Obstetrics and Gynecology

Rubella in Pregnancy

Rubella in Pregnancy

1. What every clinician should know

A major worldwide epidemic of rubella spread to the United States in 1964, resulting in 12 million cases of rubella, 11,000 fetal deaths, and 20,000 cases of congenital rubella syndrome (CRS). This prompted a vaccination program in 1969 that reduced the incidence of rubella cases from 58 per 100,000 in 1968 to < 0.5 per 100,000 in 1983.

Although there was a resurgence of cases in California and Pennsylvania in 1990-1991, the CDC was able to announce the elimination of rubella in the United States on October 24, 2004. The latest data show that a median of 11 cases are reported each year, translating into an incidence of <0.005 per 100,000. Vaccine coverage among school entrants is >95%, and >90% of children aged 19-35 months have been vaccinated.

Women at risk for rubella will be limited to those who have not been vaccinated. This is more likely in foreign born women immigrating to the United States. The fact that rubella is endemic in many parts of the world ensures that the risk of importation into the United States remains, even after rubella elimination is documented. To maintain elimination, we must maintain high vaccination rates among children and ensure vaccination of women of childbearing age, particularly those born outside of the United States. Good surveillance for both rubella and congenital rubella syndrome (CRS) must also be maintained, with rapid response to outbreaks.

2. Diagnosis and differential diagnosis

Incubation for this togavirus infection ranges from 14 to 18 days. Viremia occurs 5 to 7 days after infection. The common clinical manifestations include sore throat, coryza, and cough. A maculopapular rash (viral exanthem) is also characteristic and can be associated with lymphadenopathy. Less common symptoms include a mild arthralgia, arthritis, and non-exudative conjunctivitis. Forchheimer spots may be noted on the soft palate.

Up to 50% of infections in pregnancy are asymptomatic. The viral infection should be considered in susceptible gravidas with a fetus with intrauterine growth restriction. Diagnosis is particularly important in the first half of pregnancy, as this time frame is associated with a significant chance of congenital rubella syndrome. The diagnosis can be confirmed with serology or virus detection (culture or PCR) from cord blood. After delivery, the virus can be detected in the placenta, cord blood, fetal nasopharynx, and urine.

The diagnosis can be confirmed serologically or by isolation of the rubella virus. Both IgM and IgG antibody tests should be obtained. Detection of rubella specific IgM antibodies using enzyme immunoassay (EIA) is the preferred initial test. IgM can be detected 4 days following rash and up to 6 to 8 weeks after primary infection. A four-fold increase in IgG antibody titer drawn 2 to 6 weeks apart also confirms infection.

Viral detection by culture or polymerase chain reaction (PCR) is possible from the nasopharynx, blood, cord blood, placenta, urine, and cerebral spinal fluid.

The differential diagnosis includes other infections, both bacterial and viral, that are associated with exanthems, such as scarlet fever, roseola, parvovirus, enterovirus, infectious mononucleosis, toxoplasmosis, and drug reactions.

3. Management

There is no known therapy for active rubella infection. Supportive care with acetominophen for fever and malaise is suggested. IVIG use during pregnancy for this condition is controversial.

Prevention of rubella is important. The rubella vaccine is a live attenuated virus which is usually given as part of the MMR (measles, mumps and rubella) vaccine. MMR is recommended for children 12 to 15 months of age (not earlier), with a second dose (booster) when the child is 4 to 6 years old (before kindergarten or first grade).

Live virus vaccines, like rubella, are contraindicated for pregnant women because of the theoretical risk of transmission of the vaccine virus to the fetus. CRS has not been associated with pregnancies in which rubella vaccine was inadvertently administered. Ordinarily, inadvertent rubella vaccination during pregnancy or within 4 weeks of vaccination is not an indication to terminate the pregnancy.

4. Complications

Acute rubella infection in the first trimester results in fetal infection 80% to 90% of the time. This risk decreases to approximately 10% at 13-14 weeks and <5% in the second half of pregnancy. Fortunately, the risk of CRS is much lower, but still significant. CRS occurs in up to 25% of cases at < 11 weeks gestation, and <1% in pregnancies at 13-16 weeks gestation. No defects have been detected in fetuses infected after 20 weeks gestation.

Maternal to fetal transmission occurs by hematogenous spread during maternal viremia. The virus infects the placenta and spreads through the vascular system, causing cytopathic damage to blood vessels and ischemia to organs.

5. Prognosis and outcome

Maternal outcome is routinely uncomplicated. However, CRS can lead to significant morbidity in the fetus. The sequelae associated with CRS most commonly are associated with hearing loss (67%). Severe central nervous system defects can occur, including mental retardation (13%), psychomotor retardation, and microcephaly related to a chronic meningoencephalitis. This chronic inflammation can be associated with intracranial calcifications noted on ultrasound.

Cardiac defects, responsible for 50% of reported defects, include patent ductus arteriosus, cardiac septal defects, and pulmonary artery hypoplasia. Cataracts occur in 25% of neonates, and other opthalmaologic disorders, such as glaucoma, retinopathy with chorioretinitis, and micropthalmia (10% to 20%) may also occur.

Like other congenital viral infections, the rubella virus persists after birth in the nasopharynx and feces, leading to the infant being a source of infection for more than a year.

Late manifestations associated with CRS include diabetes (20%), thyroid dysfunction (5%), and growth hormone deficiency.

6. What is the evidence for specific management and treatment recommendations?

Andrade, JQ, Bunduki, V, Curti, SP, Figueiredo, CA, de Oliveira, MI. "Rubella in pregnancy: Intrauterine transmission and perinatal outcome during a Brazilian epidemic". J Clin Virol. vol. 35. 2006. pp. 285-91.

"CDC. Measles, mumps, and rubella — vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. vol. 47 (No. RR-8). 1998. pp. 32-33.

Reef, SE, Redd, SB, Abernathy, E, Kutty, P, Icenogle, JP. "Evidenced used to support the achievement and maintenance of elimination of rubella and congenital rubella syndrome in the United States". JID. vol. 204. 2011. pp. S593-S597.

Freij, BJ, South, MA, Sever, JL. "Maternal rubella and congenital rubella syndrome". Clin Perinatol. vol. 15. 1988. pp. 247-57.

Shirley, JA, Revill, S, Cohen, BJ, Buckley, MM. "Serological study of rubella-like illness". J Med Virol. vol. 21. 1987. pp. 369-79.

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