NEWBORN SCREENING PILOT STUDIES

新生儿筛查试点研究

• 批准号: 10710760
• 负责人: MICHELE CAGGANA
• 金额: $ 136.19万
• 依托单位: NYSDOH/HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2024-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710760
• 关键词: 5 year old; Address; Advisory Committees; Affect; American; Antiviral Agents; Anxiety; Biological Assay; Birth; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Child Health; Clinical; Cochlear Implants; Contractor; Cytomegalovirus; DNA; DNA-Directed DNA Polymerase; Data; Detection; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Disease; Early Diagnosis; Early treatment; Ethics; Evaluation; Future; Ganciclovir; Goals; Hearing; Hepatosplenomegaly; Hereditary Disease; Icterus; Infant; Infection; Intellectual functioning disability; Language; Language Delays; Left; Life; Medical Genetics; Methods; Microcephaly; Minnesota; Monitor; Neonatal Screening; Nervous System Trauma; Neurologic; Neutropenia; Newborn Infant; Oral; Petechiae; Pilot Projects; Polymerase Chain Reaction; Population; Population Heterogeneity; Pregnancy; Prevalence; Public Health; Randomized; Rare Diseases; Recommendation; Reporting; Risk; Saliva; Sampling; Seizures; Sensorineural Hearing Loss; Severities; Source; Specificity; Speech; Spottings; Symptoms; Syndrome; Testing; Time; Tissues; Treatment Side Effects; United States; Universities; Urine; Valganciclovir; Viral Load result; Visual impairment; base; congenital cytomegalovirus; congenital infection; follow-up; hearing impairment; hearing loss risk; hearing screening; high risk population; improved; improved outcome; infant death; infant infection; language outcome; long-term sequelae; medical schools; neonatal infection; neonate; overtreatment; physically handicapped; population based; prevent; programs; salivary assay; screening; screening guidelines; screening panel; screening program; symptom treatment

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.

新生儿筛查（NBS）的目的是检测新生儿的潜在致命或残疾状况，从而为早期治疗提供机会窗口，而孩子通常仍然无症状。这种早期检测和治疗可能会对受影响儿童的病情的临床严重程度产生深远的影响。如果未诊断和未经治疗，靶向疾病的后果可能是可怕的，许多人会造成不可逆转的神经系统损害。智力，发展和身体残疾；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，建议对所有新生婴儿进行35个“核心条件”的筛查，并报告了核心评估期间确定的26个二级疾病。这些建议被新生儿和儿童（ACHDNC）的HHS秘书秘书咨询委员会（2000年《儿童健康法》授权）和HHS秘书，并构成了推荐统一筛查小组（RUSP）的基础。现在，大多数州都使用RUSP或非常相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，数百种可能会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，估计在所有妊娠的0.6％中发生，每年影响约23,000个出生。1这使得CCMV比目前在RUSP上的大多数情况更常见。 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。 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患有CCMV的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，因为它可能会发作迟到或渐进式。 如果诊断为CCMV的婴儿会出现症状，则使用抗病毒药物治疗（IV Ganciclovir，口服Valganciclovir）已显示可改善听力和 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在这个高危人群中。在该人群中建议在6个月间隔内进行频繁的听觉监测，直到5岁，每3个月进行听力水平发生变化或直到儿童说话时进行一次更频繁的监控。11建议患有严重听力损失的儿童，以改善语言和语言的结果。对未诊断和过度诊断，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症的关注以及对州公共卫生计划的增加负担。