NEWBORN SCREENING FOLLOW-UP STUDY OF CONGENITAL CYTOMEGALOVIRUS (CCMV) INFECTION

先天性巨细胞病毒 (CCMV) 感染的新生儿筛查随访研究

• 批准号: 10937099
• 负责人: MICHELE CAGGANA
• 金额: $ 349.47万
• 依托单位: NYSDOH/HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-28 至 2026-09-27
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10937099
• 关键词: 5 year old; Address; Advisory Committees; Advocate; Age; Antiviral Agents; Anxiety; Appointment; Audiology; Award; Birth; Birth Weight; Callback; Caregiver Burden; Caregivers; Child; Childhood; Clinic; Clinical; Cochlear Implants; Collection; Communication; Consultations; Contractor; Data; Data Collection; Detection; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Early Diagnosis; Educational Materials; Electronic Health Record; Electronics; Eligibility Determination; Enrollment; Ethics; Ethnic Origin; Evaluation; Family; Focus Groups; Follow-Up Studies; Ganciclovir; Geography; Gestational Age; Goals; Health; Health Personnel; Health system; Hearing; Hearing Tests; Hepatosplenomegaly; Icterus; Infant; Infant Care; Infection; Infrastructure; Intervention; Language; Language Delays; Length; Measurement; Measures; Medical Records; Mental Depression; Microcephaly; Modality; Monitor; National Institute of Child Health and Human Development; Natural History; Neonatal Screening; Neurologic; Neurological outcome; Neutropenia; Newborn Infant; Oral; Outcome; Outcome Assessment; Parents; Persons; Petechiae; Pilot Projects; Population; Predictive Factor; Pregnancy; Pregnancy Histories; Prevalence; Privatization; Process; Protocols documentation; Public Health; Qualitative Methods; Quality of Life Assessment; Quality of life; Race; Recommendation; Reflex action; Resources; Risk; Screening Result; Seizures; Sensorineural Hearing Loss; Sign Language; Social Impacts; Specialist; Speech; Stigmatization; Suggestion; Support Contracts; Surveys; Symptoms; Syndrome; Terminology; Testing; Therapeutic Intervention; Time; Translational Research; Treatment Protocols; Treatment Side Effects; United States; Valganciclovir; Viral; Visual impairment; Well Child Visits; Work; caregiver stress; cohort; congenital cytomegalovirus; congenital infection; cost effective; data repository; data resource; delivery complications; evidence base; follow-up; health assessment; hearing impairment; hearing screening; high risk population; improved; improved outcome; infant death; infant infection; infant outcome; instrument; interest; language outcome; long-term sequelae; medical specialties; neonatal infection; outcome prediction; overtreatment; prevent; primary care provider; programs; prospective; screening; screening panel; screening program; sex; side effect; telehealth; tool; trait; virtual

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. This makes cCMV more common than most conditions currently on the Recommended Uniform Screening Panel (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. In addition, of those newborns who are symptomatic, 50-90% will have long-term neurologic and developmental complications. 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. 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, although some of these gains have not been sustained in more recent reviews. 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. 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. Cochlear implants are recommended for children with acquired severe hearing loss to improve speech and language outcomes. 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. The recent RUSP nomination for cCMV was returned to the submitters for lack of evidence including the need for more data on how to identify which cases will benefit from treatment, uncertain clinical utility afforded by population-wide early diagnosis relative to reflex testing for failed hearing screens, and the recommended follow-up and treatment protocol for screen-positive infants. A prospectively identified cCMV-positive cohort of infants with longitudinal data collection would help record the natural history of the infection, thereby enhancing our understanding of outcomes and of potential risk and modifying factors that predict outcomes for these newborns. The Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) is interested in expanding on the awarded cCMV pilot study by supporting a follow-up study of screen positive infants to better understand the impacts of incorporating cCMV screening into NBS programs, in order to address important evidence gaps for state programs considering adding cCMV screening to their NBS program. This effort will support additional follow-up data collection on screen-positive infants to gather longitudinal data on audiologic, developmental, and neurological outcomes, as well as measurements of quality of life for infected infants and their caregivers.

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。 这使得cCMV比目前推荐的统一筛选小组（RUSP）上的大多数条件更常见。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%的感染新生儿发生，5-10%有症状的新生儿死亡。 此外，在有症状的新生儿中，50-90%将有长期的神经和发育并发症。 然而，其余约90%的cCMV新生儿在出生时将无临床症状。对于无症状新生儿，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。 如果诊断为cCMV的婴儿出现症状，抗病毒药物治疗（IV更昔洛韦，口服缬更昔洛韦）已被证明可以改善听力和发育方面的结果，尽管其中一些成果在最近的综述中并没有持续。 然而，一过性中性粒细胞减少症是治疗的已知副作用，这导致一些专家不建议对无症状感染的婴儿进行常规抗病毒治疗。 尽管如此，识别无症状的cCMV婴儿可以进行神经发育评估，随访和听力损失监测，并及时治疗，以防止这一高危人群的语言延迟或语言丧失。 在5岁之前，建议在该人群中以6个月为间隔进行频繁的听力监测，当听力水平发生变化时或直到儿童开始说话时，每3个月进行更频繁的监测。 建议对获得性严重听力损失的儿童进行耳蜗植入，以改善言语和语言结果。 国家统计局对cCMV的筛查，无论是全人群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问题，包括对诊断不足和过度诊断的担忧，对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，以及对国家公共卫生计划的额外负担。 由于缺乏证据，最近RUSP对cCMV的提名被退回给提交者，包括需要更多关于如何确定哪些病例将从治疗中受益的数据，与听力筛查失败的反射测试相关的人群范围内早期诊断提供的临床效用不确定，以及筛查阳性婴儿的推荐随访和治疗方案。一个前瞻性确定的cCMV阳性婴儿队列与纵向数据收集将有助于记录感染的自然史，从而提高我们的结果和潜在的风险和修改因素，预测这些新生儿的结果的理解。 Eunice Kennedy Shriver国家儿童健康与人类发展研究所（NICHD）有兴趣通过支持筛查阳性婴儿的后续研究来扩大已授予的cCMV试点研究，以更好地了解将cCMV筛查纳入NBS计划的影响，以解决考虑将cCMV筛查纳入其NBS计划的州计划的重要证据差距。 这项工作将支持对筛查阳性婴儿进行额外的随访数据收集，以收集有关听力学、发育和神经学结果的纵向数据，以及受感染婴儿及其护理人员生活质量的测量结果。