Evaluation Of Pregnant Woman

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Most acquired rubella infections are asymptomatic or cause only mild disease. Low-grade fever, an erythematous nonconfluent macular papular rash that begins on the face and spreads to the trunk, and generalized lymphadenopathy are the typical signs of infection. Cough, coryza, and conjunctivitis may also be present; in adults, arthritis or arthralgias may occur at the time of the onset of the rash or soon after its appearance. The arthritis is often slow to resolve, but it usually does not cause chronic symptoms. Women are affected more frequently than men with arthritis; as many as one-third of women may have joint symptoms (14,15).

In the United States, rubella serology is obtained prenatally to document the woman's susceptibility to rubella. If rubella immunity is documented, the woman is protected from primary infection, and the fetus is not at risk for congenital anomalies. Rubella immunity is defined according to the type of serologic assay used. For example, assays measuring antibodies using the hemagglutinin inhibition require a titer above 1:8 for immunity, whereas the optical density required by the enzyme immunoassay (EIA) depends on the limit set by the assay's manufacturer (16). Any pregnant woman who is not seroimmune and has exposure to rubella during her pregnancy should be followed carefully for the next few weeks after exposure. (The incubation period for rubella is 2-3 weeks.) If she has fever, a rash, lymphadenopathy, arthralgias, or arthritis, an evaluation for infection is indicated.

Diagnosis of an acute rubella infection in a woman during pregnancy may be made by culture of the nose or throat. In acquired rubella, virus shedding is most consistent and intense in the nasopharynx, but the period of shedding is limited to the period from about 1 week prior to the rash to about 14 days after the rash (10). A more common and practical approach for diagnosis is the use of rubella-specific IgM antibody. IgM antibodies can be detected at low levels at the time of onset of the rash and are generally present within 5-10 days after the onset of the rash (10). After reaching their peak in titer at about 3 weeks after the rash begins, they then decline rapidly (Fig. 1). Knowledge of the kinetics of the IgM response to infection will allow serum to be obtained at

VIRUS

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14 21 28 35 DAYS AFTER ONSET

Fig. 1. Schematic of the immune response in acute rubella infection. CF, complement fixation; EIA, enzyme immunoassay; FIA/FIAX and IFA, immunofluorescence; HI, hemagglutination inhibition; IgM, immunoglobulin M; LA, latex agglutination; Nt, neutralization; PHA, passive agglutination; RIA, radioimmunoassay. (From refs. 10 and 17, with permission.)

14 21 28 35 DAYS AFTER ONSET

Fig. 1. Schematic of the immune response in acute rubella infection. CF, complement fixation; EIA, enzyme immunoassay; FIA/FIAX and IFA, immunofluorescence; HI, hemagglutination inhibition; IgM, immunoglobulin M; LA, latex agglutination; Nt, neutralization; PHA, passive agglutination; RIA, radioimmunoassay. (From refs. 10 and 17, with permission.)

a time when the antibodies are most likely to be present. If IgM antibodies are not present in the initial serum, consideration should be given to obtaining another sample from the woman for testing because the initial test may have been done prior to the development of IgM. The presence of IgM antibody in high titers is diagnostic of a recent infection with rubella.

Because false-positive and false-negative IgM antibodies may occur, serological evidence of infection should be confirmed with rubella IgG antibody measurement. Serum collected at the time of exposure or as soon as possible after the onset of rash and 2-4 weeks later is tested for IgG antibody to determine if seroconversion has occurred. If seroconversion has occurred, the IgM is positive in high titers, or the culture is positive, the risk of fetal infection and malformation is considerable if the mother was exposed during the first trimester. Because of the risk associated with congenital rubella and the not-infrequent problems with serological assays, the assays should be repeated to confirm the accuracy of the diagnosis. Because rubella may be asymptomatic or very mild in some individuals, evaluating a pregnant woman for evidence of a recent infection should also be considered in any woman with known exposure to rubella even if she has had no symptoms.

EVALUATION OF THE NEWBORN

Intrauterine infection with rubella can affect any organ system, and infants often have multiple organ systems involved. The spectrum of clinical abnormalities reported with congenital rubella is extremely diverse. The most common abnormalities, however, are ophthalmological, cardiac, auditory, and neurological. Common ophthalmo-logical abnormalities include cataracts, retinopathy, and congenital glaucoma. Patent ductus arteriosus, the most common cardiac anomaly, occurs in about one-third of infants with symptomatic infection. Pulmonary artery stenosis and pulmonary valvular stenosis are also common. Sensorineural hearing loss occurs more frequently than any other anomaly, may be the only manifestation of infection, and may not be detected at birth (4). Meningoencephalitis and microcephaly are two of the most common central nervous system abnormalities that may be present at birth in some infants. Infants often have growth retardation at birth, and other frequently associated findings are hepatomegaly, splenomegaly, thrombocytopenia, and the "blueberry muffin" skin rash. These symptoms are often self-limited and resolve with time (15).

For an infant born to a mother with known exposure to rubella, the diagnosis of rubella is usually not difficult if the infant has any of these anomalies at birth. Viro-logic or serologic confirmation, however, is important because the clinical disease associated with rubella can mimic disease caused by other microbial pathogens that can be transmitted to an infant in utero, including cytomegalovirus, toxoplasmosis, and syphilis. In the absence of known maternal exposure, rubella should be considered in infants with intrauterine growth retardation who have other clinical anomalies consistent with rubella. Consideration of rubella is particularly important in infants if their mother's rubella serology is not known, if their mother did not receive prenatal care, or if their mother immigrated from a country where rubella vaccine is not routinely given.

The diagnosis of congenital rubella can be confirmed with virus isolation, which is the most reliable method of making the diagnosis. Unlike individuals who acquire rubella postnatally, infants with congenital rubella excrete the virus for months. Cultures are most sensitive for isolation of virus when done soon after birth because the quantity of virus present decreases over time. The nasopharynx and throat are probably the best sites for isolation of virus, but it may also be cultured from the urine, blood, feces, and cerebrospinal fluid (10).

For most clinicians, a more practical approach to diagnosis is the use of serology because diagnosis of infection may be made with rubella-specific IgM antibody. Either cord blood or neonatal serum may be used. A limitation of IgM antibody for diagnosis includes the occurrence of false-positive assays because of the presence of rheumatoid factor. False-negative assays may also occur because the infant does not make detectable levels of antibody, IgM antibodies are no longer present when the diagnosis is considered, or there is variation in the performance of serologic assays. To enhance the sensitivity of the IgM assay for diagnosis, it has been recommended that the test be done within the first 2 months of life (4).

IgG antibodies can also be used to diagnose congenital infection by observing the pattern of antibody in the serum over time. Titers should be obtained at birth, 3 months, and at about 6 months and then run concurrently (10). If IgG antibodies persist at 6-12 months with a titer that is similar to or greater than that which occurred at birth, it is likely the infant had an intrauterine infection. A potential confounding factor when IgG antibodies are used for diagnosis is that infants can become infected with rubella after birth, and IgG antibodies would be present in response to a postnatal infection. Diagnosis of intrauterine infection using IgG antibodies requires consideration of the possibility that rubella exposure and infection occurred after birth.

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