The goal of newborn screening (NBS) is to detect potentially fatal or disabling conditions in newborns, thereby providing a window of opportunity for early treatment, often while the child is still asymptomatic. Such early detection and treatment can have a profound impact on the clinical severity of the condition in the affected child. If left undiagnosed and untreated, the consequences of the targeted disorders can be dire, many causing irreversible neurological damage; intellectual, developmental, and physical disabilities; and even death. In 2006, the American College of Medical Genetics (ACMG) developed newborn screening guidelines that recommend that all newborn infants be screened for 35 "core conditions" and that 26 secondary conditions identified during the core evaluations be reported. These recommendations were accepted by the HHS Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000) and by the Secretary of HHS, and formed the basis of the Recommended Uniform Screening Panel (RUSP). Most states now use the RUSP or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening. Congenital cytomegalovirus (cCMV) is the most common congenital infection and is estimated to occur in 0.6% of all pregnancies, impacting ~23,000 births in the United States each year.1 This makes cCMV more common than most conditions currently on the RUSP. The manifestations of cCMV are highly variable and include sensorineural hearing loss (SNHL), developmental delays, and visual impairment. The extreme presentation at birth is one of microcephaly, hepatosplenomegaly, petechiae, seizures, and jaundice, occurring in ~10-15% of infected newborns and resulting in infant death in 5-10% of those with symptoms.2,3 In addition, of those newborns who are symptomatic, 50-90% will have long-term neurologic and developmental complications.4 However, the remaining ~90% of newborns with cCMV will be clinically asymptomatic at birth. For asymptomatic newborns, the risk of long-term sequelae is ~10% to 15%, which often presents as isolated SNHL, and may not be detected through newborn hearing screening as it may be late onset or progressive, presenting through age 5 years.5, 6 If an infant diagnosed with cCMV develops symptoms, treatment with antiviral medications (IV ganciclovir, oral valganciclovir) has been shown to improve outcomes with regard to hearing and development, 7,8 although some of these gains have not been sustained in more recent reviews.9 However, transient neutropenia is a known side effect of the treatment, which has led some experts to not routinely recommend antiviral treatment of asymptomatic infected infants.10 Nonetheless, identification of asymptomatic infants with cCMV allows for neurodevelopmental evaluation, follow-up, and monitoring for hearing ...