Perinatal cytomegalovirus and toxoplasmosis: challenges of antepartum therapy.

The purpose of antepartum and neonatal therapy for congenital infections is to reduce the potential for short-term and long-term morbidity and mortality. The degree of clinical acceptance of antepartum and/or neonatal therapy varies greatly among the congenital infections classified as "TORCH" (Toxoplasma, rubella, cytomegalovirus, herpes simplex) infections. The use of acyclovir to prevent or reduce the severity of neonatal herpes infections is considered standard therapy for infants with potential perinatal exposure. Maternal antepartum therapy for syphilis with penicillin targeting achievement of adequate fetal drug levels is considered the standard of care to reduce the sequelae of congenital syphilis. Although there is no real "therapy" for congenital rubella, the prevention of sequelae of congenital rubella is best achieved by primary prevention (preventing maternal infection) by vaccination of all women of childbearing age with rubella vaccine before conception (because it contains a live-attenuated virus, rubella vaccine is contraindicated during pregnancy). The status of antepartum therapy and primary prevention to decrease the sequelae of congenital cytomegalovirus (CMV) and toxoplasmosis is much less clear than for the other TORCH infections. To validate the utility of antepartum or neonatal therapy in reducing the sequelae of congenital infection, one must first understand the patterns of morbidity (both short-term and long-term) and mortality associated with a specific congenital infection in the absence of treatment. This must include an understanding of the severity as well as the frequency of each of the significant sequelae reported for that type of infection. Only after exploring the natural history of congenital infection can we proceed to determining the efficacy of potential therapeutic regimens. Congenital infections can produce a wide variety of sequelae, some immediately apparent (structural defects, intrauterine fetal demise), others discovered only after the passage of time (developmental delay, progressive sensory loss). Congenital rubella is associated with structural defects, and congenital syphilis may cause fetal demise. Congenital infections with CMV and Toxoplasma gondii are more commonly linked with long-term sequelae that may not be apparent at birth and even until the child reaches school age. The long-term sequelae associated with congenital CMV and toxoplasmosis can be categorized into sensory deficits, developmental delay/mental retardation, and central nervous system lesions. Ocular abnormalities including chorioretinitis, optic nerve atrophy, and retinal detachment occur more commonly after congenital toxoplasmosis. In contrast, sensorineural hearing loss due to cochlear or eighth nerve lesions occurs more typically as a sequelae of congenital CMV.1 Central nervous system lesions that may occur after either CMV or toxoplasmosis include intracranial calcifications, microcephaly, hydrocephalus, and periventricular radiolucencies (low brain substance density extending from the frontal and occipital horns to surround the lateral ventricles). Central nervous system lesions can be diagnosed by ultrasound (intrauterine or neonatal), computed tomography (CT), or magnetic resonance imaging (MRI). Developmental delay and mental retardation commonly are assessed using the Bayley Scales of Infant Development and/or the Wechsler Primary and Preschool Scale of Intelligence.2 Ocular abnormalities are detected by fundoscopic examination, pupillary reflexes, visual acuity, and refractive status.1 Sensorineural hearing loss must be differentiated from conductive hearing loss (due to external or middle ear lesions) by Auditory Evoked Brainstem Responses or Impedance Audiometry. For both CMV and toxoplasmosis, we will describe prevalence, modes of transmission, mechanisms of congenital infection, immediate and long-term sequelae of congenital infection, potential for antepartum prophylaxis/therapy to reduce neonatal sequelae, and methods for primary prevention by prevention of maternal infection.