CONGENITAL RUBELLA SYNDROME PREVENTION Patricia Wang, R1 10/24/2013

CONGENITAL RUBELLA SYNDROME
PREVENTION
Patricia Wang, R1
10/24/2013
EPIDEMIOLOGY
Incidence significantly
decreased since introduction of
vaccine in 1969
Last decade, rate less than 10
cases of congenital rubella
syndrome per year
Cases mostly affect mother
born outside of US
TERMINOLOGY
Congenital rubella infection
All outcomes associated with intrauterine rubella infection
Ie miscarriage, stillbirth, birth defects, asymptomatic infection
Congenital rubella syndrome
Constellations of birth defects
Ie hearing impairment, congenital heart defects,
cataracts/congenital glaucoma, pigmentary retinopathy
TRANSMISSION
Single-stranded RNA togavirus
Occurs via hematogenous spread during maternal viremia, which usually
occurs 5 to 7 days after maternal inoculation
Infects placenta, virus spreads through the vascular system of the developing
fetus
2 proposed mechanisms
 Cytopathic damage to blood vessels and ischemia in affected organs
 Direct viral damage of infected cells
 Reduced mitotic activity resulting from chromosomal breakage or due to
production of a protein that inhibits mitosis
CLINICAL MANIFESTATIONS OF CONGENITAL
RUBELLA
May have transient features
 Generalized lymphadenopathy, hepatosplenomegaly, intrauterine growth restriction,
hepatitis, jaundice, thrombocytopenic purpura, with petechiae and "blueberry muffin" lesions
 Can resolve in days or weeks
 Usually without long-term sequelae
Most common permanent features
 Sensorineural deafness, cataracts, peripheral pulmonary stenosis, mental retardation, central
language defects, diabetes mellitus type 1, hypogammaglobulinemia
CLINICAL FEATURES OF CONGENITAL RUBELLA
Bilateral sensorineural hearing loss (~66%)
Cataracts (~25%), infantile glaucoma, pigmentary retinopathy
Congenital heart disease (~50% infected during 1st two months of gestation)
 Patent ductus arteriosus and branch pulmonary artery stenosis- most common
 Pulmonary valvular stenosis, aortic valve stenosis, VSD, tetralogy of Fallot, and coarctation of aorta
CNS abnormalities
 Microcepaly (27%)
 Intellectual disability (13%)
 Motor delay, behavioral disorders, autism, and psychiatric disorders
Radiolucent bone disease
CLINICAL FEATURES OF ACUTE MATERNAL
INFECTION
Incubation- 2-3 weeks
Exanthematous erythematous and sometimes pruritic
rash that appears on face/trunk, then arms/legs
Following signs and symptoms usually appear 1-5
days before onset of rash:









Conjunctivitis
Sore throat
Headache
General body aches
Low-grade fever
Chills
Anorexia
Nausea
Tender lymphadenopathy (particularly posterior auricular
and suboccipital lymph nodes)
Can be subclinical
RISKS OF MATERNAL INFECTION
Risk of congenital defects essentially limited to maternal infection in first 16 weeks of
pregnancy
 Up to 20% maternal infections in first 8 weeks result in miscarriage, spontaneous abortion, or stillbirth
 Fetuses infected before 11 weeks have multiple organ damage
 After 11 to 12 weeks more likely to have only retinopathy and/or retinopathy
Little risk of congenital rubella syndrome after 20 weeks gestation
 IUGR may be only sequelae of 3rd trimester infection
DIAGNOSIS OF ACUTE RUBELLA IN MOTHER
Fourfold rise in IgG titer between acute and convalescent serum specimens
 Obtained within 7 to 10 days after onset of rash
 Repeated 2 to 3 weeks later
Presence of rubella specific IgM
Positive rubella culture
 Can be isolated from nasal, blood, throat, urine, or cerebrospinal fluid
 Generally isolated from pharynx one week before to two weeks after rash
TREATMENT FOR ACUTE MATERNAL RUBELLA
INFECTION
Acetaminophen for symptomatic relief
IgG- controversial, CDC recommends limiting use of immune globulin to women
with known rubella exposure who decline pregnancy termination
Glucocorticods, platelet transfusion, and other supportive measures for
complications
Should be counseled about maternal-fetal transmission and offered
