bubble_chart Overview

If a pregnant woman contracts rubella in the early stages of pregnancy, the rubella virus can infect the fetus through the placenta. The newborn may be premature and may suffer from congenital heart defects, cataracts, deafness, developmental disorders, etc. This condition is known as congenital rubella or congenital rubella syndrome.

bubble_chart Epidemiology

According to U.S. literature reports, approximately 20% of women of childbearing age in urban areas are susceptible to rubella. During the 1964 rubella pandemic, about 3.6% of pregnant women were infected with rubella, while in non-pandemic years, the infection rate was only about 0.1% to 0.2%. The earlier a pregnant woman is infected with rubella, the more likely the fetus is to be affected. By the pregnancy intermediate stage [second trimester], the infection rate becomes very low, and in the late stage [third trimester], the fetus may be less susceptible to infection. During that pandemic, Siegal et al. observed 333 pregnant women infected with rubella in early pregnancy, of whom 213 (64%) underwent induced late abortion, and 38 (11.4%) experienced spontaneous late abortion. Among infected fetuses, 10–20% of infants died within the first year after birth, and rubella virus could be isolated from the tissues and body fluids of the deceased. The virus could also be excreted from the throat and urine for several months after birth. This prolonged viral shedding poses a serious threat to surrounding healthy susceptible individuals, particularly pregnant women.

bubble_chart Pathogenesis

The mechanism by which the rubella virus causes specific fetal malformations is not yet fully understood. When a pregnant woman is infected with rubella, viremia occurs as early as one week before the eruption. Whether maternal rubella infection can be transmitted to the fetus depends on the timing of the infection in the mother. Infection during the 2nd to 6th day-night cycle of the embryo has the greatest impact on the heart and eyes. During the intermediate stage of pregnancy (second trimester), the fetus gradually develops immunity (such as the appearance of plasma cells and the production of IgM), and congenital rubella infection is less likely to result in chronic infection compared to early pregnancy. According to observations by Kibrick et al. (1974), if a pregnant woman is infected with rubella during the first month of pregnancy, the incidence of congenital rubella syndrome in the fetus can be as high as 50%; in the second month, 30%; in the third month, 20%; and in the fourth month, 5%. It is also noted that rubella infection after the fourth month of pregnancy is not entirely without risk to the fetus.

bubble_chart Clinical Manifestations

Congenital rubella infection can result in late abortion, stillbirth, live births with malformations, or completely normal newborns, and may also present as a latent infection. Almost all fetal organs may develop temporary, progressive, or permanent pathological changes.

1. Manifestations at birth Live-born infants may exhibit some acute sexually transmitted disease changes, such as neonatal thrombocytopenic purpura, characterized by scattered purplish-red spots of varying sizes present at birth, often accompanied by other temporary lesions, poor calcification of the epiphyses of long bones, hepatosplenomegaly, hepatitis, hemolytic anemia, and a bulging anterior fontanelle. There may also be an increase in cerebrospinal fluid cells. These conditions represent severe manifestations of congenital infection. Other manifestations at birth include low birth weight, congenital heart disease, white internal visual obstruction, deafness, and microcephaly, among others, with a poor prognosis. Based on a one-year follow-up of 58 infants with purpura, the mortality rate was as high as 35%. During the neonatal period, rubella viral hepatitis and interstitial pneumonia may also occur.

2. Cardiac malformations The most common heart blood vessel abnormalities include a stirred pulse ductus arteriosus, with some even isolating the rubella virus from the ductal wall tissue. Pulmonary stirred pulse stenosis or branch stenosis is also relatively common. Other conditions may include atrial septal defects, ventricular septal defects, aortic arch anomalies, and more complex malformations. Most infants do not exhibit severe heart blood vessel symptoms at birth; however, some may develop heart failure within the first month of life, which carries a poor prognosis.

3. Deafness Hearing loss can range from mild to severe and may affect one or both ears. The lesion is located in the Corti cochlea of the inner ear, though middle ear lesions may also occur. Hearing loss can also present as the sole manifestation of congenital rubella, particularly in infections occurring after the 8th week of pregnancy.

4. Ocular defects The most characteristic ocular lesion is pear-shaped nuclear white internal visual obstruction, which is usually bilateral but may also be unilateral, often accompanied by microphthalmia. At birth, the white internal visual obstruction may be very small or invisible and must be carefully examined with an ophthalmoscope. In addition to white internal visual obstruction, congenital rubella can also cause glaucoma, which is difficult to distinguish from hereditary infantile glaucoma. Congenital rubella glaucoma manifests as enlarged and cloudy corneas, deepened anterior chambers, and increased intraocular pressure. Normal newborns may also exhibit transient corneal clouding, which resolves spontaneously and is unrelated to rubella. Congenital rubella glaucoma requires surgical intervention, whereas transient corneal clouding does not require treatment. The retina often shows scattered black pigment patches of varying sizes. These pigments usually do not affect vision but can aid in the diagnosis of congenital rubella.

