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

基本信息

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
项目类别：
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

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

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项目摘要

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，估计在所有怀孕的0.6％中发生，每年影响约23,000例出生。这使得CCMV比当前在建议的统一筛选面板（RUSP）上的大多数条件更为常见。 CCMV的表现高度可变，包括感官听力损失（SNHL），发育延迟和视觉障碍。出生时的极端表现是小头畸形，肝脾肿大，petechiae，癫痫发作和黄疸，发生在约10-15％的被感染的新生儿中，并导致5-10％的患有症状患者的婴儿死亡。此外，在那些有症状的新生儿中，有50-90％的新生儿将具有长期神经系统和发育并发症。但是，剩下的约90％的CCMV新生儿在出生时在临床上是无症状的。对于无症状的新生儿，长期后遗症的风险约为10％至15％，通常以孤立的SNHL表示，并且可能不会通过新生儿听力筛查来检测到，因为它可能迟到或渐进式，直到5岁。如果被诊断出患有CCMV的婴儿会出现症状，则证明使用抗病毒药药治疗（IV Ganciclovir，口服Valganciclovir）可以改善听力和发育的结果，尽管其中一些收益在最近的评论中尚未持续。然而，瞬时中性粒细胞减少是该治疗的已知副作用，这导致一些专家不常规建议对无症状感染的婴儿进行抗病毒治疗。尽管如此，对患有CCMV的无症状婴儿的识别允许神经发育评估，随访和监测听力损失，并迅速治疗以防止这种高危人群的语言延迟或语言丧失。建议在该人群中以6个月的间隔进行频繁的听力监测，直到5岁，每3个月听力水平发生变化或直到孩子说话时，每3个月进行一次监测。建议对获得严重听力损失的儿童进行耳蜗植入物，以改善言语和语言结果。 NBS筛查CCMV，无论是在人口范围内还是针对新生儿听力筛查的婴儿，都提出了重要的道德和公共卫生考虑因素，包括对不足和过度诊断的担忧，无症状的筛查阳性婴儿的过度治疗，父母的焦虑和易受伤害的儿童综合症，以及对国家公共卫生综合计划的负担。最近的RUSP提名将CCMV提名退回提交者，原因是缺乏证据，包括需要更多有关如何识别哪些病例将受益于治疗的数据，不确定的临床效用，从人群范围的早期诊断提供的临床效用，而不是对听力屏幕的反射测试，以及建议的筛查阳性婴儿的建议随访和治疗方案。前瞻性鉴定出的具有纵向数据收集的婴儿的CCMV阳性队列将有助于记录感染的自然历史，从而增强我们对结果以及潜在风险和修改因素的理解，以预测这些新生儿的结果。 Eunice Kennedy Shriver国家儿童健康与人类发展研究所（NICHD）有兴趣通过支持对筛查阳性婴儿进行的后续研究来扩展授予的CCMV试点研究，以更好地了解将CCMV筛选纳入NBS计划的影响，以解决对CCMV ccmv coding to and nbs计划的国家计划的重要证据差距。这项工作将支持有关筛查阳性婴儿的其他后续数据收集，以收集有关听力，发育和神经系统结果的纵向数据，以及对感染婴儿及其护理人员的生活质量的测量。