Most common heart defect in congenital rubella syndrome

Congenital Rubella Syndrome

In 1941 an ophthalmologist first described a syndrome of cataracts and congenital heart disease that he correctly associated with rubella infections in the mothers during early pregnancy [Table 274.2]. Shortly after the first description, hearing loss was recognized as a common finding often associated with microcephaly. In 1964-1965 a pandemic of rubella occurred, with 20,000 cases reported in the United States, leading to more than 11,000 spontaneous or therapeutic abortions and 2,100 neonatal deaths. From this experience emerged the expanded definition of CRS that includes numerous other transient or permanent abnormalities.

Nerve deafness is the single most common finding among infants with CRS. Most infants have some degree of intrauterine growth restriction. Retinal findings described assalt-and-pepper retinopathy are the most common ocular abnormality but have little early effect on vision. Unilateral or bilateral cataracts are the most serious eye finding, occurring in about a third of infants [Fig. 274.4]. Cardiac abnormalities occur in half of the children infected during the first 8 wk of gestation. Patent ductus arteriosus is the most frequently reported cardiac defect, followed by lesions of the pulmonary arteries and valvular disease. Interstitial pneumonitis leading to death in some cases has been reported. Neurologic abnormalities are common and may progress following birth. Meningoencephalitis is present in 10–20% of infants with CRS and may persist for up to 12 mo. Longitudinal follow-up through 9-12 yr of infants without initial retardation revealed progressive development of additional sensory, motor, and behavioral abnormalities, including hearing loss and autism. PRP has also been recognized rarely after CRS. Subsequent postnatal growth retardation and ultimate short stature have been reported in a minority of cases. Rare reports of immunologic deficiency syndromes have also been described.

A variety of late-onset manifestations of CRS have been recognized. In addition to PRP, they include diabetes mellitus [20%], thyroid dysfunction [5%], and glaucoma and visual abnormalities associated with the retinopathy, which had previously been considered benign.

Diagnosis

Rubella

Congenital rubella was first recognized in 1941, when after a rubella epidemic, a large number of children born to infected mothers were noted to have cataracts. Immunization against the rubella virus in the United States, Canada, and many European countries has decreased maternal rubella and thus congenital rubella. In the United States, only a few cases of congenital rubella are reported per year. Attention is now directed at its eradication in developing countries [Banatvala, 1998].

Although maternal infection can be subclinical, it usually presents 14 to 21 days after exposure with a maculopapular rash that begins on the face and spreads to the neck, trunk, arms, and legs. It is associated with lymphadenopathy, malaise, arthralgias, and petechiae. There is no therapy other than supportive. Pregnant women found not to have immunity to rubella should be instructed to avoid individuals who have viral illnesses. Suspected infection should be documented by specific rubella IgG and IgM measurement or by viral culture of the mother.

Maternal rubella acquired in the first trimester of pregnancy has a high risk of conferring damage to the developing fetus, and documented cases should be counseled and pregnancy interruption offered. In congenital rubella syndrome, many abnormalities can be found, such as cataracts, chorioretinitis, microphthalmia, congenital heart disease, myocarditis, microcephaly, deafness, mental retardation, and bone lesions, as well as signs of systemic infection [pneumonitis, hepatosplenomegaly, hepatitis, thrombocytopenia] [Stamos and Rowley, 1994].

Rubella

Congenital rubella is rare in developed countries but is still a risk among nonimmunized pregnant women in the developing world.154,155 The congenital syndrome is devastating and well described and includes cardiac and ocular anomalies as well as growth restriction and neurocompromise.156-158 Placental findings are nonspecific and depend on gestational age.159 Chronic villitis, with or without necrosis and fibrin agglutination, has been described [Fig. 18.18]. Occasionally, inclusions are present, which can assist in the differential diagnosis.159 A publication describes the immunolocalization of the antigen in fetal and placental tissues and reports that antigen is widespread in the tissues known to be associated with malformations in congenital rubella syndrome [heart and brain] as well as in the lung and placenta.160

D. Rubella

Preventing congenital rubella is important because it can affect all organ systems. Deafness is the most common sequela of congenital rubella syndrome. Parents should be counseled on the importance of immunization. Routine screening should be offered to all women of reproductive age who have not been vaccinated. Women should be counseled not to become pregnant for 3 months after receiving vaccination because of a theoretical risk for transmission. A woman who does become pregnant can be reassured that no documented cases of congenital rubella as a result of vaccination have been reported. A woman with rubella in early gestation is at risk for prematurity, spontaneous abortion, and fetal death. Neonatal infections are rare when maternal infection occurs after 20 weeks. However, in women who are infected in the first trimester, 85% will have an infected fetus or infant. Women should be counseled that infants with congenital rubella are highly contagious and caretakers who are not immunized are at risk for infection.

RUBELLA

Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications. A worldwide rubella epidemic from 1963 to 1965 affected thousands of infants, many of whom continue to be seen as adults. Ocular disease was the most commonly noted disorder [78%], followed by sensorineural hearing deficits [66%], psychomotor retardation [62%], cardiac abnormalities [58%], and mental retardation [42%]. Multiorgan disease was typical [88%].293

Glaucoma, cataract, microcornea, keratitis, uveitis, and a pigmented retinopathy [Fig. 19-37] are the most common ocular manifestations of congenital rubella infection.294 There is no correlation with gestational age of infection and a specific ophthalmologic defect.293

Rubella keratitis, often of relatively short duration, causes deep corneal clouding in either a diffuse or disciform pattern. This must not be confused with corneal edema resulting from glaucoma. The glaucoma may present in infancy and have the appearance of isolated trabeculodysgenesis. This form is best managed by goniotomy.

Glaucoma can also arise from iridocyclitis. These patients respond poorly to goniotomy and should be treated with aqueous suppressants, anti-inflammatory therapy, and cycloplegics during the acute phase, which frequently subsides over several weeks. Later onset glaucoma is commonly seen in rubella eyes with microcornea and cataract extraction under the age of 1 year.289

Clinical Presentation

CRS refers to a variable constellation of birth defects often including hearing impairment, congenital heart defects, cataracts/glaucoma, and retinopathy,42 as well as fetal growth restriction, hypotonia, developmental delay, and seizures.50 Miller et al. followed 1016 cases with confirmed maternal rubella infection.51 The frequency of congenital infection varied with gestational age; it occurred in more than 80% of women infected in the first trimester, and 54% infected between 13 and 14 weeks, decreasing to 25% by the end of the second trimester.51 Improved fetal immune response and transfer of maternal antibodies across the placenta after 16 weeks are thought to make congenital damage less severe after 16 weeks.40