever.
The actual vaccine-related fre-
women is in the order of 5% each. However, there is no evi-
dence of any increased risk of new onset chronic
arthropathies or neurological conditions in women receiv-
ing the RA27/3 rubella vaccine. There are no epidemiologic
data supporting an association of CRS or autism to the
Contraindications to rubella vaccinations include febrile ill-
to neomycin, and pregnancy.
Rubella vaccine virus has the
mended for these patients.
Given the potential risks to the
period of 28 days after immunization.
The vaccine can be given safely to postpartum women who
since infection is not transmitted from recently immunized
individuals. Breastfeeding is NOT contraindicated.
immune globulin preparations such as Rh-immune globulin.
4. Rubella immunization should not be administered in
pregnancy but may be safely given post partum. (III-B)
5. Women who have been inadvertently vaccinated in early
pregnancy or who become pregnant immediately follow-
ing vaccination can be reassured that there have been no
cases of congenital rubella syndrome documented in the-
ses situations. (III-B)
The best therapy for CRS is prevention. All girls should be
vaccinated against rubella before entering the child-bearing
1. Providing universal infant immunization to decrease
circulation of virus (instituted in all provinces in 1983).
2. Using measles, mumps, and rubella or measles-rubella
vaccine as the immunizing agent in catch-up
campaigns and as the second dose in the new
two-dose routine immunization program for measles.
(This may expedite the elimination of rubella).
3. Ensuring that girls are immune before they reach
child-bearing age and using every opportunity to asses
the immunity of women of child-bearing age and
providing vaccination if necessary (pre-conceptual and
4. Screening to determine the antibody status of all
pregnant women to determine susceptibility.
5. Providing programs to ensure postpartum
immunization of non-immune women before they are
discharged from the hospital.
6. Screening for immunity and vaccination, if necessary,
of all health care personnel, including students in
7. Immunizing all immigrant and refugee women at their
first encounter with the Canadian health care system,
unless they have documentation of effective
vaccination or natural immunity.
6. Women wishing to conceive should be counselled and
encouraged to have their antibody status determined and
undergo rubella vaccination if needed. (I-A)
Rubella infection of a pregnant woman may have devastat-
ing effects on the developing fetus. The mainstay of preven-
tion is the universal immunization of all Canadian infants
and identification and immunization of immigrant women
at risk. The diagnosis of infection should be made as soon
as possible. Contact with rubella should be avoided
throughout the first two trimesters of pregnancy, even in
IgG-positive pregnant women. Women should be coun-
selled about the possible risk of vertical transmission and
offered pregnancy termination, especially if primary infec-
tion occurs prior to 16 weeks’ gestation. Unfortunately,
there is no in utero treatment available for infected fetuses.
Thus, prevention remains the best strategy to eliminate all
cases of CRS.
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