Infections in Newborns:
A Common Cause of Hearing Loss
With the advent of newborn screening programs, there have recently been exciting developments in research to identify not only the newborn with hearing loss, but to ascertain the causes of hearing loss in newborns. Recently, my colleague at the University of Minnesota Children 's Hospital, Dr. Lisa Schimmenti, reviewed the genetic causes of hearing loss in newborns. As Dr. Schimmenti pointed out, up to 40% of what is called "nonsyndromic" hearing loss may be caused by mutations in genes known as the "connexin" family of genes. In this article, I want to review the role that infections play in causing hearing loss in newborn infants. Of the infections that cause hearing loss in infants, the most common and important is an infection caused by a virus called cytomegalovirus (CMV).
Signs & Symptoms of Congenital Cytomegalovirus Infection
• Small for gestational age
• Growth failure
• Skin rashes
• Enlarged abdominal organs
• Blood count abnormalities
• Reduced head growth
• Developmental Delay
• Hearing loss, often delayed in onset
A variety of infections can be the cause of hearing loss in infants and children. An infection can cause hearing loss either by infecting the baby before birth, while still in the womb, or by infecting the baby or young child after birth. A number of infectious pathogens, including syphilis, rubella ("German Measles"), and CMV, can cross from mother to baby before birth. When this happens, the inner ear (the cochlea) can be injured, leading to hearing loss. At one time, rubella (German Measles) was the most common infection causing deafness in newborn infants. Congenital infection (infection acquired by the baby before birth) occurred in over 25,000 newborn infants in the United States in the early 1960s, and the majority of these babies were born with hearing loss. Among those infections which cause deafness in infants after birth, the most common are two kinds of bacteria, known as Hemophilus influenzae type B (HIB), and Streptococcus pneumoniae. These bacteria, usually acquired by person-to-person transmission in early childhood, cause bacterial meningitis ("spinal meningitis") in early childhood, which results in 10-15% of cases in hearing loss. Fortunately, these diseases are all very rare today. Rubella was controlled by the development of a vaccine in the 1960's which has essentially eliminated this infection in the developed world. HIB and streptococcus pneumoniae vaccines became available in the 1990's. All of these vaccines are given as a part of a child's routine immunization series. It is almost unheard of today for any of these infections to be associated with deafness in infants or children.
In the United States today, CMV is the most common infection which causes deafness in childhood. For CMV to cause deafness, the infection, like rubella, must be transmitted to the baby prior to birth. CMV is a virus which is a member of a family of viruses known as Herpesviruses. Thus, it is similar at the genetic (DNA) level to the same viruses which cause chicken pox (Varicella-Zoster virus), cold sores (Herpes Simplex virus), and infectious mononucleosis (Epstein-Barr virus). CMV virus is transmitted very easily from person-to-person. About 50% of all adults have had CMV infection. Usually a CMV infection causes few if any symptoms when you initially "catch" it. However, if a woman is pregnant when she first gets a CMV infection, the virus can cross the placenta to the infant, producing what is called "congenital CMV infection". Once a CMV infection is acquired in this fashion, there is a risk to the baby for a number of symptoms. (See sidebar). In severe cases, infants with congenital CMV infection can have enlarged abdominal organs (caused by liver and spleen enlargement), growth problems, blood count abnormalities requiring transfusions, and brain injury. If there is brain injury, developmental delay and mental retardation can occur. There can be a wide range of severity of symptoms, but not all babies have symptoms. In fact, the majority of babies born with congenital CMV infection look and act entirely normally as newborns. However, even these completely "asymptomatic" babies are at risk for deafness in up to 15% of cases. Thus, even in the "mildest" of cases, there is a significant risk that congenital CMV infection can cause hearing loss.
Congenital CMV infection is very common. About 1% of all newborns are born with congenital CMV infection (Figure 1). Since approximately 4,000,000 babies are born in the United States every year, this corresponds to about 40,000 infants (1%) with congenital CMV infection annually. There is an overall risk of approximately 15% that there will be some element of hearing loss caused by CMV in a congenitally infected baby. The total number of infants with neurodevelopmental injury, including hearing loss, caused by congenital CMV in the United States is estimated to be between 4,000-6,000 babies/year. It is estimated that somewhere between 30-40% of cases of deafness in children are related to congenital CMV infection.
Currently, there is no vaccine for CMV licensed. Thus, efforts to decrease the likelihood of acquiring CMV infection during pregnancy should be focused on prevention. CMV is often transmitted from child-to-parent (just as rubella was in the 1960s). Children in group day care centers often acquire CMV infections from other children, which in turn, if transmitted to a pregnant parent, can lead to congenital CMV when the baby is born. Thus, women can decrease their risk of catching CMV by minimizing their exposure to infectious secretions of young children, such as urine and saliva. Women of child-bearing age can discuss their risk of CMV with their obstetrician, and be tested for CMV antibodies to see if they are at risk. If a baby is born with congenital CMV infection, it is important for families to be aware that there is an antiviral drug available which appears to be useful in preventing CMV-induced deafness in some babies. The drug is called ganciclovir, and it is highly active against CMV. It should be used only following consultation with an expert on antiviral treatment in children. In cases of CMV-induced deafness in which antiviral therapy does not provide any improvement, hearing aids can be utilized. In cases of severe, bilateral deafness caused by congenital CMV, cochlear implantation has been used and is highly effective. The University of Minnesota Children 's Hospital in the Division of Infectious Diseases is one of a number of participating sites in the Collaborative Antiviral Study Group (CASG) and can, in collaboration with the Lion's Hearing Center at the University of Minnesota , provide families with up-to-date information regarding treatment options for hearing-impaired infants with congenital CMV infection (612-624-1112).
Ultimately, the control of CMV in newborn infants and the prevention of CMV-induced deafness will likely depend upon the development of an effective vaccine. Until a vaccine is available, better recognition of CMV as a cause of deafness in newborns, and increased knowledge of CMV in the lay and medical communities, will be necessary. One aspect of the natural history of CMV in congenitally infected newborns that complicates recognition of this disease is the fact that hearing loss caused by congenital CMV may be progressive. Thus, a newborn with congenital CMV infection may "pass" the newborn hearing screen, only to go on to develop CMV-induced deafness months or, in some cases, years later. Newborn hearing screening programs may therefore miss a large number of cases of congenital CMV-induced deafness, since the deafness is not yet present in the immediate newborn period when hearing screening occurs. A solution to this problem would be to not only perform universal newborn hearing screening, but also to perform universal newborn screening for CMV infection. Those babies found to test positive could then be monitored carefully for hearing loss, and possibly treated with anti-viral medications. Current research at the University of Minnesota is examining the feasibility of doing this kind of testing on newborns using blood spots obtained as a part of the newborn metabolic screen. Future research will focus on integrating newborn hearing screening programs with newborn CMV screening programs. When CMV testing is combined with genetic testing, it should be feasible in the not-too-distant-future to quickly identify not only the presence of hearing loss, but also the cause of that hearing loss, in order to offer specific interventions to families in a more timely, efficient fashion.
Dr. Schliess is the American Legion Professor of Pediatrics and Director of the Division of Pediatric Infectious Diseases at University of Minnesota Children's Hospital in Minneapolis, Minnesota.
For more information, see the University of Minnesota Department of Pediatrics home web page at http://www.med.umn.edu/peds/id/home.html, or the chapter on "Cytomegalovirus" at emedicine.com/PED/topic544.htm, and the National Congenital Cytomegalovirus Registry, at http://www.bcm.edu/pedi/infect/cmv.