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Congenital Rubella Syndrome Prevention

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.

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Congenital Rubella Syndrome Prevention

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  1. Congenital Rubella Syndrome Prevention Patricia Wang, R1 10/24/2013

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Recommendations • Screening at first post-conceptual appointment, first-trimester screening • Routine screening of child-bearing age women not recommended • Routine vaccination of all women of childbearing age not recommended

  12. 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

  13. 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

  14. 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

  15. Workup for infant • Review maternal history • Clinical assessment • CBC and platelet count • LFTs • Radiograph of long bones • Ophthalmologic evaluation • Audiologic evaluation • Neuroimaging

  16. 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

  17. 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

  18. 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

  19. 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

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