pregnancy termination, especially prior to 16 wks’ gestation
After 20 wks’ gestation- individualized management
RECOMMENDATIONS
Screening at first post-conceptual appointment, firsttrimester screening
Routine screening of child-bearing age women not
recommended
Routine vaccination of all women of childbearing age not
recommended
MATERNAL PREVENTION
CDC and ACOG- rubella susceptible women should MMR vaccine postpartum
 Tetratogenic risk cannot be excluded
 Rubella vaccine virus can cross placenta and infect fetus potentially
 No reported cases of rubella vaccine-related birth defects after inadvertent vaccination
 Routine pregnancy testing of women of childbearing age before administering not recommended
 Avoid pregnancy for 28 days after vaccination
 If a pregnant woman is inadvertently vaccinated or becomes pregnant within 4 weeks after MMR,
should be counseled about the theoretical basis of concern for the fetus
 Pregnancy termination not recommended
Breastfeeding not contraindicated
 Been isolated in breast milk and in breast-fed infants after postpartum vaccination, but no adverse
consequences from such exposure reported
VACCINATION
MMR- at 12-15 months and 4-6 years
 Live attenuated rubella virus- virus strain RA 27/3 prepared in human
diploid cell culture
 Confers long-term, likely lifelong, protection
Vaccinate unless immunity documented by serology
Contraindications= immunodeficiency disorder, history of
anaphylaxis to neomycin, and pregnancy
Side effects- arthritis, arthralgia, rash, adnopathy, or fever
EVALUATION OF INFANT
Suspicion
Any infant born to a woman who had documented or suspected
rubella infection at any time during pregnancy
Any infant with IUGR or other features of congenital rubella
syndrome regardless of maternal history
Newborns who fail hearing screening
WORKUP FOR INFANT
Review maternal history
Clinical assessment
CBC and platelet count
LFTs
Radiograph of long bones
Ophthalmologic evaluation
Audiologic evaluation
Neuroimaging
DIAGNOSIS IN INFANT
Isolation of rubella virus
 Most frequently isolated from nasopharyngeal secretions
 Can be cultured from blood, urine, CSF, lens tissue, etc
Demonstration of rubella-specific IgM antibodies
 Most useful in infants younger than 2 months, but may persist for up to 12 months
 False- negative- 20% of infected infants tested for rubella igM may not detectable titers before 1
m
 If clinically consistent and test negative after birth, should be retested at 1 month
 False- positive- rheumatoid factor, viral infections (EBV, IM, parvovirus), and heterophile antibodies
DIAGNOSIS IN INFANT
Serial rubella-specific IgG levels at 3, 6, and 12 months
 Rubella-specific IgG antibodies that persist at higher concentration or longer duration than expected
from passive transfer of maternal antibody
 Maternal rubella antibody- half-life= 1 month, should decrease by 4 to 8 fold by 3 months of age
and should disappear by 6 to 12 months
 Can delay diagnosis
Detection of rubella virus RNA
Presence of rubella-specific hemagglutination inhibition (HAI) after nine months of
age
REPORTING
Report as soon as they are suspected
 Demographic information
 Maternal history- date of rubella vaccinations, dates and results of previous
serological tests for rubella immunity, history or documentation of rubella
infection during pregnancy, history of pregnancies inside and outside US,
country of birth and length of residence in the US, history of exposure to
rubella, travel history
 Clinical features
 Types and results of labs done on mother and child
REFERENCES
US Preventive Services Task Force. Guide to Clinical Preventive Services:
Report of the U.S. Preventive Services Task Force. 2nd edition. Washington
(DC): US Department of Health and Human Services; 1996. 32, Screening for
Rubella— Including Immunization of Adolescents and Adults. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK15478/
http://www.cdc.gov/vaccines/pubs/preg-guide.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm
Up-to-date