NEWBORN SCREENING PILOT STUDIES

新生儿筛查（NBS）的目标是发现新生儿中可能致命或致残的疾病，从而为早期治疗提供机会，通常是在儿童仍无症状时进行治疗。这种早期发现和治疗可对受影响儿童病情的临床严重程度产生深远影响。如果不加以诊断和治疗，目标疾病的后果可能是可怕的，许多会造成不可逆转的神经损伤；智力、发育和身体残疾；甚至死亡。2006年，美国医学遗传学学院（ACMG）制定了新生儿筛查指南，建议对所有新生儿进行35项“核心疾病”筛查，并报告在核心评估期间确定的26项次要疾病。这些建议被卫生与公众服务部部长新生儿和儿童遗传性疾病咨询委员会（ACHDNC）（由2000年《儿童健康法》授权）和卫生与公众服务部部长接受，并构成了建议统一筛查小组（RUSP）的基础。大多数州现在使用RUSP或非常类似的小组进行新生儿筛查。目前，已经确定了数千种罕见疾病，数百种可能从新生儿筛查中受益。

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 loss, with prompt treatment to prevent language delays or language loss in this high-risk population. Frequent audiologic monitoring at 6-month intervals has been recommended in this population until age 5 years, with more frequent monitoring every 3 months when hearing levels are changing or until the child is talking.11 Cochlear implants are recommended for children with acquired severe hearing loss to improve speech and language outcomes.12 NBS screening for cCMV, whether population-wide or targeted only to infants who fail their newborn hearing screening, raises important ethical and public health considerations, including concerns about both under- and over-diagnosis, overtreatment of asymptomatic screen-positive infants, parental anxiety and vulnerable child syndrome, and the added burden on state public health programs.