5. Developmental disorders and neurological malformations Intrauterine rubella infection can also affect the central nervous system. Autopsies of affected infants confirm that the rubella virus has strong neurotoxic effects, causing varying degrees of developmental defects. Cerebrospinal fluid often shows changes such as increased cell counts and elevated protein concentrations, and the virus may even be isolated from the cerebrospinal fluid up to one year of age.

Impairments in intelligence, behavior, and motor development are also major features of congenital rubella. These early developmental disorders are caused by rubella encephalitis and may result in permanent intellectual disability.

Generally, congenital heart malformations, white internal visual obstruction, and glaucoma are often caused by viral infection during the first 2-3 months of pregnancy, whereas hearing loss and central nervous system lesions are often due to infections later in pregnancy. Newborns may also exhibit transient congenital rubella manifestations, usually transmitted from early pregnancy infections, though occasionally due to advanced pregnancy infections where both the mother and fetus are affected simultaneously.

bubble_chart Auxiliary Examination

1. Virus Isolation Congenital rubella infants may have chronic infections and persistently carry the virus for many months after birth, becoming a source of pestilence for contacts. Rubella virus can be isolated from the pharyngeal secretions, urine, cerebrospinal fluid, and other organs of affected infants, with higher isolation rates in severe cases. In contrast, individuals with acquired rubella infections rarely shed the virus for more than 2–3 weeks. The positive rate of rubella virus isolation in congenital cases decreases with age, often becoming undetectable by one year of age. Unless the infant has congenital immunodeficiency and cannot produce antibodies, the virus is rarely isolated from the blood.

2. Serological Testing When a pregnant woman has a history of rubella exposure or clinical symptoms suggestive of rubella, serum rubella antibodies should be measured. If specific anti-rubella IgM is positive (using the ELA IgM test kit supplied by the Beijing Institute of Biological Products), it indicates recent primary rubella infection, especially in the early stages of pregnancy, and consideration should be given to artificial late abortion. In congenital rubella infants at birth, the serum rubella antibody titer is similar to that of the mother, primarily consisting of maternally transmitted IgG, which diminishes 2–3 months after birth. The infant's own anti-rubella IgM (which cannot cross the placenta) peaks at 3–4 months of age and disappears around one year. The infant's own anti-rubella IgM begins to rise within the first month after birth, peaks at one year, and can persist for several years. Therefore, if rubella-specific IgM is detected in the serum of a newborn or if rubella IgM antibodies remain significantly elevated 5–6 months after birth without postnatal infection, it confirms congenital rubella. As mentioned earlier, individuals with acquired rubella infections maintain hemagglutination inhibition antibodies for life, whereas about 20% of congenital rubella cases lose detectable antibodies by age five. Generally, 95% of susceptible children develop antibodies after rubella vaccination, whereas congenital rubella infants who have lost their antibodies rarely respond to vaccination. Thus, if a child over three years old fails to produce hemagglutination inhibition antibodies after rubella vaccination (after excluding immunodeficiency and other causes), along with a maternal history of rubella infection during pregnancy and other clinical manifestations, it can help confirm a diagnosis of congenital rubella.

bubble_chart Diagnosis

1. Epidemiological data: The pregnant woman has a history of rubella exposure or onset during the initial stage [first stage] of pregnancy, and laboratory tests have confirmed maternal rubella infection.

2. The newborn exhibits one or several manifestations of congenital defects.

3. Specific rubella IgM antibodies are present in the infant's serum or cerebrospinal fluid samples during the early postnatal period.

4. When passively acquired maternal antibodies are no longer detectable 8–12 months after birth, the infant's serial serum samples still show sustained levels of rubella antibodies. {|103|}

bubble_chart Treatment Measures

The treatment for congenital rubella syndrome is only symptomatic, and care should be provided by individuals with rubella antibodies. After discharge, contact with pregnant women must be avoided.

bubble_chart Prevention

Methods to prevent congenital rubella syndrome, refer to the prevention of rubella mentioned above. It is noteworthy that rubella reinfection during pregnancy can still affect the fetus. Among pregnant women who have been vaccinated against rubella, the chance of reinfection is much higher than in those who have naturally contracted rubella. During pregnancy, the increase in adrenal corticosteroids in the body and the reduction in cellular immune function make it easier for the virus to spread within the body, thereby affecting the fetus.

For non-pregnant individuals, rubella reinfection is almost always asymptomatic, without viremia, and merely acts like a vaccine booster, leading to an increase in antibodies. However, reinfection in pregnant women can still result in congenital rubella syndrome. Therefore, even if a pregnant woman has been vaccinated against rubella, strict isolation from rubella patients remains crucial.