NEWBORN SCREENING PILOT STUDIES

新生儿筛查（NBS）的目标是检测新生儿中潜在的致命或致残性疾病，从而为早期治疗提供机会，通常在儿童仍无症状时进行。这种早期发现和治疗可以对受影响儿童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，美国医学遗传学学会（ACMG）制定了新生儿筛查指南，建议对所有新生儿进行35种“核心疾病”的筛查，并报告在核心评估期间发现的26种次要疾病。这些建议被HHS秘书的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HHS秘书接受，并构成了推荐统一筛查小组（RUSP）的基础。大多数州现在使用RUSP或非常类似的面板进行新生儿筛查。目前，已经发现了数千种罕见疾病，数百种可能从新生儿筛查中受益。 先天性巨细胞病毒（cCMV）是最常见的先天性感染，估计发生在所有妊娠的0.6%中，每年影响美国约23，000例新生儿。1这使得cCMV比目前RUSP上的大多数疾病更常见。cCMV的表现是高度可变的，包括感音神经性听力损失（SNHL）、发育迟缓和视力损害。出生时的极端表现是小头畸形、肝脾肿大、瘀点、癫痫发作和黄疸，约10-15%的感染新生儿会发生，5-10%的感染新生儿会导致婴儿死亡。2，3此外，在有症状的新生儿中，50-90%会有长期的神经系统和发育并发症。4然而，其余约90%的cCMV新生儿在出生时无临床症状。对于无症状的新生儿，长期后遗症的风险约为10%至15%，通常表现为孤立的SNHL，并且可能无法通过新生儿听力筛查检测到，因为它可能是迟发性或进行性的，直到5岁。 如果被诊断患有cCMV的婴儿出现症状，则应使用抗病毒药物（IV）治疗 更昔洛韦、口服缬更昔洛韦）已经显示出改善听力方面的结果， 然而，一过性中性粒细胞减少症是治疗的已知副作用，这使得一些专家不建议对无症状感染婴儿进行常规抗病毒治疗。10尽管如此，无症状cCMV婴儿的鉴定允许神经发育评估，随访和听力损失监测，及时治疗，以防止这一高危人群的语言延迟或语言丧失。建议在该人群中以6个月为间隔进行频繁的听力学监测，直到5岁，当听力水平发生变化时或直到儿童开始说话时，每3个月进行一次更频繁的监测。11建议对获得性重度听力损失的儿童进行耳蜗植入术，以改善言语和语言结果。12 NBS筛查cCMV，无论是在整个人群中还是仅针对新生儿听力筛查失败的婴儿，都提出了重要的伦理和公共卫生考虑，包括对诊断不足和过度诊断、无症状筛查阳性婴儿的过度治疗、父母焦虑和脆弱儿童综合征的担忧，以及州公共卫生项目的额外负担。

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.